Systems-Based Emergency Medicine Course Objectives: Psychiatric/Behavioral Health Emergencies PA 605 ER

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For each of the following psychiatric/behavioral medicine conditions, students should describe the underlying pathophysiology, presenting signs and symptoms, basic epidemiology, modifiable (when applicable) and non-modifiable risk factors, differential diagnosis, appropriate diagnostic studies, clinical intervention, treatment guidelines, pharmaceutical therapies, and health maintenance concerns: Posttraumatic stress disorder

ACUTE STRESS DISORDER • Acute stress disorder (ASD) is characterized by acute stress reactions that may occur in the initial month after a person is exposed to a traumatic event (threatened death, serious injury, or sexual violation), lasting for 3 days - 30 days. DIAGNOSTIC CRITERIA • Symptoms similar to PTSD except the traumatic event occurred < 1 month ago and the symptoms last 3 days up to 1 month after the trauma exposure. • The symptoms include intrusive symptoms, avoidance, increased arousal, and negative alterations in thought and mood (see PTSD for list of symptoms). • The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. • The disturbance is not attributable to the physiological effects of a substance (eg, medication or alcohol) or another medical condition. MANAGEMENT: • Cognitive behavioral therapy: Counseling & Trauma-focused cognitive-behavioral therapy (CBT) as first-line treatment of patients with acute stress disorder (ASD) rather than other psychotherapies or medication because by definition the symptoms will resolve in 1 month. • Exposure, a component of trauma-focused CBT, has been found to be more effective when provided as monotherapy than cognitive restructuring in patients with ASD. • If symptoms > 1 month, treat as PTSD. • Pharmacotherapy: For patients with ASD and acute, intense anxiety, agitation, or sleep disturbance in the immediate period following the traumatic event, adjunctive treatment with a Benzodiazepine rather than other medications may be considered, but should be limited to 2-4 weeks. • EXAM TIP • Posttraumatic stress disorder (PTSD) and Acute stress disorder (ASD) have the same symptoms. The difference is time of event & duration of symptoms. • ASD: trauma occurs <1 month AND symptoms < 1 month in duration • PTSD: trauma occurred at any time in the past >1 month OR symptoms > 1 month POSTTRAUMATIC STRESS DISORDER (PTSD) • STD is a syndrome resulting from exposure to real, threatened, or perceived serious injury or sexual assault with symptoms lasting > 1 month &/or the event occurred >1 month ago. DIAGNOSTIC CRITERIA • (A) Stressor: Exposure to actual or threatened death, serious injury, or sexual violence via 1) direct experience of the traumatic event, 2) witnessing the event in person, 3) learning the event happened to someone close (family member or friend) or 4) experiencing extreme or repeated exposure to aversive details of the traumatic event (eg first responders collecting human remains during 9/11, war, sexual assault, natural disasters). • (B) Duration: Symptoms last > 1 month. Traumatic event occurred anytime in the past (may occur immediately after the trauma or with delayed expression). • (C) Recurrent intrusions: Presence of at least 1 of the following intrusion symptoms after the event that may lead to significant distress or impairment in function (eg, occupational, social or other areas). Re-experiencing: >1 month of recurrent intrusions, such as repetitive recollections (eg, distressing dreams, nightmares, memories) & dissociative reactions (eg, flashbacks in which the person feels/acts as if the event is recurring), leading to physiologic distress &/or physiologic reactions. Intense distress at exposure to cues relating to the trauma; or physiological reactions to cues relating to the trauma. • (D) Active avoidance of triggering stimuli associated with the traumatic event (reminders of the events, such as memories, feelings, people, places, objects). • (E) Negative alterations in mood: At least 2 negative alterations in cognition & mood: inability to remember an important aspect of the event, dissociative amnesia, negative feelings of self, world or others, anhedonia, negative emotions (eg, horror guilt, anger or shame, self-blame), dissociation (eg, feelings of detachment from oneself or reality), or inability to experience or express positive emotions. • (F) Alterations in Arousal & Reactivity: At least 2 arousal & reactivity symptoms: angry outbursts, irritable behavior, reckless or self-destructive behaviors, hypervigilance, sleep disturbances, concentration issues, & exaggerated startle response. • (G) The disturbance causes significant functional impairment or distress in various areas of life, such as social or occupational. • (H) Symptoms not the direct cause of a substance or another medical condition. MANAGEMENT Behavioral therapy: • For most adults newly treated for PTSD, first-line treatment with a trauma-focused psychotherapy that includes exposure rather than a serotonergic reuptake inhibitor (SRI) is often recommended. • Trauma-focused psychotherapy is considered as the first-line treatment in adults as well as children, and it includes trauma-focused CBT (cognitive-behavioral therapy), eye movement desensitization and reprocessing (EMDR), cognitive processing therapy, and imaginal exposure. Pharmacotherapy: • SSRIs first-line medical treatment (eg, Paroxetine, Sertraline, Fluoxetine) or SNRIs (eg, Venlafaxine). Tricyclic antidepressants (eg, Imipramine). MAO inhibitors. May be augmented with atypical antipsychotics. • Trazodone may be helpful for insomnia. • Prazosin is an alpha-1 agonist that may be used to reduce nightmares, sleep disturbance, and some symptoms, such as hypervigilance. • Prazosin and Clonidine are useful in decreasing trauma-related nightmares. • Clonidine and Guanfacine may be used for agitation. ADIUSTMENT DISORDER • Adjustment disorder occurs when maladaptive behavioral or emotional symptoms develop after a stressful or non-life threatening event - eg, relationship issues (eg, divorce, breakups, marital problems, getting married), death of a loved one, work issues (eg, loss of a job, failing to meet goals), having a baby, serious health issues, school issues, financial difficulties. CLINICAL MANIFESTATIONS: • One or both of the following - marked distress out of proportion to the severity of stressor and/or significant impairment in areas of functioning (eg, occupational, social, etc.). • May manifest as depressed mood, lack of enjoyment, anxiety, hopelessness, disturbance of conduct, nervousness, anxiety, desperation, feeling overwhelmed and thoughts of suicide, performing poorly in school/work etc. DIAGNOSTIC CRITERIA • Maladaptive emotional or behavioral reaction to an identifiable stressor (eg, job loss, physical illness, leaving home, divorce, etc.) or a non-life threatening event that causes a disproportionate response than would normally be expected within 3 months of the stressor (does not include bereavement) & resolves usually within 6 months of the stressor. • These symptoms produce either excessive distress in relation to the event, significant impairment in daily functioning. • The stress-related disturbance does not meet criteria for another mental disorder. MANAGEMENT: • Psychotherapy initial management of choice (including individual or group therapy). • Medications may be used in selected cases but they are not the preferred treatment. • Patients may self-medicate with alcohol or other drugs. PROGNOSIS • Unlike major depression, Adjustment disorder is caused by an outside stressor and generally resolves once the individual is able to adapt to the situation.

Extrapyramidal symptoms

ADVERSE EFFECTS OF ALL ANTIPSYCHOTICS Extrapyramidal symptoms (EPS): • EPS due to dopamine blockade in nigrostriatal pathway, especially with the first-generation (typical agents) Haloperidol and Fluphenazine due to higher affinity for the D2 receptor. • Second-generation (atypical) antipsychotics are associated with less EPS and anticholinergic side effects as compared to traditional antipsychotics • Acute dystonia muscle spasms of the face, neck, tongue, and other muscles leading to abnormal movements or postures as well as trouble swallowing. Most common within 3-4 hours to days of use. Management: Anticholinergics (Benztropine, Diphenhydramine, Trihexyphenidy]). • Parkinsonism resting tremor, rigidity, bradykinesia. Occurs within 3 days weeks. Management: Anticholinergics (Benztropine, Diphenhydramine, Trihexyphenidy]). • Akathisia sustained feeling of motion or restlessness may occur after a month - 3 months of use. Management: Benzodiazepines and/or Beta blockers may be used. • Tardive dyskinesia repetitive, involuntary, stereotypical movements like grimacing, chewing, lip-smacking, writhing movement of hands. TD is most common in older women after at least 6 months of therapy, usually after years. Management: stop high potency D2 blockers and switch to atypicals (Clozapine preferred - Clozapine is unusual in that it suppresses Tardive dyskinesia). Vitamin E has been shown to prevent further deterioration of Tardive dyskinesia. Valbenazine and Deutetrabenazine may also help TD. Hyperprolactinemia: • Dopamine 2 receptor (D2) blockade in the tuberoinfundibular pathway results in hyperprolactinemia (normally dopamine inhibits prolactin). Prominent with Risperidone. Metabolic adverse effects: • Hyperlipidemia, weight gain, hyperglycemia, and hypertension • 2nd generation > 1st. • Significant weight gain and hyperglycemia due to a diabetogenic action occur with several of the second-generation agents, especially Olanzapine and Clozapine. • Aripiprazole has little or no tendency to cause hyperglycemia, hyperprolactinemia, or weight gain QT prolongation • Can be seen with most of the atypicals, especially Quetiapine and Ziprasidone. • Thioridazine, a low-potency typical antipsychotic, is associated with prolonged QT and increased incidence of Ventricular arrhythmias. Anti-HAM effects: AntiHistamine, AntiAdrenergic, and AntiMuscarinic (anticholinergic) effects. • Antillistaminic effects: weight gain and sedation especially with Chlorpromazine and less with Aripiprazole, Lurasidone, and Haloperidol. Weight gain (5H1 and 5HT-2 blockade). • AntiAdrenergic effects: Orthostatic hypotension (due to alpha adrenoreceptor blockade). Sexual side effects, and tachycardia. • AntiMuscarinic (anticholinergic) effects include dry mouth, constipation, urinary retention, and visual problems are often pronounced with the use of Thioridazine and Chlorpromazine, as well as Clozapine and most of the atypical drugs but not with Ziprasidone or Aripiprazole. Confusion due to blockage of the muscarinic receptors.

AGORAPHOBIA •Intense fear or anxiety about being in places or situations from which escape or obtaining help may be difficult (eg, open spaces such as bridges, enclosed spaces, crowds, public transportation or being outside of the home alone). •Although commonly seen with Panic disorder, Agoraphobia is now seen as a separate entity from panic disorders & can occur with other psychiatric disorders. •The triggering situation causes anxiety or fear out of proportion to the potential danger of the situation. •Symptoms last at least 6 months, cause significant social or occupational dysfunction, & not better explained by another disorder. •Risk factors; strong genetic factor & may follow a traumatic event MANAGEMENT •Similar to Panic disorder: Cognitive behavioral therapy & SSRIs. GENERALIZED ANXIETY DISORDER •More common in females than males 2:1. Onset of symptoms usually occurs in early 20s. •Comorbidity with major depression or other anxiety disorders in the majority of cases of GAD. •Multifocal worry: eg, finance, family, health, interpersonal relationships, work, minor matters, the future. DIAGNOSTIC CRITERIA: •(A) Excessive anxiety and worry (apprehensive expectation), occurring a majority of days (more days than not) for at least 6 months, about a number of and various events or activities (such as work or school performance). It is not episodic (as in panic disorders), situational (as in phobias), nor focal. •[B) The individual finds it difficult to control the worry. •(C) The anxiety and worry are associated with 3 (or more) of the following 6 symptoms (with at least some symptoms having been present for more days than not for the past 6 months): (1) restlessness or feeling keyed up or on edge; (2) being easily fatigued; (3) difficulty concentrating or mind going blank; (4) irritability; (5) muscle tension, (6) Sleep disturbance [difficulty falling or staying asleep, or restless, unsatisfying sleep]. •(D) The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. •(E) The disturbance is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition (eg, hyperthyroidism). •[F) The disturbance is not better explained by another mental disorder. MANAGEMENT: •The combination of psychotherapy + pharmacotherapy is more effective than either alone. •Antidepressants - SSRIs (eg, Fluoxetine, Paroxetine, Escitalopram, Sertraline) and SNRIs (eg, Duloxetine, Venlafaxine) are first-line agents. •Buspirone can be an adjunct to SSRIs or SNRIs (does not cause sedation). •Benzodiazepines can be used for short-term use only until long-term therapy takes effect (watch for dependence or abuse). •Beta-blockers (eg, Propranolol) may be used to help control autonomic symptoms (eg, palpitations, diaphoresis, tachycardia) of panic attacks or performance anxiety. •Tricyclic antidepressants (TCAs) & MAO inhibitors may be used if above medications are not helpful. Psychotherapy: •Cognitive-behavioral therapy (CBT) has proven effective for anxiety disorders, Psychodynamics. SOCIAL ANXIETY DISORDER (Formerly Social Phobia •Most common type of phobia (public speaking). DIAGNOSTIC CRITERIA •(A) Disabling, persistent (at least 6 months) intense fear of social or performance situation in which the person is exposed to the scrutiny of others for fear of embarrassment (eg, public speaking, meeting new people, eating or drinking in front of people, using public restrooms). •(B) The individual fears he or she will act in a way or show anxiety symptoms that will be negatively evaluated (will be humiliating or embarrassing; will lead to rejection or offend others). •(C) The social situations almost always provoke fear or anxiety (expected attacks). •(D) The social situations are avoided or endured with intense fear or anxiety. MANAGEMENT •Psychotherapy (individual Cognitive behavioral therapy) is the mainstay of treatment for Social anxiety disorder and other phobias (desensitization, relaxation, insight-oriented therapy). •Pharmacotherapy: SSRIs (eg, Fluoxetine, Sertraline) or SNRIs (eg, Venlafaxine). Adjunctive use of Benzodiazepines can be used until full effect of SSRIs for patients with need of faster relief. •Most with moderate-severe cases benefit from combination pharmacotherapy & psychotherapy. •Performance only SAD: Medication treatment is often prescribed on an "as needed" basis for performance-only SAD, such as (1) Beta-blockers (eg, Propranolol, Atenolol) preferred or (2) Benzodiazepines (eg, Clonazepam or Lorazepam). SPECIFIC PHOBIAS •Specific phobia: an anxiety disorder characterized by significant fear of a specific object or situation that leads to endurance of the anxiety and /or avoidance of the feared object or situation. DIAGNOSTIC CRITERIA •(A) Persistent (at least 6 months) intense fear or anxiety of a specific situation (eg, heights, flying), object (eg, pigeons, snakes, blood) or place (eg, hospital). •(B) Exposure to the situation triggers an immediate fear response. •(C) The fear is out of proportion to any real danger or threat. •(D) The phobic object or situation is actively avoided when possible or endured (tolerated) with intense fear or anxiety. •(E) Everyday activities must be impaired by distress or avoidance of the situation or object. •(F) Not due to substance use, medical condition, or other mental disorder. SPECIFIERS •Animal (eg, spiders, dogs, mice), situational (eg, airplanes, elevators), natural environment (eg, heights, thunder, water), blood-injection injury (injuries, needle injections, or blood), & other. MANAGEMENT •Exposure & desensitization therapy treatment of choice for Specific phobia (most effective). •Short-term benzodiazepines or Beta-blockers can be used in some patients.

