chapter 25: psychopharmacology copyright © 2012, 2007 mosby, inc., an affiliate of elsevier inc....

Chapter 25:Chapter 25:

PsychopharmacologyPsychopharmacology

Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

22Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Did You Know?Did You Know?

During any given year, 1 in 4 adults suffer fromDuring any given year, 1 in 4 adults suffer from

a diagnosable mental disorder.a diagnosable mental disorder.

The percent of Americans who will experience: The percent of Americans who will experience: A mental illness in their lifetime, especially in A mental illness in their lifetime, especially in

their teen years: 46.6%their teen years: 46.6% A mood disorder: 20%A mood disorder: 20% An anxiety disorder: 28.8%An anxiety disorder: 28.8% An impulse control disorder: 24.8%An impulse control disorder: 24.8% A substance abuse disorder: 14.6%A substance abuse disorder: 14.6%


NeurotransmittersNeurotransmitters

Acetylcholine (Ach)Acetylcholine (Ach) Dopamine (DA)Dopamine (DA) Serotonin (5-HT)Serotonin (5-HT) Glutamate (Glu)Glutamate (Glu)


AcetylcholineAcetylcholine

Receptors:Receptors: Nicotine Nicotine MuscarinicMuscarinic MemoryMemory Anticholinergic side effectsAnticholinergic side effects


DopamineDopamine

Receptors:Receptors: Nigrostriatal: movementNigrostriatal: movement Mesolimbic: pleasure, Mesolimbic: pleasure,

delusions/hallucinationsdelusions/hallucinations Mesocortical: mediates positive and negative Mesocortical: mediates positive and negative

symptoms, cognitive side effectssymptoms, cognitive side effects Tuberoinfundibular: prolactin releaseTuberoinfundibular: prolactin release


SerotoninSerotonin

Inhibitory catecholamineInhibitory catecholamine Mediates:Mediates:

Cognitive effectsCognitive effects Emotions, including panicEmotions, including panic Memory and anxietyMemory and anxiety Violence and aggressionViolence and aggression Sexual functionSexual function Sleep-wake cyclesSleep-wake cycles


GlutamateGlutamate

Excitatory neurotransmitterExcitatory neurotransmitter


Variables that Affect Drug Variables that Affect Drug Therapy Therapy

Mode/mechanism of actionMode/mechanism of action Dosage formDosage form BioavailabilityBioavailability Onset, peak, duration of actionOnset, peak, duration of action Serum, half-lifeSerum, half-life Elimination methodElimination method Side effects/toxicitiesSide effects/toxicities CostCost


Patient-Related VariablesPatient-Related Variables

DiagnosisDiagnosis Other disease statesOther disease states Age Age WeightWeight Anticholinergic susceptibilityAnticholinergic susceptibility History of side effectsHistory of side effects Previous responsePrevious response ComplianceCompliance Financial/insuranceFinancial/insurance Support systemSupport system


Antipsychotic MedicationsAntipsychotic Medications

Conventional or TypicalConventional or Typical Block DBlock D22 receptors in limbic region receptors in limbic region Differ in potency and side effectsDiffer in potency and side effects

AtypicalAtypical Differ in mode of action, side effect, potencyDiffer in mode of action, side effect, potency Fewer EPSFewer EPS Greater efficacy with negative symptoms, Greater efficacy with negative symptoms,

cognitive symptoms, refractory illnesscognitive symptoms, refractory illness Lower potential to increase prolactinLower potential to increase prolactin


Symptom Dimensions of PsychosisSymptom Dimensions of Psychosis

1.1. Positive symptoms: overactive dopamine Positive symptoms: overactive dopamine neurons in mesolimbic pathwayneurons in mesolimbic pathway

Examples:Examples: Delusions, hallucinations Delusions, hallucinations Disorganized speech, behavior Disorganized speech, behavior CatatoniaCatatonia AgitationAgitation

Relieved by typical antipsychotics, anticipate Relieved by typical antipsychotics, anticipate response 2 to 8 weeksresponse 2 to 8 weeks


Symptom Dimensions of Symptom Dimensions of Psychosis, cont’d.Psychosis, cont’d.

