Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

BACKGROUND: 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). OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

ANTECEDENTES: Aunque los antipsicóticos son la base del tratamiento de los trastornos del espectro de la esquizofrenia, ha habido numerosos intentos de identificar biomarcadores que puedan predecir la respuesta al tratamiento. Un posible marcador podrían ser las anomalías psicomotoras, incluidos los síntomas catatónicos. Los estudios más antiguos indican que los síntomas catatónicos predicen una respuesta deficiente al tratamiento, mientras que se han alegado informes anecdóticos de eventos adversos poco frecuentes contra los antipsicóticos. La eficacia y la seguridad de los antipsicóticos en el tratamiento de este subtipo de esquizofrenia rara vez se han estudiado en ensayos controlados aleatorizados (ECA). OBJETIVOS: Comparar los efectos de cualquier fármaco antipsicótico único con otro antipsicótico o con otros agentes farmacológicos, terapia electroconvulsiva (TEC), otras terapias de neuromodulación no farmacológicas (p. ej., estimulación magnética transcraneal) o placebo para el tratamiento de los síntomas positivos, negativos y catatónicos en personas que presentan trastornos del espectro de la esquizofrenia con síntomas catatónicos. MÉTODOS DE BÚSQUEDA: El 19 de septiembre de 2021 se realizaron búsquedas en el registro de ensayos basados en estudios del Grupo Cochrane de Esquizofrenia (Cochrane Schizophrenia Group), que se basa en CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, el registro ISRCTN y la ICTRP de la OMS. No hubo limitaciones de idioma, fecha, tipo de documento o estado de publicación para la inclusión de los registros en el registro. También se realizaron búsquedas manuales en las listas de referencias de los estudios incluidos y se estableció contacto con los autores de los estudios cuando fue pertinente. CRITERIOS DE SELECCIÓN: Todos los ECA que compararan cualquier fármaco antipsicótico único con otro antipsicótico o con otros agentes farmacológicos, TEC, otras terapias de neuromodulación no farmacológicas o placebo en personas que presentan trastornos del espectro de la esquizofrenia con síntomas catatónicos. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión inspeccionaron de forma independiente las citas, seleccionaron los estudios, extrajeron los datos y evaluaron la calidad de los estudios. Para los desenlaces binarios se planeó calcular las razones de riesgos y sus intervalos de confianza (IC) del 95% sobre la base de la intención de tratar. Para los desenlaces continuos se planeó calcular las diferencias de medias entre los grupos y sus IC del 95%. Se evaluó el riesgo de sesgo de los estudios incluidos y se creó una tabla de resumen de los hallazgos. Sin embargo, no se evaluó la certeza de la evidencia mediante el método GRADE porque no hubo evidencia cuantitativa en el estudio incluido. RESULTADOS PRINCIPALES: De los 53 informes identificados, un ECA que incluyó a 14 adultos hospitalizados con esquizofrenia y síntomas catatónicos cumplió con los criterios de inclusión de la revisión. El estudio, realizado en la India y que sólo duró tres semanas, comparó la risperidona con la TEC en personas que no respondieron a una prueba inicial con lorazepam. No se informaron datos utilizables sobre los desenlaces principales de eficacia de cambios clínicamente importantes en los síntomas positivos, negativos o catatónicos. Aunque ambos