Antipsychotic doses should not be reduced below standard dose range recommendations during treatment for multiepisode schizophrenia, according to recent research published in The Lancet Psychiatry.

“Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimize adverse effects, but evidence for this strategy is unclear,” wrote Mikkel Hojlund, MD, Department of Psychiatry Aabenraa, Metal Health Services Region of Southern Denmark, Aabenraa, and co-researchers.

Researchers aimed to see if there is a benefit and/or disadvantage to reducing doses of antipsychotics below the standard dose range for patients with schizophrenia.

Randomized trials in adults with schizophrenia or schizoaffective disorder were gathered through Embase, Medline, PsycINFO, and the Cochrane Library. All studies included patients with diagnosis lasting at least 24 weeks who were clinically stable at baseline, in addition to the studies comparing 2 dosages of the same treatment option. Trials in first-episode psychosis were excluded. A total of 22 studies reporting on 24 trials and 3282 patients were included in this meta-analysis.

The Pharmacologic Properties of LAIs and Patient Preferences

Dosages within 50% to 99% of the lower limit of the standard dose (low dose) and dosages of less than 50% of the lower limit (very low dose) were compared with the standard dose.

“Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes,” Hojlund wrote.

Primary outcomes included all-cause discontinuation and relapse.

Patients receiving a low dose saw a 44% increase in relapse risk when compared with standard dose, while patients receiving very low dose saw an increase of 72%. Patients receiving a low dose saw a 12% increase in risk of all-cause discontinuation when compared with the standard dose, while patients receiving very low dose saw a 31% increase.

“During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilization, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation,” concluded Hojlund et al.

Højlund M, Kemp AF, Haddad PM, Neill JC, Correll CU. Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials. Lancet Psychiatry. 2021;8(6):P471-P486.