psychotherapeutic agents

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Psychotherapeutic AgentsPsychotherapeutic Agents
AntidepressantsAntidepressants
and Antipsychoticsand Antipsychotics

PsychotherapeuticsPsychotherapeutics
• The therapy of emotional and mentalThe therapy of emotional and mental
disordersdisorders

• AnxietyAnxiety
• GriefGrief
• DepressionDepression
are normal human emotionsare normal human emotions

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

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

Three main emotional and mental disorders:Three main emotional and mental disorders:
• PsychosesPsychoses
• Affective disordersAffective disorders
• AnxietyAnxiety

PsychosisPsychosis
• A major emotional disorder that impairs the mentalA major emotional disorder that impairs the mental
function of the affected individual to the point thatfunction of the affected individual to the point that
the individual cannot participate in everyday life.the individual cannot participate in everyday life.
• Hallmark: loss of contact with realityHallmark: loss of contact with reality

Affective DisordersAffective Disorders
• Major emotional disorders that impair theMajor emotional disorders that impair the
mental function of the affected individual tomental function of the affected individual to
the point that the individual cannotthe point that the individual cannot
participate in everyday life.participate in everyday life.

• Mania: abnormally pronounced emotionsMania: abnormally pronounced emotions
• Depression: abnormally reduced emotionsDepression: abnormally reduced emotions
• Bipolar affective disorder: exhibits both maniaBipolar affective disorder: exhibits both mania
and depressionand depression

PathophysiologyPathophysiology
Biochemical ImbalanceBiochemical Imbalance
• Mental disorders are associated with abnormalMental disorders are associated with abnormal
levels of endogenous chemicals, such aslevels of endogenous chemicals, such as
neurotransmitters, in the brain.neurotransmitters, in the brain.

• Brain levels of certain catecholamines play anBrain levels of certain catecholamines play an
important role in maintaining mental health.important role in maintaining mental health.
– DopamineDopamine
– SerotoninSerotonin
– HistamineHistamine

• Other biochemicals are necessary for normalOther biochemicals are necessary for normal
mental function.mental function.
– GABAGABA
– acetylcholineacetylcholine
– lithiumlithium

Etiology of DepressionEtiology of Depression
Biogenic Amine HypothesisBiogenic Amine Hypothesis
• Depression and mania are due to an alteration inDepression and mania are due to an alteration in
neuronal and synaptic catecholamine concentrationneuronal and synaptic catecholamine concentration
at adrenergic receptor sites in the brain.at adrenergic receptor sites in the brain.
– Depression: deficiency of catecholamine,Depression: deficiency of catecholamine,
especially norepinephrineespecially norepinephrine
– Mania: excess aminesMania: excess amines

Instructors may wish to insertInstructors may wish to insert
EIC Image #45:EIC Image #45:
Biogenic Amine HypothesisBiogenic Amine Hypothesis

Drug CategoriesDrug Categories
• AntidepressantsAntidepressants
• tricyclics, tetracyclics, SSRIs, MAOIstricyclics, tetracyclics, SSRIs, MAOIs
• Antimanic AgentsAntimanic Agents
• lithiumlithium

Cyclic antidepressantsCyclic antidepressants
– tricyclicstricyclics
– tetracyclicstetracyclics
• Monoamine oxidase inhibitors (MAOIs)Monoamine oxidase inhibitors (MAOIs)
• Second-generation antidepressantsSecond-generation antidepressants
and SSRIsand SSRIs

Cyclic AntidepressantsCyclic Antidepressants
• Tricyclic antidepressants—primary:Tricyclic antidepressants—primary:
amitriptyline (Elavil), doxepin (Sinequan),amitriptyline (Elavil), doxepin (Sinequan),
imipramine (Tofranil)imipramine (Tofranil)
• Tricyclic antidepressants—secondary:Tricyclic antidepressants—secondary:
desipramine (Norpramin), nortriptylinedesipramine (Norpramin), nortriptyline
(Aventyl), protriptyline (Vivactil)(Aventyl), protriptyline (Vivactil)
• Tetracyclic antidepressants:Tetracyclic antidepressants:
amoxapine (Asendin), maprotiline (Ludiomil)amoxapine (Asendin), maprotiline (Ludiomil)

Mechanism of ActionMechanism of Action
• Block reuptake of neurotransmitters, causingBlock reuptake of neurotransmitters, causing
accumulation at the nerve endings.accumulation at the nerve endings.
• It is thought that increasing concentrations ofIt is thought that increasing concentrations of
neurotransmitters will correct the abnormallyneurotransmitters will correct the abnormally
low levels that lead to depression.low levels that lead to depression.

