A systematic review and meta-analysis of the effect of depot antipsychotic frequency on compliance and outcome

Background: Depot antipsychotics are commonly used to improve adherence and clinical outcomes such as relapse and readmission. Dosing regimens vary but are commonly two- and four-weekly. To date, the effect of administration at two-weekly or four-weekly intervals on outcome has not been examined in a meta-analysis.

Aims: A systematic review and meta-analysis on whether the frequency of depot antipsychotic administration (e.g., two- vs four-weekly) makes any difference to compliance and outcome.

Methods: A systematic search of Medline, EMBASE and PsycInfo for RCTs that compared the frequency of depot administration (e.g., two- vs four-weekly) for an equivalent dose. Outcomes were compliance, psychiatric symptomatology, quality of life, adverse drug reactions (ADRs), patient preference, admission rates, bed-days and costs.

Results: Seven studies from eight papers (n=3994) were found covering olanzapine, paliperidone, risperidone, haloperidol and fluphenazine enanthate/decanoate with follow-up of up to one year. Meta-analyses were possible for psychotic symptoms and ADRs. There were no differences in psychotic symptoms or quality of life between two- and four-weekly doses. Health service use was not reported. For ADRs, the only significant difference detected was that two-weekly injections were less likely to lead to site pain (RR 0.16, 95% CI 0.07-0.38; 2 studies n=1667). There were no differences in other ADRs.

Conclusions: There were surprisingly little data on the effect of dosing frequency for an equivalent dose on clinical outcomes. There is a need for long-term studies of a wide range of outcomes including cost-effectiveness. Claims for advantages of new preparations over others require careful evaluation.