ALZHEIMER DEMENTIA •Most common type of dementia. Usually a disease of older age (>65 years of age). RISK FACTORS •Increasing age, genetics, family history. PATHOPHYSIOLOGY •Unknown - 3 hypotheses: (1) Amyloid hypothesis: extracellular amyloid-beta protein deposition (senile plaques) in the brain are neurotoxic. (2) Tau hypothesis: neurofibrillary tangles (hyperphosphorylated tau proteins) are neurotoxic. (3) Cholinergic hypothesis: acetylcholine deficiency leads to memory, language, & visuospatial changes. •Histologic findings: amyloid-beta protein deposition (senile plaques) in the brain. Amyloid precursor proteins (APP) are normally degraded by alpha-cleavage. Beta cleavage of APP results in Amyloid-beta accumulation. Neurofibrillary tangles = intracellular aggregations of tau protein (an insoluble cytoskeletal microtubule element). CLINICAL MANIFESTATIONS •Short-term memory loss (often first symptom). Progresses to long-term memory loss and cognitive deficits: disorientation, behavioral & personality changes, language difficulties, loss of motor skills etc. Usually gradual in nature. DIAGNOSIS •Clinical diagnosis (no specific test). Workup to rule out other causes include MRI of the brain, CBC, CMP, renal and liver tests, alcohol levels, VDRL or RPR to rule out Syphilis, B12, and thyroid function studies. •Decline in 2+ areas of cognition in MMSE •MRI preferred neuroimaging test - cortex atrophy + ventricular enlargement (eg, medial temporal lobe atrophy), reduced hippocampal volume, white matter lesions. MEDICAL MANAGEMENT •Acetylcholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine. Used to improve memory function & symptom relief for patients with newly diagnosed Alzheimer disease (AD) dementia (does not slow down the disease progression). •NMDA antagonist: Memantine - can be adjunctive or used as monotherapy in moderate to advanced dementia (eg, MMSE <18). Mechanism: blocks NMDA receptor, slowing calcium influx & nerve damage. Glutamate is an excitatory neurotransmitter of the NDMA receptor. Excitotoxicity causes cell death. NMDA antagonists reduce glutamate excitotoxicity. May be adjunctive. •Avoid anticholinergics •time to death = 5-10 years •Aducanumab is approved by the US Food and Drug Administration (FDA) for the treatment of mild AD.

Question: What over-the-counter pain reliever should be avoided in patients with elevated liver enzymes?

Answer: Acetaminophen.

Question: What is the pathophysiology that causes hyperthermia in neuroleptic malignant syndrome?

Answer: Increased metabolic myocyte activity and hypothalamic thermoregulation dysfunction.

Question: What is the mechanism of action of lactulose and rifaximin in treating hepatic encephalopathy?

Answer: Lactulose acidifies gut contents and causes a loss of NH4+ in the stool, and rifaximin is an antibiotic against colonic flora that produce ammonia.

Question: Why would a patient with a medication-induced dystonic reaction develop airway compromise?

Answer: Laryngeal dystonia leading to airway obstruction.

Question: Which frequently used benzodiazepine is unaffected by hepatic metabolism status?

Answer: Lorazepam. In contrast, diazepam, midazolam, and chlordiazepoxide all undergo significant hepatic metabolism, which can result in accumulation of parent drug and associated prolonged drug effects in those with impaired liver function.

Question: What is a common cause of cathartic colon in bulimia nervosa?

Answer: Prolonged laxative use.

Question: Which nicotinic acetylcholine receptor partial agonist is commonly used for smoking cessation?

Answer: Varenicline.

Benzodiazepine Toxicity RAPID REVIEW

Ataxia, lethargy, respiratory depression No change in pupil size (unlike opioid toxicity) Supportive care, flumazenil in benzodiazepine-naive patients (can precipitate seizures)

BIPOLAR I DISORDER •Risk factors: family history (1st-degree relatives) strongest risk factor (10 times more likely). Men = women. •1% of population. Average age of onset is 20s - 30s. New onset rare after 50y •The earlier the onset, the greater likelihood of psychotic features & the poorer the prognosis. DIAGNOSTIC CRITERIA •At least 1 Manic or mixed episode (only requirement). The manic episodes often cycle with occasional depressive episodes but major depressive episodes are not required for the diagnosis. • Mania = abnormal & persistently elevated, expansive or irritable mood at least 1 week (or less if hospitalization is required) with marked impairment of social/occupational function At least 3: Mood: euphoria, irritable, labile or dysphoric; Thinking; racing, flight of ideas, disorganized, easily distracted, expansive or grandiose thoughts (highly inflated self-esteem). Judgment is impaired (g, spending sprees); Behavior: physical hyperactivity, pressured speech, decreased need for sleep (may go days without sleep), increased goal directed activity. Excessive involvement in activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, risk-taking or foolish business investments). • Psychotic symptoms (paranoia, delusions, hallucinations) may be seen in these patients. • Symptoms not due to medical condition or substance use. MANAGEMENT • Mood stabilizers (eg, Lithium, Valproic acid, and Carbamazepine), or second- generation (atypical) antipsychotics are often used for Bipolar disorder. • Mood Stabilizers: Lithium first-line (acute mania & long-term management). Lithium also decreases suicide risk. Valproic acid or Carbamazepine used for rapid cycling or mixed features. • 2nd-generation (atypical) antipsychotics: (eg, Risperidone, Quetiapine, Olanzapine & Ziprasidone) are effective as monotherapy or as adjunctive therapy to mood stabilizers combination of mood stabilizers and antipsychotics is faster & more effective than monotherapy. • Psychotherapy: cognitive, behavioral & interpersonal. Good sleep hygiene recommended. • Bipolar depression: The FDA has approved 4 psychotropics in the setting of acute bipolar depression: Lurasidone, Cariprazine, Quetiapine, & the Olanzapine-Fluoxetine combination. Bipolar depression often persists longer, and it is very challenging to treat, needing a different approach from that used in unipolar depression. • Antidepressant therapy may be used as adjunct to mood stabilizers for severe depression but antidepressant monotherapy may precipitate mania or hypomania. ACUTE MANIA • Mood stabilizers (eg, Lithium, Valproic acid) or Antipsychotics (eg, Risperidone or Olanzapine > Haloperidol). • Antipsychotics or benzodiazepines can be used for acute psychosis or agitation. • Electroconvulsive therapy especially helpful for refractory or life-threatening acute mania or depression (also best treatment for pregnant women with manic episodes). Decreased suicidality

Marijuana intoxication and withdrawal

CLINICAL MANIFESTATIONS • Euphoria, giddiness, anxiety, disinhibition, intensification of sensory experiences, dry (cotton) mouth, increased appetite, and motor impairment. • Some patients may experience fear and depression. Psychosis may occur. • Chronic use can lead to cognitive performance issues. Conjunctivitis, tachycardia, and hypotension. MANAGEMENT • Treatment is usually not needed. Symptomatic management if needed. • Hyperemesis syndrome: Chronic severe emesis in chronic users. Managed with cessation of marijuana use and antiemetics (Ondansetron & Metoclopramide). WITHDRAWAL • Irritability, insomnia, depression, restlessness, diaphoresis, diarrhea, and twitching.

Cocaine intoxication and withdrawal

COCAINE INTOXICATION • Cocaine can be snorted, swallowed, injected, or smoked. MECHANISM: CNS effects: • Cocaine produces a stimulant effect via inhibition of the reuptake of the CNS neurotransmitters dopamine, norepinephrine and epinephrine in the synaptic cleft (has marked Amphetamine. like effects). • Dopamine plays a role in the "reward" system of the brain. • The euphoria, self-confidence, and mental alertness produced by Cocaine are short-lasting and positively reinforce its continued use. Cardiovascular effects; • The principal actions of Cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. • Cocaine toxicity may cause tachycardia, dysrhythmia, hypertension, and coronary vasospasm, leading to pathological sequelae such as acute coronary syndrome, stroke, and death. • Tachycardia: Excess catecholamine release can lead to tachycardia. Cocaine causes sodium channel blockade (unlike Methamphetamine), which may trigger refractory tachydysrhythmias & re- entry ventricular arrhythmias. • Hypertension: Cocaine-induced hypertension results from excess monoamines, such as dopamine, norepinephrine, and epinephrine, in the central nervous system and peripheral circulation, causing alpha- and beta-adrenergic stimulation. Like Methamphetamine, Cocaine prevents the reuptake of catecholamines, increasing sympathetic tone, causing hypertension and coronary vasospasm. • Thrombosis: Cocaine-induced platelet activation and thrombus formation caused by alpha-adrenergic-and adenosine diphosphate-mediated increase in platelet aggregation may result in macro- and microvascular occlusion, ischemia, and increased risk of cardiac dysrhythmia. • Long-term use of Cocaine can also alter cardiac histology leading to fibrosis, myocarditis, and contraction band necrosis. CLINICAL MANIFESTATIONS: • CNS stimulation: Elevated or euphoric mood, psychomotor agitation, paranoia, pressured speech, altered mental status. • May progress to nausea, vomiting & seizures. Chest pain. Physical examination: • Sympathetic hyperactivity - increased motor activity, tremor, flushing, hyperthermia (may be as high as 45°C), diaphoresis, cold sweats, & pupillary dilation. • The excess catecholamines may cause hypertension, tachycardia, agitation, and aggression (however, bradycardia &/or hypotension may also be seen). Severe intoxication: • Respiratory depression, arrhythmias, hypertension, seizures, repetitive behaviors (eg, picking at skin), agitation, aggression, hallucinations, and paranoia. • Deaths from Cocaine are usually the result of cardiac arrest, arrhythmias, stroke, myocardial infarction, seizures, or respiratory arrest. Cardiac toxicity is partly due to blockade of norepinephrine reuptake by Cocaine; its local anesthetic action contributes to the production of seizures. The powerful vasoconstrictive action of Cocaine may lead to severe hypertensive episodes, resulting in myocardial infarcts and strokes. DIAGNOSIS; • Depending on the patient's presentation, laboratory testing for suspected Cocaine toxicity may include complete blood count, comprehensive chemistry panel, troponin, -type natriuretic peptide, creatinine kinase, urinalysis, urine toxicology screen, and electrocardiogram. • Creatine kinase and Urinalysis may detect myoglobinuria if Rhabdomyolysis is suspected. • A urine drug screen is a must to detect other illicit substances. Most cocaine disappears from the body within 24 hours, but the metabolite, benzoylecgonine, may persist for weeks. This metabolite can also cause neurotoxicity. Troponin if myocardial infarction is suspected. • An ECG should be done if the patient has chest pain, dyspnea, irregular pulse, or hypoxia. MANAGEMENT: • Patients with Cocaine toxicity need to be stabilized, and the ABCDEs should be assessed. The treatment should be based on clinical symptoms, and one should avoid physical restraints. • Benzodiazepines are first-line management of cocaine-induced agitation and cardiovascular toxicity to decrease CNS sympathetic outflow. Mild: • Reassurance and Benzodiazepines. Severe agitation or psychosis: • Benzodiazepines is first-line treatment with agitation, but antipsychotics such as Haloperidol and Olanzapine may also be useful. • Diphenhydramine is often added to enhance sedation and as prophylaxis against dystonia and akathisia. A common example of this is the "B-52" with its combination of Haloperidol (5 mg), Diphenhydramine (50 mg), and Lorazepam (2 mg). Do not place in restraints (may lead to Rhabdomyolysis). Cardiovascular effects: • Benzodiazepines are first-line because to decreased CNS stimulation because most of the cardiovascular effects (eg tachycardia, tachydysrhythmia, hypertension) in cocaine toxicity are centrally mediated via the sympathetic system. • Phentolamine, an alpha blocker, may be used in patients with refractory or symptomatic cocaine- induced hypertension to counteract the alpha-adrenergic vasoconstrictive effects of cocaine. • Nitroglycerin or Nitroprusside are suitable alternative medications for the management of refractory hypertension because they are vasodilators without beta blocking effects. Nitroglycerin also helpful for Myocardial infarction. • Non-dihydropyridine calcium channel blockers (eg, Diltiazem and Verapamil) have been shown to reduce hypertension reliably, but not tachycardia. Dihydropyridines (eg, Nifedipine) should be avoided, as reflex tachycardia may occur. • If a beta-blocker is used, a mixed alpha-1/beta blocker (eg, Labetalol) is often preferred over the other beta blockers to prevent "unopposed alpha-stimulation" Hyperthermia: • External cooling methods: eg, Cooling blankets and possibly ice baths. Tepid water misting with convection cooling from a fan may be used. COCAINE WITHDRAWAL • The abstinence syndrome associated with withdrawal from Cocaine is similar to that after Amphetamine discontinuance. • Characterized by craving with resultant dysphoria, apathy, irritability, post-intoxication depression, anhedonia, hypersomnia (increased sleep time), disorientation, increased appetite, constricted pupils. • Patients may develop nightmares, suicide ideation, headache, and increased irritability, • Severe depression of mood is common and strongly reinforces the compulsion to use the drug. Antidepressant drugs may be indicated. MANAGEMENT: • Mainly symptomatic. Hospitalization may be required for severe psychiatric symptoms

Work-up of first episode psychosis.

Complete examination, including neurologic examination CBC Electrolytes including BUN/creatinine Liver function tests Thyroid function tests (TSH, free T4) HIV, hepatitis C, syphilis Urine toxicology screen MRI or CT Lipid panel ECG

