Antidepressants

TCAs

* * * *Lipophilic and well distributed in the body, including CNS (achieve high tissue concentrations within few hours of ingestion) **Commonly tested as being lethal in overdose and used to commit suicide. Thus must assess suicide risk before prescribing TCAs* **Flumazenil is contraindicated in TCA Overdose, can lead to seizures* **Ipecac syrup is contraindicated in TCA overdose, can lead to*

SSRIs can cause sleep disturbances such as insomnia or somnolence. The more activating SSRIS such as __for_________ and __________ are known to cause insomnia while the more sedating SSRIs such as ___________ and ___________ cause somnolence

Activating: Fluoxetine, Sertraline Sedating: Paroxetine, Fluvoxamine

What types of patients should not be given bupropion?

Bupropion should be avoided in patients who are susceptible to seizures (e.g. bulimics and patients with seizure disorders).

Which tricyclic antidepressant can be used in obsessive compulsive disorder?

Clomipramine

A certain tumor-associated syndrome may manifest as diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular heart disease. These symptoms are attributable to high circulating levels of particular tumor-secreted substance.Which of the following acts primarily by blocking the reuptake of this same substance? A) Buspirone B) Maprotiline C) Quetiapine D) Trazodone E) Fluphenazine F) Isocarboxazid

D) Trazodone list what type the others are Quetiapine may have some blocking of serotonin but it primarily blocks dopamine

A 25-yo woman comes to the emergency department because of nausea, diarrhea, and anxiety for 2 days. She also has noticed dizziness and tingling sensations shooting down her forearms. Her sleep and appetite have been normal. She has a 3 year history of social phobia well controlled for the past year with paroxitine. She is attending an out-of-town conference and forgot to pack her medication; her last dose was 3 days ago. She does not drink alcohol or use illicit drugs. She is 163cm tall and weighs 89 kg. BMI is 30 kg/m2. Her temperature is 37C, pulse is 80/min, and blood pressure is 110/75 mm Hg. Physical examination shows no other abnormalities. Mental status examination shows an irritable mood with a full range of affect. Her speech is of normal rate and rhythm. There is no evidence of suicidal ideation or hallucination. She can recall three objects after 5 minutes. Long-term memory is intact. Serum studies show no traces of paroxitine. Which of the following is the most appropriate next step in management? A) Begin behavioral therapy B) Begin alprazolam therapy C) Begin bupropion therapy D) Begin clomipramine therapy E) Begin gabapentin therapy F) Resume paroxetine

F) Resume paroxetine SSRI discontinuation syndrome *Occurs in about 20% of patients who abruptly discontinue antidepressants that were taken for at least 6 weeks *Typical symptoms: flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. *Symptoms are typically mild and rapidly resolve after reinstitution of antidepressant medication *Risk for discontinuation syndrome is generally greater with potent, short-acting antidepressants (paroxetine, venlaflaxine)

Mnemonic to remember 5 of the common SNRIs

FAX FAX DELUXE NACIPRAN Venlafaxine Desvenlafaxine Duloxetine Levomilnacipran Milnacipran

Mnemonic to remember 6 of the common SSRIs

FLU FLU PECS Fluoxetine Fluvoxamine Paroxetine Escitalopram Citalopram Sertraline OR FLashbacks PARalyze SEnior CITizens Fluoxetine/Fluvoamine Paroxetine Sertraline Citalopram (Escitalopram)

Which SSRI is FDA approved for the treatment of Bulimia?

Fluoxetine

Which SSRI is least likely to cause SSRI discontinuation syndrome?

Fluoxetine *Fluoxetine has the longest half life of SSRIs* with active metabolites; therefore one doesn't need to taper the dose because of low risk of SSRI discontinuation syndrome.

Which tricyclic antidepressant can be used as a treatment for bed-wetting (enuresis)?

Imipramine

Imipramine and treatment of Enuresis

Imipramine controls bed wetting in children older than 6 years old by causing relaxation of the detrusor muscle of the bladder wall (anticholinergic effect), contraction of the trigone/sphincter and stimulation of ADH secretion Also proposed that it decreases the delta wave period of sleep during which enuresis occurs (remember that cholinergic agonists cause the opposite. Urination is produced by contraction of the detrusor and relaxation of the trigone/sphincter)

The risk for Antidepressant Discontinuation Syndrome is greater with ____________ (longer/shorter) duration of treatment and _____________ (longer/shorter) half life of the drug

Increased risk with *Longer treatment *Shorter half life

Which tca is tetracyclic?

Maprotiline

SSRIs and SIADH

Mechanism not known but SSRIs may enhance release or effect of ADH

Which SNRI is indicated in the treatment of Fibromyalgia?

