Chapter 16

Types of psychotherapeutic drugs

Anxiolytic drugs Mood-stabilizing drugs Antidepressant drugs Antipsychotic drugs

Antipsychotic drugs

Are used to treat serious mental illnesses such as drug-induced psychoses, schizophrenia, and autism. Are also used to treat extreme mania (as an adjunct to lithium), bipolar disorder, depression that is resistant to other therapy, certain movement disorders (e.g., Tourette's syndrome), and certain other medical conditions (e.g., nausea, intractable hiccups).

Reduce anxiety by reducing overactivity in CNS

Benzodiazepines: depress activity in the brainstem and limbic system Miscellaneous drug: buspirone (BuSpar) Nonsedating and non-habit forming May have drug interaction with SSRIs (serotonin syndrome) Do not administer with MAOIs

Lithium

Blood levels are best measured 8 to 12 hours after the last dose (roughly the midpoint of the drug half-life), because the half-life is usually between 18 and 24 hours. Both sodium and this ion are monovalent positive ions, and one can affect the other. Therefore, the patient's serum sodium levels require monitoring

The second-generation antidepressants

Considered superior to TCAs and MAOIs in terms of their adverse effect profiles. They are associated with significantly fewer and less severe systemic adverse effects, especially anticholinergic and cardiovascular adverse effects. It takes approximately the same amount of time to reach maximum clinical effectiveness with the second-generation antidepressants as it does with the TCAs and MAOIs, typically 4 to 6 weeks.

Contraindications to lithium therapy

Contraindication for this drug include dehydration, known sodium imbalance, and major renal or cardiovascular disease, because all of these conditions increase the risk of this drug's toxicity

Second-Generation Antidepressants: miscellaneous

trazodone (Desyrel, Oleptro) bupropion (Wellbutrin) nefazodone (Serzone) mirtazapine (Remeron)

Mood stabilizers are drugs

used to treat bipolar illness (cycles of mania, hypomania, and depression).

Second-Generation Antidepressants: SNRIs

venlafaxine (Effexor) duloxetine (Cymbalta) desvenlafaxine (Pristiq)

Bupropion

was originally indicated for treatment of depression but is now also indicated as an aid in smoking cessation. It is sometimes added as an adjunct antidepressant for patients experiencing sexual adverse effects secondary to SSRI therapy. Although the mechanism is unclear, the drug is often effective in this situation

Fluoxetine (Prozac)

was the first SSRI marketed for the treatment of depression and is considered the prototypical SSRI. Since that time, it has become the top-prescribed antidepressant in the United States and one of the most commonly prescribed of all drugs. Although it was initially indicated for the treatment of depression, the indications for fluoxetine have since expanded to include bulimia, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder

Tricyclic antidepressants (TCAs)

were the original first-generation antidepressants. Their use has largely been replaced with the SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs). Theys are considered second-line drug therapy in patients for whom the SSRIs are ineffective or as adjunct therapy with newer drugs

MAOIs

A variety of over-the-counter drugs (especially for cough and cold) also can interact with this drug class to cause adverse cardiovascular effects. Sympathomimetic drugs can also interact withthem, and together these drugs can cause a hypertensive crisis. They can markedly potentiate the effects of meperidine, and therefore their concurrent use is contraindicated.

Buspirone (BuSpar)

A washout period of at least 14 days after discontinuation of MAOI therapy must be allowed before started. Other drugs that interact with it include inhibitors of the cytochrome P-450 enzyme system - specifically with CYP3A4 (e.g., ketoconazole, clarithromycin—which can reduce its clearance; and inducers of these same enzymes, which can enhance its clearance and decrease its therapeutic effect

Foods that contain tyramine!

