Combination of clozapine with an atypical antipsychotic: a meta-analysis
| Pages | 277-288 |
| Date | 11 December 2017 |
| DOI | https://doi.org/10.1108/MHRJ-01-2017-0001 |
| Published date | 11 December 2017 |
| Author | Lauren Rolph,Ken McGarry |
| Subject Matter | Health & social care,Mental health |
Combination of clozapine with an atypical
antipsychotic: a meta-analysis
Lauren Rolph and Ken McGarry
Abstract
Purpose –The purpose of this paper is to review the efficacy of atypical antipsychotics in combination with
clozapine. Previous meta-analyses have assessed the use of both typical and atypical antipsychotics in
combination with clozapine, combination treatment being withheld only for those patients deemed
treatment resistant.
Design/methodology/approach –Outcomes assessed included: positive, negative and overall symptom
score. The total numbers of participants (n ¼588) were scored using the Positive and Negative Symptom
Scale/the Brief Psychiatric Rating Scale and effect sizes were used to judge the efficacy of the combination
treatments. Data gained from the ten randomized, double blind, placebo controlled trials were analysed using
the R statistical software.
Findings –The effect sizes gained from analysis showed a small benefit of combination therapy over
clozapine monotherapy. Therefore, it is the recommendation of this analysis that alternative avenues be
sought in order to treat patients who have a sub-optimal response to clozapine with a combination other than
two second generation antipsychotics.
Research limitations/implications –The initial trials search unveiled 1,412 studies. After the inclusion and
exclusion criteria were applied, ten trials were used in this meta-analysis.
Practical implications –The recommendation of this a nalysis that alternat ive medications be sough t in
order to treat patients who have a sub-optimal response to clozapine with a combination other than two
second generation antipsychotics. This route should only be used once all other treatment options have
been exhausted.
Originality/value –This meta-analytical study looks specifically at the combination of atypical antipsychotics
with clozapine in comparison to clozapine monotherapy. This work extends existing meta-analysis by
incorporating data from more recent trials.
Keywords Antipsychotics, Schizophrenia, Aripiprazole, Combination therapy, Risperidone
Paper type Research paper
1. Introduction
It is generally accepted that over the course of their lifetime, about 1 per cent of the UK population
will develop schizophrenia, although one study suggests the true figure may be closer to
0.72 per cent (Saha et al., 2005). Furthermore, we should be clear as to the working definition of
treatment-resistant schizophrenia as defined by Howes et al. in their systematic review
of randomized antipsychotic clinical trials where definitions of treatment resistance were
extracted (Howes et al., 2017).
Clozapine is an atypical antipsychotic reserved only for those patients who have been adequately
trialled unsuccessfully on at least two previous antipsychotics (NICE178, 2014). The failure is
usually due to hematological side effects (Pirmohamed and Park, 1997), which is one of the
several side effects that can be attributed to non-clozapine atypical antipsychotics. A patient
should trialled on clozapine for a minimum of eight to ten weeks before being classed as
treatment resistant.
The term treatment-resistant schizophrenia was first coined by Kane et al. (1988) where it was
determined that those patients who have not responded to two previous antipsychotic therapies
Received 10 January 2017
Revised 1 July 2017
Accepted 18 July 2017
The authors would like to thank
the reviewers for their comments
for improving this paper. The
authors would also like to thank
Dr Clare Brizzolara and Dr Gabriel
Boachie-Ansah for several helpful
discussions regarding the use of
antipsychotic drugs and in
clarifying the pathophysiology of
schizophrenia.
Lauren Rolph is a Rotational
Pharmacist and Ken McGarry
is a Senior Lecturer, both at the
Department of Pharmacy and
Pharmaceutical Sciences,
University of Sunderland,
Sunderland, UK.
DOI 10.1108/MHRJ-01-2017-0001 VOL. 22 NO. 4 2017, pp. 277-288, © Emerald Publishing Limited, ISSN 1361-9322
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MENTALHEALTH REVIEW JOURNAL
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