Antipsychotic polypharmacy in schizophrenia: evolving evidence and rationale

Area of Science:

• Psychiatry
• Pharmacology
• Clinical Neuroscience

Background:

• Antipsychotic polypharmacy (APP), the concurrent use of multiple antipsychotics, is prevalent in schizophrenia treatment.
• Current clinical guidelines largely advocate for antipsychotic monotherapy due to limited supporting evidence for APP.

Purpose of the Study:

• To systematically review the evidence for the efficacy and tolerability of antipsychotic polypharmacy (APP) in schizophrenia.
• To evaluate the effectiveness of APP in real-world clinical practice.
• To discuss theoretical models supporting APP use.

Main Methods:

• Systematic literature search of PubMed (1995-2020).
• Review and discussion of meta-analyses of randomized controlled trials (RCTs).
• Inclusion of effectiveness studies and theoretical models.

Main Results:

• Growing evidence from efficacy and effectiveness studies suggests potential benefits of APP for select schizophrenia patients.
• The combination of clozapine and aripiprazole demonstrates the most substantial supporting evidence.
• This combination aligns with the dopamine supersensitivity hypothesis in schizophrenia.

Conclusions:

• Guidelines may require updating to reflect the increasing evidence for APP.
• Further research is essential to confirm the efficacy and effectiveness of specific APP combinations, particularly in first-episode schizophrenia.