06 psychotherapeutic agents upd

Antidepressants and Antipsychotics

The therapy of emotional and mental disorders

Anxiety Grief Depression

are normal human emotions

The ability to cope with these emotions can range from occasional depression or anxiety to constant emotional distress to the point ofinterfering with the ability to carry on normal daily living.

When these emotions significantly affect an individual’s ability to carry out normal daily functions, treatment with a psychotherapeutic drug is a possible option.

Three main emotional and mental disorders:

Psychoses Affective disorders Anxiety

Psychosis A major emotional disorder that impairs the

mental function of the affected individual to the point that the individual cannot participate in everyday life.

Hallmark: loss of contact with reality

Affective Disorders Major emotional disorders that impair the

mental function of the affected individual to the point that the individual cannot participate in everyday life.

Affective Disorders Mania: abnormally pronounced emotions Depression: abnormally reduced emotions Bipolar affective disorder: exhibits both mania

and depression

Pathophysiology Biochemical Imbalance Mental disorders are associated with abnormal

levels of endogenous chemicals, such as neurotransmitters, in the brain.

Pathophysiology Biochemical Imbalance Brain levels of certain catecholamines play an

important role in maintaining mental health. Dopamine Serotonin Histamine

Pathophysiology Biochemical Imbalance Other biochemicals are necessary for normal

mental function. GABA acetylcholine lithium

Biogenic Amine Hypothesis Depression and mania are due to an alteration

in neuronal and synaptic catecholamine concentration at adrenergic receptor sites in the brain. Depression: deficiency of catecholamine,

especially norepinephrine Mania: excess amines

Drug Categories Antidepressants tricyclics, tetracyclics, SSRIs, MAOIs Antimanic Agents lithium

Cyclic antidepressants tricyclics tetracyclics

Monoamine oxidase inhibitors (MAOIs) Second-generation antidepressants

and SSRIs

Tricyclic antidepressants—primary: amitriptyline (Elavil), doxepin (Sinequan), imipramine (Tofranil)

Tricyclic antidepressants—secondary: desipramine (Norpramin), nortriptyline (Aventyl), protriptyline (Vivactil)

Tetracyclic antidepressants: amoxapine (Asendin), maprotiline (Ludiomil)

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.

Blockade of norepinephrine: antidepressant, tremors, tachycardia,

additive pressor effects with sympathomimetic drugs

Blockade of serotonin: antidepressant, nausea, headache, anxiety,

sexual dysfunction

Depression Childhood enuresis (imipramine) Obsessive-compulsive disorders

(clomipramine) Adjunctive analgesics Trigeminal neuralgia

Sedation Impotence Orthostatic hypotension Older patients:

dizziness, postural hypotension, constipation, delayed micturation, edema, muscle tremors

Lethal—70 to 80% die before reaching the hospital

CNS and cardiovascular systems are mainly affected

Death results from seizures or dysrhythmias

No specific antidote Decrease drug absorption with activated

charcoal Speed elimination by alkalinizing urine Manage seizures and dysrhythmias Basic life support

Highly effective Considered second-line treatment for

depression not responsive to cyclics Disadvantage: potential to cause

hypertensive crisis when taken with tyramine

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

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

Depression, especially types characterized by reverse vegetative symptoms such as increased sleep and appetite

Depression that does not respond to other agents such as tricyclics

Few side effects—orthostatic hypotension most commonTachycardia Palpitations

Dizziness Drowsiness

Insomnia Headache

Anorexia Nausea

Blurred vision Impotence

Symptoms appear 12 hours after ingestion

Tachycardia, circulatory collapse, seizures, coma

Treatment: protect brain and heart, eliminate toxin Gastric lavage

Urine acidification

Hemodialysis

Ingestion of foods and/or drinks with the amino acid TYRAMINE leads to hypertensive crisis, which may lead to cerebral hemorrhage, stroke, coma, or death

Avoid 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)

Newer Fewer side effects than tricyclics, but not

superior in overall efficacy or onset of action trazodone (Desyrel) bupropion (Wellbutrin, Zyban) selective serotonin reuptake inhibitors (SSRIs)

Selectively inhibit serotonin reuptake Little or no effect on norepinephrine

or dopamine reuptake Results in increased serotonin

concentrations at nerve endingsAdvantage over tricyclics and MAOIs:

Little or no effect on cardiovascular system

Used for depression—very few serious side effects

Bipolar affective disorder Obesity Eating disorders Obsessive-compulsive disorder Panic attacks Myoclonus Treatment of various substance abuse problems

(bupropion [Zyban] is used for smoking cessation treatment)

Body System EffectsCNS Headache, dizziness,

tremor, nervousness, insomnia, fatigue

GI Nausea, diarrhea,constipation, dry

mouthOther Sweating, sexual

dysfunction

Highly bound to plasma proteins Compete with other protein-binding

drugs, resulting in more free, unbound drug to cause a more pronounced drug effect

