• Michael W Huang, Roger Carl Gibson, Mahesh B Jayaram, and Stanley N Caroff.
• Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
• Cochrane Db Syst Rev. 2022 Jul 12; 7 (7): CD013100CD013100.

BackgroundWhilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs).ObjectivesTo compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms.Search MethodsWe searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant.Selection CriteriaAll RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms.Data Collection And Analysistwo review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study.Main ResultsOut of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial.   There were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/- estimated standard deviation; 0.68 +/- 4.58; N = 8) than the risperidone group (6.04 +/- 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol.  Although no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis.  Our results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported.Authors' ConclusionsWe found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples.  High-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia.Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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