Milnacipran

Which antidepressant is associated with the greatest weight gain?

Mirtazapine

MOA of SNRIs

SNRIs block the reuptake of Serotonin and Norepinephrine

Secondary TCAs are generally more potent in blocking reuptake of ______________ and Tertiary TCAS are generally more potent in blocking reuptake of ________________

Secondary: Norepinephrine Tertiary: Serotonin

Secondary vs Tertiary tricyclic antidepressants (TCAs)

Secondary: Preferentially raise NE levels Tertiary: Preferentially raise Serotonin levels Secondary: less sedative effects including confusion and hallucinations as well as less anticholinergic effects

Serotonin Syndrome vs NMS vs Malignant Hyperthermia

Serotonin Syndrome -Precipitated by: *Any drug that increases 5-HT: SSRI/SNRI, MAOI, TCA* -Onset: *Within hours* -*Hyperactive bowel sounds* -*Dilated pupils* -*Hyper*reflexia, myoclonus, tremor -Diaphoresis, Diarrhea -Patient often agitated -Tx: 5-Ht2 antagonist *Cyproheptadine* NMS -Precipitated by: *D2 blocking antipsychotics* -Onset: *Within 1-3 days* -Normal or reduced bowel sounds -Lead Pipe Rigidity, *Hypo*reflexia -Normal Pupils -Patient often mute, in stupor -Tx: *Bromocriptine (Dopamine agonist); Dantrolene (muscle relaxant)* Malignant Hyperthermia -Precipitated by: *Volatile anesthetics, succinyl choline* -Onset: *Within minutes to hours* - -Normal Pupils -Tx: *Dantrolene* Hyperthermia, tachycardia, hypertension, and muscle rigidity common to all 3 elevated CK and metabolic acidosis also can be seen in all 3

According to the Biogenic Amine Theory, Depression is due to a relative deficiency of ______________ and ____________ while conversely Mania is due to an excess of these monoamines

Serotonin and Norepinephrine

Which SSRI is most likely to cause GI disturbances?

Sertraline Sertraline is most likely to cause GI disturbances

What is the mainstay of treatment for tricyclic antidepressant-related cardiotoxicity?

Sodium Bicarbonate

A 52-year-old woman is brought to the emergency room by an ambulance after being found at home lying on the bedroom floor. The paramedic accompanying her hands you an empty medication bottle of nortriptyline. A neighbor who comes with her states that the patient has had a previous history of seizures, depression, and multiple suicide attempts. They were together just two hours prior to the incident. The patient is obtunded and only responds to painful stimuli. Examination reveals dilated and equally reactive pupils, flushed skin, and generalized muscle twitching. The abdominal examination reveals hypoactive bowel sounds. Her blood pressure is 72/48 mm Hg, the respiratory rate is 22/min, pulse is 68/min, and temperature is 102.5 F. The EKG shows a prolonged QT interval. What is the next best step in the management of this patient? (A) Immediate emesis with ipecac (B) Bicarbonate (C) Ceftriaxone and vancomycin (D) Activated charcoal (E) Hemodialysis

(B) Bicarbonate The patient presents to the emergency room with a tricyclic antidepressant (TCA) overdose. TCAs are among the most common drugs that are used in suicidal overdose attempts. Along with their anticholinergic effects, TCAs also have a cardiac depressant effect similar to that of quinidine (blocks sodium-channel conduction) when taken in large doses. For this reason, TCA overdose can also induce QT-interval prolongation, as shown in this patient's EKG. This results in ventricular arrhythmias and atrioventricular block. As with the majority of the TCA toxicities, the QT interval correlates more reliably than does the serum drug levels with the severity of intoxication. Other symptoms of TCA toxicity include tachycardia, hypotension, hyperthermia secondary to decreased perspiration, dry mouth, flushed skin, dilated pupils, decreased peristalsis, and muscle twitching. Bicarbonate is used to protect the heart from cardiac dysrhythmia. The alkaline environment blocks the quinidine-like effect upon the heart of the tricyclics. Induction of emesis is contraindicated because of an associated increase in the risk of aspiration pneumonia in a patient with altered mental status. Activated charcoal, as with most other poisonings, is a mainstay of therapy and can be combined with gastric lavage. If gastric lavage is performed in a patient with altered mental status, the patient should undergo endotracheal intubation to protect the airway and prevent aspiration of the gastric contents. TCAs achieve high tissue concentrations within a few hours of ingestion and are therefore not effectively cleared from the serum by hemodialysis. Treating meningitis is not the correct answer, given the clear history of a tricyclic antidepressant overdose as both a cause of her fever and altered mental statu

A 27-year-old man is brought by his friends to the emergency room. They tell you that they were all at a party, having a great time, when the patient suddenly collapsed. He had some facial twitching and "weird body movements." They were drinking alcohol and saw that some people at the party were taking pills. He has a history of depression. He has a temperature of 100.9 F, with a blood pressure of 164/94 mm Hg. He is awake but seems confused. His pupils are equal and 7 mm in diameter. He has dry mucous membranes and normal heart, lung, and abdominal examinations. His EKG shows a sinus tachycardia at a rate of 112/min. The PR interval is 180 milliseconds, and the QRS interval is 150 milliseconds. What would be the initial treatment of choice in the management of this patient? (A) Phenytoin (B) Sodium bicarbonate (C) Ipecac (D) Gastric lavage (E) Physostigmine

(B) Sodium bicarbonate This patient most likely has an overdose of tricyclic antidepressants (TCA). This patient exhibits anticholinergic side effects, along with being postictal, and there is evidence of cardiotoxicity with QRS prolongation secondary to TCA ingestion. Sodium bicarbonate should be given as a bolus following a seizure and as an infusion to maintain a serum pH of 7.40 to 7.50 in patients with QRS prolongation. Acidosis increases the likelihood of arrhythmia and should be corrected. Administration of phenytoin is of uncertain benefit, and seizures should be treated with benzodiazepines and barbiturates. Administration of syrup of ipecac is contraindicated with tricyclic ingestion because of the risk of seizures and subsequent aspiration. Gastric lavage is indicated in comatose patients with massive ingestions of toxic substances -- but only if it is clear that the ingestion occurred within the past two hours. Physostigmine is given in situations of mild poisoning with anticholinergic agents in which the EKG is normal and there are anticholinergic effects, such as agitation and hallucinations. Physostigmine is contraindicated in the presence of cardiac-conduction defects or ventricular arrhythmias because it can cause asystole.

Buspirone

* *First line agent for treatment of Generalized Anxiety Disorder (GAD) * * *

A 35-year-old man with depression presents to the emergency department with flushing, diarrhea, sweating, and muscle rigidity. During the physical examination, he says that he began seeing a new psychiatrist because his sertraline was not working for him. His new doctor gave him a different medication, but he decided to use both medicines to "get rid of the depression." Which of the following medications did the new doctor most likely prescribe for this patient? (A) Citalopram (B) Lithium (C) Nortriptyline (D) Tranylcypromine (E) Trazodone

******** although many of them can cause serotonin syndrome, mao inhibitors most contraindicated

What is the mechanism by which Sodium Bicarbonate treats cardiotoxicity related to TCA use?

*Alkalizing the plasma, which reduces the binding of TCAs to fast sodium channels and increases binding of TCAs to plasma proteins *Increasing extracellular sodium, which increases the electrochemical gradient across cardiac cells and reduces the efficiency of TCA-induced fast sodium channel inhibition

Selective Serotonin Reuptake Inhibitors (SSRIs)

*Exert effect by selectively inhibiting serotonin receptors *300 to 3000 fold greater selectivity for the serotonin receptor as compared to the norepinephrine receptor *Little blocking activity **Normally takes 4-8 weeks for antidepressants to have an effect* *Little blocking activity at muscarinic, a-adrenergic, and histaminic H1 receptors *Therefore, common side effects associated with TCAs, such as orthostatic hypotension, sedation, dry mouth, and blurred vision, are not commonly seen with SSRIs **Fluoxetine is approved for Bulimia*

SSRI Discontinuation Syndrome

*Occurs in about 20% of patients who abruptly discontinue antidepressants that were taken for at least 6 weeks *Typical symptoms: flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. *Symptoms are typically mild and rapidly resolve after reinstitution of antidepressant medication *Risk for discontinuation syndrome is generally greater with potent, short-acting antidepressants (paroxetine, venlaflaxine) *Fluoxetine has longest half life of SSRI and lowest risk *Avoid by slow tapering of drug and discontinuation over 4 week period

What is the mechanism by which TCAs cause cardiotoxicity?

