Antipsychotics and Mood Stabilizers: Pharmacokinetics Adverse Effects Drug InteractionsGoalsAntipsychotics: Diagnostic IndicationsImpact of Schizophrenic Symptoms on Overall FunctioningPharmacokinetics of AntipsychoticsAntipsychotic AgentsAntipsychotic Agents (con’t)Slide 8Acute EPSDementia PatientsWeight Gain: OverviewThe Metabolic SyndromeSGAs and Metabolic AbnormalitiesBaseline MonitoringAnticholinergic EffectsHematologicalCardiovascularPotential Consequences of QTc Interval ProlongationQT intervalAntipsychotics: Drug InteractionsBipolar Disorder: Symptom DomainsMood Disorders: Therapeutic OptionsMood Stabilizer PharmacokineticsLITHIUMFactors Affecting Lithium CpLithium: Adverse EffectsAnticonvulsants for Mood DisordersVALPROATEValproic Acid PharmacokineticsCBZ PharmacokineticsCarbamazepine MetabolismLAMOTRIGINESlide 331Antipsychotics andAntipsychotics andMood Stabilizers:Mood Stabilizers:PharmacokineticsPharmacokineticsAdverse EffectsAdverse EffectsDrug InteractionsDrug InteractionsPhilip G. Janicak, MDPhilip G. Janicak, MDProfessor of PsychiatryProfessor of PsychiatryRush University Medical CenterRush University Medical Center2GoalsGoalsAntipsychoticsAntipsychoticsDiagnostic indicationsDiagnostic indicationsClassification Classification Relevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug InteractionsMood StabilizersMood StabilizersDiagnostic indicationsDiagnostic indicationsClassification Classification Relevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug Interactions23Antipsychotics:Antipsychotics:Diagnostic IndicationsDiagnostic IndicationsPsychiatricPsychiatricSchizophreniaSchizophreniaSchizoaffective disorderSchizoaffective disorderMood disorders with psychosisMood disorders with psychosisDelusional disorderDelusional disorderNonpsychiatricNonpsychiatricDementia/DeliriumDementia/DeliriumPsychosis secondary to a non-psychiatric medical disorder Psychosis secondary to a non-psychiatric medical disorder Developmental disability with psychosis and/or aggressionDevelopmental disability with psychosis and/or aggressionTourette’s disorderTourette’s disorderNausea, vomitingNausea, vomiting34Positive symptoms:Delusions*Hallucinations*Disorganized speechCatatonia Cognitive symptoms:AttentionMemoryExecutive functionsMoodsymptoms:DysphoriaSuicidalityHelplessnessNegativesymptoms:Affective flatteningAlogiaAvolitionAnhedoniaSocial inattentivenessOccupationalInterpersonalSelf- careSocialWorkImpact of Schizophrenic Impact of Schizophrenic Symptoms on Overall Symptoms on Overall FunctioningFunctioning*Schneiderian First Rank Symptoms45Pharmacokinetics of Pharmacokinetics of AntipsychoticsAntipsychoticsADME profilesADME profiles-All are readily absorbedAll are readily absorbed-All are metabolized by the hepatic cytochrome All are metabolized by the hepatic cytochrome P450 systemP450 system-prone to drug interactionsprone to drug interactions-TT1/21/2 is generally 20 hours except: is generally 20 hours except:-ziprasidone, quetiapine, aripiprazole ziprasidone, quetiapine, aripiprazole -Dosing adjustment in elderly renal and/or Dosing adjustment in elderly renal and/or hepatic impairmenthepatic impairment56Antipsychotic AgentsAntipsychotic Agents© JanicakClass/Trade Name Generic Name Dosage (average range; PO, qd) PhenothiazinesAliphaticsThorazine Chlorpromazine 100-1000 mgSparine Promazine 25-1000 mgVesprin Triflupromazine 20-150 mgPiperidinesMellaril Thioridazine 30-800 mgSerentil Mesoridazine 20-200 mgQuide Piperacetazine 20-160 mgPiperazinesStelazine Trifluoperazine 2-60 mgProlixin Fluphenzine 5-40 mgTrilafon Perphenazine 2-60 mgTindal Acetophenazine 40-80 mgCompazine Prochlorperazine 15-125 mgThioxanthenes Navane Thiothixene 6-60 mg Taractan Chlorprothixene 10-600 mgDibenzoxapines Loxitane Loxapine 20-250 mgButyrophenones Haldol Haloperidol 3-50 mg Inapsine Droperidol 2.5-10 mg (IM)Dihydroindolones Moban Molindone 15-225 mg67Antipsychotic Agents (con’t)Antipsychotic Agents (con’t)Class/Trade Name Generic Name Dosage (average range; PO, qd)DibenzodiazepinesClozaril Clozapine 100-900 mgBenzisoxazoleRisperdal InvegaRisperidonePaliperidone2-10 mg3-12 mgThienobenzodiazepinesZyprexa Olanzapine 5-20 mgDibenzothiazepinesSeroquel Quetiapine 75-750 mgBenzisothiazolylsGeodon Ziprasidone 40-160 mgQuinolinonesAbilify Aripiprazole 10-30 mgDiphenytbutyrylpiperidinesSemap Penfluridol 100 mg/wkOrap Pimozide 1-10 mg© Janicak78EPS*EPS*HPDLHPDLCLOZCLOZRISPRISPOLZOLZQTPQTPZIPZIPARIPARIPNeurologicalNeurological++++++00++0/+0/+000/+0/+0/+0/+Weight gain/ Weight gain/ EndocrineEndocrine++++++++++++++++++++++0/+0/+0/+0/+AnticholinergicAnticholinergic00++++++0/+0/++/+++/++0/+0/+0/+0/+00HematologicalHematological00++++++0000000000CardiovascularCardiovascular++0/+0/+++++++++++00ProlactinProlactin++++0/+0/+++++++0/+0/+0/+0/+0/+0/+00SedationSedation+++++++++++/+++/++++++++++++PALIPALI++++++0/+0/+00++++++++++Adapted from Masand PS et al. Handbook of Psychiatry in Primary Care. 1998.Antipsychotics:Antipsychotics:Adverse Effect ProfilesAdverse Effect Profiles*At appropriate doses; 0 = none; + = mild; ++ = moderate; +++ = substantial*At appropriate doses; 0 = none; + = mild; ++ = moderate; +++ = substantial9Maximum MinimumHIGH POTENCY RISPERIDONE OLANZAPINE CLOZAPINEFGAs PALIPERIDONE ZIPRASIDONE (DOSE-RELATED) QUETIAPINE ARIPIPRAZOLE*ADVERSE EFFECTS OF ANTIPSYCHOTICSADVERSE EFFECTS OF ANTIPSYCHOTICSAcute EPSAcute EPS*Based on clinical trial data• Psuedoparkinsonism• Dystonia• Akathisia• Tardive Dyskinesia910Dementia PatientsDementia PatientsRisksRisksMortality rateMortality rateCVA in 4% vs 2%CVA in 4% vs 2%Risks may be Risks may be higher for all APshigher for all APsRecommendationsRecommendationsAvoid in those with Avoid in those with vascular dementiavascular dementiaAvoid with TIA, Avoid with TIA, hypertension, Afibhypertension, AfibUse low doses Use low doses Monitor for Monitor for hypotension, hypotension, sedation, EPSsedation, EPS1011Weight Gain: OverviewWeight Gain: OverviewGeneral populationGeneral populationIncreased morbidity and mortalityIncreased morbidity and mortalityStigmatizationStigmatizationMajor mental disordersMajor
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