Mental health

Combination of two or more antipsychotic medications for psychotic disorders

Question 2: In individuals with psychotic disorders (including schizophrenia), is the use of two or more antipsychotic medications concurrently more effective and safer than the use of one antipsychotic only?

Management of psychosis and bipolar disorders

  • Population: patients with psychotic disorders, including schizophrenia (partial or non-response)
  • Interventions: antipsychotic combination therapy (two antipsychotics concurrently)
  • Comparison: antipsychotic monotherapy
  • Outcomes:
    • symptoms severity
    • prevention of relapses
    • disability and functioning
    • adverse effects of treatment
    • quality of life
    • all-cause mortality, including by suicide
    • treatment adherence or concordance
    • users' and families' satisfaction with care (including users and families involvement).


Routinely, one antipsychotic should be prescribed at a time in individuals with psychotic disorders (including schizophrenia).
Strength of recommendation: STRONG

For individuals with psychoses (including schizophrenia) who do not respond to adequate dose and duration of more than one antipsychotic medicine (using one medicine at a time), antipsychotic combination treatment may be considered by primary health care professionals preferably under the supervision of mental health professionals with close clinical monitoring.
Strength of recommendation: STANDARD