DELUSIONAL DISORDER • The presence of one or more nonbizarre delusions for at least a month in an individual who, except for the delusions and their behavioral ramifications, does not appear odd or bizarre and is not markedly functionally impaired (eg, no accompanying prominent hallucinations, thought disorder, mood disorder, significant flattening of the affect, or dementia). • Nonprominent hallucinations and odd behaviors related to the delusional theme may be present. DEFINITIONS: • Delusion = fixed belief of an external reality despite evidence to the contrary. • Nonbizarre delusion = false belief that is plausible (could occur) but highly unlikely (eg, being poisoned, followed, infected, loved at a distance, deceived by a spouse, or having a disease). EPIDEMIOLOGY • A very small proportion of the population (~0.03%) experience persistent, relatively fixed delusions in the absence of the characteristic features of other psychotic disorders, such as Schizophrenia. • Mean age of onset is about 40 years, but the range is from 18 years to 90 years. • Depression has been the most commonly observed co-occurring condition, anxiety can also occur. • Risk factors include a family history of Paranoid personality disorder and sensory impairment. DIAGNOSTIC CRITERIA • (A) At least 1 delusion, lasting at least 1 month (see next page for Delusion types). • (B) Criterion A for Schizophrenia are not met - there should not be significant hallucinatory experiences, marked thought disorder, prominent negative symptoms, thought disorder, or psychosocial deterioration. Note: Hallucinations, if present, are not prominent and are related to the delusional theme. • (C) Apart from the delusion and its ramifications, behavior is not obviously odd or bizarre & there is no significant impairment of function. An individual's cultural beliefs merit consideration before coming to the diagnosis. • (D) If manic or major depressive episodes have occurred, these have been brief relative to the duration of the delusional periods. • (E) Not explained by another psychiatric disorder, medical condition, medications, or substance use MANAGEMENT • Atypical (2nd-generation) antipsychotics first-line medical management. • Individual psychotherapy (eg, Cognitive behavioral, Supportive) may be additive in some patients rather than group therapy, as patients are often suspicious and sensitive around their delusions. • Because of the lack of insight, patients often refuse to see a mental health clinician and usually reject antipsychotic medication &/ or psychotherapy, making treatment challenging. EXAM TIP PSYCHOTIC DISORDERS • Disorder of abnormal thinking, behavior, & emotion. The duration of symptoms is important. Schizophrenia diagnostic criteria: • 2 or more of the following symptoms - positive symptoms, negative symptoms, grossly disorganized or catatonic behavior for at least 6 months. Schizophreniform: • Symptoms of Schizophrenia but duration between 1- 6 months. Brief psychotic disorder: • At least 1 psychotic symptom with onset & remission <1 month Schizoaffective disorder: • Schizophrenia + mood disorder (major depressive or manic episode). SCHIZOPHRENIA • Disorder of abnormal thinking, behavior, & emotion. • ~1% of population. Men & women are affected equally but men present earlier (early to mid 20s) compare to late 20s as seen in women. Rarely initially presents before 15 or after 55 years. • Strong genetic predisposition _ 50% concordance among monozygotic twins. 40% risk if both parents have schizophrenia. 12% risk if a first-degree relative is affected. • Substance use is common - nicotine most common (>50%), alcohol, cannabis and cocaine. • Better prognosis; later age at onset, acute onset, positive symptoms, good social support, female gender, few relapses, good premorbid function, mood symptoms, & no family history. • Worse prognosis: early age of onset, gradual onset, negative symptoms, poor social support, male gender, many relapses, poor premorbid function. PATHOPHYSIOLOGY: • Several studies postulate that the development of Schizophrenia results from abnormalities in multiple neurotransmitters, such as dopaminergic, serotonergic, and alpha-adrenergic hyperactivity or glutaminergic and GABA hypoactivity. • The positive symptoms are thought to be due to excess dopamine in the mesolimbic pathway; negative symptoms due to dopamine imbalance in the mesocortical pathway. LABORATORY EVALUATION: • Urine toxicology to rule out reversible causes for symptoms, such use of recreational drugs. • ECG: check baseline QT interval before starting antipsychotic. • Serum labs: CBC, electrolytes including calcium & magnesium (rule out delirium & hyperglycemia), LFTs, thyroid stimulating hormone (rule out hypothyroidism), 24-h cortisol (rule out Hypercortisolism), fasting glucose to rule out metabolic causes & have a baseline. HIV & Syphilis. DIAGNOSTIC CRITERIA • 2 or more of the following 5 symptoms at least 6 months - positive symptoms, such as (1) hallucinations, (2) delusions, (3) disorganized speech, (4) grossly disorganized or catatonic behavior; (5) negative symptoms (eg, diminished emotional expression or avolition). • At least 1 of these symptoms must be hallucination, delusion, or disorganized speech & must manifest for at least a 1-month period. • Must impair function in one or more major areas of life (eg, work, social or interpersonal relationships, self-care) substantially below the level achieved prior to the onset of symptoms. • Symptoms not due to the effects of a substance, medication, or medical condition Positive symptoms: these symptoms are "added to" normal behavior • Hallucinations (sensory perception without physical stimuli) - auditory most common, visual. gustatory, tactile, olfactory, or somatic. • Delusions (firmed, fixed beliefs despite evidence to the contrary) - persecutory, grandiose, reference, control, nihilism, erotomania, doubles, & jealousy. • Disorganized speech - thoughts are disconnected & tangential rambling. • Behavioral disturbances. Negative symptoms: these symptoms "take away" from normal behavior. 6 As • Absence of normal cognition - impairment in attention, working memory, & executive function. • Affect flattening - poor eye contact, unchanging facial expression, little change in affect, little spontaneous movement, lack of vocal inflections. • Alogia - poverty of speech, increased latency of response. • volition (lack of will) - poor hygiene & grooming, anergy, failure of proper role responsibilities. • Anhedonia - lack of interest in stimulating activities, intimacy, or sex. • Asociality - failure to engage with others socially, socially withdrawn. Not part of diagnostic criteria but findings asked on exams: Neuroimaging: • CT scan - ventricular enlargement (lateral & third) as well as decreased cortical volume & grey matter. • PET scan - hypoactive frontal lobes, hyperactivity in the basal ganglion. MANAGEMENT OF SCHIZOPHRENIA • Second-generation (atypical) antipsychotics first-line management Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole, & Lurasidone. Mechanism of action: Dopamine antagonists (D4 & D3 > D2 receptors) in the ventral striatum & Serotonin (5-HTZA and 5-HT1A) antagonists (Clozapine and Quetiapine are weak D2 antagonists) as well as histamine, muscarinic (cholinergic), and alpha-adrenergic antagonism. They calm the patient, blunt emotional responses, reduce hallucinosis and aggressive and impulsive behavior, while leaving cognitive functions relatively intact. Lower risk of extrapyramidal adverse effects but increased risk of metabolic adverse effects. Clozapine is not used first-line but is the most effective medication for treatment-resistant psychosis (eg, after 2 medications have been tried). Medications should be tried for at least 4 weeks before efficacy is determined. • First-generation (typical) antipsychotics: (eg, Haloperidol, Droperidol, Fluphenazine, Chlorpromazine, Perphenazine, & Thioridazine). Most effective drugs for positive symptoms. Minimal effect on negative symptoms but increased risk of extrapyramidal symptoms, tardive dyskinesia, & neuroleptic malignant syndrome. • Behavioral therapy & family therapy. • Long-acting IM versions of Risperidone, Fluphenazine, Paliperidone, Aripiprazole, or Haloperidol can be used in patients who don't take their oral medications regularly. • Lithium. ACUTE PSYCHOSIS • Emergency: - Risperidone or Aripiprazole are appropriate choices due to their relatively favorable side effect profiles; Paliperidone can be used. • Severely agitated psychotic: intramuscular Ziprasidone, Olanzapine, or Aripiprazole may be used. IM Haloperidol may be used, but has more adverse effects. Sometimes, if clinically needed, alongside a benzodiazepine such as Diazepam, Clonazepam, or Lorazepam to control behavioral disturbances and non-acute anxiety. • Hospitalize patient. Urine toxicology to rule out substance abuse & routine labs

Bipolar II disorder

DIAGNOSTIC CRITERIA FOR BIPOLAR II • History of at least 1 major depressive episode + at least 1 hypomanic episode. Any current or prior Manic episode makes the diagnosis Bipolar I. • Hypomania = abnormal & persistently elevated, expansive or irritable mood at least 4 days that (1) does not require hospitalization, (Z) is not associated with marked impairment of social/occupational function, & (3) not associated with psychotic features. At least 3 symptoms affecting mood, thinking, or behavior (symptoms otherwise similar to Manic episodes). DIAGNOSTIC CRITERIA (HYPOMANIA) • (A) Mood disturbance: A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day. • (B) During the period of mood disturbance & increased energy & activity, 3 (or more) of the following {4 if the mood is only irritable) have persisted, represent a noticeable change from usual behavior, & have been present to a significant degree: (1) Inflated self-esteem or grandiosity; (2) Decreased need for sleep (eg, feels rested after only 3 hours of sleep); (3) More talkative than usual or pressure to keep talking; (4) Flight of ideas or subjective experience that thoughts are racing; (5) Distractibility (eg, attention too easily drawn to unimportant or irrelevant external stimuli); (6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation; (7) Excessive involvement in activities that have a high potential for painful consequences • (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments). • (C) The episode is an unequivocal change uncharacteristic of the individual when not symptomatic. • (D) The disturbance in mood and the change in functioning are observable by others. • (E) The episode is (1) not severe enough to cause marked impairment in social or occupational functioning or (2) to necessitate hospitalization. • (F) Not attributable to the physiological effects of a substance (eg, a drug of abuse or medication) MANAGEMENT • Same as Bipolar I - (1) Mood stabilizers (eg, Lithium, Valproic acid, and Carbamazepine), or (2) second-generation antipsychotics (eg, Aripiprazole, Haloperidol, Olanzapine, Quetiapine). • Psychotherapy: cognitive, behavioral & interpersonal. Good sleep hygiene recommended.

Bulimia Nervosa RAPID REVIEW

DSM-5: recurrent episodes of binge eating followed by inappropriate compensatory behavior via self-induced vomiting, laxative misuse, excessive exercise, or caloric restriction (occurring at least once per week for 3 months) Sense of lack of control during eating episodes Self-evaluation is unduly influenced by body shape or weight PE: body weight usually within or above normal range, dental erosions, parotid gland swelling, callused knuckles Tx options: cognitive behavioral therapy, fluoxetine or other SSRIs, or combined CBT/pharmacotherapy

Alcohol Withdrawal Syndrome RAPID REVIEW

Early symptoms: anxiety, nausea, restlessness Risk of seizure Delirium tremens may start after 48 hours Treat with benzodiazepines Correct nutritional deficiencies Offer alcohol cessation support and resources

Dystonic Reaction RAPID REVIEW

History of taking antipsychotics, antidopaminergic drugs PE will show muscle spasms (e.g., torticollis), stiffness Treatment is diphenhydramine, benztropine

Serotonin Syndrome RAPID REVIEW

History of taking multiple medications that increase the amount of serotonin PE will show mental status changes, autonomic instability, and neuromuscular abnormalities Treatment is BZDs, cyproheptadine, removing the offending agent(s)

Lithium Toxicity RAPID REVIEW

Kidney excretion Predisposing factors: NSAIDs, kidney failure, dehydration, thiazide diuretics Acute: GI Sx Chronic: neurologic Sx Complications: diabetes insipidus, syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) ECG: bradycardia, T wave flattening, and QTc prolongation IV fluids (mild-moderate) Avoid diuretics Hemodialysis (serious)

Bipolar Disorder RAPID REVIEW

Lifelong, recurrent mood episodes of either mood pole Mania, hypomania Bipolar I requires manic episode for Dx Inflated self-esteem Decreased need for sleep Pressured speech Flight of ideas Excessive pleasurable activity First-line Tx: atypical antipsychotic

MAJOR DEPRESSIVE DISORDER (MDD)/UNIPOLAR DEPRESSION •Risk factors: family history, female: male (2:1). Peak onset of age in the 20s. PATHOPHYSIOLOGY •Alteration in neurotransmitters - serotonin, epinephrine, norepinephrine, dopamine, acetylcholine, & histamine. Genetic factors. •Neuroendocrine dysregulation: adrenal, thyroid, or growth hormone dysregulation. •15% of patients commit suicide (especially men 25-30y & women 40-50y). Higher suicide rates in patients with a detailed suicide plan, white males >45y, & concurrent substance abuse. •Patient Health Questionnaire (PHQ-2 form for initial screen. If positive, may use PHQ-9 form DIAGNOSTIC CRITERIA: •At least 2 distinct episodes of at least 5 associated symptoms (must include either depressive mood or anhedonia) almost every day for most of the days for at least 2 weeks: depressive mood anhedonia, fatigue almost all day, insomnia or hypersomnia, feelings of guilt or worthlessness, recurring thoughts of death or suicide, psychomotor agitation or retardation (restlessness or slowness), significant weight change (gain or loss), decreased or increased appetite, & decreased concentration or indecisiveness. Not associated with mania or hypomania. •The symptoms must cause significant distress or impairment (social or occupational). •The symptoms are not due to substance use, bereavement, or medical conditions. •(A) At least 5 associated symptoms [must include either (1) depressive mood OR (2) anhedonia] almost every day for most of the days for at least 2 weeks: (1) depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels sad, empty, hopeless) or observation made by others (eg, appears tearful); (2) Anhedonia - markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day; (3) Significant weight loss when not dieting or weight gain (eg, a change of >5% of body weight in a month), or decrease or increase in appetite nearly every day; (4) insomnia or hypersomnia nearly every day; (5) psychomotor agitation or retardation nearly every day); (6) Fatigue or loss of energy nearly every day; (7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick); (8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others); (9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a plan, or a suicide attempt or specific plan. •(B) The symptoms must cause significant distress or impairment in social, occupational, or other important areas of functioning. •(C) Not attributable to physiologic effects of a substance, bereavement, or another medical condition. •(D) The occurrence of the major depressive episode is not better explained by seasonal affective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders. •(E) There has never been a manic episode or a hypomanic episode. MANAGEMENT •Psychotherapy (eg, cognitive behavioral therapy, interpersonal therapy, & supportive therapy) •SSRIs first-line medical management. If no effect after 4 weeks, switch to other SSRI. •Second-line: SNRIs (eg, Duloxetine, Venlafaxine); Bupropion. •Tricyclic antidepressants, Tetracyclics, MAO inhibitors. •Electroconvulsive therapy: rapid response in patients unresponsive to medical therapy, unable to tolerate pharmacotherapy (eg, pregnancy), or rapid reduction of symptoms. SUBTYPES "COURSE SPECIFIERS" OF MDD 1. SEASONAL AFFECTIVE DISORDER/SEASONAL PATTERN: the presence of depressive symptoms at the same time each year (ex, most common in the winter - "winter blues" - due to reduction of sunlight & cold weather). Management: SSRIs, light therapy, Bupropion. 2. ATYPICAL DEPRESSION: shares many of the typical symptoms of major depression but patients experience mood reactivity (improved mood in response to positive events). Symptoms include significant weight gain/ appetite increase, hypersomnia, heavy/leaden feelings in arms or legs & oversensitivity to interpersonal rejection. Management: MAO inhibitors. 3. MELANCHOLIA: characterized by anhedonia (inability to find pleasure in things), lack of mood reactivity, depression, severe weight loss/loss of appetite, excessive guilt, psychomotor agitation or retardation & sleep disturbance (increased REM time & reduced sleep). Sleep disturbances may lead to early morning awakening or mood that is worse in the morning. 4. CATATONIC DEPRESSION: motor immobility, stupor, & extreme withdrawal.

Differential of Depression

Major depressive disorder or bipolar disorder Substance use, PTSD, anxiety disorders Hypothyroidism, diabetes mellitus, Addison disease, menopause, or endocrine tumors TBI, poststroke, Parkinson disease, multiple sclerosis, Huntington, pain disorders Side effect of common medications Opioids, antihypertensives, neurologic or psychiatric medications, steroids Post-MI, heart failure EBV, HIV/AIDS, hepatitis C Anemia

Lithium

Mechanism of action: • Exact mechanism of action unknown but thought to alter neuronal sodium transport and influence the reuptake of serotonin and/or norepinephrine. Indications: • Bipolar disorder (both manic & depressive episodes). Lithium decreases suicide risk. • Acute mania (mood stabilizer) • Schizoaffective disorder Adverse effects: • Endocrine: hyperparathyroidism, hypercalcemia, hypermagnesemia, sodium depletion, hypothyroidism, nephrogenic diabetes insipidus, increased thirst (should drink 8-10 glasses of water daily). • Neurologic; seizures, tremor, headache, sedation. • Gl: nausea, vomiting, diarrhea, weight gain. • Cardiac: edema, arrhythmias, and ECG changes. Hematological: Leukocytosis • Narrow therapeutic index: prior to initiating therapy, a basic ECG, chemistries, thyroid function, beta-hCG, and CBC should be performed. Initially levels should be checked after 5 days then every 2-3 days until therapeutic. Once therapeutic, monitor plasma levels every 4- 8 weeks. Therapeutic range is 0.8-1.2. Levels may be toxic if > 1.5. Contraindications: • Pregnancy - may be associated with Ebstein anomaly if taken during the first trimester. • Severe renal disease (may increase Lithium levels), cardiac disease. Drug interactions: • Blood level is increased by dehydration, thiazides, tetracyclines, nonsteroidal anti- inflammatory drugs (NSAIDs), Angiotensin converting enzyme inhibitors (ACEls), and loop diuretics. They may result in an increase of Lithium in the blood to toxic levels. • Blood levels decreased by bronchodilators, Verapamil, Theophylline, carbonic anhydrase inhibitors.