grupos del estudio mejoraron en las puntuaciones de catatonia en la Bush­Francis Catatonia Rating Scale (BFCRS), el grupo de TEC mostró una mejoría significativamente mayor en el desenlace a las tres semanas (media +/­ desviación estándar estimada; 0,68 +/­ 4,58; n = 8) que el grupo de risperidona (6,04 +/­ 4,58; n = 6; p = 0,035 de un análisis de varianza (ANOVA) de dos vías para medidas repetidas realizado originalmente en el ensayo). Asimismo, ambos grupos mejoraron en las puntuaciones de la Positive and Negative Syndrome Scale (PANSS) a las tres semanas, pero la TEC mostró una mejoría significativamente mayor en las puntuaciones de los síntomas positivos en comparación con la risperidona (p = 0,04). Sin embargo, los datos sobre las puntuaciones de la BFCRS en el grupo de TEC parecieron estar sesgados, y no se informaron las puntuaciones medias de la PANSS, lo que impidió realizar más análisis de los datos de la BFCRS y la PANSS según el protocolo. Aunque no se informaron casos de síndrome neuroléptico maligno, en tres casos del grupo de risperidona se notificaron síntomas extrapiramidales como un desenlace principal de seguridad. Por el contrario, en las personas que recibieron TEC se informó cefalea (n = 6), pérdida de memoria (n = 4) y una convulsión prolongada. Estos efectos adversos, que se evaluaron como específicos de los antipsicóticos y de la TEC, respectivamente, fueron los únicos efectos adversos notificados en el estudio. Sin embargo, el número exacto de participantes con eventos adversos no se informó claramente en ambos grupos, lo que impidió realizar un análisis más profundo. Los resultados de esta revisión se basaron en un solo estudio con un tamaño muestral muy pequeño, una duración corta del tratamiento, un riesgo de sesgo incierto o alto debido a métodos de asignación al azar poco claros, un posible desequilibrio en las características iniciales, datos sesgados y un informe selectivo. No se informaron datos sobre los desenlaces de funcionalidad general, estado global, calidad de vida ni uso de los servicios, así como tampoco datos sobre la fenomenología específica ni la duración de los síntomas catatónicos. CONCLUSIONES DE LOS AUTORES: Solo se encontró un ensayo pequeño, a corto plazo, que indica que la risperidona podría mejorar las puntuaciones de la escala de síntomas catatónicos y positivos entre las personas con trastornos del espectro de la esquizofrenia y síntomas catatónicos, pero que la TEC podría producir una mayor mejoría en las primeras tres semanas de tratamiento. Debido al pequeño tamaño muestral, las deficiencias metodológicas y la breve duración del estudio, así como el riesgo de sesgo, la evidencia de esta revisión es de calidad muy baja. No hay confianza en que estos efectos sean verdaderos, lo que limita cualquier conclusión que se pueda sacar a partir de la evidencia. No se notificaron casos de síndrome neuroléptico maligno, pero no se puede descartar el riesgo de este u otros eventos adversos poco frecuentes en muestras poblacionales más grandes. Aún se necesitan ensayos de calidad alta para diferenciar los tratamientos en las personas con síntomas de catatonia en los trastornos del espectro de la esquizofrenia. La falta de consenso sobre la psicopatología de la catatonia todavía es un obstáculo para definir los tratamientos para las personas con esquizofrenia. Un mejor conocimiento de la eficacia y la seguridad de los antipsicóticos podría aclarar el tratamiento de este subtipo único de esquizofrenia.

Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation).

BACKGROUND: People experiencing psychosis may become aggressive. Antipsychotics, such as aripiprazole in intramuscular form, can be used in such situations. OBJECTIVES: To evaluate the effects of intramuscular aripiprazole in the treatment of psychosis-induced aggression or agitation (rapid tranquillisation). SEARCH METHODS: On 11 December 2014 and 11 April 2017, we searched the Cochrane Schizophrenia Group's Study-based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. SELECTION CRITERIA: All randomised controlled trials (RCTs) that randomised people with psychosis-induced aggression or agitation to receive either intramuscular aripiprazole or another intramuscular intervention. DATA COLLECTION AND ANALYSIS: We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. We included studies that met our selection criteria. At least two review authors independently extracted data from the included studies. We chose a fixed-effect model. We analysed dichotomous data using risk ratio (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their CIs. We assessed risk of bias for included studies and used GRADE to create 'Summary of findings' tables. MAIN RESULTS: Searching found 63 records referring to 21 possible trials. We could only include three studies, all completed over the last decade, with 885 participants, of which 707 were included for quantitative analyses in this systematic review. Due to limited comparisons, small size of trials and a paucity of investigated and reported 'pragmatic' outcomes, evidence was mostly graded as low or very low quality. No trials reported useful data for one of our primary outcomes of tranquil or asleep by 30 minutes. Economic outcomes were also not reported in the trials.When compared with placebo, fewer people in the aripiprazole group needed additional injections compared to the placebo group (2 RCTs, n = 382, RR 0.69, 95% CI 0.56 to 0.85, very low-quality evidence). Clinically important improvement in agitation at two hours favoured the aripiprazole group (2 RCTs, n = 382, RR 1.50, 95% CI 1.17 to 1.92, very low-quality evidence). The numbers of non-responders after the first injection also favoured aripiprazole (1 RCT, n = 263, RR 0.49, 95% CI 0.34 to 0.71, low-quality evidence). Although no effect was found, more people in the aripiprazole compared to the placebo group experienced adverse effects (1 RCT, n = 117, RR 1.51, 95% CI 0.93 to 2.46, very low-quality evidence).Aripiprazole required more injections compared to haloperidol (2 RCTs, n = 477, RR 1.28, 95% CI 1.00 to 1.63, very low-quality evidence), with no significant difference in agitation (2 RCTs, n = 477, RR 0.94, 95% CI 0.80 to 1.11, very low-quality evidence), and similar non-responders after first injection (1 RCT, n = 360, RR 1.18, 95% CI 0.78 to 1.79, low-quality evidence). Aripiprazole and haloperidol did not differ when taking into account the overall number of people that experienced at least one adverse effect (1 RCT, n = 113, RR 0.91, 95% CI 0.61 to 1.35, very low-quality evidence).Compared to aripiprazole, olanzapine was better at reducing agitation (1 RCT, n = 80, RR 0.77, 95% CI 0.60 to 0.99, low-quality evidence) and had a more favourable effect on global state change scores (1 RCT, n = 80, MD 0.58, 95% CI 0.01 to 1.15, low-quality evidence), both at two hours. No differences were found in terms of experiencing at least one adverse effect during the 24 hours after treatment (1 RCT, n = 80, RR 0.75, 95% CI 0.45 to 1.24, very low-quality evidence). However, participants allocated to aripiprazole experienced less somnolence (1 RCT, n = 80, RR 0.25, 95% CI 0.08 to 0.82, low-quality evidence). AUTHORS' CONCLUSIONS: The available evidence is of poor quality but there is some evidence aripiprazole is effective compared to placebo and haloperidol, but not when compared to olanzapine. However, considering that evidence comes from only three studies, caution is required in generalising these results to real-world practice. This review firmly highlights the need for more high-quality trials on intramuscular aripiprazole in the management of people with acute aggression or agitation.

De-escalation techniques for psychosis-induced aggression or agitation.

BACKGROUND: Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user. OBJECTIVES: To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis. SEARCH METHODS: We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016). SELECTION CRITERIA: Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis. MAIN RESULTS: Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial. AUTHORS' CONCLUSIONS: Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.

Risperidone versus placebo for schizophrenia.