*Rate dependent blockade of inactivated fast sodium channels (blockade is higher at higher rates) => tachycardia and life threatening dysrhythmias *Reversible inhibition of potassium channels => myocardial depression

A 28-year-old woman with no significant past medical history presents to your office with complaints of "feeling sad all the time." Despite a previous psychiatrist prescribing paroxetine, she continues to experience depressive symptoms. When you probe into her feelings about the medication, she states that she stopped taking the medication because she did not like the associated weight gain. What is the best pharmacologic alternative for this patient? 1. Fluoxetine 2. Sertraline 3. Mirtazapine 4. Citalopram 5. Buspirone

1. Fluoxetine The patient described requires an antidepressant with the least predisposition for weight gain, which, of the given choices, is fluoxetine (Prozac). Sertraline and Mirtazapine are associated with weight gain How about Citalopram and Buspirone

A 32-year-old female with a history of depression presents to the emergency department after a suspected ingestion. She is confused, reporting blurry vision, and responding to visual hallucinations. Vital signs are as follows: Temperature: 98.9 degrees Farenheit (37.2 Celsius) Heart Rate: 105 bpm Blood Pressure: 90/65 mmHg Respiratory Rate: 21 respirations per minute O2 Saturation: 99% on room air Upon reviewing her ECG (shown in Image A), the emergency room physician orders sodium bicarbonate. What medication was the likely cause of this patient's cardiac abnormality? 1. Lithium 2. Amitriptyline 3. Paroxetine 4. Quetiapine 5. Sertraline

2. Amitriptyline Amitriptyline, a tricyclic antidepressant (TCA), toxicity includes anticholinergic effects and the ECG changes seen in Figure A. Initial treatment for the cardiac manifestations is hypertonic sodium bicarbonate. Intentional or accidental overdose with TCAs can lead to coma, seizures, or cardiac arrhythmias due to anticholinergic effects. TCAs are rapidly absorbed by the gastrointestinal tract and have a large volume of distribution, and thus their half-lives are relatively long and unpredictable. Onset of effects are usually within 2-6 hours of ingestion. Sodium bicarbonate is indicated for dysrhythmias, hypotension, or QRS prolongation > 100 milliseconds. TCA overdose can cause respiratory depression, cardiac arrhythmias, hypothermia, seizures, hallucinations, and hypertension for as long as five days."

What are the more severe, life-threatening complications seen in tricyclic antidepressant (TCA) toxicity?

3 C's: *Convulsions *Coma *Cardiotoxicity (due to blockade of fast Na+ channels) Respiratory depression Hyperpyrexia

A 28-year-old female comes to clinic complaining of insomnia and decreased appetite. After interviewing the patient, the physician notes that the patient has been experiencing symptoms of anhedonia and guilt. The patient complains that her energy level and concentration are "not what they used to be." Thyroid function tests are normal. The physician decides to start the patient on a medication. What length of time must be given in order to allow the medication to provide symptomatic relief? 1. 4-6 minutes 2. 4-6 hours 3. 4-6 days 4. 4-6 weeks 5. 4-6 months

4. 4-6 weeks Because these medications require 4-6 weeks to take effect, it is important to educate patients on this subject and provide them with reassurance during this time.

A 42-year-old female complains of feeling anxious and worrying about nearly every aspect of her daily life. She cannot identify a specific cause for these symptoms and admits that this tension is accompanied by tiredness and difficulty falling asleep. To treat this problem, the patient is prescribed the first-line therapy, a medication which notably lacks any anticonvulsant or muscle relaxant properties. This drug most likely acts at which of the following receptors? 1. GABA receptor 2. Alpha adrenergic receptor 3. Glycine receptor 4. 5HT-1A receptor 5. Beta adrenergic receptor

4. 5HT-1A receptor Buspirone is a a first-line agent for Generalized Anxiety Disorder (GAD) that acts as a selective agonist at 5HT-1A serotonin receptors. Buspirone is especially useful in patients who have a history of drug abuse with anti-anxiety medications, as dependence does not occur with chronic buspirone therapy. The response to buspirone typically does not occur until after several weeks of daily use. Buspirone lacks both anticonvulsant and muscle relaxant side effects which makes it quite different from benzodiazepines. Gliatto reviews the diagnosis and management of GAD, concluding that benzodiazepines are useful for short-term treatment. However, because GAD is often chronic in nature, additional pharmacotherapy such as buspirone or antidepressants are frequently used in management of the disorder as well.

A 58-year-old caucasian man comes into the psychiatry office complaining of depressed mood. For the past two months, he has had trouble sleeping, even though he feels tired throughout the day, and decreased appetite. During this time, he's had little interest in his former hobbies. His only other medical complaint is pre-existing sexual dysfunction. Which of the following is the most appropriate treatment for this patient's depression? 1. Duloxetine 2. Sertraline 3. Amoxapine 4. Paroxetine 5. Bupropion

5. Bupropion Bupropion, unlike other antidepressants, is not associated with sexual dysfunction. A depressed patient exhibiting signs or symptoms of sexual dysfunction (whether medication induced or pre-existing condition) should be started on bupropion.