2.2. Negative symptoms: dopamine deficiency in Negative symptoms: dopamine deficiency in mesocortical pathwaymesocortical pathway

Examples:Examples: Blunted affect, decreased spontaneityBlunted affect, decreased spontaneity Passivity, social apathy/withdrawalPassivity, social apathy/withdrawal Alogia, avolition, anhedoniaAlogia, avolition, anhedonia

Best treated with atypical antipsychotics, Best treated with atypical antipsychotics,

response: slowresponse: slow



3.3. Cognitive symptomsCognitive symptoms

Examples:Examples: Thought disorderThought disorder IncoherenceIncoherence Loose associationLoose association Difficulty processing informationDifficulty processing information

Atypical antipsychotics may improve cognitive Atypical antipsychotics may improve cognitive

functionfunction



4.4. Aggressive symptomsAggressive symptoms

Examples:Examples: HostilityHostility Verbal abuseVerbal abuse AssaultAssault Sexual acting outSexual acting out Poor impulse controlPoor impulse control

Treated with typical antipsychotics, response Treated with typical antipsychotics, response

within hourswithin hours



5.5. Depressive/anxious symptomsDepressive/anxious symptoms

Examples:Examples: WorryWorry GuiltGuilt IrritabilityIrritability AnxietyAnxiety DepressionDepression


Goals of TherapyGoals of Therapy

Enable patient to:Enable patient to: Return to normal daily functionsReturn to normal daily functions Provide self-careProvide self-care

Minimize side effects:Minimize side effects: Use lowest possible doseUse lowest possible dose Manage side effects to increase complianceManage side effects to increase compliance


Absorption, Distribution, Absorption, Distribution, Metabolism, and ExcretionMetabolism, and Excretion

AbsorptionAbsorption Well absorbed by GI tractWell absorbed by GI tract Influenced by:Influenced by:

FoodFood

AntacidsAntacids

AnticholinergicsAnticholinergics

SmokingSmoking

DistributionDistribution Depends on route of administrationDepends on route of administration

IM: greater bioavailabilityIM: greater bioavailability


Absorption, Distribution, Absorption, Distribution, Metabolism, and Excretion, cont’d.Metabolism, and Excretion, cont’d.

MetabolismMetabolism Half-life: 20 to 40 hoursHalf-life: 20 to 40 hours Metabolized in liverMetabolized in liver

ExcretionExcretion Via kidneysVia kidneys

Serum level monitoringSerum level monitoring Not routinely usefulNot routinely useful


Acute Episode Acute Episode

Olanzapine (Zyprexa) 10-20 mg dailyOlanzapine (Zyprexa) 10-20 mg daily Risperidone (Risperdal) 3-6 mg dailyRisperidone (Risperdal) 3-6 mg daily Quetiapine (Seroquel) 300-800 mg dailyQuetiapine (Seroquel) 300-800 mg daily Ziprasidone (Geodon) 120-180 mg dailyZiprasidone (Geodon) 120-180 mg daily Aripiprazole (Abilify) 10-30 mg dailyAripiprazole (Abilify) 10-30 mg daily


Anticholinergic Side EffectsAnticholinergic Side Effects

Low Potency Conventional Antipsychotics Atropine-like Low Potency Conventional Antipsychotics Atropine-like side effects:side effects:

Dry mouthDry mouth Blurred visionBlurred vision Sinus tachycardiaSinus tachycardia Urinary retentionUrinary retention ConstipationConstipation Nasal congestionNasal congestion Ejaculatory inhibitionEjaculatory inhibition

Treatment: supportive measuresTreatment: supportive measures


Adverse Effects of AntipsychoticsAdverse Effects of Antipsychotics

Extrapyramidal Side Effects (EPS)Extrapyramidal Side Effects (EPS) Dystonia:Dystonia: IM diphenhydramine or benztropine followed IM diphenhydramine or benztropine followed

by oral antiparkinsonism drugby oral antiparkinsonism drug PseudoparkinsonismPseudoparkinsonism: change to low-potency drug: Oral : change to low-potency drug: Oral

antiparkinsonism drugantiparkinsonism drug AkathisiaAkathisia: decrease antipsychotic dose: Propranolol : decrease antipsychotic dose: Propranolol