BACKGROUND: Risperidone is the first new-generation antipsychotic drug made available in the market in its generic form. OBJECTIVES: To determine the clinical effects, safety and cost-effectiveness of risperidone compared with placebo for treating schizophrenia. SEARCH METHODS: On 19th October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. We checked the references of all included studies and contacted industry and authors of included studies for relevant studies and data. SELECTION CRITERIA: Randomised clinical trials (RCTs) comparing oral risperidone with placebo treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, assessed the risk of bias of included studies and extracted data. For dichotomous data, we calculated the risk ratio (RR), and the 95% confidence interval (CI) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD) and the 95% CI. We created a 'Summary of findings table' using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: The review includes 15 studies (N = 2428). Risk of selection bias is unclear in most of the studies, especially concerning allocation concealment. Other areas of risk such as missing data and selective reporting also caused some concern, although not affected on the direction of effect of our primary outcome, as demonstrated by sensitivity analysis. Many of the included trials have industry sponsorship of involvement. Nonetheless, generally people in the risperidone group are more likely to achieve a significant clinical improvement in mental state (6 RCTs, N = 864, RR 0.64, CI 0.52 to 0.78, very low-quality evidence). The effect withstood, even when three studies with >50% attrition rate were removed from the analysis (3 RCTs, N = 589, RR 0.77, CI 0.67 to 0.88). Participants receiving placebo were less likely to have a clinically significant improvement on Clinical Global Impression scale (CGI) than those receiving risperidone (4 RCTs, N = 594, RR 0.69, CI 0.57 to 0.83, very low-quality evidence). Overall, the risperidone group was 31% less likely to leave early compared to placebo group (12 RCTs, N = 2261, RR 0.69, 95% CI 0.62 to 0.78, low-quality evidence), but Incidence of significant extrapyramidal side effect was more likely to occur in the risperidone group (7 RCTs, N = 1511, RR 1.56, 95% CI 1.13 to 2.15, very low-quality evidence).When risperidone and placebo were augmented with clozapine, there is no significant differences between groups for clinical response as defined by a less than 20% reduction in PANSS/BPRS scores (2 RCTs, N = 98, RR 1.15, 95% CI 0.93 to 1.42, low-quality evidence) and attrition (leaving the study early for any reason) (3 RCTs, N = 167, RR 1.13, 95% CI 0.53 to 2.42, low quality evidence). One study measured clinically significant responses using the CGI, no effect was evident (1 RCT, N = 68, RR 1.12 95% CI 0.87 to 1.44, low quality evidence). No data were available for extrapyramidal adverse effects. AUTHORS' CONCLUSIONS: Based on low quality evidence, risperidone appears to be benefitial in improving mental state compared with placebo, but it also causes more adverse events. Eight out of the 15 included trials were funded by pharmaceutical companies. The currently available evidence isvery low to low quality.

Zuclopenthixol versus placebo for schizophrenia.

BACKGROUND: Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). Although it has been in common use for many years no previous systematic review of its efficacy compared to placebo in schizophrenia has been undertaken. OBJECTIVES: To evaluate the effectiveness of all formulations of zuclopenthixol when compared with a placebo in schizophrenia. SEARCH METHODS: On 6 November 2013 and 20 October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. We also checked the references of all included studies and contacted authors of included studies for relevant studies and data. SELECTION CRITERIA: We included all randomised controlled trials comparing zuclopenthixol of any form with placebo for treatment of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted and cross-checked data independently. We identified only a small number of studies so we cross checked all studies. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. Where possible we converted continuous outcomes into dichotomous outcomes. When this was not possible we used mean differences (MD) for continuous variables. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. MAIN RESULTS: Only two studies, with a total of 65 participants, were eligible for inclusion in the review. Overall the quality of the two studies was low, with small study populations and significant sources of bias, so we were not able to use all the data in our comparisons. . The studies were old from 1968 and 1972, and would be unlikely to pass modern peer review standard. We were only able to find short-term data and only trials randomising zuclopenthixol dihydrochloride. We also hoped to identify data for zuclopenthixol acetate versus placebo and zuclopenthixol decanoate versus placebo comparisons. We were unable to identify any studies that included data on these two fairly widely used drugs.For our primary outcome of interest, clinically significant improvement, we found one study that provided useable data. Global state measured by clinical global impression scale (CGI) improvement showed different ratings when assessed by a psychiatrist or a nurse.The psychiatrist scores failed to achieve statistical significance, however when assessed by nursing staff, the difference favouring zuclopenthixol did reach statistical significance (1 RCT n = 29, RR 2.57 95% CI 1.06 to 6.20, very low quality data). There was also evidence of increased sedation with those treated with zuclopenthixol when compared with placebo (1 RCT n = 29, RR 4.67 95% CI 1.23 to 17.68, very low quality data). 'Leaving the study early' data were equivocal. No useable data were available for outcomes such as relapse, mental state, death, quality of life, service use or economic costs. AUTHORS' CONCLUSIONS: For people with schizophrenia this review shows that zuclopenthixol dihydrochloride may help with the symptoms of schizophrenia. The review provides some trial evidence that, if taking zuclopenthixol dihydrochloride, people may experience some adverse effects and sedation compared with placebo. However this evidence is of very low quality and with some significant sources of bias. There are no data for zuclopenthixol decanoate or zuclopenthixol acetate.For clinicians, the available trial data on the absolute effectiveness of zuclopenthixol dihydrochloride do support its use but the limited nature of the data and significant sources of bias make conclusions hard to draw. Zuclopenthixol in all three forms is a commonly used antipsychotic and it is disappointing that there are so few data regarding its use.

