Depot flupenthixol decanoate for schizophrenia or other similar mental illnesses

Schizophrenia is a severe mental illness that affects thinking and perception. It often develops in early adult-hood and can have a lifelong impact on not only the mental well-being of the sufferer, but their social and general functioning. Worldwide around 15 people per 100,000 are diagnosed with schizophrenia every year. The mainstay of treatment for schizophrenia is antipsychotic drugs.

Antipsychotics are usually given as tablets by mouth (orally). However, people with mental illness often have difficulties with accepting medication (compliance). Their illness affects their thinking, which can erode their understanding of their illness and they often do not see the need for treatment. Taking antipsychotics can also have unpleasant side effects. Oral medication requires regular self-administration otherwise effectiveness is reduced and the risk of relapse is high.

A solution to poor compliance is depot medication where medication is given by injection and is slowly released over a period of weeks. For people with schizophrenia it was hoped to be able to maintain care in the community with regular injections administered by community psychiatric nurses. Initial enthusiasm and the favourable results of clinical trials gave rise to the extensive use of depots as a means of long-term treatment. Flupenthixol decanoate is one of the most widely used depot antipsychotics in the UK.

This review looks at the effectiveness of depot flupenthixol decanoate in comparison with no active treatment (placebo), oral antipsychotics and other depot preparations for people with schizophrenia and other severe mental illnesses. An electronic search for relevant trials was carried out in 2013. Fifteen trials with 626 participants could be included. All evidence from these trials was rated by the authors to be low or very low quality. Currently, from the data reported, there is nothing to choose between depot flupenthixol decanoate and other depot or oral antipsychotics. There was some evidence that it would be understandable to offer a standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. Overall, this review highlights the lack of evidence based information available for the review question and the need for large, well-designed and reported randomised clinical trials to address the medical, social, personal and economic effects of flupenthixol decanoate.

This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert: Rethink Mental Illness.

Authors' conclusions: 

In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.

Read the full abstract...
Background: 

Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia.

Objectives: 

To evaluate the effects of flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes.

Search strategy: 

We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.

Selection criteria: 

All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought.

Data collection and analysis: 

Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies.

Main results: 

The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.

One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23, very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).

Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).

Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (~40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (~6 mg) with a low dose (~9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence).

Share/Save