(Inderal)(Inderal) Tardive dyskinesiaTardive dyskinesia: change to atypical antipsychotic: change to atypical antipsychotic Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome: medical emergency, : medical emergency,

initia; treatment involves admission to ICUinitia; treatment involves admission to ICU


Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome

Level of consciousnessLevel of consciousness Muscle toneMuscle tone Autonomic dysfunctionAutonomic dysfunction

HyperpyrexiaHyperpyrexia Labile hypertensionsLabile hypertensions TachycardiaTachycardia TachypneaTachypnea DiaphoresisDiaphoresis DroolingDrooling

MyoglobinuriaMyoglobinuria


Treatment of NMSTreatment of NMS

Discontinue antipsychoticsDiscontinue antipsychotics HydrateHydrate AcetaminophenAcetaminophen HeparinHeparin Management of arrhythmias Management of arrhythmias DantroleneDantrolene DopaminergicsDopaminergics

Bromocriptine, amantadineBromocriptine, amantadine


Cardiovascular Side EffectsCardiovascular Side Effects

Postural hypotensionPostural hypotension Arrhythmias Arrhythmias PalpitationsPalpitations Changes in QT interval Changes in QT interval


Side Effects Related to Clozapine, Side Effects Related to Clozapine, Olanzapine, Low-Potency Typical Olanzapine, Low-Potency Typical

AntipsychoticsAntipsychotics

SedationSedation Weight gainWeight gain


Other Side EffectsOther Side Effects

PhotosensitivityPhotosensitivity PoikilothermiaPoikilothermia GalactorrheaGalactorrhea GynecomastiaGynecomastia


Depot MedicationDepot Medication

Fluphenazine decanoateFluphenazine decanoate Intramuscularly or subcutaneouslyIntramuscularly or subcutaneously

Haloperidol decanoateHaloperidol decanoate IntramuscularlyIntramuscularly

Administration PointersAdministration Pointers Inspect solution.Inspect solution. Use dry syringe and needle.Use dry syringe and needle. Do not exceed 3 ml per site.Do not exceed 3 ml per site.


Atypical Antipsychotic: ClozapineAtypical Antipsychotic: Clozapine

High receptor affinity for DHigh receptor affinity for D44 and 5HT2 and 5HT2 Reserved for refractory illnessReserved for refractory illness Risk: agranulocytosisRisk: agranulocytosis Side effects:Side effects:

Anticholinergic, extrapyramidalAnticholinergic, extrapyramidal NMSNMS Tachycardia, postural hypotensionTachycardia, postural hypotension Weight gainWeight gain HypersalivationHypersalivation Fever, seizuresFever, seizures


Figure 25-1 A transaxial positron emission tomography (PET) scan image at the level of Figure 25-1 A transaxial positron emission tomography (PET) scan image at the level of the basal ganglia. (Data from Tamminga CA et al., Maryland Psychiatric Research the basal ganglia. (Data from Tamminga CA et al., Maryland Psychiatric Research Center, University of Maryland at Baltimore, unpublished research.)Center, University of Maryland at Baltimore, unpublished research.)


Other Atypical AntipsychoticsOther Atypical Antipsychotics

Risperidone (Risperdal)Risperidone (Risperdal) Olanzapine (Zyprexa)Olanzapine (Zyprexa) Quetiapine (Seroquel)Quetiapine (Seroquel) Ziprasidone (Geodon)Ziprasidone (Geodon)


AntidepressantsAntidepressants

Selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs)(SSRIs)

Tricyclic antidepressantsTricyclic antidepressants Monoamine oxidase inhibitorsMonoamine oxidase inhibitors


Figure 25-2 Neurotransmitter responses to antidepressant therapy. Figure 25-2 Neurotransmitter responses to antidepressant therapy. AA, In the depressed , In the depressed state, sparse amounts of neurotransmitter are available in the synapse of a depressed state, sparse amounts of neurotransmitter are available in the synapse of a depressed person.person.