A 21-year-old female presents to her doctor for a wellness exam. She complains that over the last 3 weeks she has had decreased interest in her usual athletic activities, and is now considering quitting the swimming team she has been competitively racing for during the last 9 years. She also says that she has only been able to get about 6 hours of sleep per night and has had difficulty staying asleep once she falls asleep. This is much less than her usual 8-9 hours per night. She admits to feeling guilty regarding her parent's recent divorce. She denies thinking about death and wants to feel better again. What is the most appropriate pharmacological management of this patient? A Sertraline B Risperidone C Lithium D Phenelzine E Amitriptyline

A Sertraline The patient is presenting with classic symptoms of major depression. She has decreased interest in her usual activities, has difficulty sleeping and is having thoughts of guilt. In patients with major depression, SSRI treatment is the first line intervention. A SSRI like sertraline should be initiated before any of the other types of medications are tried. *Phenylzine is a MAOI used for atypical depression *Risperidone is an atypical antipsychotic (patient has no psychotic symptoms) *Lithium is used to treat Bipolar Disorder *Amitryptiline is a TCA that can be used for Major depression but given its side effect profile, it is not first line

A 77-year-old man screens positive for urinary incontinence at a routine clinic visit. He relates 6 months of small-volume urine loss if he bends over and at times when he sneezes. He notes some urinary hesitancy and occasionally has a sense of incomplete emptying. He awakens to urinate one or two times a night but has no dysuria or constipation. His medical problems are hypertension treated with hydrochlorothiazide, large-joint osteoarthritis managed with celecoxib and acetaminophen with codeine, and depression treated with nortriptyline. On examination, vital signs (taken supine and standing) and heart and lungs are normal. Lower extremity strength and sensation are intact. Sphincter tone is normal, and the prostate gland is soft and normal in size. Urinalysis shows 1 + glucose and 1 + protein but no cellular elements; serum electrolytes and creatinine are normal; random serum glucose level is 138 mg/dL, and a post-void residual volume is 100 mL. Which of the following are the most likely cause and most appropriate intervention for this patient's urinary incontinence? A. Overflow incontinence; stop nortriptyline and codeine B. Stress incontinence; stop hydrochlorothiazide C. Overflow incontinence; stop nortriptyline and start finasteride D. Stress incontinence; teach timed voids and Kegel exercises E. Overflow incontinence; treat diabetes

A. Overflow incontinence; stop nortriptyline and codeine This patient has overflow incontinence based on his elevated post-void residual volume of 100 mL. He is taking two medications that can decrease bladder emptying: nortriptyline via its anticholinergic effects and sympathomimetic activity, and codeine which can decrease bladder smooth-muscle contractility. The most appropriate first step in managing this patient is to stop both medications and reassess. Even though he has a history of leakage with bending and sneezing these symptoms can also occur with overflow incontinence and the elevated post-void residual volume implicates overflow rather than stress incontinence. He may well have some degree of prostatism contributing to his symptoms and stopping nortriptyline is appropriate; *however, codeine should also be stopped, and it is more appropriate to reassess after stopping medications than to simultaneously proceed with a new medication*. Also, if a new treatment for prostatism were to be added, an a1-blocker would be more effective and have a faster onset than finasteride. Although this patient has glucose in his urine and a mildly elevated random serum glucose, a diagnosis of diabetes cannot be established based on the laboratory data provided. Furthermore, overflow incontinence due to diabetes-related neuropathy is highly unlikely in this patient lacking other signs of autonomic or sacral nerve dysfunction.

Adverse Effects of SSRIs

Although the SSRIs are considered to have fewer and less severe adverse effects than the TCAs and MAOIs, the SSRIs are not without adverse effects *Headache *Sweating *Anxiety and Agitation *GI effects (n/v/d) *Changes in weight *Weakness and fatigue *Sleep disturbances (insomnia or somnolence) *Sexual dysfunction *Serotonin Syndrome **SIADH* **Bruxism*

Which TCA is most commonly used as prophylaxis for migraines and tension headaches

Amitriptyline

Name seven examples of tricyclic antidepressants (TCAs).