Aged, mature cheeses (cheddar, blue, Swiss) Smoked/pickled or aged meats, fish, poultry (herring, sausage, corned beef, salami, pepperoni, paté) Yeast extracts Red wines (Chianti, burgundy, sherry, vermouth) Italian broad beans (fava beans)

Monoamine oxidase inhibitors (MAOIs)

Along with TCAs, represent the first generation of antidepressant drug therapy; they are rarely used as antidepressants, but are used to treat Parkinson's disease. A serious disadvantage to MAOI use is their potential to cause a hypertensive crisis when taken with stimulant medications or with a substance containing tyramine,

Buspirone (BuSpar)

An anxiolytic drug that is different both chemically and pharmacologically from the benzodiazepines. Its precise mechanism of action is unknown, but it appears to have agonist activity at both serotonin and dopamine receptors. It is indicated for the treatment of anxiety and is always administered on a scheduled (not "as-needed") basis, as opposed to the benzodiazepines that may be administered as needed or on a schedule

Risperidone (Risperdal)

An atypical antipsychotic that was introduced a few years after clozapine. It is even more active than clozapine at the serotonin (5-HT2A and 5-HT2C) receptors. It also has a high affinity for alpha1- and alpha2-adrenergic receptors and histamine H1 receptors. This drug is indicated for schizophrenia, including negative symptoms, and causes minimal extrapyramidal adverse effects at therapeutic dosages of 1 to 6 mg/day.

Benzodiazepines: Adverse Effects

An overexpression of their therapeutic effects Decreased CNS activity, sedation Hypotension Drowsiness, loss of coordination, dizziness, headaches Nausea, vomiting, dry mouth, constipation

Antipsychotics: Mechanism of Action

Block dopamine receptors in the brain (limbic system, basal ganglia)—areas associated with emotion, cognitive function, motor function Dopamine levels in the CNS are decreased Result: tranquilizing effect in psychotic patients

Tricyclic Antidepressants: Mechanism of Action

Block reuptake of neurotransmitters, causing accumulation at the nerve endings It is thought that increasing concentrations of neurotransmitters will correct the abnormally low levels that lead to depression

Psychotherapeutic Drugs: Nursing Implications

Caffeine and cigarette smoking may decrease effectiveness of medication therapy

Affective Disorders (Mood Disorders)

Changes in mood that range from mania (abnormally pronounced emotions) to depression (abnormally reduced emotions) Some patients may exhibit both mania and depression: bipolar disorder (BPD)

Second-Generation Antidepressants: Indications

Depression Bipolar disorder Obesity Eating disorders Obsessive-compulsive disorder Panic attacks or disorders Social anxiety disorders Posttraumatic stress disorders (PTSDs) Myoclonus Treatment of various substance abuse problems (bupropion [Zyban] is used for smoking cessation treatment)

Tricyclic Antidepressants: Indications

Depression Childhood enuresis (imipramine) Obsessive-compulsive disorders (clomipramine) Adjunctive analgesics for chronic pain conditions, such as trigeminal neuralgia

MAOIs: Indications

Depression, especially types characterized by reverse vegetative symptoms such as increased sleep and appetite Depression that does not respond to other drugs such as tricyclics

Lithium

Drug of choice for the treatment of mania It is thought to potentiate serotonergic neurotransmission Narrow therapeutic range: maintenance serum levels should range between 0.6 and 1.2 mEq/L

Antipsychotics

Drugs used to treat serious mental illness Behavioral problems or psychotic disorders Have been known as tranquilizers or neuroleptics Conventional drugs Atypical antipsychotics

Tricyclic antidepressants (TCAs)

Effective drugs in the treatment of various affective disorders, but they are associated with serious adverse effects- monitored closely. Only with a prescription. Some herbal products used to treat depression, such as St. John's wort are available over the counter but should not be taken with this drug category. Many drugs in this class are rated as pregnancy category D drugs

MAOIs: Adverse Effects

Few adverse effects—orthostatic hypotension most common Tachycardia Dizziness Insomnia Anorexia Blurred vision Palpitations Drowsiness Headache Nausea Impotence

Second-Generation Antidepressants

Fewer adverse effects than tricyclics and MAOIs Very few drug-drug or drug-food interactions Still take about 4 to 6 weeks to reach maximum clinical effectiveness Now considered first-line drugs for depression

Tricyclic Antidepressants

Have largely been replaced by SSRIs as first-line antidepressant drugs, so considered second line. For patients who fail with SSRIs or other newer-generation antidepressants As adjunct therapy with newer-generation antidepressants amitriptyline (Elavil)

Second-Generation Antidepressants: Adverse Effects

Headache, dizziness, tremor, nervousness, insomnia*, fatigue Nausea, diarrhea, constipation, dry mouth Sexual dysfunction, weight gain*, weight loss*, sweating

Monoamine Oxidase Inhibitors (MAOIs)

