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