Amitriptyline Nortriptyline Imipramine Desipramine Clomipramine Doxepin Amoxapine -triptyline -pramine + doxepin, amoxapine Tertiary: imipramine, clomipraminen amitriptyline Secondary: nortriptyline, desipramine

Treatment of Fibromyalgia

Amitriptyline is DOC?? * * * *Studies show that TCAs are the best antidepressant drugs for people with fibromyalgia. About 32% of fibromyalgia sufferers experience relief with tricyclics. The most commonly prescribed TCA is amitriptyline; other tricyclics include doxepin, nortriptyline, and cyclobenzaprine. Though TCAs are highly effective, they are also associated with more severe side effects than other, new antidepressant medications. These side effects include: dry mouth, constipation, blurred vision, fatigue, and low blood pressure. People with glaucoma, heart conditions, or seizure disorders should not take TCAs *Always combine pharmacologic approaches with nonpharmacologic therapy in the treatment of fibromyalgia (FM), especially stress management, aerobic exercise, and, in some cases, psychotherapy. Aggressively treat comorbid depression. Opioids, hypnotics, anxiolytics, and certain skeletal-muscle relaxants must be used with caution because of the potential for abuse. Tricyclic antidepressants (TCAs) are of proven benefit, the DOC is Amitriptylline . Certain anticonvulsants and antidepressants clearly decrease pain sensitivity. Corticosteroids and nonsteroidal anti-inflammatory medications are useful only as management for coexisting inflammatory processes. Pharmacologic and nonpharmacologic treatment of poor sleep is crucial for improving the patient's overall sense of well-being *Check emedicine and uptodate

Which tricyclic antidepressant is used in the treatment of Major Depressive Disorder (MDD) with psychotic features? Why?

Amoxapine Amoxapine is used in Major Depressive Disorder with psychotic features because it is metabolized into 2 active metabolites, one that inhibits re-uptake of NE (an antidepressant effect) and another that blocks dopamine receptors in the CNS (an antipsychotic effect).

What are the three primary groups of side effects of tricyclic antidepressants, grouped by receptor action?

Antihistaminic -sedation, confusion, hallucinations, and weight gain Antiadrenergic -orthostatic hypotension Anticholinergic -dry mouth, tachycardia, constipation, and urinary retention ***********DO this better https://books.google.com/books?id=gZnQAQAAQBAJ&pg=PA912&lpg=PA912&dq=TCA+blockade+of+inactivated+fast+sodium+channels+i&source=bl&ots=umWxNflfXV&sig=AKkh9_b-VcgEip2NnAcmc-TKJjA&hl=en&sa=X&ved=0ahUKEwiDubquiK3SAhUKh1QKHXNjC_8Q6AEIMzAE#v=onepage&q=TCA%20blockade%20of%20inactivated%20fast%20sodium%20channels%20i&f=false

A 22-year-old college student who has been treated for anxiety and depressed mood for 6 weeks develops episodes in which she feels light-headed and almost faints. Pulse is 110/min, and blood pressure is 110/70 mm Hg while lying down and 85/60 mm Hg while standing. Which of the following drugs is most likely to have caused the orthostatic hypotension? A) Alprazolam B) Amitriptyline C) Buspirone D) Diazepam E) Fluoxetine

B) Amitriptyline TCAs commonly cause orthostatic hypotension

SNRIs and treatment of pain

Both SNRIs and the TCAs, with their dual inhibition of both serotonin and norepinephrine reuptake, are sometimes effective in relieving pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain

A variety of antidotes have been reported to treat SSRI-induced sexual dysfunction effectively. Name four of these drugs

Bupropion Mirtazapine Buspirone Nefazodone

A 29-y-old man comes to the physician because of a 4-month history of premature ejaculation. He states that about half of the time, he ejaculates prior to sexual intercourse and the other half of the time, he ejaculates immediately on vaginal penetration. Physical examination shows no abnormalities. If pharmacotherapy is indicated, which of the following is most appropriate? A) Atropine B) Cyproheptadine C) Paroxetine D) Sidenafil E) Trazondone

C) Paroxetine SSRIs are associated with ejaculation delay and are helpful in treating premature ejaculation (especially paroxetine)

A 28-year-old female complains to her doctor that she is in danger of losing her job. She states that she is late to work almost everyday because, before she leaves for work, she must check all of the faucets to make sure the water is turned off. She also needs to repeatedly check to make sure that her stove is off. When she is finally ready to leave, she returns from her car several times to ensure that her doors and windows are locked. Which of the following drugs will her physician most likely prescribe? A. Buspirone B. Chlorpromazine C. Clomipramine D. Imipramine E. Phenelzine F. Zolpidem

C. Clomipramine

A 54-year-old woman complains of a rapid heart rate and dry mouth. She states that the symptoms occur in the morning after taking her medication. Which of the following medications is most likely the cause of these symptoms? A. Captopril B. Conjugated estrogens C. Doxepin D. Naproxen E. Medroxyprogesterone