Mechanism of Action—Drug EffectsMechanism of Action—Drug Effects
Blockade of norepinephrine:Blockade of norepinephrine:
– antidepressant, tremors, tachycardia, additiveantidepressant, tremors, tachycardia, additive
pressor effects with sympathomimetic drugspressor effects with sympathomimetic drugs
Blockade of serotonin:Blockade of serotonin:
– antidepressant, nausea, headache, anxiety,antidepressant, nausea, headache, anxiety,
sexual dysfunctionsexual dysfunction

Therapeutic UsesTherapeutic Uses
• DepressionDepression
• Childhood enuresis (imipramine)Childhood enuresis (imipramine)
• Obsessive-compulsive disordersObsessive-compulsive disorders
(clomipramine)(clomipramine)
• Adjunctive analgesicsAdjunctive analgesics
• Trigeminal neuralgiaTrigeminal neuralgia

Side EffectsSide Effects
• SedationSedation
• ImpotenceImpotence
• Orthostatic hypotensionOrthostatic hypotension
• Older patients:Older patients:
– dizziness, postural hypotension, constipation,dizziness, postural hypotension, constipation,
delayed micturation, edema, muscle tremorsdelayed micturation, edema, muscle tremors

Tricyclic Antidepressants OverdoseTricyclic Antidepressants Overdose
• Lethal—70 to 80% die before reachingLethal—70 to 80% die before reaching
the hospitalthe hospital
• CNS and cardiovascular systems areCNS and cardiovascular systems are
mainly affectedmainly affected
• Death results from seizures or dysrhythmiasDeath results from seizures or dysrhythmias
• No specific antidoteNo specific antidote
– Decrease drug absorption with activated charcoalDecrease drug absorption with activated charcoal
– Speed elimination by alkalinizing urineSpeed elimination by alkalinizing urine
– Manage seizures and dysrhythmiasManage seizures and dysrhythmias
– Basic life supportBasic life support

Monoamine Oxidase Inhibitors: MAOIsMonoamine Oxidase Inhibitors: MAOIs
• Highly effectiveHighly effective
• Considered second-line treatment forConsidered second-line treatment for
depression not responsive to cyclicsdepression not responsive to cyclics
• Disadvantage: potential to causeDisadvantage: potential to cause
hypertensive crisis when taken with tyraminehypertensive crisis when taken with tyramine

Antidepressants: MAOIsAntidepressants: MAOIs
• phenelzine (Nardil)phenelzine (Nardil)
• tranylcypromine (Parnate)tranylcypromine (Parnate)
• isocarboxazid (Marplan)isocarboxazid (Marplan)

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

• Depression, especially types characterizedDepression, especially types characterized
by reverse vegetative symptoms such asby reverse vegetative symptoms such as
increased sleep and appetiteincreased sleep and appetite
• Depression that does not respond to otherDepression that does not respond to other
agents such as tricyclicsagents such as tricyclics

• Few side effects—orthostatic hypotensionFew side effects—orthostatic hypotension
most commonmost common
TachycardiaTachycardia PalpitationsPalpitations
DizzinessDizziness DrowsinessDrowsiness
InsomniaInsomnia HeadacheHeadache
AnorexiaAnorexia NauseaNausea
Blurred visionBlurred vision ImpotenceImpotence

OverdoseOverdose
• Symptoms appear 12 hours after ingestionSymptoms appear 12 hours after ingestion
• Tachycardia, circulatory collapse,Tachycardia, circulatory collapse,
seizures, comaseizures, coma
• Treatment: protect brain and heart,Treatment: protect brain and heart,
eliminate toxineliminate toxin
– Gastric lavageGastric lavage
– Urine acidificationUrine acidification
– HemodialysisHemodialysis

Hypertensive Crisis and TyramineHypertensive Crisis and Tyramine
• Ingestion of foods and/or drinks withIngestion of foods and/or drinks with
the amino acid TYRAMINE leads tothe amino acid TYRAMINE leads to
hypertensive crisis, which may leadhypertensive crisis, which may lead
to cerebral hemorrhage, stroke,to cerebral hemorrhage, stroke,
coma, or deathcoma, or death

Hypertensive Crisis and TyramineHypertensive Crisis and Tyramine
Avoid foods that contain tyramine!Avoid foods that contain tyramine!
• Aged, mature cheeses (cheddar, blue, Swiss)Aged, mature cheeses (cheddar, blue, Swiss)
• Smoked/pickled or aged meats, fish, poultrySmoked/pickled or aged meats, fish, poultry
(herring, sausage, corned beef, salami, pepperoni,(herring, sausage, corned beef, salami, pepperoni,
paté)paté)
• Yeast extractsYeast extracts
• Red wines (Chianti, burgundy, sherry, vermouth)Red wines (Chianti, burgundy, sherry, vermouth)
• Italian broad beans (fava beans)Italian broad beans (fava beans)