Bupropion

Mechanism of action: •Norepinephrine-Dopamine reuptake inhibitor: (NDRI) Bupropion's activity is not fully understood but Bupropion is a relatively weak inhibitor of the neuronal presynaptic uptake of norepinephrine & dopamine; the primary mechanism of action is thought to be dopaminergic and/or noradrenergic (also responsible for most of Bupropion's adverse effects). •Has minimal serotonin effects such as nausea, somnolence [sedation], and weight gain and no activity at histamine (H1) receptors, so doesn't cause sedation. •It is also a nicotine antagonist. This effect, in addition to increasing dopamine concentration in the nucleus accumbens, makes it useful for the management of nicotine dependence. •Has an exceptionally short half-life, requiring frequent dosing. Indications: •Major depressive disorder & Seasonal affective disorder (marketed as Wellbutrin). •Bupropion is associated with less GI symptoms, weight gain, & sexual adverse effects compared to SSRIs & SRNIs (useful in depressed patients who are fearful of sexual adverse effects or weight gain). It causes weight loss initially but this effect is not usually sustained. •Mirtazapine and Bupropion are often prescribed as monotherapy or as augmenting agents when patients develop sexual adverse effects due to SSRIs or SNRIs. •Smoking cessation: Useful for in depressed smokers also interested in smoking cessation and in patients attempting to withdraw from nicotine dependence (marketed as Zyban). Adverse effects: •The most serious adverse effects of Bupropion are a lowered seizure threshold and potential worsening of suicidal ideation (especially in adolescents & young adults <25 years). •Noradrenergic activity: CNS stimulant like side effects (eg, insomnia, agitation, anxiety), tachycardia, dizziness, diaphoresis, headache, dry mouth, constipation, hypertension, tremor. •Dopaminergic activity: nausea, increased psychosis at high doses. Respiratory: pharyngitis, rhinitis. Avoid abrupt withdrawal. Contraindications: •Epilepsy or conditions with increased seizure risk (eg, eating disorders, such as Bulimia & Anorexia or patients undergoing abrupt discontinuation of alcohol, benzodiazepine, barbiturate, of antiepileptic medications). Avoid in patients with MAO inhibitor use in the past 2 weeks.

Differential diagnosis of delirium

Medications Benzodiazepines, opioids, anticholinergics Drugs of abuse PCP, cocaine, stimulants, synthetic marijuana, GHB, MDMA, inhalants Withdrawal states Alcohol, benzodiazepines Infection Intracranial or systemic Trauma Head trauma Neurologic Dementia, CVA, multiple sclerosis, epilepsy, anti-NMDA receptor encephalitis Cardiac MI, CHF, arrhythmia Endocrine Thyroid, adrenal, pituitary Metabolic Electrolytes, vitamin deficiencies

NEUROLEPTIC MALIGNANT SYNDROME

NMS is a rare but serious complication of antipsychotic use, estimated to occur in 0.01-3% of patients treated with antipsychotics. Classic symptoms include mental status changes, muscular rigidity, and autonomic instability including fever (hyperthermia >38°C). Laboratory studies should include serum creatine kinase (CK) as elevations (especially >1000 IU/L) suggest the diagnosis. The most important tenet of treatment is to stop the offending agent and provide aggressive supportive care with a goal of 3 mL/kg/h of urine output.

Neuroleptic Malignant Syndrome (NMS)

Neuroleptic malignant syndrome (NMS): • NMS is suspected when any 2 of the 4 cardinal clinical features (1) mental status change, (2) rigidity, (3) fever, or (4) dysautonomia appear in the setting of antipsychotic use or dopamine withdrawal. • Malignant hyperthermic syndrome characterized by muscle rigidity, impairment of sweating, hyperpyrexia (high fever), and autonomic instability (unstable vital signs), increased WBCs, rhabdomyolysis (increased creatine kinase, hyperkalemia), which may be life threatening. • Management: prompt immediate discontinuation of the antipsychotic (first-line), supportive (IV fluids & cooling blankets). Start Benzodiazepines (Lorazepam, Diazepam), add Dantrolene in moderate to severe cases (Dantrolene is a muscle relaxant most effective for the rigidity and fever), which may be followed by adding Dopamine agonists (Bromocriptine, Amantadine). NEUROLEPTIC MALIGNANT SYNDROME Fever (most common presenting symptom) + "ALTERED" mental status Autonomic instability - tachycardia, tachypnea, hyperthermia, fever, blood pressure changes, hypersalivation, diaphoresis & incontinence. Lead-pipe muscle rigidity - almost universal. Tremor Elevated WBC (leukocytosis) & CPK, LDH & LFTs (rhabdomyolysis) Regular-sized pupils (distinguishes it from mydriasis in Serotonin syndrome) Excessive sweating (diaphoresis) Delirium (altered mental status changes), Decreased TR (hypOreflexia) Management: • Prompt immediate discontinuation of the antipsychotic (first-line), • supportive: IV fluids and cooling blankets •Benzodiazepines (eg, Lorazepam or Diazepam) (especially if agitated), along with Dantrolene in moderate to severe cases (Dantrolene is a muscle relaxant most effective for the rigidity and fever). •Dopamine agonists: (eg, Bromocriptine, Amantadine) may be added.

Nonselective MAO inhibitors

Nonselective: Tranylcypromine, Phenelzine, Isocarboxazid; MAO B only: Selegiline Mechanism of action: •Blocks breakdown of neurotransmitters (increased levels of norepinephrine, serotonin, dopamine, epinephrine, & tyramine) by inhibiting monoamine oxidase (MAO). Indications: •Atypical or refractory depression or refractory anxiety disorders. Adverse effects: •Orthostatic hypotension most common, insomnia, anxiety, weight gain, & sexual dysfunction. •Hypertensive crisis after ingesting foods high in tyramine (eg, aged or fermented cheese, all aged, smoked, pickled or cured meats/poultry/fish, red wine, draft beer, & chocolates). Nonselective MAO inhibition prevents the breakdown of tyramine, leading to hypertension. Drug interactions: •Increased risk of Serotonin syndrome if MAO inhibitors are combined with SSRIs, SNRIs, St. John's wort, MDMA, cocaine, Meperidine, Tramadol, & Dextromethorphan. •Wait at least 2 weeks before switching from MAO inhibitors to SSRIs or vice versa (5 weeks for Fluoxetine due to its longer half-life). MAOI + tCAs may cause delirium & hypertension.

Opioid withdrawal

OPIOID WITHDRAWAL: •Signs and symptoms of withdrawal begin as early as 4 to 12 hours after the last dose of a short-acting opioid and are often delayed 24 to 48 hours after cessation of a longer-acting opioid (eg, Methadone). Withdrawal symptoms typically peak within 24 to 48 hours of onset and persist for several days with short-acting agents and up to two weeks with Methadone. •Symptoms: lacrimation, rhinorrhea, pruritus, nausea, vomiting, abdominal cramping, diarrhea, sweating, yawning, joint pains (arthralgias), myalgias, dysphoria, restlessness, craving for opioid. Withdrawal is often unpleasant but is not life threatening. •Physical examination: piloerection (goose bumps), pupillary dilation (mydriasis), yawning, diaphoresis, increased bowel sounds, flu-like symptoms: rhinorrhea, hypertension, and tachycardia. MANAGEMENT Opioid withdrawal: • Symptomatic control: Clonidine (decreases sympathetic symptoms), Loperamide for diarrhea, Dicyclomine for abdominal cramps, & NSAIDs for joint pains & muscle cramps. • Benzodiazepines may be helpful in some cases of mild withdrawal. • Severe symptoms can be treated with detox with Methadone or Buprenorphine + Naloxone. Long-term management of dependence: • Methadone maintenance program. • Suboxone (Buprenorphine + Naloxone), or Naltrexone. • Naloxone, Nalmefene, and Naltrexone are pure opioid receptor antagonists that have few other effects at doses that produce marked inhibition of agonist effects. • Buprenorphine is a mixed agonist-antagonist. Methadone • Mechanism of action: long-acting opioid receptor agonist used in the control withdrawal from opioid in patients with opioid addiction. Can be used in pregnant opioid-dependent women. Given orally. • Indications: In withdrawal states, Methadone permits a slow tapering of opioid effect that diminishes the intensity of abstinence symptoms and the prolonged action of Methadone blocks the euphoria inducing effects of doses of shorter acting opioids (eg, Heroin, Morphine). • Adverse effects: can cause prolonged QT interval. Buprenorphine • Mechanism of action: partial opioid receptor agonist. • Suboxone is a combination of Buprenorphine + Naloxone (Naloxone prevents intoxication from IV injection) • Indications: Buprenorphine has an even longer duration of action and is sometimes used in withdrawal states. Naltrexone • Mechanism of action: competitive opioid antagonist. Naltrexone decreases the craving for ethanol and is approved for adjunctive use in alcohol dependency programs. • Administration; Oral or monthly depot injection. • Adverse effects: Precipitates withdrawal if used within 7 days of heroin use Other: • Unlike the older drugs, two new antagonists, Methylnaltrexone and Alvimopan, do not cross the blood- brain barrier. These agents block adverse effects of strong opioids on peripheral mu receptors, including those in the gastrointestinal tract responsible for constipation, with minimal effects on analgesic actions and without precipitating an abstinence syndrome. • Naloxegol, a pegylated form of Naloxone, is also used to reverse opioid constipation.

PANIC ATTACKS •Fear response characterized by a sudden, abrupt, discrete episode of intense fear, anxiety, or discomfort that usually peaks within 10 minutes & usually resolve within 1 hour (most end within 30 minutes). •Patients may feel anxious for hours after the attack. CLINICAL MANIFESTATIONS •At least 4 of the following symptoms of sympathetic system overdrive - sense of impending doom or dread (hallmark) PANIC ATTACK SYMPTOMS: sympathetic overdrive 1. Dizziness 2. Trembling 3. Choking feeling 4. Paresthesias 5. Sweating 6. Shortness of breath 7. Chest pain/discomfort 8. Chills or hot flashes 9. Fear of losing control 10. Fear of dying 11. Palpitations, increased heart rate 12. Nausea or abdominal distress 13. Depersonalization (being detached from oneself) or derealization (feelings of unreality) MANAGEMENT OF ACUTE ATTACK •Benzodiazepines first-line medical management (eg, Alprazolam, Lorazepam, Diazepam). Watch for dependence or abuse. •With a panic attack (even in patients with Panic disorder), one must rule out potentially life-threating conditions (eg, Myocardial infarction, thyrotoxicosis, Aortic dissection etc.). •Panic attacks are a feature of many different anxiety disorders but is not a disorder in & of itself. PANIC DISORDER •Average age of onset in early - mid 20s. Greater risk if 1st-degree relative is affected. •Up to 65% of patients with Panic disorder also have major depression. •More common in females compared to males (2:1) DIAGNOSTIC CRITERIA: •Recurrent, unexpected panic attacks (at least 2 attacks) may or may not be related to a trigger. •At least one of the following must occur for at least 1 month: (1) Panic attacks often followed by persistent concern about future attacks, (2) persistent worry about the implication of the attacks (eg, losing control) or (3) significant maladaptive behavior related to the attacks. •Symptoms are not due to substance use, medical condition (eg, thyroid, hypoglycemia, cardiac), or other mental disorder. Specifiers: •Agoraphobia: anxiety about being in places or situations from which escape may be difficult (eg, open spaces, enclosed spaces, crowds, public transportation, or outside of the home alone). Agoraphobia now seen as a separate entity from panic disorders (can occur with other disorders). MANAGEMENT •The main approaches to the treatment of Panic disorder including both psychological (eg, cognitive behavioral therapy) and pharmacological interventions is the most effective management. •Long-term: SSRIs first-line medical treatment (eg, Sertraline, Citalopram, Fluoxetine). May initiate therapy with SSRIs + Benzodiazepines, then taper and discontinue the Benzodiazepine. SNRIs also used (eg, Venlafaxine). TCAs are options if SSRIs are ineffective. •Cognitive Behavioral Therapy (CBT): adjunctive treatment that focuses on thinking & behavior (eg relaxation, desensitization, examining behavior consequences etc.). Psychotherapy may be used in mild cases as initial therapy. Pharmacotherapy + CBT most effective. •Acute panic attacks: Benzodiazepines (eg, Alprazolam, Clonazepam). Watch for dependence or abuse

PSYCHOSIS

Psychosis impairs both thinking and behavior manifesting in delusions, hallucinations, and disorganization. Delusions are fixed, false beliefs and can be related to a number of different subjects. Most often patients have minimal insight about the content of their delusions. The most commonly identified delusions are paranoid in nature. Hallucinations are sensory experiences that occur when there is no actual input. Patients may experience auditory or visual hallucinations during primary psychotic episode; however, tactile hallucinations (such as those that occur during delirium tremens) and olfactory or gustatory hallucinations are more indicative of an underlying medical etiology and warrant further work-up. Thought and behavioral disorganization may also be in the psychotic spectrum. If a patient presents with new- or acute-onset psychotic symptoms, a general medical condition should be ruled out as the cause of psychotic symptoms. Delirium, with symptoms noted above, is high on the list of possibilities with acute-onset psychosis. Primary psychotic disorders, such as schizophrenia and schizoaffective disorder, may have a prodromal period before onset known as first-episode psychosis. First-episode psychosis classically appears in the second or third decade of life (age 18-25 in men and 25-35 in women). Even if medical causes have been explored, it is typically recommended that those patients with a first-episode psychosis undergo further evaluation, including neuroimaging and baseline laboratory studies, to establish a medical baseline (Table 49-6). One challenge, however, establishing a diagnosis in an ED may not have long-term concordance with longitudinal evaluation. Therefore, patients may require further follow-up and mental health evaluation in order to best establish an ultimate diagnosis.

SSRIs

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) Fluoxetine, Paroxetine, Citalopram, Escitalopram, Sertraline, Fluvoxamine, Vilazodone. Mechanism of action: •Increase CNS serotonin activity by inhibiting serotonin reuptake. They block the serotonin (5HT1A) transporter, increasing extracellular levels of serotonin within the synaptic cleft. •Little or no effect on dopamine, norepinephrine (adrenergic), histamine, or acetylcholine. •SSRIs cause a lower frequency of anticholinergic, sedating, & cardiovascular side effects but a possibly greater incidence of Gl symptoms, sleep impairment, & sexual dysfunction than do TCAs. Indications: •SSRIs first-line medical therapy for depression, PTSD, Obsessive compulsive disorder, Panic disorder, Premenstrual dysphoric disorder, & Anxiety disorder in most cases - effective, relatively mild adverse effects and less toxic in overdose compared to other antidepressants (because they don't affect norepinephrine, acetylcholine, histamine, or dopamine). •Fluoxetine: only antidepressant approved for treatment of Bulimia. Fluoxetine has a long-half life (2-4 days) compared to other SSRIs (~1 day). Because of the longer half-life, there is a longer washout period for switching to MAOI (5 weeks) compared to other SSRIs (at least 2 weeks). •Antidepressants take 4-6 weeks for maximum efficacy. If no response, switch to another SSRI. Adverse effects: •GI distress (nausea & diarrhea). Headache, changes in energy level (fatigue, restlessness). •Sexual dysfunction (eg, decreased libido, anorgasmia). Xerostomia, sleep disturbance (eg, insomnia). •Anxiety, insomnia, weight changes (eg, weight gain), SIADH, & serotonin syndrome. •Increased suicidality in children & young adults up to age 25y (black box warning). Follow-up usually at 2 weeks is recommended because suicide risk is greatest following initial use of antidepressants. •Serotonin syndrome. Paroxetine in particular amongst the SSRIs has more significant anticholinergic activity and can cause dry mouth, dizziness, and weight gain. QT prolongation: especially Citalopram (avoid Citalopram in patients with long QT syndrome). •In general, SSRIs are first-line medical therapy in most cases because they are effective, have relatively mild adverse effects and less toxic in overdose compared to other antidepressants •On average, antidepressants take 4-6 weeks to reach maximum efficacy. •In patients not responsive to initial SSRI therapy after 4-6 weeks, switch to another SSRI. •Duloxetine first-line if depression + neuropathic pain. •Bupropion may be preferred if patient is fearful of sexual dysfunction or weight gain (also good for smoking cessation). Mirtazapine also less sexual effects but is associated with weight gain.

