PSYCHOTHERAPEUTIC AGENTS
ANTIDEPRESSANTS
and
ANTIPSYCHOTICS
Psychotherapeutics
•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:
•Psychosis
•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.
•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.
•Brain levels of certain catecholamines play an important role in maintaining mental health.
–Dopamine
–Serotonin
–Histamine
•Other biochemicals are necessary for normal mental function.
–GABA
–acetylcholine
–lithium
•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:
•Psychosis
•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.
•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.
•Brain levels of certain catecholamines play an important role in maintaining mental health.
–Dopamine
–Serotonin
–Histamine
•Other biochemicals are necessary for normal mental function.
–GABA
–acetylcholine
–lithium
Etiology of Depression
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
•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
Instructors may wish to insert
EIC Image #45:
Biogenic Amine Hypothesis
EIC Image #45:
Biogenic Amine Hypothesis
Affective Disorders
Drug Categories
•Antidepressants
•tricyclics, tetracyclics, SSRIs, MAOIs
•Antimanic Agents
•lithium
•Antidepressants
•tricyclics, tetracyclics, SSRIs, MAOIs
•Antimanic Agents
•lithium
Antidepressants
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)
–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)
Cyclic 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.
•It is thought that increasing concentrations of neurotransmitters will correct the abnormally low levels that lead to depression.
Cyclic Antidepressants
Mechanism of Action—Drug Effects
Blockade of norepinephrine:
–antidepressant, tremors, tachycardia, additive pressor effects with sympathomimetic drugs
Blockade of serotonin:
–antidepressant, nausea, headache, anxiety, sexual dysfunction
–antidepressant, tremors, tachycardia, additive pressor effects with sympathomimetic drugs
Blockade of serotonin:
–antidepressant, nausea, headache, anxiety, sexual dysfunction
Cyclic Antidepressants
Therapeutic Uses
•Depression
•Childhood enuresis (imipramine)
•Obsessive-compulsive disorders (clomipramine)
•Adjunctive analgesics
•Trigeminal neuralgia
Side Effects
•Sedation
•Impotence
•Orthostatic hypotension
•Older patients: –dizziness, postural hypotension, constipation, delayed micturation, edema, muscle tremors
Tricyclic Antidepressants Overdose
•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
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
•phenelzine (Nardil)
•tranylcypromine (Parnate)
•isocarboxazid (Marplan)
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
Therapeutic Uses
•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
Side Effects
•Few side effects—orthostatic hypotension most common
Tachycardia
Palpitations
Dizziness
Drowsiness
Insomnia
Headache
Anorexia
Nausea
Blurred vision
Impotence
Overdose
•Symptoms appear 12 hours after ingestion
•Tachycardia, circulatory collapse, seizures, coma
•Treatment: protect brain and heart, eliminate toxin
–Gastric lavage
–Urine acidification
–Hemodialysis
Hypertensive Crisis and Tyramine
•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)
Second-Generation Antidepressants
•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)
Antidepressants and SSRIs
Mechanism of Action
•Selectively inhibit serotonin reuptake
•Little or no effect on norepinephrine or dopamine reuptake
•Results in increased serotonin concentrations at nerve endings
Advantage over tricyclics and MAOIs: Little or no effect on cardiovascular system
Therapeutic Uses
•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)
Side Effects
Body System Effects
CNS Headache dizziness, tremor, nervousness, insomnia, fatigue
GI Nausea, diarrhea,constipation, dry mouth
Other Sweating, sexual dysfunction
Drug Interactions
•Highly bound to plasma proteins
•Compete with other protein-binding drugs, resulting in more free, unbound drug to cause a more pronounced drug effect
Antipsychotics
•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
Phenothiazine 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
Atypical Antipsychotics
•clozapine (Clozaril)
•risperidone (Risperdal)
•olanzapine (Zyprexa)
•quetiapine (Seroquel)
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
•The newer, atypical antipsychotics also block specific serotonin receptors (serotonin-2 [5HT2] receptors).
•This is responsible for their improved efficacy and safety profiles.
Drug Effects
•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
Therapeutic Uses
•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
Side Effects
Body System Effects
CNS Sedation, delirium
Cardiovascular Orthostatic hypotension, syncope, dizziness, ECG changes
Dermatologic Photosensitivity, skin rash, hyperpigmentation, pruritus
GI Dry mouth, constipation
GU Urinary hesitancy or retention, impaired erection
Hematologic Leukopenia and agranulocytosis
Metabolic/endocrine Galactorrhea, irregular menses, increased appetite, polydipsia
Nursing Implications
•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.
•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.
•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.
•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
•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
•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
•For antipsychotics:
–Improved mood and affect, alleviation of psychotic symptoms and episodes
–Decrease in hallucinations, paranoia, delusions, garbled speech, inability to cope
•Childhood enuresis (imipramine)
•Obsessive-compulsive disorders (clomipramine)
•Adjunctive analgesics
•Trigeminal neuralgia
Side Effects
•Sedation
•Impotence
•Orthostatic hypotension
•Older patients: –dizziness, postural hypotension, constipation, delayed micturation, edema, muscle tremors
Tricyclic Antidepressants Overdose
•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
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
•phenelzine (Nardil)
•tranylcypromine (Parnate)
•isocarboxazid (Marplan)
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
Therapeutic Uses
•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
Side Effects
•Few side effects—orthostatic hypotension most common
Tachycardia
Palpitations
Dizziness
Drowsiness
Insomnia
Headache
Anorexia
Nausea
Blurred vision
Impotence
Overdose
•Symptoms appear 12 hours after ingestion
•Tachycardia, circulatory collapse, seizures, coma
•Treatment: protect brain and heart, eliminate toxin
–Gastric lavage
–Urine acidification
–Hemodialysis
Hypertensive Crisis and Tyramine
•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)
Second-Generation Antidepressants
•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)
Antidepressants and SSRIs
Mechanism of Action
•Selectively inhibit serotonin reuptake
•Little or no effect on norepinephrine or dopamine reuptake
•Results in increased serotonin concentrations at nerve endings
Advantage over tricyclics and MAOIs: Little or no effect on cardiovascular system
Therapeutic Uses
•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)
Side Effects
Body System Effects
CNS Headache dizziness, tremor, nervousness, insomnia, fatigue
GI Nausea, diarrhea,constipation, dry mouth
Other Sweating, sexual dysfunction
Drug Interactions
•Highly bound to plasma proteins
•Compete with other protein-binding drugs, resulting in more free, unbound drug to cause a more pronounced drug effect
Antipsychotics
•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
Phenothiazine 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
Atypical Antipsychotics
•clozapine (Clozaril)
•risperidone (Risperdal)
•olanzapine (Zyprexa)
•quetiapine (Seroquel)
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
•The newer, atypical antipsychotics also block specific serotonin receptors (serotonin-2 [5HT2] receptors).
•This is responsible for their improved efficacy and safety profiles.
Drug Effects
•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
Therapeutic Uses
•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
Side Effects
Body System Effects
CNS Sedation, delirium
Cardiovascular Orthostatic hypotension, syncope, dizziness, ECG changes
Dermatologic Photosensitivity, skin rash, hyperpigmentation, pruritus
GI Dry mouth, constipation
GU Urinary hesitancy or retention, impaired erection
Hematologic Leukopenia and agranulocytosis
Metabolic/endocrine Galactorrhea, irregular menses, increased appetite, polydipsia
Nursing Implications
•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.
•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.
•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.
•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
•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
•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
•For antipsychotics:
–Improved mood and affect, alleviation of psychotic symptoms and episodes
–Decrease in hallucinations, paranoia, delusions, garbled speech, inability to cope