Second-Generation AntidepressantsSecond-Generation Antidepressants
• NewerNewer
• Fewer side effects than tricyclics, but notFewer side effects than tricyclics, but not
superior in overall efficacy or onset of actionsuperior in overall efficacy or onset of action
– trazodone (Desyrel)trazodone (Desyrel)
– bupropion (Wellbutrin, Zyban)bupropion (Wellbutrin, Zyban)
– selective serotonin reuptake inhibitors (SSRIs)selective serotonin reuptake inhibitors (SSRIs)

Second-GenerationSecond-Generation
Antidepressants and SSRIsAntidepressants and SSRIs
• Selectively inhibit serotonin reuptakeSelectively inhibit serotonin reuptake
• Little or no effect on norepinephrine orLittle or no effect on norepinephrine or
dopamine reuptakedopamine reuptake
• Results in increased serotoninResults in increased serotonin
concentrations at nerve endingsconcentrations at nerve endings
Advantage over tricyclics and MAOIs:Advantage over tricyclics and MAOIs:
Little or no effect on cardiovascular systemLittle or no effect on cardiovascular system

• Used for depression—very few serious side effectsUsed for depression—very few serious side effects
• Bipolar affective disorderBipolar affective disorder
• ObesityObesity
• Eating disordersEating disorders
• Obsessive-compulsive disorderObsessive-compulsive disorder
• Panic attacksPanic attacks
• MyoclonusMyoclonus
• Treatment of various substance abuse problemsTreatment of various substance abuse problems
(bupropion [Zyban] is used for smoking cessation(bupropion [Zyban] is used for smoking cessation
treatment)treatment)

Body SystemBody System EffectsEffects
CNSCNS Headache, dizziness,Headache, dizziness,
tremor, nervousness,tremor, nervousness,
insomnia, fatigueinsomnia, fatigue
GIGI Nausea, diarrhea,Nausea, diarrhea,
constipation, dry mouthconstipation, dry mouth
OtherOther Sweating, sexualSweating, sexual
dysfunctiondysfunction

Drug InteractionsDrug Interactions
• Highly bound to plasma proteinsHighly bound to plasma proteins
• Compete with other protein-binding drugs,Compete with other protein-binding drugs,
resulting in more free, unbound drug toresulting in more free, unbound drug to
cause a more pronounced drug effectcause a more pronounced drug effect

AntipsychoticsAntipsychotics
• Drugs used to treat serious mental illnessDrugs used to treat serious mental illness
• Behavioral problems or psychotic disordersBehavioral problems or psychotic disorders

• Thioxanthenes: chlorprothixene, thiothixeneThioxanthenes: chlorprothixene, thiothixene
(Navane)(Navane)
• Butyrophenones: haloperidol (Haldol)Butyrophenones: haloperidol (Haldol)
• Dihydroindolones: molindone (Moban)Dihydroindolones: molindone (Moban)
• Dibenzoxazepine: loxapine (Loxitane)Dibenzoxazepine: loxapine (Loxitane)
• Phenothiazines: three structural groupsPhenothiazines: three structural groups

Phenothiazine Structural GroupsPhenothiazine Structural Groups
• Aliphatic: chlorpromazine (Thorazine),Aliphatic: chlorpromazine (Thorazine),
triflupromazine (Vesprin)triflupromazine (Vesprin)
• Piperidine: mesoridazine (Serentil),Piperidine: mesoridazine (Serentil),
thioridazine (Mellaril)thioridazine (Mellaril)
• Piperazine: fluphenazine (Prolixin),Piperazine: fluphenazine (Prolixin),
perphenazine (Trilafon), prochlorperazineperphenazine (Trilafon), prochlorperazine
(Compazine), trifluoperazine (Stelazine)(Compazine), trifluoperazine (Stelazine)
Largest group of psychotropic agentsLargest group of psychotropic agents

Atypical AntipsychoticsAtypical Antipsychotics
• clozapine (Clozaril)clozapine (Clozaril)
• risperidone (Risperdal)risperidone (Risperdal)
• olanzapine (Zyprexa)olanzapine (Zyprexa)
• quetiapine (Seroquel)quetiapine (Seroquel)