Psychoeducation (brief) for people with serious mental illness.

BACKGROUND: Those with serious/severe mental illness, especially schizophrenia and schizophrenic-like disorders, often have little to no insight regarding the presence of their illness. Psychoeducation may be defined as the education of a person with a psychiatric disorder regarding the symptoms, treatments, and prognosis of that illness. Brief psychoeducation is a short period of psychoeducation; although what constitutes 'brief psychoeducation' can vary. A previous systematic review has shown that the median length of psychoeducation is around 12 weeks. In this current systematic review, we defined 'brief psychoeducation' as programmes of 10 sessions or less. OBJECTIVES: To assess the efficacy of brief psychoeducational interventions as a means of helping severely mentally ill people when added to 'standard' care, compared with the efficacy of standard care alone.The secondary objective is to investigate whether there is evidence that a particular kind (individual/ family/group) of brief psychoeducational intervention is superior to others. SEARCH METHODS: We searched the Cochrane Schizophrenia Group register September 2013 using the phrase:[*Psychoeducat* in interventions of STUDY]. Reference lists of included studies were also inspected for further relevant studies. We also contacted authors of included study for further information regarding further data or details of any unpublished trials. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) comparing brief psychoeducation with any other intervention for treatment of people with severe mental illness. If a trial was described as 'double blind' but implied randomisation, we entered such trials in a sensitivity analysis. DATA COLLECTION AND ANALYSIS: At least two review authors extracted data independently from included papers. We contacted authors of trials for additional and missing data. We calculated risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data. For continuous data, we calculated the mean difference (MD), again with 95% CIs. We used a fixed-effect model for data synthesis, and also assessed data using a random-effects model in a sensitivity analysis. We assessed risk of bias for each included study and created 'Summary of findings' tables using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: We included twenty studies with a total number of 2337 participants in this review. Nineteen studies compared brief psychoeducation with routine care or conventional delivery of information. One study compared brief psychoeducation with cognitive behavior therapy.Participants receiving brief psychoeducation were less likely to be non-compliant with medication than those receiving routine care in the short term (n = 448, 3 RCTs, RR 0.63 CI 0.41 to 0.96, moderate quality evidence) and medium term (n = 118, 1 RCT, RR 0.17 CI 0.05 to 0.54, low quality evidence).Compliance with follow-up was similar between the two groups in the short term (n = 30, 1 RCT, RR 1.00, CI 0.24 to 4.18), medium term (n = 322, 4 RCTs, RR 0.74 CI 0.50 to 1.09) and long term (n = 386, 2 RCTs, RR 1.19, CI 0.83 to 1.72).Relapse rates were significantly lower amongst participants receiving brief psychoeducation than those receiving routine care in the medium term (n = 406, RR 0.70 CI 0.52 to 0.93, moderate quality evidence), but not in the long term.Data from a few individual studies supported that brief psychoeducation: i) can improve the long-term global state (n = 59, 1 RCT, MD -6.70 CI -13.38 to -0.02, very low quality evidence); ii) promote improved mental state in short term (n = 60, 1 RCT, MD -2.70 CI -4.84 to -0.56,low quality evidence) and medium term; iii) can lower the incidence and severity of anxiety and depression.Social function such as rehabilitation status (n = 118, 1 RCT, MD -13.68 CI -14.85 to -12.51, low quality evidence) and social disability (n = 118, 1 RCT, MD -1.96 CI -2.09 to -1.83, low quality evidence) were also improved in the brief psychoeducation group. There was no difference found in quality of life as measured by GQOLI-74 in the short term (n = 62, 1 RCT, MD 0.63 CI -0.79 to 2.05, low quality evidence), nor the death rate in either groups (n = 154, 2 RCTs, RR 0.99, CI 0.15 to 6.65, low quality evidence). AUTHORS' CONCLUSIONS: Based on mainly low to very low quality evidence from a limited number of studies, brief psychoeducation of any form appears to reduce relapse in the medium term, and promote medication compliance in the short term. A brief psychoeducational approach could potentially be effective, but further large, high-quality studies are needed to either confirm or refute the use of this approach.

