antipsychotic medications in the primary care practice angelo potenciano, m.d
TRANSCRIPT
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Antipsychotic Medications in the Primary Care Practice
Angelo Potenciano, M.D.
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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.
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Antipsychotics in the Primary Care Setting
• Lieberman (2002) noted that PCP Rx
Of APs has increased 18-20% since 1996
PCPs treat a variety of psychiatric disorders including depression, anxiety, bipolar disorders, sleep disorders, psychosis,
and behavioral problems assoc. with dementia, and delirium
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Reasons Why PCPs Are Vital in the Treatment of Psychiatric
Patients• Not enough psychiatric services available • Psychiatric symptoms arising from medical d/o or
during the course of treatment• Patients are more comfortable seeing their PCP• Stable Patients who require maintenance meds
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History of Antipsychotics
• 1891 – Paul Ehrlich and Paul Guttman pioneered the use of Methylene Blue –a phenothiazine derivative in the Tx of Malaria
• 1890s- noted the tranquilizing and antidepressant effects
• Became the lead compound in the development of Chlorpromazine
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History of Antipsychotics
• 1951 –French surgeon, Henry Leborit used Chlorpromazine as a sedating agent
• 1952 John Delay and Pierre Deniker treated 38 schizophrenics with CPZ 75-100mg/day/IM
• Dramatic improvements in thinking and emotional symptoms and overall behavior
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History of Antipsychotics
• 1954-1975 development of typical ApsThioridazine – Mellaril
Haloperidol- Haldol
Trifluoperazine- Stelazine
Perphenazine- Trilafon
Fluphenazine- Prolixin
Molindone-Moban
Pimozide
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History of Antipsychotics
• 1980s-Janssen developed Risperidone
• The earliest Atypical APs
• Followed the LSD model of psychopathology- Risperidone-antagonized effects of LSD
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History of Antipsychotics
• 1989 Clozapine was approved by the FDA
In treating treatment-resistant schizophrenia
1971 introduced in Europe but was withdrawn in 1975 due to angranulocytosis
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Atypical Antipsychotics
Aripiprazole- Abilify Quetiapine- Seroquel
Asenaphine- Saphris Ziprasidone- Geodon
Clozapine- Clozaril
Iloperidone- Fanapt
Lurasidone- Latuda
Olanzapine- Zyprexa
Risperidone- Risperdal
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Mechanism of Action of Antipsychotics
• Dopamine antagonist- D1-4 R
• Typical APs / Neuroleptics- D2R (tightly bound)
• Atypical Aps- D1 & 2R (loosely bound or rapid dissociation), 5HT 2A and 5HT2C
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Mechanism of Action
• D2R antagonism – EPS (akatishia, dystonia, parkinsonism, tardive dyskinesias)
• Rapid dissociation from DA receptor- less EPS risk
• 5HT binding(2A) – mood and cognitive effects, decreased DA blockade
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Clinical Uses of Antipsychotics
FDA Approved Indications
1. Psychotic symptoms due to Schizophrenia or Schizoaffective disorder
2. Mood disorders: Bipolar disorder and Major depressive disorder
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Clinical Uses of Antipsychotics
“Off-Label” or Non-FDA Approved
1. Psychotic symptoms of various etiology- substance-induced, dementia, delirium
2. Behavioral problems secondary to developmental disorders (autism, ADHD), dementia, delirium, other neurological disorders
3. Sleep disorders
4. Anxiety disorders
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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
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Clinical Uses of Antipsychotics
• FDA Approved Indications Schizoaffective Disorder- Iloperidone (Fanapt) Treatment-Resistant Schizophrenia (failure to respond
after 6 weeks of trials with 2-3 different antipsychotic- Clozapine (Clozaril)
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Clinical Uses of Antipsychotics
• FDA Approved Indications
