Search

Background: Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to require hospitalisation and highly supervised care than those without the disorder. They also have an increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of treatment has been drug therapies and electroconvulsive therapy., Objectives: To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for catatonia in people with schizophrenia or other similar serious mental illnesses (SMIs)., Search Methods: We updated our previous search (28 February 2007) by searching the Cochrane Schizophrenia Group's Study-Based Register of Trials (9 November 2016; 6 February 2019). This register is compiled by systematic searches of major resources (including CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We also manually searched reference lists from studies selected by the search., Selection Criteria: All controlled clinical trials that randomised people who have schizophrenia or other similar SMI and experiencing catatonia to receive benzodiazepines or another relevant treatment. We included studies that met our inclusion criteria and reported usable data. We excluded those not meeting our inclusion criteria or those not reporting usable data. We contacted authors when we required further information; and if we received no response, we put those studies aside as 'awaiting assessment'., Data Collection and Analysis: Review authors extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We completed a 'Risk of bias' assessment for the included study and generated a 'Summary of findings' table using GRADE., Main Results: The searches found 130 citations, from which we could identify 22 possibly relevant studies. From these, we could only include one study. This study had a relatively small sample size of 17 participants who received lorazepam or oxazepam and were drug free for one week before the trial started. The only usable data reported by this study were clinically important change in symptoms of catatonia measured as 50% improvement on the Visual Analogue Scale (VAS). There was no difference in the numbers of participants showing a clinically important change in their catatonic symptoms (RR 0.95, 95% CI 0.42 to 2.16; participants = 17; studies = 1; very low quality evidence).No data were reported for other important outcomes of hospital stay, clinically important change in satisfaction with care, global state, adverse effects or general functioningWe did find a few studies meeting our inclusion criteria but they reported no usable data. We had to exclude these. Although poorly reported, these studies do illustrate that relevant studies have been undertaken - they are not impossible to design and conduct., Authors' Conclusions: Analysis of the results from this review, which was a head-to-head comparison of two benzodiazepine monotherapies, does not show a clear difference in effect. No data were available for benzodiazepines compared to placebo or standard care. The lack of usable data and very low quality of data available makes it impossible to draw firm conclusions and further studies with a high-quality methodology and reporting are required in order to determine more definitively the outcomes associated with benzodiazepine use in the clinical management of catatonia in persons with schizophrenia and other SMI.

Background: Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome., Objectives: To examine whether benzodiazepines, alone or in combination with other pharmacological agents, is an effective treatment for psychosis-induced aggression or agitation when compared with placebo, other pharmacological agents (alone or in combination) or non-pharmacological approaches., Search Methods: We searched the Cochrane Schizophrenia Group's register (January 2012, 20 August 2015 and 3 August 2016), inspected reference lists of included and excluded studies, and contacted authors of relevant studies., Selection Criteria: We included all randomised controlled trials (RCTs) comparing benzodiazepines alone or in combination with any antipsychotics, versus antipsychotics alone or in combination with any other antipsychotics, benzodiazepines or antihistamines, for people who were aggressive or agitated due to psychosis., Data Collection and Analysis: We reliably selected studies, quality assessed them and extracted data. For binary outcomes, we calculated standard estimates of risk ratio (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we calculated the mean difference (MD) between groups. If there was heterogeneity, this was explored using a random-effects model. We assessed risk of bias and created a 'Summary of findings' table using GRADE., Main Results: Twenty trials including 695 participants are now included in the review. The trials compared benzodiazepines or benzodiazepines plus an antipsychotic with placebo, antipsychotics, antihistamines, or a combination of these. The quality of evidence for the main outcomes was low or very low due to very small sample size of included studies and serious risk of bias (randomisation, allocation concealment and blinding were not well conducted in the included trials, 30% of trials (six out of 20) were supported by pharmaceutical institutes). There was no clear effect for most outcomes.Benzodiazepines versus placeboOne trial compared benzodiazepines with placebo. There was no difference in the number of participants sedated at 24 hours (very low quality evidence). However, for the outcome of global state, clearly more people receiving placebo showed no improvement in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). Benzodiazepines versus antipsychoticsWhen compared with haloperidol, there was no observed effect for benzodiazepines for sedation by 16 hours (n = 434, 8 RCTs, RR 1.13, 95% CI 0.83 to 1.54, low quality evidence). There was no difference in the number of participants who had not improved in the medium term (n = 188, 5 RCTs, RR 0.89, 95% CI 0.71 to 1.11, low quality evidence). However, one small study found fewer participants improved when receiving benzodiazepines compared with olanzapine (n = 150, 1 RCT, RR 1.84, 95% CI 1.06 to 3.18, very low quality evidence). People receiving benzodiazepines were less likely to experience extrapyramidal effects in the medium term compared to people receiving haloperidol (n = 233, 6 RCTs, RR 0.13, 95% CI 0.04 to 0.41, low quality evidence).Benzodiazepines versus combined antipsychotics/antihistaminesWhen benzodiazepine was compared with combined antipsychotics/antihistamines (haloperidol plus promethazine), there was a higher risk of no improvement in people receiving benzodiazepines in the medium term (n = 200, 1 RCT, RR 2.17, 95% CI 1.16 to 4.05, low quality evidence). However, for sedation, the results were controversial between two groups: lorazepam may lead to lower risk of sedation than combined antipsychotics/antihistamines (n = 200, 1 RCT, RR 0.91, 95% CI 0.84 to 0.98, low quality evidence); while, midazolam may lead to higher risk of sedation than combined antipsychotics/antihistamines (n = 200, 1 RCT, RR 1.13, 95% CI 1.04 to 1.23, low quality evidence).Other combinationsData comparing benzodiazepines plus antipsychotics versus benzodiazepines alone did not yield any results with clear differences; all were very low quality evidence. When comparing combined benzodiazepines/antipsychotics (all studies compared haloperidol) with the same antipsychotics alone (haloperidol), there was no difference between groups in improvement in the medium term (n = 185, 4 RCTs, RR 1.17, 95% CI 0.93 to 1.46, low quality evidence), but sedation was more likely in people who received the combination therapy (n = 172, 3 RCTs, RR 1.75, 95% CI 1.14 to 2.67,very low quality evidence). Only one study compared combined benzodiazepine/antipsychotics with antipsychotics; however, this study did not report our primary outcomes. One small study compared combined benzodiazepines/antipsychotics with combined antihistamines/antipsychotics. Results showed a higher risk of no clinical improvement (n = 60, 1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality evidence) and sedation status (n = 60, 1 RCT, RR 12.00, 95% CI 1.66 to 86.59, very low quality evidence) in the combined benzodiazepines/antipsychotics group., Authors' Conclusions: The evidence from RCTs for the use of benzodiazepines alone is not good. There were relatively few good data. Most trials were too small to highlight differences in either positive or negative effects. Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects. Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify. Much more high-quality research is still needed in this area.