Figure 24-2 Neurotransmitter responses to antidepressant therapy. Figure 24-2 Neurotransmitter responses to antidepressant therapy. BB, With treatment, the , With treatment, the reuptake of neurotransmitter is blocked by the antidepressant drug (in red). The result is reuptake of neurotransmitter is blocked by the antidepressant drug (in red). The result is increased amounts of neurotransmitter in the synapse, and, finally, after several weeks increased amounts of neurotransmitter in the synapse, and, finally, after several weeks the postsynaptic receptors have decreased (i.e., downregulated), which is associated the postsynaptic receptors have decreased (i.e., downregulated), which is associated with resolving depression. with resolving depression.


Selective Serotonin Reuptake Selective Serotonin Reuptake Inhibitors (SSRIs)Inhibitors (SSRIs)

Approved for depression, panic, OCD, PTSD,Approved for depression, panic, OCD, PTSD,

bulimia nervosa, social phobiabulimia nervosa, social phobia Citalopram (Celexa)Citalopram (Celexa) Escitalopram (Lexapro)Escitalopram (Lexapro) Fluvoxamine (Luvox)Fluvoxamine (Luvox) Paroxetine (Paxil)Paroxetine (Paxil) Sertraline (Zoloft)Sertraline (Zoloft)


Serotonin SyndromeSerotonin Syndrome

ConfusionConfusion HypomaniaHypomania RestlessnessRestlessness MyoclonusMyoclonus HyperreflexiaHyperreflexia DiaphoresisDiaphoresis ShiveringShivering TremorTremor DiarrheaDiarrhea


Tricyclic Antidepressants: Tricyclic Antidepressants: Second-Line TherapySecond-Line Therapy

Amitriptyline (Elavil)Amitriptyline (Elavil) Clomipramine (Anafranil)Clomipramine (Anafranil) Desipramine (Norpramin)Desipramine (Norpramin) Imipramine (Tofranil)Imipramine (Tofranil) Nortriptyline (Aventyl)Nortriptyline (Aventyl) Protriptyline (Vivactil)Protriptyline (Vivactil) Trimipramine (Surmontil)Trimipramine (Surmontil)


Response to AntidepressantsResponse to Antidepressants

Week 1Week 1 AnxietyAnxiety Improved sleepImproved sleep

Weeks 1 to 3Weeks 1 to 3 Activity, self-care, sex driveActivity, self-care, sex drive Concentration, memoryConcentration, memory Psychomotor retardationPsychomotor retardation

Weeks 2 to 4Weeks 2 to 4 Relief of depressed moodRelief of depressed mood HopelessnessHopelessness Suicidal ideation subsidesSuicidal ideation subsides


MAOI Dietary RestrictionsMAOI Dietary Restrictions

Prohibited:Prohibited: Aged cheese, ripe avocadosAged cheese, ripe avocados Ripe figs, anchovies, bean curdRipe figs, anchovies, bean curd Broad beans, yeast, liverBroad beans, yeast, liver Deli meats, pickled herringDeli meats, pickled herring Meat extracts, fermented foodsMeat extracts, fermented foods Chianti and sherryChianti and sherry


MAOI Dietary MAOI Dietary Restrictions, cont’d. Restrictions, cont’d.

Moderate use:Moderate use: Beer, aleBeer, ale Wine, distilled spiritsWine, distilled spirits Cottage cheese, cream cheeseCottage cheese, cream cheese Yogurt, sour creamYogurt, sour cream Coffee, chocolateCoffee, chocolate Spinach, raisins, tomatoes, eggplantSpinach, raisins, tomatoes, eggplant


Other Restrictions Other Restrictions with Use of MAOIswith Use of MAOIs

Anti-asthmaticsAnti-asthmatics AntihypertensivesAntihypertensives EpinephrineEpinephrine Allergy, hay fever decongestantsAllergy, hay fever decongestants Cough and cold productsCough and cold products BuspironeBuspirone MeperidineMeperidine SSRIsSSRIs YohimbineYohimbine


Hypertensive CrisisHypertensive Crisis

HeadacheHeadache Stiff neckStiff neck SweatingSweating Nausea and vomitingNausea and vomiting

TreatmentTreatment NifedipineNifedipine Monitor vital signsMonitor vital signs


Other AntidepressantsOther Antidepressants

Venlafaxine (Effexor)Venlafaxine (Effexor) NefazodoneNefazodone TrazodoneTrazodone BupropionBupropion MirtazapineMirtazapine


Treatment of Bipolar DisorderTreatment of Bipolar Disorder

LithiumLithium ValproateValproate CarbamazepineCarbamazepine OxcarbazepineOxcarbazepine LamotrigineLamotrigine GabapentinGabapentin TopiramateTopiramate TiagabineTiagabine ZonisamideZonisamide LevetiracetamLevetiracetam


Lithium Side Effects Within Lithium Side Effects Within Therapeutic RangeTherapeutic Range

Fine tremorFine tremor Nausea, vomiting, diarrheaNausea, vomiting, diarrhea Mild polydipsia, polyuriaMild polydipsia, polyuria Lethargy, muscle weaknessLethargy, muscle weakness Weight gainWeight gain Increased WBCIncreased WBC Acne, alopeciaAcne, alopecia HypothyroidismHypothyroidism


Lithium Side Effects: Lithium Side Effects: Moderate ToxicityModerate Toxicity

Lithium level >1.5 mEq/LLithium level >1.5 mEq/L Coarsening of tremorCoarsening of tremor Worsening GI symptomsWorsening GI symptoms Confusion, slurred speechConfusion, slurred speech Sedation, lethargySedation, lethargy


Lithium Side Effects: Lithium Side Effects: Severe ToxicitySevere Toxicity

Lithium level >2.5 mEq/LLithium level >2.5 mEq/L ArrhythmiasArrhythmias AB block AB block BradycardiaBradycardia MyocarditisMyocarditis SeizuresSeizures ComaComa DeathDeath


Generalized Anxiety DisorderGeneralized Anxiety Disorder

AntidepressantsAntidepressants VenlafaxineVenlafaxine SSRIsSSRIs ImipramineImipramine NefazodoneNefazodone MirtazapineMirtazapine

BenzodiazepinesBenzodiazepines ClonazepamClonazepam LorazepamLorazepam AlprazolamAlprazolam

BuspironeBuspirone


Obsessive Compulsive DisorderObsessive Compulsive Disorder

AntidepressantsAntidepressants SSRIsSSRIs ClomipramineClomipramine

Augmentation therapyAugmentation therapy


Posttraumatic Stress DisorderPosttraumatic Stress Disorder

AntidepressantsAntidepressants SSRIsSSRIs

BenzodiazepinesBenzodiazepines ClonazepamClonazepam

Mood stabilizersMood stabilizers


Social PhobiaSocial Phobia

AntidepressantsAntidepressants SSRIsSSRIs

BenzodiazepinesBenzodiazepines GabapentinGabapentin


HypnoticsHypnotics

BenzodiazepinesBenzodiazepines Triazolam (Halcion)Triazolam (Halcion) Temazepam (Restoril)Temazepam (Restoril) Flurazepam (Dalmane)Flurazepam (Dalmane)

NonbenzodiazepinesNonbenzodiazepines Zolpidem (Ambien)Zolpidem (Ambien) Zaleplon (Sonata)Zaleplon (Sonata)


Other Agents Used for SleepOther Agents Used for Sleep

TrazodoneTrazodone Chloral hydrate (Notec)Chloral hydrate (Notec) Diphenhydramine (Benadryl)Diphenhydramine (Benadryl) Melatonin (Circadian)Melatonin (Circadian) Herbal productsHerbal products

Kava-kavaKava-kava ValerianValerian

BarbituratesBarbiturates


Acute Agitation and Aggression Acute Agitation and Aggression

AntipsychoticsAntipsychotics HaloperidolHaloperidol ZiprasidoneZiprasidone QuetiapineQuetiapine RisperidoneRisperidone OlanzapineOlanzapine

BenzodiazepinesBenzodiazepines LorazepamLorazepam Trazodone (for older adults)Trazodone (for older adults)


Chronic AggressionChronic Aggression

SchizophreniaSchizophrenia AntipsychoticsAntipsychotics

ManiaMania LithiumLithium ValproateValproate

Seizure disorderSeizure disorder CarbamazepineCarbamazepine ValproateValproate

Older adultsOlder adults TrazodoneTrazodone

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