antipsychotic medications in the primary care practice

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Antipsychotic Medications in the Primary Care Practice. Angelo Potenciano, M.D. Antipsychotic Medications. Antipsychotics have been around since 1951 Approximately 40 APs in the market globally 15 are Typical APs / “Neuroleptics 21 are Atypical APs – 9 are in the U.S. - PowerPoint PPT Presentation

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  • Antipsychotic Medications in the Primary Care PracticeAngelo Potenciano, M.D.

  • Antipsychotic Medications Antipsychotics have been around since 1951Approximately 40 APs in the market globally15 are Typical APs / Neuroleptics21 are Atypical APs 9 are in the U.S.

  • Antipsychotics in the Primary Care SettingLieberman (2002) noted that PCP RxOf APs has increased 18-20% since 1996PCPs treat a variety of psychiatric disorders including depression, anxiety, bipolar disorders, sleep disorders, psychosis, and behavioral problems assoc. with dementia, and delirium

  • Reasons Why PCPs Are Vital in the Treatment of Psychiatric PatientsNot enough psychiatric services available Psychiatric symptoms arising from medical d/o or during the course of treatmentPatients are more comfortable seeing their PCPStable Patients who require maintenance meds

  • History of Antipsychotics1891 Paul Ehrlich and Paul Guttman pioneered the use of Methylene Blue a phenothiazine derivative in the Tx of Malaria1890s- noted the tranquilizing and antidepressant effects Became the lead compound in the development of Chlorpromazine

  • History of Antipsychotics1951 French surgeon, Henry Leborit used Chlorpromazine as a sedating agent 1952 John Delay and Pierre Deniker treated 38 schizophrenics with CPZ 75-100mg/day/IMDramatic improvements in thinking and emotional symptoms and overall behavior

  • History of Antipsychotics1954-1975 development of typical ApsThioridazine MellarilHaloperidol- HaldolTrifluoperazine- StelazinePerphenazine- TrilafonFluphenazine- ProlixinMolindone-MobanPimozide

  • History of Antipsychotics1980s-Janssen developed Risperidone The earliest Atypical APsFollowed the LSD model of psychopathology- Risperidone-antagonized effects of LSD

  • History of Antipsychotics1989 Clozapine was approved by the FDA In treating treatment-resistant schizophrenia1971 introduced in Europe but was withdrawn in 1975 due to angranulocytosis

  • Atypical AntipsychoticsAripiprazole- Abilify Quetiapine- SeroquelAsenaphine- Saphris Ziprasidone- GeodonClozapine- ClozarilIloperidone- FanaptLurasidone- LatudaOlanzapine- ZyprexaRisperidone- Risperdal

  • Mechanism of Action of AntipsychoticsDopamine antagonist- D1-4 RTypical APs / Neuroleptics- D2R (tightly bound) Atypical Aps- D1 & 2R (loosely bound or rapid dissociation), 5HT 2A and 5HT2C

  • Mechanism of ActionD2R antagonism EPS (akatishia, dystonia, parkinsonism, tardive dyskinesias)Rapid dissociation from DA receptor- less EPS risk5HT binding(2A) mood and cognitive effects, decreased DA blockade

  • Clinical Uses of Antipsychotics FDA Approved Indications1. Psychotic symptoms due to Schizophrenia or Schizoaffective disorder2. Mood disorders: Bipolar disorder and Major depressive disorder

  • Clinical Uses of AntipsychoticsOff-Label or Non-FDA Approved Psychotic symptoms of various etiology- substance-induced, dementia, deliriumBehavioral problems secondary to developmental disorders (autism, ADHD), dementia, delirium, other neurological disordersSleep disordersAnxiety disorders

  • Antipsychotics and Schizophrenia-First-line psychiatric treatment-psychotic symptom reduction in 1-2 weeks-almost 80% response rate (partial good)-choice is based on cost, side effects / safety, dosing

  • Clinical Uses of AntipsychoticsFDA Approved Indications Schizoaffective Disorder- Iloperidone (Fanapt) Treatment-Resistant Schizophrenia (failure to respond after 6 weeks of trials with 2-3 different antipsychotic- Clozapine (Clozaril)

