What is a suitable alternative medication for a patient with psychosis not responding to Saphris (asenapine) 2.5mg, Risperdal (risperidone) 12mg, Haldol (haloperidol) 10mg, and Zyprexa (olanzapine) 10mg daily?

From the Guidelines

For a patient with psychosis not managed with Saphris 2.5 mg, Risperdal 12 mg, Haldol 10 mg, and Zyprexa 10 mg daily, Clozapine would be the recommended next medication option. This recommendation is based on the American Psychiatric Association's practice guideline for the treatment of patients with schizophrenia, which suggests that patients with treatment-resistant schizophrenia be treated with clozapine 1. Clozapine is considered the gold standard for treatment-resistant psychosis after multiple antipsychotics have failed.

Key Considerations

• The typical starting dose is 12.5 mg once or twice daily, gradually increasing to an effective dose range of 300-450 mg daily, divided into two doses.
• The titration should be slow to minimize side effects, with weekly blood monitoring required due to the risk of agranulocytosis.
• Before starting Clozapine, it's essential to consolidate the current regimen by tapering off some of the existing antipsychotics, as the current combination represents significant polypharmacy with overlapping side effect profiles.
• Clozapine works differently from other antipsychotics with unique receptor binding profiles, which explains its effectiveness in treatment-resistant cases.
• Close monitoring for side effects including sedation, hypersalivation, constipation, metabolic changes, and myocarditis is essential, especially during the initial titration period.

Monitoring and Side Effects

• Weekly blood cell counts are obtained during the first 6 months of treatment, then every 2 weeks thereafter, including testing during the 4 weeks after the medication is stopped 1.
• The patient should be monitored for infection, with daily checks of blood cell counts if the WBC drops below 2,000/mm3 or the absolute neutrophil count (ANC) drops below 1,000/mm3.
• If the WBC drops to 2,000–3,000/mm3 or the ANC drops to 1,000–1,500/mm3, the medication must be stopped immediately and the patient monitored for infection, with daily checks of blood cell counts.

Treatment Plan

• A comprehensive treatment plan should include evidence-based nonpharmacological and pharmacological treatments, as recommended by the American Psychiatric Association 1.
• The treatment plan should be person-centered, taking into account the patient's goals and preferences for treatment.
• Regular assessments and monitoring should be conducted to evaluate the effectiveness of the treatment plan and make adjustments as needed.

From the Research

Alternative Medication Options

If psychosis is not managed with Saphris 2.5 and Risperdal 12 mg daily and HALDOL 10 mg daily and Zyprexa 10 mg, alternative medication options may be considered.

• Clozapine has been shown to be effective in reducing psychotic symptoms and aggression in treatment-resistant patients 2.
• Aripiprazole, olanzapine, and risperidone have been found to be effective in the treatment of first-episode psychosis, with advantages in terms of effectiveness and tolerability 3.
• Quetiapine and ziprasidone may also be considered, although they have been associated with higher discontinuation rates due to lack of efficacy, adherence, and tolerability issues 3.

Considerations for Medication Selection

When selecting an alternative medication, several factors should be considered, including:

• Efficacy in reducing psychotic symptoms and aggression
• Tolerability and potential side effects, such as extrapyramidal symptoms, weight gain, and sedation
• Patient-specific factors, such as medical history, concomitant medications, and personal preferences
• The potential for dose reduction and discontinuation, and the associated risks of relapse and other adverse outcomes 4.

Neurocognitive Effectiveness

The neurocognitive effectiveness of different antipsychotic medications should also be considered.

• Haloperidol, olanzapine, and risperidone have been found to be equally effective in improving cognitive deficits in first-episode psychosis, with significant improvements in cognitive scores after 1 year of treatment 5.
• The effect of practice and repeated cognitive assessments may contribute to cognitive score improvements after treatment with antipsychotics 5.