SUICIDE RISK FACTORS • Plan: previous attempt strongest single predictive factor (70% of people who committed suicide succeeded on their first try). Organized plan > no organized plans. • Access to firearms is an increased risk. • Gender: females attempt suicide more than men but men are more successful at committing suicide. • Age: increases with age. Elderly white men have the highest risk in the US. • Race: whites > blacks. • Psychiatric disorders: majority who attempt or commit suicide have underlying psychiatric disorders. • Substance abuse: increased risk. • Marital status: alone > never married > widowed > separated or divorced > married without children > married with children (marriage is protective). • Others: positive family history of suicide, history of impulsivity, chronic illness. Among highly skilled workers, physicians are at an increased risk of suicide. MANAGEMENT • Assuring the patient's safety to prevent the patient from committing suicide. • Admission and psychiatric evaluation. • Once safety is established, treatment is aimed at diagnosing and treating any underlying mental disorder, including psychotherapy. INTIMATE PARTNER ABUSE • According to the CDC, 1 in 4 women and 1 in 7 men will experience physical violence by their intimate partner at some point during their lifetimes. About 1 in 3 women and nearly 1 in 6 men experience some form of sexual violence during their lifetimes. • A woman who leaves an abusive partner has a 70% greater risk of being killed by the abuser compared to staying. • Abuse during pregnancy can make up about 10% of pregnant pregnancy-related hospital admissions. • Barriers to screening include lack of privacy, low self-esteem, fear and sensitive nature of intimate partner violence. • Clues to violence: contusions to breast, chest, abdomen, face, neck, musculoskeletal injuries, and "accidental" iniuries. They may have multiple injuries in various stages of healing. Patients may have nonspecific general symptoms, such as fatigue & headache. MANAGEMENT • All healthcare facilities should have a plan that includes screening, assessing and referring patients for intimate partner violence. • Once suspected, patients should be addressed directly with a nonthreatening question to confirm if intimate partner abuse has occurred. If it has occurred, then alternatives should be discussed with referral if the patient accepts as it is the patient's right to accept or refuse help. SEXUAL ABUSE • According to the National sexual Violence Resource Center 2015 report, more than one-quarter to one-third of female children have experienced sexual abuse before 18 years of age. • Common ages of sexual abuse is between ages 9-12 years. • Perpetrators are most commonly males and most are relatives to the child or known by the child (have access). • ~33% of sexual offenders were once themselves victims of sexual abuse. • Any of the following should increase the index of suspicion for child abuse - children that exhibit sexual knowledge, initiate sex acts with peers, show knowledge of sexual acts, bruises, pain, or pruitus in the genital or anal area or evidence of a sexually transmitted infection. PHYSICAL ABUSE • Abuser often female and usually the primary caregiver. • Signs may include cigarette burns, burns in a stocking glove pattern, lacerations, healed fractures on radiographs, subdural hematoma, multiple bruises, or retinal hemorrhages. • Hyphema or retinal hemorrhages seen in shaken baby syndrome CHILD NEGLECT • Failure to provide the basic needs of a child (ex, supervision, food, shelter, affection, education) etc. • Signs include malnutrition, withdrawal, poor hygiene, and failure to thrive.

Serotonin syndrome (ROSH)

Serotonin syndrome is a potentially life-threatening adverse reaction to serotonergic drugs and is one of many causes of drug fevers. Pathophysiology involves overstimulation of central postsynaptic serotonin receptors, particularly 5-HT1A and 5-HT2A. The most common class of drugs associated with serotonin syndrome is antidepressants such as selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI), serotonin and norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and atypical antidepressants such as trazodone and bupropion. Several other drugs are associated with serotonin syndrome such as tramadol, lithium, linezolid, triptans, meperidine, and dextromethorphan. Symptoms typically begin 2-24 hours within dosage of a serotonergic drug, or the addition of a new serotonergic drug. This patient was taking tramadol for chronic back pain and was recently prescribed a cough medication, most likely dextromethorphan, which triggered serotonin syndrome. Patients with serotonin syndrome present with a triad of cognitive, autonomic, and neuromuscular related symptoms. Cognitive symptoms may manifest as altered mental status, agitation, or pressure speech. Autonomic effects cause vital sign abnormalities such as hyperthermia, hypertension, and tachycardia and symptoms such as diarrhea, mydriasis, and diaphoresis. Neuromuscular symptoms include tremor, hyperreflexia, rigidity, and myoclonus. Myoclonus is an important distinguishing feature of serotonin syndrome since it is uncommon in other similarly presenting causes of drug fevers. Treatment is immediate cessation of offending medications as well as supportive management. Benzodiazepines and cyproheptadine have activity as serotonin receptor antagonists and are often used for symptomatic management, although they have not been consistently shown to have a significant effect.

Delirium work-up.

Serum glucose Urinalysis/urine culture Urine drug screen ASA, acetaminophen, and tricyclic antidepressants Complete blood count Electrolytes Renal and liver function panels Thyroid (TSH, FT4) Blood gas HIV, RPR (inpatient follow-up) Vitamin levels (B12, folate) ECG CXR CT of head or other imaging

Coma or central nervous system depression with essentially normal vital signs and midposition pupils are characteristic findings in isolated benzodiazepine toxicity, making chlordiazepoxide the most likely culprit in this case.

Similar findings would be expected with other benzodiazepines such as diazepam and lorazepam. Unlike phenobarbital and other barbiturates, benzodiazepines require endogenous GABA to open the chloride channel and exert clinical effects. Most benzodiazepine overdoses are best treated with supportive care (e.g., cardiac monitoring, end-tidal CO2 measurements, pulse oximetry, measures to prevent aspiration such as head of bed elevation), exclusion of other coingestants, and investigations into other possible coexisting diagnoses such as trauma, hypoglycemia, rhabdomyolysis, and aspiration pneumonitis. A six-hour ED observation period is reasonable in these patients, with subsequent admission to a monitored unit if they remain symptomatic.

Mirtazapine

TETRACYCLIC Mirtazapine Mechanism of action: •Alpha-2 adrenergic receptor antagonist: tetracyclic antidepressant (TeCA) that has antagonist effects on the central presynaptic alpha-2-adrenergic receptors involved in feedback inhibition, which causes an increased release of the amines serotonin & norepinephrine from nerve endings. •High affinity for histamine H1 receptors (leading to its sedative, calming properties); antagonist postsynaptic serotonin receptors (5-HT2A, 5-HT2C, and 5-HT3), leading to the remaining serotonin concentration left to interact with the free 5-HT1 receptor. Indications: •Depression, especially patients with insomnia or significant weight loss (has appetite stimulating & sedating properties). Fewer sexual adverse effects compared to SSRIs. •Anxiety disorders (has anxiolytic properties). May be used with Trazodone. Adverse effects: •Antihistaminic: drowsiness, sedation most common (54%), weight gain (appetite stimulant). •Dry mouth, constipation, tremor, dizziness, & agranulocytosis. Increased transaminitis. •Increased risk of suicidality in children, adolescents, and young adults. •Contraindications: Use with MAO inhibitors (may cause Serotonin syndrome).

TOBACCO USE/DEPENDENCE EPIDEMIOLOGY •Smoking is the most important modifiable risk factor in the US for preventable pulmonary, cardiac, and cancer deaths and the leading cause of preventable death in the US and worldwide. Smoking cessation should be discussed with all smokers at every clinical contact. CLINICAL MANIFESTATIONS •Effects: Restlessness, anxiety, insomnia, and increase in gastrointestinal motility. Nicotine toxicity •Acute toxicity from overdosage of caffeine or nicotine includes excessive CNS stimulation with tremor, insomnia, nervousness; cardiac stimulation with arrhythmias and respiratory paralysis. •Cigarette smoking during pregnancy is associated with low birth weight, SIDS, & postnatal effects. Nicotine withdrawal: •The anxiety and mental discomfort experienced from discontinuing nicotine are major impediments to quitting the habit - symptoms include intense craving, dysphoria, restlessness, anxiety, irritability, poor concentration, sleep abnormalities (eg, insomnia), headaches, depression, increased appetite, weight gain, chest tightness, and intense nicotine craving. MANAGEMENT OF DEPENDENCE: •Includes counseling, support therapy, and cognitive behavioral therapy as part of the management, often with medical management. Combination therapy most effective than any single treatment. Relapse after abstinence is common. •First-line pharmacotherapies for smoking cessation include (1) Nicotine replacement therapy (NRT), (2) Varenicline, and (3) Bupropion. For the general population, the choice among the therapies is based largely on patient preference, with a few notable exceptions for patients with comorbidities or contraindications to certain drugs. •Pharmacotherapy is usually recommended for at least 3 months. If there is no response to initial therapy, switching to another first-line therapy is indicated. Regimen options: •For most patients, treatment with either (1) Varenicline or (2) a combination of two Nicotine replacement products (a patch which a long-acting form, plus a short-acting form such as the gum or lozenge) is first-line pharmacologic therapy; the choice depends upon patient preference after shared clinical decision-making. In studies, Varenicline produced higher quit rates than Bupropion or the Nicotine patch, which were comparable in efficacy. •Combination treatment with Varenicline and Nicotine patch is also an option when selecting initial therapy. • Bupropion appears to be somewhat less effective than combination NRT or Varenicline. However, Bupropion is a reasonable alternative first-line choice if the patient had short-term success with Bupropion in a previous quit attempt, if cost is an issue, if the patient has depression that would also benefit from treatment, or if the patient wishes to temporarily avoid post-cessation weight gain. Considerations for special populations: •Varenicline is also associated with depression and suicidal ideation; thus, patients with a history of depression should be closely monitored. •Bupropion is a reasonable alternative in patients with Depression. •Cardiovascular disease - Varenicline, NRT, and Bupropion are all options. NRT is often used in hospitalized patients with CVD due to its widespread ability and rapid relief of symptoms. •Seizures - Bupropion is contraindicated in patients with a seizure disorder or a predisposition to seizures, as it reduces the seizure threshold (eg, eating disorders such as Bulimia nervosa, Anorexia nervosa, alcohol withdrawal). Varenicline and NRT are options for patients with seizure disorders. •Pregnancy - For all pregnant individuals who smoke, a behavioral counseling program. In addition, for pregnant individuals who smoke heavily or are unable to quit with behavioral counseling alone, adjunctive pharmacotherapy with Nicotine replacement therapy (NRT) may be needed. Bupropion is a reasonable alternative to RT as adjunctive pharmacotherapy. Because of lack of safety data, Varenicline is not usually used for smoking cessation in pregnant individuals. VARENICLINE Mechanism of action: •Blocks the nicotine receptors, reducing nicotine activity. •Partial agonist of the alpha4 beta-2 subtype nicotinic receptors that mimics the effects of nicotine, reducing the reward effect and preventing withdrawal symptoms. Efficacy: •In studies, Varenicline produced higher quit rates than bupropion or the nicotine patch, which were comparable in efficacy. Initiation: •Therapy should begin 1 week prior to quit date and continued 4 months after quit date. Adverse effects: •Nausea (most common), headache, insomnia, increased suicidality or neuropsychiatric conditions. NICOTINE REPLACEMENT THERAPY • Nicotine replacement therapy with gum, nasal sprays, transdermal patches, inhaler, & lozenges allows for tapering. Indications: • Nicotine replacement therapy (NRT) is for those who want to quit smoking, as abruptly stopping can cause withdrawal symptoms and cravings. • Using NRT helps one to reduce the motivation of smoking cigarettes because the body still gets nicotine from another safer method. Dosing: • The initial dosing for nicotine replacement therapy is usually based on the number of cigarettes smoked per day. • Heavier smokers should use an increased strength/dose of nicotine therapy. Regimens: •2 Nicotine replacement products (a patch which a long-acting form and gives a basal rate of nicotine, plus a short-acting form such as the gum or lozenge) is first-line pharmacologic therapy; The patch is used to provide sustained withdrawal symptom relief for 24 hours; the short-acting nicotine product is added to be used "as needed" to control any breakthrough cravings or other withdrawal symptoms. •When using NRT, combination NRT is considered standard of care; however, using single-type NRT may be a reasonable alternative based on cost, side effect profiles, and patient preference. BUPROPION •Antidepressant drug often used in combination with nicotine tapering therapy. Mechanism of action: •Dopamine & norepinephrine reuptake inhibitor that reduces nicotine cravings and withdrawal symptoms. Adverse effects: •Increased anxiety, increased risk of seizures, & psychosis at high doses. Contraindications: •Epilepsy or conditions with increased seizure risk (eg, eating disorders such as Bulimia & Anorexia, or patients undergoing abrupt discontinuation of alcohol)

Tricyclic Antidepressants (TCAs)

Tertiary amines; Amitriptyline, Clomipramine, Imipramine, Doxepin, Amoxapine Secondary amines: Desipramine, Nortriptyline, Maprotiline •Amitriptyline & Imipramine form active metabolites, Nortriptyline and Desipramine, respectively. Mechanism of action: •Inhibits reuptake of both Serotonin (5-HT) & Norepinephrine, which leads to increased concentration of these neurotransmitters in the synaptic cleft, leading to its antidepressive effect. •Additionally, they act as competitive antagonists on post-synaptic alpha cholinergic (alpha-1 & alpha-2), muscarinic (cholinergic), and histaminergic (H1) receptors. Indications: •Depression, insomnia, neuropathies, & pain disorders (eg, Diabetic neuropathic pain, Post-herpetic neuralgia) due to their sodium channel blocker effects, Migraine, & Urge incontinence. •Used less often because of their adverse effect profile & severe toxicity with overdose. •Clomipramine is FDA approved for obsessive-compulsive disorder (OCD) in ages ≥10 years. •Insomnia and anxiety due to their sedative effects. •Migraine prophylaxis (Doxepin and Amitriptyline), urge incontinence, bipolar affective disorders, acute panic attacks, phobic disorders, enuresis (eg, Imipramine), attention deficit hyperactivity disorder. Nocturnal enuresis (eg, Imipramine) after the failure of Desmopressin. Adverse effects: •Anticholinergic (antimuscarinic) effects most common (dry mouth, constipation, urinary retention, tachycardia, & orthostatic hypotension. Confusion or hallucinations in the elderly. Amitriptyline & Doxepin are the most anticholinergic. •Antihistamine (H1) effects - sedation and drowsiness (lassitude, fatigue, confusion), increased appetite, weight gain, and confusion. Doxepin most antihistaminic. •Alpha-1 adrenergic receptor blockade: orthostatic hypotension, dizziness, reflex tachycardia. • Serotonergic effects: sexual dysfunction -- erectile/ejaculatory dysfunction in males; anorgasmia. •Prolonged QT interval (best indicator of overdose), lowered seizure threshold, & SIADH. •Increased suicidality in adolescents and young adults <25 years of age. Serotonin syndrome. Overdose: •3 C's: Cardiotoxicity: sinus or wide complex tachycardia (due to its Na+ channel blocker effects), Convulsions (seizures) or other neurologic symptoms (eg, respiratory depression), & Coma. •Management: sodium bicarbonate may be used for cardiotoxicity. Contraindications/cautions: •Use of MAO Inhibitors, recent MI or other cardiac conditions, seizure history. TRICYCLIC ANTIDEPRESSANTS TERTIARY AMINES SPECIFIC FACTS Amitriptyline Clomipramine Doxepin Imipramine SECONDARY AMINES Desipramine Nortriptyline • Most anticholinergic, antihistaminic (sedating) and antiadrenergic so higher toxicity with overdose • Useful in neuropathies & chronic pain (due to its sodium channel blocking properties) & insomnia. • Useful in Obsessive compulsive disorder (most serotonin specific) • Good for chronic pain • Useful for enuresis in children and panic disorder. • Least anticholinergic, antiadrenergic & antihistaminic (less sedating) • Least sedating (least antihistaminic) and least anticholinergic. • Good for chronic pain. Best tolerated. • Least likely to cause orthostatic hypotension.