  • Clinical Uses of AntipsychoticsFDA Approved IndicationsBipolar Disorder: Asenapine, Aripiprazole, Lurasidone, Olanzapine, Quetiapine, Risperidone, Ziprasidone

  • Antipsychotics and Bipolar DisordersFDA Approved IndicationsBipolar disorder-Mixed or Manic Episode: Asenapine, Aripiprazole, Olanzapine, Quetiapine, Risperidone, ZiprasidoneBipolar Disorder- Depressive episode: Lurasidone, Olanzapine-Fluoxetine (symbyax), QuetiapineMonotherapy or adjunctive therapy with Lithium or valproate

  • Antipsychotics and Bipolar DisorderClinical Advantages: 1. does not require blood levels (Valproate, lithium) 2. safer in patients with co-morbid substance abuse, liver/kidney diseases 3. Safer in overdoses / toxicities

  • Injectable AntipsychoticsAcute agitation associated with Schizophrenia or Bipolar Disorder: Haloperidol, Olanzapine, Ziprasidone

  • Antipsychotics Use in ChildrenBipolar disorder in children and adolescents (aged 10-17) (Monotherapy): Quetiapine, RisperidoneSchizophrenia in Adolescents (aged 13-17): Aripiprazole, RisperidoneBehavioral issues associated with Autistic d/o (irritability, aggression, self-injurious beh.,temper tantrums, rapidly changing moods): Risperidone, Aripiprazole

  • Antipsychotics and Depressive DisordersTreatment-Resistant Depression: Olanzapine-Fluoxetine CombinationAdjunctive / Augmentive Treatment of Major Depression: Aripiprazole, Quetiapine XR

  • Off-Label Uses of AntipsychoticsBehavioral issues associated with Dementia and Delirium: agitation/ aggression, psychosis, sleep disturbances, anxiety, confusionIncreasing consensus in the efficacy of APsAtypical APs-less EPS and anticholinergic effectsHaloperidol (low doses) as safe and effective as atypical APs

  • Antipsychotics for DementiaClinical Antipsychotic Trials of InterventionEffectiveness-Alzheimers Disease 2008 (CATIE-AD): Effectiveness of Olanzapine, Quetiapine, Risperidone in improving anger, aggression, paranoia / hostile suspiciousness but NOT overall functioning, care needs, and quality of life

  • Antipsychotics for DeliriumHaloperidol- antipsychotic of choice (Society of Critical Care Medicine 2007)Risk of EPS and Cardiac Conduction ChangesOlanzapine, Quetiapine, Risperidone- as efficacious, with less side effects, quicker improvement, less agitation, better sleep patterns

  • Antipsychotics in the Elderly1.6-1.7 times risk of death in patients taking APsDuration of treatment: 10 weeksCommon causes: sudden death, CV-Heart failure, infectious (pneumonia)1.7-2 times risk of CVAs in dementia patients taking Antipsychotics

  • Off-label Uses of AntipsychoticsSleep disorderssedative effects of Aps can promote sleepMost sedating APs: Olanzapine, Quetiapine, Chlorpromazine, ThioridazineMetabolic and EPS side effects are concerns in long-term use

  • Off-label Uses of AntipsychoticsAnxiety disorders / symptomsOCD, GAD, Panic Disorders tranquilizing / anxiolytic effects of most APs used in combination with SSRIs or Benzos. Mostly inconclusive study resultsMay be more useful in patients with co-morbid disturbances or psychosis

  • Tourettes DisorderRisperidone and Pimozidebest evidenceAripiprazole-promising data; lower risk for side effects

  • Side EffectsEPS-Parkinsonian, Dystonia, Akatishia,Tardive DyskinesiaElderly patients are at higher risk for EPS and TDs develops more readily and are more persistentMostly seen in use of Conventional APs or neuroleptics and Risperidone

  • Side EffectsMetabolic: weight gain, hyperglycemia, hyperlipidemia Most likely to cause Metabolic side effects: Olanzapine, Quetiapine, Risperidone Less Likely: Ziprasidone, Asenapine, Lurasidone

  • Side EffectsProlonged QTc Interval and Sudden Death:Most APs will carry this risk (Haloperidol, Droperidol, Pimozide)Highest risk: ThioridazineZiprasidone (no evidence yet to suggest that this leads to sudden death)

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