Highly effective Considered second-line treatment for depression, not responsive to cyclics Disadvantage: potential to cause hypertensive crisis when taken with tyramine

MAOIs and Tyramine

Ingestion of foods or drinks with tyramine leads to hypertensive crisis, which may lead to cerebral hemorrhage, stroke, coma, or death

Second-Generation Antidepressants: Mechanism of Action: SNRIs

Inhibit reuptake of both serotonin and norepinephrine

MAOIs: Mechanism of Action

Inhibit the MAO enzyme system in the CNS Amines (dopamine, serotonin, norepinephrine) are not broken down, resulting in higher levels in the brain Result: alleviation of symptoms of depression

Psychotherapeutic Drugs: Nursing Implications :Antipsychotics—phenothiazines

Instruct patients to wear sunscreen because of photosensitivity Tell patients to avoid taking antacids or antidiarrheal preparations within 1 hour of a dose Inform patients to avoid alcohol or other CNS depressants with these medications

Trazodone (Desyrel, Oleptro)

Is in the triazolopyridine drug class. It was the first of the second-generation antidepressants that could selectively inhibit serotonin reuptake but minimally affect norepinephrine reuptake.Has minimal adverse effects on the cardiovascular system, which is an advantage over the TCAs. It is indicated for the treatment of depression, and it is also commonly used as a nonaddictive drug treatment for insomnia. has been associated in rare cases with transient nonsexual priapism

Mirtazapine (Remeron)

Is unique in that it promotes the presynaptic release of both serotonin and norepinephrine in the brain. This is due to its antagonist activity in the presynaptic alpha2-adrenergic receptors. It does not inhibit the reuptake of either of these neurotransmitters. It is strongly associated with sedation in more than 50% of patients due to its histamine 1 (H1) receptor activity and therefore is usually dosed once daily at bedtime. is indicated for treatment of depression, including that associated with bipolar disorder. It is also sometimes helpful (mechanism unknown) in reducing the sexual adverse effects in male patients receiving SSRI therapy.

Haloperidol (Haldol)

It is indicated primarily for the long-term treatment of psychosis. However, it has been largely replaced by the atypical antipsychotics because of its adverse effects (see later). Is contraindicated in patients who have shown a hypersensitivity reaction to it, those in a comatose state, those taking large amounts of CNS depressants, and those with Parkinson's disease

Tricyclic Antidepressants: Overdose

Lethal—70% to 80% die before reaching the hospital from overdose CNS and cardiovascular systems are mainly affected Death results from seizures or dysrhythmias

Lithium

Levels exceeding 1.5 to 2.5 mEq/L begin to produce toxicity, including GI discomfort, tremor, confusion, somnolence, seizures, and possibly death. The most serious adverse effect is cardiac dysrhythmia. Other effects include drowsiness, slurred speech, epilepsy-type seizures, choreoathetotic movements (involuntary wavelike movements of the extremities), ataxia (generalized disturbance of muscular coordination), and hypotension.

Duloxetine (Cymbalta)

Like venlafaxine, is a serotonin-norepinephrine reuptake inhibitor (SSNRI). It is indicated for depression and generalized anxiety disorder. It is also indicated for pain resulting from diabetic peripheral neuropathy or fibromyalgia. It is contraindicated in cases of known drug allergy and concurrent MAOI use, and it can worsen uncontrolled angle-closure glaucoma

Mood-Stabilizing Drugs

Lithium carbonate and lithium citrate Other drugs may be used in combination with lithium: Benzodiazepines Antipsychotic drugs Antiepileptic drugs Dopamine receptor agonists

Antipsychotics—phenothiazines

Long-term haloperidol therapy may result in tremors, nausea, vomiting, or uncontrollable shaking of small muscle groups; report these symptoms to the physician

Lithium long-term treatment effect

Long-term treatment may cause hypothyroidism. Potentially interacting drugs include the thiazide diuretics angiotensin-converting enzyme inhibitors, and nonsteroidal antiinflammatory drugs, all of which can increase lithium toxicity

Buspirone (BuSpar)

Miscellaneous Anxiolytic, unknown mechanism of action. Administered on a scheduled basis Adverse effects: Paradoxical anxiety Blurred vision Headache Nausea

Alprazolam (Xanax)

Most commonly used as an anxiolytic. It is also indicated for the specific anxiety disorder known as panic disorder. Adverse effects include confusion, ataxia, headache, and others. Interacting drugs include alcohol, antacids, oral contraceptives, and others.