Acetylcholinesterase inhibitors for schizophrenia.

BACKGROUND: Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial effectiveness of the antipsychotics on cognitive and negative symptoms, the search is on for drugs that may improve these domains of functioning for someone suffering from schizophrenia. Acetylcholinesterase inhibitors have long been in use for treating cognitive symptoms of dementia. OBJECTIVES: The aim of the review was to evaluate the clinical effects, safety and cost effectiveness of acetylcholinesterase inhibitors for treating people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Register (February 2009), and inspected the references of all identified studies for further trials. SELECTION CRITERIA: We included all clinical randomised trials comparing acetylcholinesterase inhibitors with antipsychotics or placebo either alone, or in combination, for schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat (ITT) basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model. MAIN RESULTS: The acetylcholinesterase inhibitor plus antipsychotic showed benefit over antipsychotic and placebo in the following outcomes.1. Mental state - PANSS negative symptoms average end point score (2 RCTs, n = 31, MD -1.69 95% CI -2.80 to -0.57), PANSS General Psychopathology average end point score (2 RCTs, n = 31, MD -3.86 95% CI -5.40 to -2.32), and improvement in depressive symptoms showed at least by one short-term study as measured by CDSS scale (data skewed).2. Cognitive domains - attention, (1 RCT, n = 73, MD 1.20 95% CI 0.14 to 2.26), visual memory (2 RCTs, n = 48 , MD 1.90 95% CI 0.52 to 3.28), verbal memory and language (3 RCTs, n = 42, MD 3.46 95% CI 0.67 to 6.26) and executive functioning (1 RCT, n = 24, MD 17.10 95% CI 0.70 to 33.50).3. Tolerability - EPSE: AIMS, (1 RCT, n = 35, MD 1.50 95% CI 1.04 to 1.96).No difference was noted between the two arms in other outcomes. The overall rate of participants leaving studies early was low (13.6 %) and showed no clear difference between the two groups. AUTHORS' CONCLUSIONS: The results seem to favour the use of acetylcholinesterase inhibitors in combination with antipsychotics on a few domains of mental state and cognition, but because of the various limitations in the studies as mentioned in the main text, the evidence is weak. This review highlights the need for large, independent, well designed, conducted and reported pragmatic randomised studies.

Levomepromazine for schizophrenia.

