- We could not answer whether antipsychotic medicines are safe and effective for schizophrenia spectrum disorders with catatonic symptoms because we found only one study including a small number of people and a brief duration of treatment, leaving us with very low confidence in the results.
- We did find that in the only included study both an antipsychotic medicine (risperidone) and electroconvulsive therapy may improve catatonic and positive symptoms of psychosis, but that electroconvulsive therapy may be better for the first three weeks in people who did not first respond to the medicine lorazepam. We found no unusual or dangerous side effects with either treatment.
- Larger, well‐designed studies are needed to give better estimates of the benefits and potential harms of antipsychotics compared with other treatments in people with symptoms of catatonia in schizophrenia spectrum disorders.
What are schizophrenia spectrum disorders and catatonic symptoms?
Schizophrenia and related spectrum disorders are serious mental disorders that present with a wide range of psychotic symptoms such as false ideas, hearing voices, and trouble thinking. Some people also have catatonic symptoms such as the inability to move or speak or repetitive movements over which they have little control. People with catatonic symptoms may be unable to interact or communicate with others.
How are schizophrenia spectrum disorders and catatonic symptoms treated?
Antipsychotic medicines are the standard treatment that improve many of the psychotic symptoms of schizophrenia spectrum disorders (such as false ideas or hearing voices), but are less effective for other symptoms (such as social withdrawal or problems with paying attention). Some evidence suggests that antipsychotic medicines may not be as effective in people with schizophrenia spectrum disorders who also have catatonic symptoms. Catatonic symptoms may also put such people at risk for side effects of antipsychotic medicines. Catatonic symptoms themselves are usually treated with sedating medicines or electroconvulsive therapy (a treatment in which brief seizures are caused by applying an electrical stimulus through electrodes on the head).
What did we want to find out?
We wanted to find out if any single antipsychotic medicine works better than other antipsychotics, other pharmacological agents, electroconvulsive therapy, other brain stimulation therapies, or placebo (an inactive or neutral treatment) for treating psychotic and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms.
What did we do?
We searched for studies that looked at any antipsychotic medicine compared with other antipsychotics, other pharmacological agents, electroconvulsive therapy, other brain stimulation therapies, or placebo in people with schizophrenia spectrum disorders with catatonic symptoms. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found one study that involved 14 people with schizophrenia spectrum disorders with catatonic symptoms that lasted three weeks and compared an antipsychotic medicine (risperidone) with electroconvulsive therapy. The study took place in India and received support from the National Institute of Mental Health and Neurosciences in Bangalore. Study authors found that both risperidone and electroconvulsive therapy improved symptoms of psychosis and catatonia, but that electroconvulsive therapy was better for the first three weeks of treatment. No unusual or dangerous side effects occurred with either treatment. Whilst both these treatments may reduce psychotic and catatonic symptoms, we are very uncertain of the results because of the small numbers of study participants and the short duration of the study. As a result, we cannot conclude that any antipsychotic is more or less safe and effective compared to other treatments. Better studies are needed to study the benefits and safety of antipsychotics to improve treatment of schizophrenia spectrum disorders with catatonic symptoms.
What are the limitations of the evidence?
We are not confident in the evidence because there are not enough studies to be certain about the results. The one included study was very small and brief, and the evidence did not cover all of the outcomes we were interested in.
How up-to-date is this evidence?
The evidence is current to September 2021.
We 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.
Whilst 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).
To 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.
We 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.
All 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.
Two 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.
Out 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.