Serotonin Syndrome

Most often occurs when taking two drugs that both affect the serotonin levels in the body Symptoms: Delirium, tachycardia, hyperreflexia, shivering, agitation, sweating, muscle spasms, coarse tremors Symptoms of severe cases: Hyperthermia, seizures, renal failure, rhabdomyolysis, dysrhythmias, disseminated intravascular coagulation (DIC)

Antipsychotics: Adverse Effects

Neuroleptic malignant syndrome (NMS) Potentially life threatening High fever, unstable BP, myoglobinemia Extrapyramidal symptoms (EPS) Involuntary muscle symptoms similar to those of Parkinson's disease Akathisia (distressing muscle restlessness) Acute dystonia (painful muscle spasms) Treated with benztropine (Cogentin) and trihexyphenidyl (Artane)

Tricyclic Antidepressants:Overdose

No specific antidote Decrease drug absorption with activated charcoal Speed elimination by alkalinizing urine Manage seizures and dysrhythmias Basic life support

Amitriptyline (Elavil)

Oldest and most widely used of all the TCAs. Its original indication was depression, but it is now more commonly used to treat insomnia and neuropathic pain. Contraindications include known drug allergy, pregnancy, and recent myocardial infarction. It has very potent anticholinergic properties, which can lead to many adverse effects such as dry mouth, constipation, blurred vision, urinary retention, and dysrhythmias

Antipsychotics—phenothiazines

Oral forms may be taken with meals to decrease GI upset These drugs may cause drowsiness, dizziness, or fainting; instruct patients to change positions slowly

Buspirone (BuSpar)

Recommended that monoamine oxidase inhibitors (MAOIs) not be used concurrently with buspirone due to the risk of hypertension.

Tricyclic Antidepressants: Adverse Effects

Sedation Impotence Orthostatic hypotension Older patients: dizziness, postural hypotension, constipation, delayed micturation, edema, muscle tremors

Antipsychotics: Adverse Effects

Sedation, delirium Orthostatic hypotension, syncope, dizziness, ECG changes Photosensitivity, skin rash, hyperpigmentation, pruritus Dry mouth, constipation Urinary hesitancy or retention, impaired erection Leukopenia and agranulocytosis Galactorrhea, irregular menses, increased appetite, polydipsia

Second-Generation Antidepressants: Mechanism of Action: SSRIs

Selectively inhibit serotonin reuptake Little or no effect on norepinephrine or dopamine reuptake Result in increased serotonin concentrations at nerve endings

Affective Disorders

Several classes of drugs are used in the treatment of the affective (emotional) disorders. The two main drug categories are mood-stabilizing drugs and antidepressant drugs.

Psychosis

Severe emotional disorder that impairs the mental function of the affected individual to the point that the individual cannot participate in activities of daily living Hallmark: loss of contact with reality Examples: schizophrenia, depressive and drug-induced psychoses

MAOIs: Overdose

Symptoms appear 12 hours after ingestion Tachycardia, circulatory collapse, seizures, coma. Treatment: protect brain and heart, eliminate toxin: Urine acidification Hemodialysis

Antipsychotics: Adverse Effects

Tardive dyskinesia (TD) Involuntary contractions of oral and facial muscles Choreoathetosis (wavelike movements of extremities) Occurs with continuous long-term antipsychotic therapy

Buspirone (BuSpar)

The only reported contraindication is drug allergy. Lacks the sedative properties and dependency potential of the benzodiazepines. Adverse effects include paradoxical anxiety, dizziness, blurred vision, headache, and nausea

Alprazolam (Xanax)

The orally dissolving tablet is indicated for the treatment of anxiety disorder, short-term relief of anxiety symptoms, treatment of anxiety associated with depression, and treatment of panic disorder with or without agoraphobia.