Fluoxetine is considered the first-line agent because of its efficacy in treating the behavioral and cognitive symptoms of bulimia nervosa, as well as its tolerability.

The first-line medication for bulimia nervosa is fluoxetine. Pharmacotherapy has been shown to be efficacious in treating bulimia nervosa and is considered first-line therapy in conjunction with nutritional rehabilitation and psychotherapy. Patients placed on medication should be counseled that it may take 4-6 weeks before a satisfactory response is observed. Potential benefits of pharmacotherapy include a reduction in binging and purging episodes, eating disorder cognitions, and depressive symptoms. Selective serotonin reuptake inhibitors (SSRIs) have been shown to be most efficacious in treating bulimia nervosa. Fluoxetine is considered the first-line agent because of its efficacy in treating the behavioral and cognitive symptoms of bulimia nervosa, as well as its tolerability. Second-line pharmacotherapy is switching to another SSRI. If the patient fails that as well, third-line pharmacotherapy involves switching the patient to a tricyclic antidepressant (TCA), trazodone, monoamine oxidase inhibitor (MAOI), or topiramate.

Serotonin modulators

Trazodone, Nefazodone, Vilazodone, and Vortioxetine. Mechanism of action: •Serotonin antagonist & agonist: postsynaptic serotonin 5-HT2A & 5-HT2C receptor inhibitor (inhibits both serotonin transporter & serotonin type 2 receptors). Weakly inhibits presynaptic serotonin uptake. Some of the active metabolites are serotonin receptor agonists. • Sedative effects: Alpha-1 adrenergic receptor antagonist leads to sedation. Trazodone also reduces levels of other neurotransmitters associated with arousal effects, such as serotonin (5-HT- 2A receptor), noradrenaline, dopamine, acetylcholine, & histamine. Indications: •Antidepressant with anxiolytic & hypnotic effects (useful for insomnia). Low dose (sleep aid). • Unlike SSRIs, Trazodone does not affect REM sleep or cause anxiety, insomnia, sexual adverse effects. Adverse effects: • Sedation (most common), dizziness, dry mouth, nausea, orthostatic hypotension, headache. • Priapism rare but classic. Increased suicidality in children & young adults. Cardiac arrhythmias. • Nefazodone has a black box warning for rare but serious fulminant Hepatitis.

Alcohol withdrawal

UNCOMPLICATED ALCOHOL WITHDRAWAL: Uncomplicated = no seizures, hallucinosis or delirium tremens. •Onset: 6 - 36 hours after last drink (time may vary). Symptoms of mild withdrawal resolve within 1-2 days. •Clinical manifestations: increased CNS activity - hand tremors, anxiety, irritability, minor agitation, restlessness, insomnia, diaphoresis, palpitations, tachycardia, hypertension, headache, GI (nausea, vomiting, diarrhea), alcohol craving. Patients often experience loss of appetite, nausea, and vomiting. •Physical signs include sinus tachycardia (heart rates > 120 beats/min), systolic hypertension, hyperactive reflexes, and tremor. • Some patients with mild withdrawal will go on to develop additional manifestations of withdrawal, such as alcohol hallucinosis, withdrawal seizures, or withdrawal delirium (delirium tremens). •Patients can have withdrawal seizures or hallucinosis without manifesting symptoms of mild withdrawal. WITHDRAWAL SEIZURES: •Onset: 6 - 48 hours after drinking either stops or is significantly reduced. Usually generalized tonic-clonic type, occurring singly or in clusters of 2-3; seen in 10-30% of patients with alcohol withdrawal. •Most commonly occurs as a single brief episode. •Risk factors may include concurrent withdrawal from Benzodiazepines or other sedative-hypnotic drugs; other risk factors include relatively low potassium and platelet levels. ALCOHOLIC HALLUCINOSIS: •Onset: 12 - 48 hours after last drink and resolves in another 24-48 hours. •Clinical manifestations: visual (most common and often seeing insects or animals in the room), auditory, and/or tactile hallucinations. Unlike withdrawal delirium, Alcoholic hallucinosis is associated with (1) a clear sensorium & (2) normal vital signs usually. •The risk for alcohol hallucinosis may be related to genetic factors and/or decreased thiamine absorption. WITHDRAWAL DELIRUM (DELIRIUM TREMENS): •Onset; 2 - 5 days after last drink and reported to occur in 1 - 4% of patients hospitalized for alcohol withdrawal and has a 5% mortality rate. •Risk factors: age >30 years, prior DTs increase risk. •Clinical manifestations; rapid-onset, fluctuating disturbance of attention and cognition delirium (altered sensorium), hallucinations, agitation. Abnormal vital signs (eg, tachycardia, hypertension, fever, drenching sweats). Patients often diaphoretic. LABORATORY & OTHER TESTING: • Laboratory testing typically includes complete blood count, serum electrolytes, including potassium, magnesium, and phosphate, glucose, creatinine, liver function tests, amylase and lipase, blood alcohol level, urine drug testing, which should include testing for benzodiazepines, cocaine, and opioids. Urine human chorionic gonadotropin test for premenopausal women •An electrocardiogram is suggested for patients over 50 years or if there is a history of cardiac problems. MANAGEMENT •Requires medical treatment & hospitalization (to prevent or treat seizures, delirium tremens, autonomic instability, and cardiac arrhythmias). Alcohol withdrawal can be fatal. •Vital signs monitoring: Abnormal vital signs indicate the progression of the withdrawal due to the autonomic nervous system becoming unstable. This includes tachycardia, hypertension, and tachypnea. IV Benzodiazepines: •Diazepam, Lorazepam, Chlordiazepoxide, & Oxazepam. •Mechanism of action: potentiates GABA-mediated CNS inhibition. Alcohol mimics GABA at the receptor sites (GABA is the most abundant inhibitory neurotransmitter in the CNS) so ETOH withdrawal causes increased CNS activity. •Benzodiazepines are titrated until they patient is slightly somnolent & then gradually tapered. •Lorazepam or Oxazepam preferred in patients with advanced cirrhosis or alcoholic hepatitis (Chlordiazepoxide may cause over titration in these patients). Other: •IV fluids, IV thiamine (B1), magnesium, multivitamins (including B12 & folate), & electrolyte repletion. Repleting thiamine (B1) can reduce the risk of Wernicke encephalopathy. •Electrolyte and fluid abnormalities should be corrected. •Beta blockers can be used to treat the elevated blood pressure and tachycardia associated with alcohol withdrawal.

SNRIs

Venlafaxine, Duloxetine, Desvenlafaxine, Levomilnacipran, Milnacipran. Mechanism of action: •Block reuptake of both norepinephrine & serotonin, enhancing the actions of both neurotransmitters (both responsible for affecting mood). They also increase dopamine levels. •Venlafaxine has less affinity for the Norepinephrine transporter than Desvenlafaxine or Duloxetine. Indications: • Duloxetine may be used as first line agent, particularly in patients with significant fatigue or neuropathy pain syndromes in association with depression (eg, neuropathic pain, diabetic neuropathic pain, Fibromyalgia). General anxiety disorders, Depression Adverse effects: •Safety, tolerability & adverse effect profile similar to those of SSRIs including hyponatremia, GI symptoms, headache, fatigue, sleep impairment, xerostomia, sexual dysfunction, and suicidality. •Norepinephrine effects: sweating, dizziness, dry mouth, constipation. Therefore, it is recommended to avoid using Venlafaxine in patients with uncontrolled or labile hypertension since the Venlafaxine can cause Hypertension. Venlafaxine can cause abnormal bleeding, altered platelets. •Anticholinergic: (dizziness, dry mouth, constipation), CNS stimulant effects, Serotonin syndrome. Contraindications & cautions: •MAOI use, renal or hepatic impairment, seizures. Avoid abrupt discontinuation. Use with caution in patients with hypertension. Increased risk of Serotonin syndrome if SNRIs + St John's Wort.

Wernicke encephalopathy (ROSH)

Wernicke encephalopathy is an acute neuropsychiatric emergency. It is characterized by oculomotor dysfunction, mental status change, and gait disturbances and is due to a depletion of intracellular thiamine. This depletion occurs in the setting of poor nutrition from poor dietary intake, malabsorption, increased loss of thiamine by dialysis, or increased metabolic requirement during systemic illness. Most cases occur due to chronic heavy alcohol use, but it can also be associated with anorexia nervosa, hyperemesis during pregnancy, prolonged poor nutrition, systemic malignancy, IV feeding or dialysis without supplementation, and acquired immunodeficiency syndrome. Alcohol overuse leads to a thiamine deficiency from poor dietary intake, decreased hepatic storage, impaired utilization, and reduced gastrointestinal absorption. Not all patients who use alcohol and are thiamine deficient develop Wernicke encephalopathy, and there is believed to be a genetic predisposition. Patients can present with encephalopathy, oculomotor dysfunction (most commonly nystagmus), and gait ataxia. Gait ataxia can present prior to the other symptoms, and the presence of only one symptom should prompt an evaluation for Wernicke encephalopathy. Wernicke encephalopathy is a primarily clinical diagnosis that should be a differential diagnosis in all patients presenting with acute delirium and ataxia. The Caine criteria are more sensitive than the classic triad of symptoms. Patients are diagnosed with Wernicke encephalopathy if they have two or more of the following: dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, altered mental status, or mild memory impairment. Prompt treatment is important as symptoms can progress to coma and death. IV thiamine is safe, inexpensive, and effective. The recommended dose is thiamine 500 mg IV over 30 minutes three times daily for 2 days and 250 mg IM or IV once daily for 5 more days. It should be given in combination with other B vitamins and should be given before glucose, as the administration of glucose can worsen Wernicke encephalopathy. Daily oral dose of 100 mg should be continued after parenteral treatment until the patient is considered no longer at risk. Improvement of ocular symptoms should occur within hours to days, and vestibular function improves during the second week of treatment. Many patients will have residual defects, including permanent horizontal nystagmus or ataxia. It has been proposed that oral supplementation should be used in all patients who misuse alcohol or others at risk for thiamine deficiency, as it has minimal side effects and is inexpensive.

Alcohol dependence

• Alcohol abuse becomes dependence when withdrawal symptoms develop or tolerance. CAGE ALCOHOL SCREENING ≥2 considered a positive screen. Cutdown Have you felt the need to cut down on drinking? Annoyed Have people told you that they were annoyed at you when you drink? Guilt Have you ever felt guilty about your drinking? Eye opener Have you ever needed an eye opener to start your day or reduce jitteriness? MANAGEMENT •Supportive: psychotherapy: eg, individual, group (eg, Alcoholics Anonymous); Inpatient & residential rehabilitation programs. •Disulfiram (Antabuse) can be a deterrent to alcohol use. Mechanism of action: inhibits aldehyde dehydrogenase (enzyme needed to metabolize alcohol), leading to increased acetaldehyde when coupled with alcohol intake - uncomfortable symptoms including: hypotension, palpitations, flushing, hyperventilation, dizziness, nausea, vomiting, & headache. Contraindications: cardiovascular disease, diabetes mellitus, hypothyroidism, epilepsy, kidney or liver disease. •Naltrexone; opioid antagonist that reduces alcohol craving & reduces alcohol-induced euphoria. •Gabapentin, Topiramate.

Anorexia nervosa

• Anorexia nervosa is characterized by an abnormally low body weight, intense fear of gaining weight, distorted perception of body weight and shape, & preoccupation with body weight, body image, & being thin. • Body mass index (BMI) 17.5 kg/m? or less OR body weight <85% of ideal weight. • Anorexia nervosa is ego-suntonic (their behaviors are acceptable to them and are in harmony with their self-image goals). EPIDEMIOLOGY • Most common in teenage girls ages 14-18. 90% are women. • Frequently seen in athletes, dancers or other conditions or sports requiring thinness, revealing attire, or weight classes (eg, figure skating, cheerleading, ballet, running, wrestling, diving). • 60% incidence of comorbid depression. Rates of Suicide is ~12% per 100,000 per year. • Anorexia nervosa has the highest mortality rate of all psychiatric conditions due to medical complications (eg, arrhythmias, cardiac failure), suicide, starvation, or substance use. CLINICAL MANIFESTATIONS: • Common symptoms include amenorrhea, cold intolerance, constipation, extremity edema, fatigue, and irritability. • Severe cases: bradycardia & hypotension can cause dizziness; hypothermia. Preoccupation with weight: • Patients with Anorexia nervosa are preoccupied with their weight, their body image, and being thin. • Many exercise compulsively for extended periods of time and may increase exercise activity after food intake if they feel they have "overeaten". 2 subtypes: • Restrictive type: strict, reduced calorie intake, dieting, fasting, excessive exercise, & diet pills. No regular engagement in binge-eating or purging behavior. • Binge eating/purging type: primarily engages in self-induced vomiting as well as diuretic, laxative use, or enema abuse. Hypogonadotropic hypogonadism: • Amenorrhea and loss of libido is common due to Hypogonadotropic hypogonadism (eg, decreased estrogen in women, decreased testosterone in men). PHYSICAL EXAMINATION: • Emaciation, hypotension (may be orthostatic), bradycardia, loss of body fat; skin or hair changes, such as dry and scaly skin, alopecia and increased lanugo (fine soft body hair type commonly found on newborns), dry skin, muscle wasting, arrhythmias, osteopenia. • Body mass index (BMI) 18.5 kg/m? or less OR body weight <85% of ideal weight. Self-induced vomiting: • Salivary gland (eg, parotid gland) hypertrophy and edema may be seen in those who engage in self- induced vomiting. Dental enamel erosion may also be seen. • Russel's sign: callouses on the dorsum of the hand from self-induced vomiting. COMPLICATIONS • Cardiovascular: bradycardia, hypotension, dilated cardiomyopathy, electrolyte-induced arrhythmias, QT prolongation, mitral valve prolapse, pericardial effusion. • Endocrine: hypothalamic hypogonadism (decreased estrogen, decreased testosterone, and amenorrhea); osteoporosis. Hematologic: cytopenias, including a normocytic normochromic anemia or leukopenia, bone marrow hypoplasia/aplasia. • Neurologic: Cognitive impairment, brain atrophy, peripheral neuropathy (mineral and vitamin deficiencies). Gastrointestinal: constipation (laxative abuse), gastroparesis, DIAGNOSTIC CRITERIA • (A) Restriction of calorie intake relative to requirements leading to significantly low body weight (less than minimally normal, or in children, minimally expected) for age, sex, and physical health. • (B) Intense morbid fear of gaining weight, or becoming fat or persistent behaviors to prevent weight gain, even though at a significantly low weight. • (C) Distorted body image self-perception of being overweight (even though they are underweight), undue influence of weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight. Specify type: • Restrictive type: • Binge eating/ purging type: Specify current severity: • Mild: BMI 17 kg/m or greater; Moderate: BMI 16 to 16.99 kg/m; Severe: BMI 15 to 15.99 kg/m LABORATORY EVALUATION: • Basic labs include coagulation panel, complete blood count, complete metabolic profile, 25-hydroxyvitamin D, testosterone (males), thyroid-stimulating hormone, and urine testing (beta-hCG [females] and drugs, either illicit or prescription). • ECG is recommended to assess for life-threatening arrhythmias and for assessment for prolonged QT interval. • Hypokalemia (GI loss from laxatives, diuretics, and/or vomiting) • Elevations of blood urea nitrogen (BUN) and serum creatinine (from dehydration), hypoglycemia. • Hypochloremic metabolic alkalosis (from vomiting) • Hypogonadotropic hypogonadism (low estrogen and/or testosterone), hypothyroidism, transaminitis, anemia (normochromic normocytic), MANAGEMENT Weight gain: • The primary goal in treating anorexia is weight gain and improvement in psychological comorbidities. Treatment involves cognitive-behavioral therapy, family therapy (eg, Maudsley approach - the gold standard for treatment of Anorexia nervosa in teenagers), and supervised weight programs. Behavior modification: • Behavioral experiments or tasks should then be assigned to help the patient establish healthy eating habits and have weight gain. Ideally, positive and negative reinforcement tasks should be assigned to help the patient achieve his/her goals - patients should receive positive behavior reinforcement through awarding privileges when weight gain occurs. Medical stabilization: • Patients may be treated as an outpatient unless they are below ideal body weight (>20-25% below) or if there are serious medical or psychiatric complications. • Hospitalization indicated if <75% expected body weight or patients who have medical complications (eg, dehydration). • Electrolyte imbalances may lead to cardiac arrhythmias. Psychotherapy: • Cognitive behavioral therapy, supervised meals, weight monitoring. Pharmacotherapy: • Pharmacotherapy is not used initially. • For acutely ill patients who do not respond to initial treatment, an atypical antipsychotic (eg, Olanzapine) is a first-line medication and may help with weight gain. Other antipsychotics have not demonstrated similar effects on weight gain.