Drugs used to treat serious mental illness Behavioral problems or psychotic

disorders

Thioxanthenes: chlorprothixene, thiothixene (Navane)

Butyrophenones: haloperidol (Haldol) Dihydroindolones: molindone (Moban) Dibenzoxazepine: loxapine (Loxitane) Phenothiazines: three structural groups

Aliphatic: chlorpromazine (Thorazine), triflupromazine (Vesprin)

Piperidine: mesoridazine (Serentil), thioridazine (Mellaril)

Piperazine: fluphenazine (Prolixin), perphenazine (Trilafon), prochlorperazine (Compazine), trifluoperazine (Stelazine)

Largest group of psychotropic agents

clozapine (Clozaril) risperidone (Risperdal) olanzapine (Zyprexa) quetiapine (Seroquel)

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

The newer, atypical antipsychotics also block specific serotonin receptors (serotonin-2 [5HT2] receptors).

This is responsible for their improved efficacy and safety profiles.

Block dopamine receptors in CNS Block alpha receptors (causing

hypertension, other cardiovascular effects)

Block histamine receptors (causing anticholinergic effects)

Block serotonin Also function as antiemetics Antianxiety effects

Treatment of serious mental illnesses: Bipolar affective disorder Depressive and drug-induced psychoses Schizophrenia Autism

Movement disorders (such as Tourette’s syndrome)

Some medical conditions Nausea, intractable hiccups

Body System EffectsCNS Sedation, delirium

Cardiovascular Orthostatic hypotension, syncope, dizziness, ECG changes

Dermatologic Photosensitivity, skin rash, hyperpigmentation, pruritus

Body System EffectsGI Dry mouth, constipationGU Urinary hesitancy or

retention, impaired erectionHematologic Leukopenia and

agranulocytosisMetabolic/endocrine Galactorrhea, irregular

mensesincreased appetite, polydipsia

Before beginning therapy, assess both the physical and emotional status of patients

Obtain baseline VS, including postural BP readings

Obtain liver and renal function tests (and baseline platelet levels for MAOIs)

Assess for possible contraindications to therapy, cautious use, and potential drug interactions

Assess LOC, mental alertness, potential for injury to self and others

Check the patient’s mouth to make sure oral doses are swallowed

Provide simple explanations about the drug, its effects, and the length of time before therapeutic effects can be expected

Abrupt withdrawal should be avoided Advise patients to change positions

slowly to avoid postural hypotension and possible injury

The combination of drug therapy and psychotherapy is emphasized because patients need to learn and acquire more effective coping skills

Only small amounts of medications should be dispensed at a time to minimize the risk of suicide attempts

Simultaneous use of these agents with alcohol or other CNS depressants can be fatal

Antidepressants Many cautions, contraindications, and

interactions exist pertaining to the use of antidepressants.

Inform patients that it may take 1 to 3, even 4, weeks to see therapeutic effects.

Monitor patients closely during this time and provide support.

Antidepressants Sedation often occurs with tricyclic therapy;

notify physician if this lasts more than 2 weeks. Assist elderly or weakened patients with

ambulation and other activities as falls may occur due to drowsiness or postural hypotension.

Antidepressants Tricyclics may need to be weaned and

discontinued before undergoing surgery to avoid interactions with anesthetic agents.

Monitor for side effects and discuss with patients.

Encourage patients to wear medication ID badges naming the agent being taken.

Antidepressants Caffeine and cigarette smoking may decrease

effectiveness of medication therapy Instruct patients and family regarding tyramine-

containing foods and signs and symptoms of hypertensive crisis

Antipsychotics—Phenothiazines Instruct patients to wear sunscreen due to

photosensitivity Avoid taking antacids or antidiarrheal

preparations within 1 hour of a dose Do not take alcohol or other CNS depressants

with these medications

Antipsychotics—Phenothiazines Long-term haloperidol therapy may result in

tremors, nausea, vomiting, or uncontrollable shaking of small muscle groups; these symptoms should be reported to the physician

Oral forms may be taken with meals to decrease

GI upset These agents may cause drowsiness, dizziness,

or fainting; instruct patients to change positions slowly

Monitor for therapeutic effects: Monitor mental alertness, cognition,

affect, mood,ability to carry out activities of daily living, appetite, and sleep patterns

Monitor the patient’s potential for self-injury during the delay between the start of therapy and symptomatic improvement

Monitor for therapeutic effects For antidepressants:

Improved sleep patterns and nutrition, increased feelings of self-esteem, decreased feeling of hopelessness, increased interest in self and appearance, increased interest in daily activities, fewer depressive manifestations or suicidal thoughts or ideations

Monitor for therapeutic effects For antipsychotics:

Improved mood and affect, alleviation of psychotic symptoms and episodes

Decrease in hallucinations, paranoia, delusions, garbled speech, inability to cope