Antipsychotics drugs

Thioxanthenes: thiothixene (Navane) Butyrophenones: haloperidol (Haldol) Dihydroindolones: molindone (Moban) Dibenzoxazepine: loxapine (Loxitane) Phenothiazines: three structural groups Atypical antipsychotics: new class

Herbal Products: Ginseng

Three varieties; has been used for over 5000 years Uses: stress reduction, improvement of physical endurance and concentration May cause elevated BP, chest pain, palpitations, anxiety, insomnia, headache, GI symptoms Interactions with anticoagulants, immunosuppressants, anticonvulsants, antidiabetic drugs

Benzodiazepines: Overdose

Treatment is generally symptomatic and supportive for an overdose. Flumazenil may be used to reverse benzodiazepine effects

Antidepressants

Tricyclic antidepressants Monoamine oxidase inhibitors (MAOIs) Second-generation antidepressants Selective serotonin reuptake inhibitors (SSRIs) Serotonin-norepinephrine reuptake inhibitors (SNRIs) Miscellaneous

Herbal Products: St. John's Wort

Used for depression, anxiety, sleep disorders, nervousness May cause GI upset, fatigue, dizziness, confusion, dry mouth, photosensitivity Severe interactions if taken with MAOIs and SSRIs; many other drug interactions Food-drug interaction with tyramine-containing foods

Diazepam (Valium)

Used to be the most commonly prescribed benzodiazepine; however, for treatment of anxiety, it has generally been replaced by the shorter-acting benzodiazepines alprazolam and lorazepam. It's indicated for the relief of anxiety, management of alcohol withdrawal, reversal of status epilepticus, preoperative sedation, and less frequently as an adjunct for the relief of skeletal muscle spasms.

Antidepressant Drugs

Very effective in treating depression, they are also useful in treating other disorders, such as dysthymia (chronic low-grade depression), schizophrenia (as an adjunctive drug), eating disorders, and personality disorders. Some of the antidepressants are also used in the treatment of various medical conditions, including migraine headaches, chronic pain syndromes, sleep disorders, premenstrual syndrome, and hot flashes associated with menopause.

Clozapine (Clozaril)

Was the first of the atypical antipsychotics. Compared to conventional antipsychotic drugs, it more selectively blocks the dopaminergic receptors in the mesolimbic region of the brain. Conventional antipsychotic drugs block dopamine receptors in an area of the brain called the neostriatum, but blockade in this area is believed to give rise to extrapyramidal adverse effects

Benzodiazepines

alprazolam (Xanax) diazepam (Valium) lorazepam (Ativan)

Lorazepam (Ativan)

can be given by intravenous push, which is useful in the treatment of an acutely agitated patient. It is often administered as a continuous infusion to agitated patients who are undergoing mechanical ventilation. It is also used to treat or prevent alcohol withdrawal (

Atypical Antipsychotics

clozapine (Clozaril) risperidone (Risperdal) olanzapine (Zyprexa) quetiapine (Seroquel) ziprasidone (Geodon) aripiprazole (Abilify) paliperidone (Invega)

serotonin syndrome

concurrent use of MAOIs with SSRIs carries the risk for serotonin syndrome. A washout period of 2 to 5 weeks between drugs is recommended.

Second-Generation Antidepressants: SSRIs

fluoxetine (Prozac) paroxetine (Paxil) sertraline (Zoloft) fluvoxamine (Luvox) citalopram (Celexa) escitalopram (Lexapro)

Diazepam (Valium)

has active metabolites that can accumulate in patients with hepatic dysfunction, because it is metabolized primarily in the liver. This can result in additive, cumulative effects that may be manifested as prolonged sedation, respiratory depression, or coma. For this reason, it is probably best avoided in patients with major hepatic compromise. Adverse drug effects include headache, confusion, slurred speech. interacts with alcohol, oral contraceptives

Antipsychotic drugs

have also been referred to as tranquilizers or neuroleptics because they produce a state of tranquility and act on abnormally functioning nerves

The selegiline transdermal patch (Emsam)

is a selective MAO-B inhibitor. It is currently indicated for major depression. The lowest strength of the selegiline transdermal patch (6 mg/24 hr) can be used without dietary restrictions

Lorazepam (Ativan)

is an intermediate-acting benzodiazepine. Of those mentioned here, is the shortest acting, whereas diazepam is the longest acting. available in oral and injectable forms. It may be given intravenously or intramuscularly. It has excellent absorption and bioavailability when given intramuscularly, but it is irritating to the muscle and must be diluted

MAOIs drugs

isocarboxazid (Marplan) phenelzine (Nardil) tranylcypromine (Parnate) selegiline (Emsam)