Clozapine

• Benefits: (1) most effective medication for treatment-resistant psychosis (eg, after at least 2 medications have been tried for at least 6 weeks), probably due to its significant D4 and 5HT2 receptor-blocking actions. (2) decreased suicide risk and decreased incidence of depression. (3) patients who develop Tardive dyskinesia (Clozapine is unusual in that it suppresses Tardive dyskinesia). • Clozapine is not used first-line due to its adverse effects of Myocarditis and agranulocytosis (1-2%) and seizures, especially at higher doses. • Indications: treatment resistant Schizophrenia - Clozapine may be indicated if symptoms still persist after 6 weeks of therapy with 2 different antipsychotics, one of which is a second generation. • Monitoring: Before initiating treatment with Clozapine, the patient's baseline absolute neutrophil count must be 1500/mm' or greater for the general population. It should be regularly monitored with CBC measurements for the duration of therapy.

Persistent Depressive Disorder (Dysthymia)

• DM V combined Dysthymia & Chronic major depressive disorder into PDD. • More common in women. Onset often in childhood, adolescence, or early adulthood. DIAGNOSTIC CRITERIA: • (A) Chronic depressed mood (required) for at least 2 years in adults (at least 1 year in children/adolescents) that lasts most of the day, more days than not. • (B) At least 2 of the following conditions present - insomnia, hypersomnia, fatigue or low energy, low self-esteem, decreased or increased appetite, hopelessness, poor concentration, indecisiveness. • (C) In that 2 year period, the patient is not symptom free for >2 months at a time during the 2- year period. May have major depressive episodes or meet the criteria for Major depressive disorder continuously. • (D) Never have had a manic episode (rules out Bipolar I) or hypomanic episode (rules out cyclothymic disorder). MANAGEMENT: • A combination of psychotherapy & pharmacotherapy is more efficacious than either alone. • Pharmacotherapy: SSRIs, SNRIs, Bupropion, Mirtazapine, TCAs, & MAO inhibitors. • Psychotherapy: Includes interpersonal, cognitive, and insight-oriented psychotherapies.

Binge eating disorder

• Eating disorder characterized by (1) frequent & recurrent binge eating episodes associated negative psychological & social problems (2) without compensatory behaviors of Bulimia nervosa. EPIDEMIOLOGY • Binge eating disorder is more common in women than men. CLINICAL MANIFESTATIONS • May be triggered by stress or mood changes. Patients are often obese. • Ego-dystonic (troublesome to the patient and patients are embarrassed by their binge eating). Dysphoria can occur after a binge, along with remorse and self-loathing. DIAGNOSTIC CRITERIA • (A) Recurrent episodes of binge eating - recurrent episodes characterized by eating within a discrete time (eg a 2-hour period) an unusually large amount of food (more than most people would in a similar period) with lack of control during an overeating episode. Binge eating episodes are marked by at least 3 of the following: eating more rapidly than normal, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of embarrassment by the amount of food consumed, and feeling disgusted with oneself, depressed, or guilty after overeating. • (B) Episodes occur, on average, at least once a week for 3 months. • (C) No regular use of inappropriate compensatory behaviors (eg, purging, fasting, or excessive exercise) as are seen in Bulimia nervosa and they are not as fixated on their body shape or weight. • (D) Binge eating does not occur solely during the course of Bulimia nervosa or Anorexia nervosa. MANAGEMENT: • Psychotherapy (eg, Cognitive behavioral therapy) with a strict diet and exercise program coordinated. Interpersonal and dialectic behavioral therapy. SSRls may also be added. • For patients with BED who are overweight or obese and do not have access to psychotherapy, decline it, or do not respond to it, alternatives include (1) behavioral weight loss therapy or (2) SSRIs or (3) use of Topiramate, Zonisamide, or Lisdexamfetamine for those with marked obesity.

Bulimia nervosa

• Eating disorder characterized by (1) frequent and recurrent binge eating combined with (2) inappropriate compensatory behaviors to counteract weight gain (eg, purging with vomiting, laxatives, diuretics, enemas). Anorexia vs. Bulimia: • Unlike Anorexia, patients with Bulimia nervosa (1) usually maintain a normal weight (or may be overweight) & (2) their compensatory behaviors are ego-dystonic (troublesome to the patient and patients are embarrassed by their binge eating). Dysphoria can occur after a binge, along with remorse and self-loathing. (3) the severe weight loss that occurs in Anorexia nervosa is accompanied by anatomic and physiologic sequelae that are not found in Bulimia nervosa. EPIDEMIOLOGY • More common in females 10:1. • Average onset of age in the late teens (mean age 12.4 years) or early adulthood. • Comorbid conditions: High incidence of comorbid mood disorders, anxiety disorders, impulse control disorders, substance use, prior physical/sexual abuse, as well as increased prevalence of borderline personality disorder. CLINICAL MANIFESTATIONS • A review of systems in patients with Bulimia nervosa demonstrates sore throat, irregular menstruation. constipation, headache, fatigue, lethargy, abdominal pain, and bloating. • Symptoms are usually exacerbated by stressful conditions. • The prototypic sequence of behavior in Bulimia nervosa consists of (1) caloric restriction, (2) binge eating, and (3) self-induced vomiting. The binge-eating episode triggers further caloric restriction, which leads to intense hunger and increases the probability of an additional binge eating episode. Episodes of binge eating: • (1) Patients are eating portions more significant than what most people would consume in a similar period (usually < 2 hours) and under comparable conditions. • (2) Sense of lack of control: During the eating episodes, patients feel they have no control over their eating and are unable to curb the servings they consume. The episode of bingeing usually continues until the patient is uncomfortable or painfully full. Compensatory behaviors: • Binging episodes are followed by inappropriate compensatory behavior to prevent weight gain: self-induced vomiting, misuse of medications, such as laxatives, diuretics, insulin, or thyroid hormone; extreme physical activity, excessive exercise, or fasting. Restrictive behaviors: • Patients often restrict their diet between binge eating episodes to influence body weight or shape. Medical complications: • Medical complications, including metabolic alkalosis, dehydration, constipation, and cardiac arrhythmias. Esophageal erosions and tears may occur due to vomiting. • Cardiac arrhythmias due to electrolyte disturbances such as hypokalemia may be potentially lethal. PHYSICAL EXAMINATION: • Common physical exam signs associated with Bulimia nervosa include hypotension, dry skin, and signs of self-induced vomiting. • Bulimia nervosa can also be associated with hair loss, edema, and epistaxis. Self-induced vomiting: • Teeth pitting or enamel erosion (from vomiting), dental caries. • Russell's sign: calluses on the dorsum of the hand from self-induced vomiting. • Parotid gland hypertrophy and swelling. LABORATORY FINDINGS: • Comprehensive metabolic panel: Hypokalemia, hypomagnesemia (electrolyte imbalance may lead to cardiac arrhythmias). • Increased amylase (due to salivary gland hypertrophy + vomiting). Transaminitis. • Metabolic alkalosis (hypochloremic hypokalemic metabolic alkalosis) from vomiting-induced volume depletion. Metabolic acidosis may be seen with laxative abuse. • Female patients should undergo a pregnancy test. Female patients with secondary amenorrhea should have testing for luteinizing hormone, prolactin, beta-HCG, and a follicle-stimulating hormone to assess for other potential contributors to amenorrhea. • Stool or urine laxative tests: Lab tests are available to test for stool or urine Bisacodyl, emodin, aloe- emodin, and rhein. However, a positive test for a stool or urine laxative is not necessary to establish the diagnosis. ECG: • OT-interval prolongation, especially in the setting of hypokalemia, indicates serious risk for cardiac arrhythmias DIAGNOSTIC CRITERIA • (A) Recurrent episodes of binge eating- recurrent episodes characterized by eating within a discrete time (eg a 2-hour period) an unusually large amount of food (more than most people would in a similar period) with lack of control during an overeating episode. • (B) Compensatory behaviors: Recurrent inappropriate attempts to compensate for overeating and prevent weight gain: Purging type - primarily engages in self-induced vomiting, diuretic, laxative or enema abuse. Restrictive type - reduced calorie intake, dieting, fasting, excessive exercise, & diet pills. • (C) The binge-eating and compensatory behaviors occur at least one a week for 3 months. May be triggered by stress or mood changes. • (D) Perception of self-worth is excessively influenced by shape and body weight. Excessive concern & preoccupation with body weight and shape, which strongly influence the patient's self- esteem. • (E) The disturbance does not occur exclusively during an episode of Anorexia nervosa. MANAGEMENT: Psychotherapy: • Cognitive Behavioral Therapy (CT) has shown to be the most effective psychotherapy in managing patients with Bulimia nervosa. The primary objective of treatment is a cessation of the binging and purging behaviors and control of concern about body weight. CBT mainly focused on core behaviors and cognitive problems, including binge eating episodes, inappropriate compensatory behaviors, and constant concern with body shape. • Nutritional counseling and education. • Other psychotherapies include Group therapy, Interpersonal therapy, and family therapy. • Combination psychotherapy & pharmacotherapy more effective than either alone. Pharmacotherapy: • Fluoxetine is the only FDA-approved medication for Bulimia nervosa - has been shown to reduce the binge-purge cycle (60-80 mg/day). Fluoxetine associated with cardiovascular adverse effects especially if electrolyte abnormalities are present. Other SSRis have been used. • Bupropion is contraindicated in patients with eating disorders due to the increased risk of seizures. Stabilization: • Always stabilize the patient's volume status and replete electrolytes prior to psychiatric therapy. • Normal saline or Lactated ringer's administration for Hypochloremic hypokalemic metabolic alkalosis from vomiting induced volume depletion, may be indicated.

Premenstrual dysphoric disorder

• PMS: cluster of physical, behavioral and mood changes with cyclical occurrence during the luteal phase of the menstrual cycle. • Premenstrual dysphoric disorder; severe PMS with functional impairment where anger, irritability, & internal tension are prominent (DSM V diagnostic criteria). CLINICAL MANIFESTATIONS • Physical: abdominal bloating & fatigue most common; breast swelling pain, or tenderness; weight gain, headache, changes in bowel habits, muscle or joint pain. • Emotional: irritability most common, anger, internal tension, anxiety, feeling on edge, hostility, aggressiveness, mood swings, sudden depressed mood, sense of hopelessness, self-critical thoughts, increased sensitivity to rejection, libido changes, feeling overwhelmed or out of control. • Behavioral: food cravings, change in appetite, poor concentration, noise sensitivity, loss of motor senses, diminished interest in usual activities, easy fatigability, decreased energy, sleep changes. DIAGNOSIS • Symptoms occurring 1-2 weeks before menses (luteal phase), relieved within 2-3 days of the onset of menses plus at least 7 symptom-free days during the follicular phase. • Patient should record a diary of symptoms for >2 cycles. MANAGEMENT • Lifestyle modifications: stress reduction & exercise most beneficial. Caffeine, alcohol, cigarette, & salt reduction. NSAIDs, vitamin B6 & E. • SSRIs first-line medical therapy for symptoms with dysfunction (eg, Fluoxetine, Sertraline). Continuous use or during the luteal phase only (started on cycle day 14 to onset of menses). • Oral contraceptives (especially Drospirenone-containing combined OCPs) can be used in patients who do not want to take SSRIs &/or who desire contraception. • Gonadotropin-releasing hormone (GnRH) agonist therapy for ovulation suppression with estrogen- progestin addback if no response to SIs or OCPs.

Conduct disorder

• Persistent pattern of behaviors that deviate sharply from the age-appropriate norms and violates the rights of other humans & animals. EPIDEMIOLOGY • Lifetime prevalence 9%. More common in males. • High incidence of comorbid ADHD and Oppositional defiance disorder. • May progress to Antisocial personality disorder in adulthood CLINICAL MANIFESTATIONS: • These individuals engage in physical and/or sexual violence, lack empathy for their victims, and may lack remorse for committing crimes. 4 main group of behaviors: "BADD" • Breaking (violation) of rules or age-appropriate norms: running away, skipping school (truancy), mischief, pranks, very early sexual activity. • Aggressive conduct: physical fights, bullying or intimidating behavior, cruelty to others or animals, using a weapon, forcing someone into sexual activity, rape, or molestation. • Destructive conduct: intentionally destroying property (vandalism), fire setting (arson). • Deceitfulness: lying, theft, shoplifting, delinquency. Gender differences: • Males: Higher risk of fighting, stealing, fire setting, and vandalism. • Females: Higher risk of lying, running away, sex-work, and substance use. DIAGNOSTIC CRITERIA: • Persistent pattern of recurrent violation of the rights of others or age-appropriate societal norms with at least 3 behaviors over the last year and at least one incidence within the last 6 months: • Aggression to humans or animals - threatens, intimidates or bullies others, use of a weapon, robbery, physically cruelty to animals or humans, sexual violence. • Destruction of property - engages in fire setting, vandalism, etc. • Serious violation of rules - runs away from home, stays out past curfew late at night, engages in truancy (often before 13 years old). • Deceitfulness or theft - lies to obtain goods and favors, burglary (eg, breaks into buildings, cars or homes etc.), steals the properties of others. Lacks remorse for actions. • <18 years of age. MANAGEMENT • Multimodal: behavioral modification, community and family involvement, parent management training (eg, enforcing rules and setting limits). PROGNOSIS Good prognosis: • Positive relationship with at least 1 parent • adolescent onset of symptoms • female gender • good interpersonal skills • high IQ good academic performance. Poor prognosis: • Onset of symptoms prior to 10 years • Low IQ, poor academic performance.