C. Doxepin Tachycardia refers to a rapid beating of the heart and usually applies to rates greater than 100 per minute. Xerostomia means dryness of the mouth, resulting from diminished or arrested secretion. Both tachycardia and dry mouth are common side effects of medications that possess anticholinergic properties. Of the medications listed, only doxepin possesses anticholinergic properties. Doxepin is a tricyclic antidepressant primarily used to treat clinical depression. It is also used to treat psychoneurotic anxiety and depressive reactions, as well as mixed symptoms of anxiety and depression. Captopril (choice A) is an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension and congestive heart failure. Although it is not associated with the development of xerostomia or tachycardia, it is known to cause angioedema, hyperkalemia, and chronic cough. Conjugated estrogens (choice B) and medroxyprogesterone (choice E), a progestin, are used together to help prevent the signs and symptoms associated with menopause. The most common side effects of these agents are nausea and vomiting. Note: estrogens are also associated with the development of clotting disorders, as well as endometrial hyperplasia. Naproxen (choice D) is a nonsteroidal anti-inflammatory drug indicated for the treatment of mild to moderate pain. The most common side effect of naproxen is gastrointestinal irritation.

Atypical Depression

Characterized by *hypersomnia *overeating *leaden paralysis (feeling of heaviness in limbs) *mood reactivity (i.e., can feel happy when happy events occur, not persistently sad) Associated with *weight gain *sensitivity to rejection Treatment *MAO inhibitors *SSRIs (combining these drugs increases the risk for serotonin syndrome)

All of the SSRIs except ______________ and _____________ have been approved for the treatment of OCD

Citalopram and escitalopram have not been approved for OCD According to Uptodate, "Because none of the individual SSRIs have shown an advantage in efficacy for OCD, the choice among the SSRIs can be made on the basis of prior treatment response, drug side effects and their acceptability to the patient"

Which SSRIs have the lowest side effect profile?

Citalopram and escitalopram: have the lowest side effect profile of SSRIs.

A 43-year-old depressed man is seen in the emergency department while on vacation. He is being treated for atypical depression by his primary doctor at home, but does not tell the emergency doctor that he is on this medication. While in the ED, the new intern gives the patient an SSRI to help his depression. The patient is at greatest risk for developing: A Acute Dystonic Reaction B Hypertensive Crisis C Neuroleptic Malignant Syndrome D Serotonin Syndrome E Nephrogenic Diabetes Insipidus

D Serotonin Syndrome The patient is being treated for atypical depression, which is usually treated with an MAOI. While in the ED, the patient is started on an SSRI to help his depression. The combination of an MAOI and SSRI can precipitate a dangerous serotonin syndrome, characterized by myoclonus, hyperthermia, cardiovascular collapse, flushing, diarrhea and seizures.

Which TCA is least sedating?

Desipramine is the least sedating *Desis are the least seductive/sedating

Name 5 clinical uses of Doxepin

Doxepin is a TCA that can be used for the treatment of depression, anxiety, and insomnia It is also available in a topical form that is used to treat atopic dermatitis and lichen simplex chronicus

Which SNRI is indicated in the treatment of Diabetic Peripheral Neuropathy?

Duloxetine

A 72-year-old male presents to the emergency room complaining of inability to urinate, constipation and hallucinations. On examination, he is noted to be confused, tachycardic and have xerostomia. An EKG shows slowing of his atrioventricular conduction. An astute medical student looks up his medical records and notes his psychiatrist placed the patient on a tricyclic antidepressant. Which of the following tricyclic antidepressants can also be used to treat enuresis? A Amitryptyline B Amoxapine C Nortriptyline D Desipramine E Imipramine

E Imipramine The patient is having side effects classic for tricyclic antidepressants. Imipramine can be used to control bed wetting in children older than 6 years old by causing contraction of the internal sphincter of the bladder and by decreasing stage 3 of sleep (when enuresis occurs). It can cause cardiac arrhythmias.

A 21-year-old female presents to her doctor for a wellness exam. She complains that over the last 3 weeks she has had decreased interest in her usual athletic activities, and is now considering quitting the swimming team she has been competitively racing for during the last 9 years. She also says that she has only been able to get about 6 hours of sleep per night and has had difficulty staying asleep once she falls asleep. This is much less than her usual 8-9 hours per night. She admits to feeling guilty regarding her parent's recent divorce. She denies thinking about death and wants to feel better again. What is the most appropriate pharmacological management of this patient? A Amitriptyline B Phenelzine C Bupropion D Risperidone E Sertraline

E Sertraline The patient is presenting with classic symptoms of major depression. She has decreased interest in her usual activities, has difficulty sleeping and is having thoughts of guilt. In patients with major depression, SSRI treatment is the first line intervention. An SSRI like sertraline should be initiated before any of the other types of medications are tried. Phenelzine is an MAOI and should be used for atypical depression. Because of the risk of hypertensive crisis, these medications are not used too frequently. Risperidone is an atypical antipsychotic. Since this patient is not having any psychotic symptoms, it would not be an appropriate choice. Bupropion is an atypical antidepressant that is used in smoking cessation. It can cause seizures as a side effect, and should be avoided in bulimic patients or those with a history of epilepsy. Amitriptyline is a TCA that can be used for major depression, but it is not a first line medication. Because of lethality in overdose, as well as the convulsions, coma or cardiotoxicity it should be avoided unless necessary.

