Fluphenazine Enanthate

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.

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.

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.

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.

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.

From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors.