Treatment resistant schizophrenia: a comprehensive survey of randomised controlled trials

Abstract

BackgroundSchizophrenia is a common serious mental health condition which has significant morbidity and financial consequences. The mainstay of treatment has been antipsychotic medication but one third of people will have a ‘treatment resistant’ and most disabling and costly illness. The aim of this survey was to produce a broad overview of available randomised evidence for interventions for people whose schizophrenic illness has been designated ‘treatment resistant’.MethodWe searched the Cochrane Schizophrenia Group’s comprehensive Trials Register, selected all relevant randomised trials and, taking care not to double count, extracted the number of people randomised within each study. Finally we sought relevant reviews on the Cochrane Library and investigated how data on this subgroup of people had been presented.ResultsWe identified 542 relevant papers based on 268 trials (Average size 64.8 SD 61.6, range 7–526, median 56 IQR 47.3, mode 60). The most studied intervention is clozapine with 82 studies (total n = 6299) comparing it against other anti-psychotic medications. Cognitive behavioural therapy (CBT), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) supplementing a standard care and risperidone supplementation of clozapine has also been extensively evaluated within trials. Many approaches, however, were clearly under researched. There were only four studies investigating combinations of non-clozapine antipsychotics. Only two psychological approaches (CBT and Family Rehabilitation Training) had more than two studies. Cochrane reviews rarely presented data specific to this important clinical sub-group.ConclusionsThis survey provides a broad taxonomy of how much evaluative research has been carried out investigating interventions for people with treatment resistant schizophrenia. Over 280 trials have been undertaken but, with a few exceptions, most treatment approaches - and some in common use - have only one or two relevant but small trials. Too infrequently the leading reviews fail to highlight the paucity of evidence in this area – as these reviews are maintained this shortcoming should be addressed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0253-4) contains supplementary material, which is available to authorized users.

Treatment of clozapine-associated weight gain: a systematic review

“…To our knowledge, this is the only systematic review that has analyzed and discussed the treatments available for weight gain specifically associated with clozapine. Patients treated with clozapine may represent a distinct sub-population of schizophrenia patients [4], and the greater weight gain seen in patients with clozapine than other APDs may mean that some weight reducing treatments that are not effective with other antipsychotic drugs do work uniquely in clozapine treated patients. The list of pharmacological interventions that has been shown to prevent or reverse weight gain associated with other APDs includes nizatidine, amantadine, reboxetine, topiramate, sibutramine, and metformin (see [65] for a comprehensive review, as well as [66] for a more recent update).…”

“…While the majority of schizophrenia patients show some therapeutic benefit and symptomatic relief with first-line APD medications, a significant proportion of patients do not. As many as 20-30 % of all patients with schizophrenia may be resistant to standard APD treatment [3,4]. For those patients who do not respond to at least two different APDs, treatment with the low-potency APD clozapine may be warranted [5,6], based on its unique clinical properties.…”

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

“…Clozapine (CLO), among the APDs, is a unique medication. Although classified simply as atypical, it has been found to be superior to other APDs in the management of treatment-resistant schizophrenia [2] and is often referred to as the gold standard [3] .…”

Basal Exposure Therapy: A New Approach for Treatment-Resistant Patients with Severe and Composite Mental Disorders

“…A review of 280 available RCT studies for treatment-resistant schizophrenia concluded that there is a paucity of trials for most types of therapeutic approaches. The exception is clozapine, but with only modest effects indicated (15). A small set of studies evaluated cognitive behavioral therapy (CBT) for non-responding schizophrenic patients, but without finding positive effect (16).…”