BACKGROUND: Levomepromazine is an 'older' typical antipsychotic medication licensed for use in schizophrenia but sparingly prescribed in the United Kingdom. OBJECTIVES: To determine the clinical effects and safety of levomepromazine compared with placebo or antipsychotic medications for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (December 2008) which is based on regular searches of, amongst others, BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information. SELECTION CRITERIA: All randomised trials comparing levomepromazine with placebo or other antipsychotics for schizophrenia and schizophreniform psychoses were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently. For dichotomous outcomes, we calculated relative risk (RR) (random-effects model), 95% confidence intervals (CI) and, where appropriate, number needed to treat (NNT) was calculated. We avoided the use of number needed to harm (NNH), as an alternative we used number needed to treat for an additional beneficial outcome (NNTB) and number needed to treat for an additional harmful outcome (NNTH) to indicate the direction of effect. For continuous outcomes, we calculated weighted mean differences (WMD). MAIN RESULTS: The review currently includes 4 RCTs with 192 participants. For our primary outcome of leaving the study early, levomepromazine was not significantly different compared with other antipsychotics. The levomepromazine arm was significantly better on CGI severity compared with chlorpromazine (n=38, 1 RCT, WMD -0.80 CI -1.51 to -0.09). Risperidone was better for CGI endpoint scores (n=42, 1 RCT, RR 2.33 CI 1.11 to 4.89, NNT 3 CI 2 to 10) compared with levomepromazine. Recipients given levomepromazine had a better BPRS endpoint score (n=38, 1 RCT, WMD -9.00, CI -17.46 to -0.54) and PANSS total score (n=38, 1 RCT, WMD -15.90, CI -30.30 to -1.50) than chlorpromazine. Risperidone recipients noticed a significant difference for the outcome 'at least 20% reduction' on BPRS endpoint score (n=42, 1 RCT, RR 3.33 CI 1.07 to 10.42, NNT 3 CI 2 to 14) compared with levomepromazine. Levomepromazine caused less tremor (n=41, 1 RCT RR 0.12 CI 0.02 to 0.87 NNTB 3 CI 2 to 8), less antiparkinsonian medication administration (n=79, 2 RCTs, RR 0.39 CI 0.17 to 0.90, NNTB 5, CI 2 to 21) compared with haloperidol. Levomepromazine caused less akathisia compared with chlorpromazine, but more hypotension compared with risperidone (n=42, 1 RCT, RR 2.50 CI 1.21 to 5.18, NNTH 3, CI 2 to 7). Dizziness was common with levomepromazine compared with other antipsychotic medications. AUTHORS' CONCLUSIONS: Available data does not enable us to confidently comment on the effectiveness of levomepromazine for schizophrenia. Larger, more robust, studies comparing levomepromazine with other antipsychotics including clozapine are much needed.

Risperidone versus placebo for schizophrenia.

BACKGROUND: Risperidone is the first new generation antipsychotic drug made available in the market in its generic form. OBJECTIVES: To examine the clinical effects of oral risperidone for people with schizophrenia and schizophrenia-like psychoses in comparison with placebo. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (February 2008), references of all included studies, and contacted industry and authors of included studies for relevant studies and data. SELECTION CRITERIA: Randomised clinical trials comparing oral risperidone with placebo treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and assessed the quality of results and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: One study (n=599) compared risperidone against placebo but the attrition rate was 60% over a period of six weeks rendering most of the efficacy and global improvement data unusable. The attrition rate was higher for placebo compared with risperidone (n=1363, 10 RCTs, RR 0.70 CI 0.57 to 0.86, NNT 13 CI 9 to 29) and less participants left the trial in the risperidone arm due to lack of efficacy (n=888, 5 RCTs, RR 0.38 CI 0.20 to 0.73, NNT 7 CI 5 to 15). Risperidone was no better than placebo on the CGI global score (n=397, 3 RCTs, RR 0.80 CI 0.55 to 1.15) but significantly more number of participants in risperidone arm had more than 20% reduction in their BPRS/PANSS score (n=856, 7 RCTs, RR 0.43 CI 0.32 to 0.58, NNT 7 CI 6 to 10). Data became considerably more homogeneous (and positive) when the one study independent of industry funding was removed (I(2) 75% to 55%). Despite poor reporting, it is clear that around 24% of all participants receiving either risperidone or placebo developed some form of extrapyramidal effects (n=723, 5 RCTs, RR 1.40 CI 0.93 to 2.10). Three people on risperidone had prolonged QTc (n=198, 1 RCT, RR 7.5 CI 0.4 to 144), more on risperidone gained weight (n=303, 2 RCTs, RR 5.14 CI 1.79 to 14.73, NNH 10 CI 3 to 51) and had a raised prolactin (n=323, 2 RCTs, RR 12.54 CI 5.11 to 30.79, NNH 3 CI 2 to 5). Fewer in the risperidone arm needed an additional psychotropic during the trial period (n=186, 1 RCT, RR 0.62 CI 0.45 to 0.85, NNT 10 CI 7 to 28). AUTHORS' CONCLUSIONS: Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are limited, poorly reported and probably biased in favour of risperidone. The margin of improvement chosen by the researchers as their outcome may not be clinically meaningful. Even after so much use of this drug, we feel that further independent trials can be justified.