Bipolar Disorder: Asenapine, Aripiprazole, Lurasidone, Olanzapine, Quetiapine, Risperidone, Ziprasidone
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Antipsychotics and Bipolar Disorders
FDA Approved Indications
Bipolar disorder-Mixed or Manic Episode:
Asenapine, Aripiprazole, Olanzapine, Quetiapine, Risperidone, Ziprasidone
Bipolar Disorder- Depressive episode:
Lurasidone, Olanzapine-Fluoxetine (symbyax), Quetiapine
Monotherapy or adjunctive therapy with Lithium or valproate
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Antipsychotics and Bipolar Disorder
• Clinical 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
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Injectable Antipsychotics
Acute agitation associated with Schizophrenia or Bipolar Disorder: Haloperidol, Olanzapine, Ziprasidone
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Antipsychotics Use in Children
Bipolar disorder in children and adolescents (aged 10-17) (Monotherapy): Quetiapine, Risperidone
Schizophrenia in Adolescents (aged 13-17):
Aripiprazole, Risperidone
Behavioral issues associated with Autistic d/o (irritability, aggression, self-injurious beh.,temper tantrums, rapidly changing moods):
Risperidone, Aripiprazole
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Antipsychotics and Depressive Disorders
Treatment-Resistant Depression:
Olanzapine-Fluoxetine Combination
Adjunctive / Augmentive Treatment of Major Depression: Aripiprazole, Quetiapine XR
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Off-Label Uses of Antipsychotics
• Behavioral issues associated with Dementia and Delirium: agitation/ aggression, psychosis, sleep disturbances, anxiety, confusion
• Increasing consensus in the efficacy of APs• Atypical APs-less EPS and anticholinergic effects• Haloperidol (low doses) as safe and effective as
atypical APs
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Antipsychotics for Dementia
Clinical Antipsychotic Trials of Intervention
Effectiveness-Alzheimer’s 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
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Antipsychotics for Delirium
• Haloperidol- antipsychotic of choice (Society of Critical Care Medicine 2007)
• Risk of EPS and Cardiac Conduction Changes
• Olanzapine, Quetiapine, Risperidone- as efficacious, with less side effects, quicker improvement, less agitation, better sleep patterns
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Antipsychotics in the Elderly
• 1.6-1.7 times risk of death in patients taking APs
• Duration of treatment: 10 weeks
• Common causes: sudden death, CV-Heart failure, infectious (pneumonia)
• 1.7-2 times risk of CVAs in dementia patients taking Antipsychotics
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Off-label Uses of Antipsychotics
• Sleep disorders—sedative effects of Aps can promote sleep
• Most sedating APs: Olanzapine, Quetiapine,
Chlorpromazine, Thioridazine
Metabolic and EPS side effects are concerns in long-term use
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Off-label Uses of Antipsychotics
• Anxiety disorders / symptoms—OCD, GAD, Panic Disorders
• tranquilizing / anxiolytic effects of most APs used in combination with SSRIs or Benzos. –Mostly inconclusive study results
• May be more useful in patients with co-morbid disturbances or psychosis
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Tourette’s Disorder
• Risperidone and Pimozide—best evidence
• Aripiprazole-promising data; lower risk for side effects
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Side Effects
• EPS-Parkinsonian, Dystonia, Akatishia,Tardive Dyskinesia
• Elderly patients are at higher risk for EPS and TDs –develops more readily and are more persistent
• Mostly seen in use of Conventional APs or neuroleptics and Risperidone
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Side Effects
• Metabolic: weight gain, hyperglycemia, hyperlipidemia
Most likely to cause Metabolic side effects: Olanzapine, Quetiapine, Risperidone
Less Likely: Ziprasidone, Asenapine, Lurasidone
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Side Effects
• Prolonged QTc Interval and Sudden Death:
• Most APs will carry this risk (Haloperidol, Droperidol, Pimozide)
• Highest risk:
Thioridazine
Ziprasidone (no evidence yet to suggest that this leads to sudden death)