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    ABSTRACT: Treatment resistant psychoses present an enormous burden. Guidelines generally prohibit more than one antipsychotic and the efficacy of this is unclear, but multiple surveys suggest such practice is common. Reasons for this include a lack of alternatives, difficulty in discontinuing, successful clinical experience, and inertia. We performed a systematic review on the efficacy of antipsychotic polypharmacy. This identified two broad categories of polypharmacy - clozapine plus a second antipsychotic and two 'non-clozapine' antipsychotics - and three domains of efficacy - effects on specific symptoms, cognition, and adverse effects. The evidence is mixed. There are high quality double blind studies supporting clozapine augmentation, but just as many such studies failing to show benefit. Less evidence supports the combination of two 'non-clozapine' drugs. However, there is more consistent emerging data supporting aripiprazole for helping reduce medication induced weight-gain and re-regulate lipid profiles. Effects on cognition do not appear to be favourable and polypharmacy is associated with more side effects. The quantity and quality of the research literature is surprisingly sparse. Clinicians can use selective evidence to support polypharmacy; but the overall context does not support this. Currently there are no clear predictors to suggest which sub-group of patients may be more likely to benefit most from such prescribing. In conclusion, polypharmacy should be carried out with caution with careful baseline and on-going monitoring of the target symptoms, the apriori rationale for initiating treatment with a deadline for cessation, accompanied by a robust assessment of adverse effects and physical health checks.
    06/2013; 2(2-Article):143-171. DOI:10.2174/22115560113029990003
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    ABSTRACT: Tardive syndromes (TS) arise from long term exposure to dopamine receptor blocking agents. Clozapine has been considered to have low risk of causing new onset TS and is considered as a treatment option in patients with TS. This review evaluates the usefulness of clozapine in patients with TS and occasional reports of clozapine causing TS. Electronic searches were carried out using the search engines of PUBMED, Science direct and Google Scholar databases. All reports describing use of clozapine in management of TS, monitoring of TS while on clozapine and onset of TS after initiation of clozapine were identified. Fifteen trials and 28 case series/case reports describe the use of clozapine in TS. Most of these reports show that clozapine is useful in patients with TS, in the dose range of 200-300mg/day and the beneficial effect is seen within 4-12 weeks of initiation. One case series and two case reports described clozapine withdrawal emergent dyskinesias suggesting a masking role of clozapine. One trial, three case series and two case reports describe beneficial effects of clozapine on long standing neurological syndromes. There is relatively less literature (2 trials and 15 case series/reports) describing the emergence of TS with clozapine. Evidence of beneficial effects of clozapine in TS is greater than its role in causation/worsening of TS. Hence, clozapine should be considered in symptomatic patients who develop TS while receiving other antipsychotics. Further research on mechanism of TS and clozapine effect on TS is required.
    12/2013; 6(6):439-51. DOI:10.1016/j.ajp.2013.08.067


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