PCP intoxication

• Phencyclidine (PCP) is a dissociative anesthetic and hallucinogenic drug that is a NMDA glutamate receptor antagonist (also known as "angel dust"). CLINICAL MANIFESTATIONS: • Short onset of action with a brief duration (1-4 hours). • Symptoms of PCP intoxication include severe agitation, hyperthermia, hypoxia, nystagmus, hypertension, tachycardia, confusion, hallucinations, delusions, violent behavior, seizures, muscle rigidity, ataxia, and coma. • Psychotomimetic: Psychomotor agitation, rage, impulsiveness, fear, homicidality, delirium. PCP intoxication often leads to bizarre and often violent behavior, hallucinations, delusions of physical prowess, and a diminished perception of pain. Impaired judgment often leads to reckless behavior, and often leads to traumatic injuries. Neuropsychiatric findings: • CNS signs and symptoms are common and vary widely. Patients may be alert with bizarre behavior, agitated or violent, or sedated and bordering on comatose. • Adrenergic stimulation is typical; patients may exhibit CNS stimulation or depression. Complications: • Hypertension, hyperthermia, seizures, Rhabdomyolysis, hypoglycemia, prolonged comatose state. PHYSICAL EXAMINATION: • Multidirectional nystagmus (both vertical and horizontal). • Marked hypertension, tachycardia, ataxia, erythematous and dry skin. MANAGEMENT: • Supportive care: eg, airway, breathing and circulation monitoring, placement in a low stimulus (quiet environment with low lights). • Physical restraints may be necessary initially and several staff members are often needed to control patients agitated from PCP. Chemical sedation should be administered as rapidly as possible. • Parenteral Benzodiazepines (eg, Diazepam, Lorazepam, Midazolam) are the first line agents for chemical sedation if agitated, hyperthermic, for PCP-induced hypertension & seizures, and to protect against seizures. • Antipsychotics (eg, Haloperidol 5 mg or Droperidol 2.5 mg) may be used as adjunctive therapy if Benzodiazepine does not adequately control symptoms of agitation and psychosis. Brief physical restraints may be required in some cases of severe agitation. • Treatment of complications - after adequate sedation, the patient with PCP intoxication should be carefully examined for secondary injuries and associated trauma.

Cyclothymic disorder

• Similar to Bipolar Il but is less severe - (1) hypomanic symptoms that fall short of meeting criteria for a full hypomanic episode and (2) numerous periods of mild to moderate depressive symptoms that fall short of meeting criteria for a major depressive episode. • ~1/3 will eventually develop Bipolar disorder. May coexist with Borderline personality disorder. DIAGNOTIC CRITERIA: • Characterized by at least 2 consecutive ears of prolonged, milder elevations and milder depressions in mood that do not meet the criteria for either (1) full hypomanic episodes or (2) major depressive episodes. At least 1 year in children. • The symptoms recur over a time interval of at least 2 consecutive years, during which patients are symptomatic at least half the time (present for more days than not) and are not symptom- free for more than 2 consecutive months (stability of mood cannot have exceeded any length of time longer than 2 consecutive months). Major depressive, manic, hypomania, or mixed episodes do not occur • In addition, the symptoms cause significant distress or psychosocial impairment at some point. • Symptoms are not the direct result of a substance (eg, drug of abuse or medication) or another medical condition. Specifier: mood symptoms are marked by anxious distress. MANAGEMENT • Similar to Bipolar I: Mood stabilizers (eg, Lamotrigine, Valproic acid, Lithium) or second- generation antipsychotics (eg, Risperidone, Olanzapine, Quetiapine, Ziprasidone). Psychotherapv • Valproate helpful if anxiety is dominant, Lamotrigine if the anxious-depressive polarity is more prominent, and Lithium for significant affective intensity.

Oppositional defiant disorder

• Type of childhood disruptive behavior characterized by a persistent pattern of negative, angry or irritable mood, argumentative or defiant behavior, & intentional vindictiveness or spitefulness that is associated with distress in the patient or close contacts or impairs ability to function in social, school, work, or other settings. Characteristics: • These interpersonal difficulties involve at least 1 non-sibling (usually an authority figure). • Disorder in which children are generally defiant towards authority but is not associated with physical aggression, violating others' basic rights, or breaking laws (unlike Conduct disorder). EPIDEMIOLOGY: ~3% prevalence. • Onset often in the preschool years; seen more often in boys before adolescence. • 50% associated with ADHD; increased incidence of comorbid substance use. • May occasionally lead to Conduct disorder (CD). Although ODD may precede CD, most do not develop CD. DSM 5 DIAGNOSTIC CRITERIA: • Characterized by at least 4 symptoms present at least 6 months (with at least one individual that is not a sibling). • Angry or irritable mood - eg, loses temper often, anger or resentment, often blames others for their misbehaviors & negative attitude. • Argumentative or defiant behavior - breaks rules, often blames others for their behavior, argues with authority figures, & deliberately annoys or aggravates others. • Vindictiveness: or spiteful at least 2 times in the past 6 months. • Behaviors are associated with distress in the individual or others, or negatively impact functioning. • Behaviors nor accounted for or explained by the diagnosis of another psychiatric disorder. MANAGEMENT: Psychotherapy: • Behavioral modification therapy, problem-solving skills, conflict management training. • Parent management training: educating parents child management (parenting skills, parent-child interaction therapy, setting limits, and enforcing consistent rules). • Medications may be used to treat comorbid conditions (eg, ADHD). EXAM TIP Both ODD and Disruptive mood dysregulation disorder are associated with a disruptive and angry child blaming others or refusing to follow rules. ODD is associated with intent behind their behavior. Children with DMDD do not do it on purpose and may feel remorseful after outbursts.

•Acute, abrupt transient confused state due to an identifiable cause (eg, medications, infections, electrolyte abnormalities, CNS injury, uremia, organ failure, illicit drugs intoxication or withdrawal etc.). •Rapid onset associated with fluctuating mental status changes & marked deficit in short-term memory. •Usually associated with full recovery within 1 week in most cases. DELIRIUM Acute alterations in mental status can encompass changes in cognition and behavioral disturbances. Often, because of the emotional or behavioral aspects, altered mental status can be misidentified as dementia or a psychiatric disorder such as depression, anxiety, or psychosis. Delirium is defined as an acute alteration in level of consciousness with change in cognition or perceptual disturbance. DSM-5 delirium criteria. A. A disturbance in attention (ie, reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment). B. The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. C. An additional disturbance in cognition (eg, memory deficit, disorientation, language, visuospatial ability, or perception). D. The disturbances in criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (ie, due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies. Delirium is typically multifactorial but is ultimately precipitated by medical causes, such as medications, drugs of abuse, withdrawal states, neurologic concerns, or infections

vascular dementia

•Any dementia that is primarily caused by cerebrovascular disease or impaired cerebral blood flow, or in which cerebrovascular disease or impaired cerebral blood flow is a contributing causative factor. •Hypertension most important risk factor. Diabetes mellitus, history of CVA, Atrial fibrillation CLINICAL MANIFESTATIONS •Sudden decline in functions with a stepwise progression of symptoms - random infarct then decline -> stable then another infarct -> decline etc. •Cortical manifestations: depends on areas affected. Medial frontal: executive dysfunction, apathy, abulia. Left parietal: apraxia aphasia or agnosia. Right parietal: hemineglect, confusion, visuospatial abnormalities. •Subcortical manifestations: focal motor deficits, gait abnormalities, urinary difficulties, personality changes. DIAGNOSIS •Clinical diagnosis. Workup similar to Alzheimer disease - rule out other causes of symptoms (eg, B12 and folate levels, RPR, etc.). Vascular dementia is the second most common cause of Dementia. •MRI: white matter lesions, cortical or subcortical infarcts. CT scan may show lacunar infarcts. PREVENTION: strict blood pressure control.

Frontotemporal Dementia

•Localized brain degeneration of the frontotemporal lobes. May progress globally. •Histology: Pick bodies (round or oval aggregates of Tau protein) seen on silver-staining of the cortex. CLINICAL MANIFESTATIONS •Marked changes in social behavior, personality, and language (aphasia) are early signs of FTD with eventual executive and memory dysfunction (dementia with advanced disease). The onset of dementia is earlier than Alzheimer disease (usually presents in the 6th decade). •Behavioral changes: disinhibition or socially inappropriate behaviors, apathy, hyperorality (binge-eating, changes in food preferences, putting large amounts of food in their mouth), compulsive ritualistic behaviors, loss of sympathy & empathy. May have deficits in executive control. PHYSICAL EXAMINATION •Preserved visuospatial. In advanced disease, they may have positive primitive reflexes (palmomental & palmar grasp). May have Parkinsonism. May have nonfluent aphasia.

Opioid intoxication

•Opiates; a drug derived from alkaloids of the opium poppy (eg, Heroin). •Opioid: The class of drugs that includes opiates, opioid peptides, and all synthetic and semisynthetic drugs that mimic the actions of the opiates. Opioid agonists: •Strong: Fentanyl, Heroin, Morphine, Meperidine, Hydromorphone, Hydrocodone, Methadone. •Moderate: Oxycodone, Hydrocodone, Codeine. •Other; Dextromethorphan (antitussive); Loperamide and Diphenoxylate (antidiarrheal agent). OPIOID INTOXICATION: Euphoria & sedation: •Most of the adverse effects of the opioid analgesics (eg, nausea, vomiting, constipation, respiratory depression) are predictable extensions of their pharmacologic effects. •A triad of pupillary constriction, comatose state, and respiratory depression is characteristic of Opioid intoxication. •Drowsiness, impaired social functioning, impaired memory, slow or slurred speech, & coma. •Drug interactions involving opioid analgesics are additive CNS depression with ethanol, sedative hypnotics, anesthetics, antipsychotic drugs, tricyclic antidepressants, and antihistamines. •Meperidine, Tramadol, and Tapentadol have also been implicated in Serotonin syndrome when used with Selective serotonin reuptake inhibitors (SSRIs). PHYSICAL EXAMINATION FINDINGS: •Pupillary constriction (narcotics are miotics) •Altered mental status & respiratory depression. May also develop Biot's breathing (groups of quick, shallow inspirations followed by regular or irregular periods of apnea). •Bradycardia, hypotension, nausea, vomiting, flushing. •Patients on long-term narcotics may develop constipation (opioid receptors in the Gl tract reduce GI motility), hypothermia. DIAGNOSIS: •Diagnosis of overdosage is confirmed if intravenous injection or nasal insufflation of Naloxone, an antagonist of the opioid receptors, results in prompt signs of recovery. MANAGEMENT OF OPIOID INTOXICATION •Airway protection must be maintained. Assisted ventilation with a bag valve mask is utilized until Naloxone reverses the respiratory depression. Adequate ventilation should be provided before Naloxone is given. •Opioid antagonists, such as Naloxone and other therapeutic measures, especially ventilatory support. •Naloxone is an opioid receptor antagonist used in acute intoxication or overdose to acutely reverse the effects of opioids. Onset of action ~2 minutes IV (~5 minutes IM), and a nasal insufflation preparation of Naloxone has recently been made available to first responders who must treat opioid overdose promptly. ~30-60 minutes duration of action. Most commonly used in patients with respiratory depression.

Serotonin syndrome

•Potentially life-threating syndrome due to increased serotonergic activity in the CNS. ETIOLOGIES •Serotonergic antidepressants: SSRIs, SNRIs, TCAs, & MAO inhibitors, Bupropion, St. John's wort. •Increased release of serotonin: Cocaine, MDMA (ecstasy), Amphetamines (eg, Dextroamphetamine, Methamphetamine, fenfluramine, dexfenfluramine, phentermine), and Mirtazapine. •Impaired serotonin reuptake from the synaptic cleft into the presynaptic neuron: Meperidine, Tramadol, Triptans, Dextromethorphan, cocaine, MDMA (ecstasy), 5-HT3 receptor antagonists (Dolasetron, Granisetron, Ondansetron, Palonosetron), Cyclobenzaprine, Methylphenidate, Metoclopramide. Lithium. Linezolid (is a MAO inhibitor). •Increased serotonin formation: Triptans, Tryptophan, Oxitriptan. CLINICAL MANIFESTATIONS: •Symptoms most commonly develop rapidly after initiation or change in precipitating drug: 30% within 1 hour, 60% within 6 hours, and nearly all patients with toxicity within 24 hours of exposure. •Cognitive effects; mental status changes - anxiety, agitation, confusion, disorientation, agitated delirium, hallucinations, hypomania. CNS stimulatory effects including seizures. •GI serotonin effects: nausea, vomiting, increased bowel sounds, & diarrhea. PHYSICAL EXAMINATION: •Autonomic instability - hyperthermia (temperature above 38°C), tachycardia, hypertension, diaphoresis, vomiting, and diarrhea. Severe cases may be associated with rapid swings in blood pressure and pulse and cardiovascular instability. •Neuromuscular hyperactivity: tremor, spontaneous or inducible clonus, ocular clonus (slow, continuous, horizontal eye movements), hypertonia (increased DTR & hyperreflexia), muscle rigidity, bilateral Babinski, akathisia (restlessness). Lower extremities involvement most severe. •Mydriasis (dilated pupils), dry mucous membranes, 1'ed bowel sounds, flushed skin, diaphoresis. DIAGNOSIS •Clinical diagnosis based on the Hunter criteria. MANAGEMENT OF MILD •Prompt discontinuation of offending drug(s) most important. •In mild cases, discontinuation of inciting medications, supportive care, and sedation with Benzodiazepines is usually sufficient. •Supportive care mainstay of therapy to help normalize vital signs - supplemental oxygen to maintain Sa02 94% or greater, IV fluids for volume depletion, continuous cardiac monitoring. •Benzodiazepines for agitation, to reduce hyperthermia, and to correct mild increases in heart rate and blood pressure. •Antipyretics such as Acetaminophen are ineffective because increased muscular activity causes hyperthermia in Serotonin syndrome. MANAGEMENT OF MODERATE •As above + Cyproheptadine (a serotonin antagonist) to improve autonomic instability. Cyproheptadine is indicated if Benzodiazepines and supportive care fail to improve agitation and correct vital signs. Cyproheptadine may cause sedation and transient hypotension that is responsive to intravenous fluids. •Hyperthermic patients are critically ill whose temperature is above 41.1°C, immediate sedation, paralysis, and tracheal intubation may be indicated. Antipyretics are ineffective. •Hypotension is often treated with IV fluids alone. Hypotension from MAOIs may need treatment with low dose direct-acting sympathomimetics (eg, Epinephrine, Phenylephrine, Norepinephrine).

Diffuse Lewy Body Disease

•Progressive dementia characterized by the diffuse presence of Lewy bodies (abnormal neuronal protein deposits) in comparison to Parkinson disease, where the Lewy bodies are localized. •Histology: Cortical Lewy bodies (abnormal deposition of alpha-synuclein proteins). CLINICAL MANIFESTATIONS •Core features that occur early: recurrent visual hallucinations, episodic delirium (cognitive fluctuations), Parkinsonism (bradykinesia, rest tremor, rigidity, and/or gait disorder), & rapid eye movement (REM) sleep behavioral disorder. Delusions, sensitivity to antipsychotic drugs, autonomic dysfunction (eg, orthostatic hypotension, constipation, incontinence, erectile issues). •Dementia is a late finding (characterized by deficits in attention & visuospatial function), MANAGEMENT •Treatment of the Parkinsonian symptoms may worsen the neuropsychiatric symptoms and vice versa. •Neuroleptics, Donepezil, Selegiline

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