Antipsychotics: Mechanism of ActionAntipsychotics: Mechanism of Action
• Block dopamine receptors in the brainBlock dopamine receptors in the brain
(limbic system, basal ganglia)—areas(limbic system, basal ganglia)—areas
associated with emotion, cognitive function,associated with emotion, cognitive function,
motor functionmotor function
• Dopamine levels in the CNS are decreasedDopamine levels in the CNS are decreased
• Result: tranquilizing effect in psychoticResult: tranquilizing effect in psychotic
patientspatients

Antipsychotics: Mechanism of ActionAntipsychotics: Mechanism of Action
• The newer, atypical antipsychotics also blockThe newer, atypical antipsychotics also block
specific serotonin receptors (serotonin-2specific serotonin receptors (serotonin-2
[5HT2] receptors).[5HT2] receptors).
• This is responsible for their improvedThis is responsible for their improved
efficacy and safety profiles.efficacy and safety profiles.

Antipsychotics: Drug EffectsAntipsychotics: Drug Effects
• Block dopamine receptors in CNSBlock dopamine receptors in CNS
• Block alpha receptors (causing hypertension,Block alpha receptors (causing hypertension,
other cardiovascular effects)other cardiovascular effects)
• Block histamine receptors (causingBlock histamine receptors (causing
anticholinergic effects)anticholinergic effects)
• Block serotoninBlock serotonin
• Also function as antiemeticsAlso function as antiemetics
• Antianxiety effectsAntianxiety effects

Antipsychotics: Therapeutic UsesAntipsychotics: Therapeutic Uses
• Treatment of serious mental illnesses:Treatment of serious mental illnesses:
– Bipolar affective disorderBipolar affective disorder
– Depressive and drug-induced psychosesDepressive and drug-induced psychoses
– SchizophreniaSchizophrenia
– AutismAutism
• Movement disorders (such as Tourette’sMovement disorders (such as Tourette’s
syndrome)syndrome)
• Some medical conditionsSome medical conditions
– Nausea, intractable hiccupsNausea, intractable hiccups

Antipsychotics: Side EffectsAntipsychotics: Side Effects
CNSCNS Sedation, deliriumSedation, delirium
CardiovascularCardiovascular Orthostatic hypotension,Orthostatic hypotension,
syncope, dizziness,syncope, dizziness,
ECG changesECG changes
DermatologicDermatologic Photosensitivity, skin rash,Photosensitivity, skin rash,
hyperpigmentation, pruritushyperpigmentation, pruritus

Antipsychotics: Side EffectsAntipsychotics: Side Effects
GIGI Dry mouth, constipationDry mouth, constipation
GUGU Urinary hesitancy orUrinary hesitancy or
retention, impaired erectionretention, impaired erection
HematologicHematologic Leukopenia andLeukopenia and
agranulocytosisagranulocytosis
Metabolic/endocrineMetabolic/endocrine Galactorrhea, irregularGalactorrhea, irregular
mensesmenses
increased appetite,increased appetite,
polydipsiapolydipsia

Psychotherapeutic Agents:Psychotherapeutic Agents:
Nursing ImplicationsNursing Implications
• Before beginning therapy, assess both theBefore beginning therapy, assess both the
physical and emotional status of patientsphysical and emotional status of patients
• Obtain baseline VS, including postural BPObtain baseline VS, including postural BP
readingsreadings
• Obtain liver and renal function tests (andObtain liver and renal function tests (and
baseline platelet levels for MAOIs)baseline platelet levels for MAOIs)

• Assess for possible contraindications toAssess for possible contraindications to
therapy, cautious use, and potential drugtherapy, cautious use, and potential drug
interactionsinteractions
• Assess LOC, mental alertness, potentialAssess LOC, mental alertness, potential
for injury to self and othersfor injury to self and others
• Check the patient’s mouth to make sureCheck the patient’s mouth to make sure
oral doses are swallowedoral doses are swallowed

• Provide simple explanations about the drug,Provide simple explanations about the drug,
its effects, and the length of time beforeits effects, and the length of time before
therapeutic effects can be expectedtherapeutic effects can be expected
• Abrupt withdrawal should be avoidedAbrupt withdrawal should be avoided
• Advise patients to change positions slowlyAdvise patients to change positions slowly
to avoid postural hypotension and possibleto avoid postural hypotension and possible
injuryinjury

