What are the recommended antipsychotics for treating psychotic disorders?

Recommended Antipsychotics for Treating Psychotic Disorders

First-line antipsychotics for psychotic disorders include atypical antipsychotics such as risperidone, olanzapine, quetiapine, and aripiprazole due to their efficacy for both positive and negative symptoms with lower risk of extrapyramidal side effects compared to typical antipsychotics. 1

Classification of Antipsychotics

First-Generation (Typical) Antipsychotics

• Haloperidol
• Fluphenazine
• Chlorpromazine
• Perphenazine
• Thioridazine

Second-Generation (Atypical) Antipsychotics

• Risperidone
• Olanzapine
• Quetiapine
• Aripiprazole
• Ziprasidone
• Paliperidone
• Amisulpride
• Clozapine (reserved for treatment-resistant cases)

Treatment Algorithm for Psychotic Disorders

Initial Treatment

1. First Episode Psychosis:

   • Start with low-dose atypical antipsychotic (e.g., risperidone 2 mg/day or olanzapine 7.5-10 mg/day) 1
   • Avoid extrapyramidal side effects to encourage future adherence
   • Allow 4-6 weeks at therapeutic dose to assess response 1

2. Inadequate Response to First Antipsychotic:

   • Switch to a different antipsychotic with different pharmacodynamic profile
   • If first treatment was a D2 partial agonist (e.g., aripiprazole), consider amisulpride, risperidone, paliperidone, or olanzapine 1
   • Ensure adequate trial (at least 4 weeks at therapeutic dose) 1

3. Treatment-Resistant Schizophrenia:

   • After failure of two adequate antipsychotic trials, initiate clozapine 1
   • Target plasma level of at least 350 ng/mL
   • Consider metformin concomitantly to attenuate weight gain 1

Acute Agitation Management

• For acute agitation requiring rapid control:
  • Combination of haloperidol (5 mg) and lorazepam (2 mg) for more rapid sedation 2
  • Alternative: droperidol (may be more effective for rapid sedation) 1, 2
  • For oral administration in cooperative patients: risperidone plus lorazepam 2

Considerations for Specific Antipsychotics

Risperidone

• Initial target dose: 2 mg/day 1
• Effective for positive and negative symptoms
• Monitor for hyperprolactinemia and weight gain

Olanzapine

• Initial target dose: 7.5-10 mg/day 1, 3
• Effective for acute manic or mixed episodes
• Higher risk of metabolic side effects (weight gain, diabetes)
• Available in oral and intramuscular formulations for agitation 3

Clozapine

• Reserved for treatment-resistant schizophrenia 1
• Superior efficacy for reducing suicide risk 1
• Requires monitoring for agranulocytosis, seizures, and metabolic effects 1
• Used after failure of at least two other antipsychotic medications 1

Long-Acting Injectable (LAI) Antipsychotics

• Consider for patients with history of poor adherence 1
• Options include risperidone, paliperidone, aripiprazole, and olanzapine LAIs

Side Effect Profiles and Management

Extrapyramidal Symptoms (EPS)

• More common with typical antipsychotics and high-dose risperidone 4
• Management options 1:
  • Lower antipsychotic dose
  • Switch to another antipsychotic
  • Add anticholinergic medication for acute dystonia

Metabolic Effects

• Monitor weight, glucose, and lipids, especially with olanzapine and clozapine
• Consider metformin for weight management with clozapine 1

Akathisia

• Management options 1:
  • Lower antipsychotic dose
  • Switch antipsychotics
  • Add benzodiazepine or beta-blocker

Tardive Dyskinesia

• Treat moderate to severe cases with VMAT2 inhibitor 1
• More common with typical antipsychotics 5

Special Populations

First-Episode Psychosis

• Lower doses often effective (e.g., maximum 4-6 mg/day haloperidol) 1, 2
• Preferably treat in coordinated specialty care program 1
• More sensitive to side effects, especially EPS 2

Elderly Patients

• Use lower doses (e.g., haloperidol 0.5-2 mg 2-3 times daily) 2
• Higher risk of sedation, falls, and anticholinergic effects
• Monitor closely for adverse effects

Common Pitfalls to Avoid

1. Inadequate trial duration: Allow 4-6 weeks at therapeutic dose before concluding lack of efficacy 1

2. Excessive dosing: Higher doses increase side effects without proportional increase in efficacy

3. Delayed recognition of treatment resistance: Consider clozapine after two failed adequate trials 1

4. Neglecting physical health monitoring: Regular screening for metabolic syndrome is essential

5. Overlooking psychosocial interventions: Combine pharmacotherapy with evidence-based psychosocial treatments for optimal outcomes 1