REVIEW OF: Kishi T et al, Psychiatry Research 2024;333:115761

STUDY TYPE: Systematic review and network meta-analysis 

In schizophrenia, long-acting injectables (LAIs) delay the time to recurrence in the event a patient discontinues their medication. Does this also apply to bipolar disorder?

In this meta-analysis, researchers compiled the results of five double-blind RCTs. They compared the discontinuation rates of oral antipsychotics vs placebo to the discontinuation rates of corresponding LAIs vs placebo during the maintenance phase of bipolar disorder. The five studies each had between 150 and 300 patients, all of whom received either placebo or one of the following: monthly aripiprazole LAI (AOM), oral aripiprazole (OARI), bimonthly risperidone LAI (RIS-LAI), or oral paliperidone (OPAL) (although paliperidone is a metabolite of risperidone, paliperidone is not FDA approved in bipolar disorder). In all studies, patients had been hospitalized for bipolar manic or mixed-mood episodes and stabilized on oral medications.

Patients were followed for at least a year. The primary outcome was the time to recurrence at 2, 4, 6, 8, 12, 16, 20, and 26 weeks. Recurrence was measured differently across studies, but all included hospitalization as one definition.

Medications were superior to placebo in all studies. The time to recurrence was delayed in all groups who discontinued LAIs compared to those who stopped oral equivalents. The difference was statistically significant at weeks 4 and 20 for aripiprazole and week 2 for risperidone. This difference may be attributable to AOM’s longer half-life (46.5 days). There was no significant difference between formulations for preventing bipolar depression.

CARLAT TAKE

Compared to their oral equivalents, LAIs delay the time to recurrence in patients with bipolar disorder who suddenly discontinue medication. For each medication, the difference was significant around the time the LAI would be expected to wear off (week 4 for AOM and week 2 for RIS-LAI, as well as week 20 for AOM). This suggests a slow taper of oral antipsychotics may delay recurrence as well.