• The combination of drug therapy andThe combination of drug therapy and
psychotherapy is emphasized becausepsychotherapy is emphasized because
patients need to learn and acquire morepatients need to learn and acquire more
effective coping skillseffective coping skills
• Only small amounts of medications shouldOnly small amounts of medications should
be dispensed at a time to minimize the riskbe dispensed at a time to minimize the risk
of suicide attemptsof suicide attempts
• Simultaneous use of these agents withSimultaneous use of these agents with
alcohol or other CNS depressants canalcohol or other CNS depressants can
be fatalbe fatal

• Many cautions, contraindications, and interactionsMany cautions, contraindications, and interactions
exist pertaining to the use of antidepressants.exist pertaining to the use of antidepressants.
• Inform patients that it may take 1 to 3, even 4,Inform patients that it may take 1 to 3, even 4,
weeks to see therapeutic effects.weeks to see therapeutic effects.
• Monitor patients closely during this time andMonitor patients closely during this time and
provide support.provide support.

• Sedation often occurs with tricyclic therapy; notifySedation often occurs with tricyclic therapy; notify
physician if this lasts more than 2 weeks.physician if this lasts more than 2 weeks.
• Assist elderly or weakened patients with ambulationAssist elderly or weakened patients with ambulation
and other activities as falls may occur due toand other activities as falls may occur due to
drowsiness or postural hypotension.drowsiness or postural hypotension.

• Tricyclics may need to be weaned and discontinuedTricyclics may need to be weaned and discontinued
before undergoing surgery to avoid interactions withbefore undergoing surgery to avoid interactions with
anesthetic agents.anesthetic agents.
• Monitor for side effects and discuss with patients.Monitor for side effects and discuss with patients.
• Encourage patients to wear medication ID badgesEncourage patients to wear medication ID badges
naming the agent being taken.naming the agent being taken.

• Caffeine and cigarette smoking may decreaseCaffeine and cigarette smoking may decrease
effectiveness of medication therapyeffectiveness of medication therapy
• Instruct patients and family regarding tyramine-Instruct patients and family regarding tyramine-
containing foods and signs and symptoms ofcontaining foods and signs and symptoms of
hypertensive crisishypertensive crisis

Antipsychotics—PhenothiazinesAntipsychotics—Phenothiazines
• Instruct patients to wear sunscreen due toInstruct patients to wear sunscreen due to
photosensitivityphotosensitivity
• Avoid taking antacids or antidiarrheal preparationsAvoid taking antacids or antidiarrheal preparations
within 1 hour of a dosewithin 1 hour of a dose
• Do not take alcohol or other CNS depressantsDo not take alcohol or other CNS depressants
with these medicationswith these medications

Antipsychotics—PhenothiazinesAntipsychotics—Phenothiazines
• Long-term haloperidol therapy may result in tremors,Long-term haloperidol therapy may result in tremors,
nausea, vomiting, or uncontrollable shaking of smallnausea, vomiting, or uncontrollable shaking of small
muscle groups; these symptoms should be reportedmuscle groups; these symptoms should be reported
to the physicianto the physician
• Oral forms may be taken with meals to decreaseOral forms may be taken with meals to decrease
GI upsetGI upset
• These agents may cause drowsiness, dizziness, orThese agents may cause drowsiness, dizziness, or
fainting; instruct patients to change positions slowlyfainting; instruct patients to change positions slowly

Monitor for therapeutic effects:Monitor for therapeutic effects:
• Monitor mental alertness, cognition, affect,Monitor mental alertness, cognition, affect,
mood,ability to carry out activities of dailymood,ability to carry out activities of daily
living, appetite, and sleep patternsliving, appetite, and sleep patterns
• Monitor the patient’s potential for self-injuryMonitor the patient’s potential for self-injury
during the delay between the start of therapyduring the delay between the start of therapy
and symptomatic improvementand symptomatic improvement

Monitor for therapeutic effectsMonitor for therapeutic effects
• For antidepressants:For antidepressants:
– Improved sleep patterns and nutrition, increasedImproved sleep patterns and nutrition, increased
feelings of self-esteem, decreased feeling offeelings of self-esteem, decreased feeling of
hopelessness, increased interest in self andhopelessness, increased interest in self and
appearance, increased interest in daily activities,appearance, increased interest in daily activities,
fewer depressive manifestations or suicidalfewer depressive manifestations or suicidal
thoughts or ideationsthoughts or ideations

Monitor for therapeutic effectsMonitor for therapeutic effects
• For antipsychotics:For antipsychotics:
– Improved mood and affect, alleviation ofImproved mood and affect, alleviation of
psychotic symptoms and episodespsychotic symptoms and episodes
– Decrease in hallucinations, paranoia, delusions,Decrease in hallucinations, paranoia, delusions,
garbled speech, inability to copegarbled speech, inability to cope

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