A 60-year-old man comes to the physician because of difficulty sleeping and concentrating and a 5-kg (10-lb) weight loss over the past 3 months. He also has become withdrawn. He has had chronic pain since sustaining fractures of the left lower extremity,pelvis, and several ribs in a motor vehicle collision 2 years ago. He has a previous history of alcohol abuse. He takes a nonsteroidal anti-inflammatory drug. Which of the following is the most appropriate pharmacotherapy? A) Carbamazepine B) Chlordiazepoxide C) Disulfiram D) Lithium carbonate E) Nortriptyline

E) Nortriptyline Depression + Chronic pain = TCA Chlordiazepoxide (benzo) would be contraindicated in this patient because of history of alcohol abuse

A 25-year-old woman has a long history of depressive symptoms accompanied by body aches and pain secondary to a car accident 2 years earlier. Physical and laboratory tests are unremarkable. Which of the following drugs might be useful in this patient? A. Fluoxetine. B. Sertraline. C. Phenelzine. D. Mirtazapine. E. Duloxetine

E. Duloxetine Duloxetine is a SNRI that can be used for depression accompanied by symptoms of pain. SSRIs (fluoxetine and sertraline), MAOIs (phenelzine), and atypical antidepressants (mirtazapine) have little activity against pain syndromes

A 50-year-old woman with a past history of recurrent major depressive disorder is currently on a maintenance dose of an antidepressant. She has been well for the past 2 years. She is complaining to her psychiatrist about her decreased ability to reach orgasm. Which of the following medications has most likely caused her anorgasmia? A. Amitriptyline B. Bupropion C. Mirtazapine D. Nefazodone E. Paroxetine

E. Paroxetine SSRIs are associated with ejaculation delay

What mnemonic can be used to remember the symptoms of Serotonin Syndrome

Mnemonic: HARMED Hyperthermia Autonomic instability Rash (Flushing) Myoclonus (clonic muscle twitching); Muscle Rigidity, Mental status changes Encephalopathy Diarrhea

Orthostatic Hypertension is particularly dangerous in the elderly as it can lead to falls and significant fractures. Which TCA is the drug of choice in elderly as it is least likely to cause orthostatic hypertension?

Nortriptyline (No tripping and falling with Nortriptyline)

Which SSRI is most likely to cause weight gain?

Paroxetine Paroxetine has more anticholinergic properties causing sedation, constipation, and weight gain.

Which two SSRIs are very potent inhibitors of Cytochrome P450 Which two SSRIs have very minimal effects on Cytochrome P450

Potent inhibitors: Fluoxetine and Paroxetine Minimal inhibitors: Citalopram and Escitalopram

A patient asks for a new medication as their first attempt with an SSRI led to unwanted side effects. Which class of medications should you prescribe next?

Prescribe another SSRI Adverse effects are the most frequent reason for discontinuing SSRIs within the first 3 months of treatment; the first option after failing an SSRI is to prescribe another SSRI with the hope there will be fewer side effects.

What class of medications used in the treatment of depression or anxiety disorders can cause persistent pulmonary hypertension in the newborn?

SNRIs (esp if taken in the 3rd trimester)

Why should antidepressants be prescribed with caution to children and adolescents?

SSRIs and SNRIs are associated with an increased risk of suicide in children and adolescents

MOA of SSRIs

SSRIs block the reuptake of Serotonin by the presynaptic neuron (SERT)

Adverse effects of SNRIs

Stimulant effects due to NE(tachycardia, increased BP, insomnia) Nausea Serotonin syndrome SNRI discontinuation syndrome (flulike symptoms and electric-like shocks)

TCAs and interaction with antihypertensive medications

TCAs can interact with several antihypertensive drugs (a2 agonists) such as clonidine, guanethidine, and bethanidine and antagonize their antihypertensive effects via interference with neuronal uptake by noradrenergic neurons

SSRIs can _____________(cause/treat) premature ejaculation

Treat SSRIs are associated with ejaculation delay and are helpful in treating premature ejaculation (especially paroxetine)