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.
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
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
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
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 75100mg/day/IM
• Dramatic improvements in thinking and
emotional symptoms and overall behavior
History of Antipsychotics
• 1954-1975 development of typical Aps
Thioridazine – Mellaril
Haloperidol- Haldol
Trifluoperazine- Stelazine
Perphenazine- Trilafon
Fluphenazine- Prolixin
Molindone-Moban
Pimozide
History of Antipsychotics
• 1980s-Janssen developed Risperidone
• The earliest Atypical APs
• Followed the LSD model of
psychopathology- Risperidone-antagonized
effects of LSD
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1971 introduced in Europe but was withdrawn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
Atypical Antipsychotics
Aripiprazole- Abilify
Asenaphine- Saphris
Clozapine- Clozaril
Iloperidone- Fanapt
Lurasidone- Latuda
Olanzapine- Zyprexa
Risperidone- Risperdal
Quetiapine- Seroquel
Ziprasidone- Geodon
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
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
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
Clinical Uses of Antipsychotics
“Off-Label” or Non-FDA Approved
1. Psychotic symptoms of various etiologysubstance-induced, dementia, delirium
2. Behavioral problems secondary to
developmental disorders (autism, ADHD),
dementia, delirium, other neurological disorders
3. Sleep disorders
4. Anxiety 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 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)
Clinical Uses of Antipsychotics
• FDA Approved Indications
Bipolar Disorder: Asenapine, Aripiprazole,
Lurasidone, Olanzapine, Quetiapine,
Risperidone, Ziprasidone
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
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
Injectable Antipsychotics
Acute agitation associated with Schizophrenia
or Bipolar Disorder: Haloperidol,
Olanzapine, Ziprasidone
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
Antipsychotics and Depressive
Disorders
Treatment-Resistant Depression:
Olanzapine-Fluoxetine Combination
Adjunctive / Augmentive Treatment of Major
Depression: Aripiprazole, Quetiapine XR
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
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
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
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
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
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 comorbid disturbances or psychosis
Tourette’s Disorder
• Risperidone and Pimozide—best evidence
• Aripiprazole-promising data; lower risk for
side effects
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
Side Effects
• Metabolic: weight gain, hyperglycemia,
hyperlipidemia
Most likely to cause Metabolic side effects:
Olanzapine, Quetiapine, Risperidone
Less Likely: Ziprasidone, Asenapine,
Lurasidone
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)