The Acceptability and Usability of Digital Health Interventions for Adults With Depression, Anxiety, and Somatoform Disorders: Qualitative Systematic Review and Meta-Synthesis.

BACKGROUND: The prevalence of mental health disorders continues to rise, with almost 4% of the world population having an anxiety disorder and almost 3.5% having depression in 2017. Despite the high prevalence, only one-third of people with depression or anxiety receive treatment. Over the last decade, the use of digital health interventions (DHIs) has risen rapidly as a means of accessing mental health care and continues to increase. Although there is evidence supporting the effectiveness of DHIs for the treatment of mental health conditions, little is known about what aspects are valued by users and how they might be improved. OBJECTIVE: This systematic review aimed to identify, appraise, and synthesize the qualitative literature available on service users' views and experiences regarding the acceptability and usability of DHIs for depression, anxiety, and somatoform disorders. METHODS: A systematic search strategy was developed, and searches were run in 7 electronic databases. Qualitative and mixed methods studies published in English were included. A meta-synthesis was used to interpret and synthesize the findings from the included studies. RESULTS: A total of 24 studies were included in the meta-synthesis, and 3 key themes emerged with descriptive subthemes. The 3 key themes were initial motivations and approaches to DHIs, personalization of treatment, and the value of receiving personal support in DHIs. The meta-synthesis suggests that participants' initial beliefs about DHIs can have an important effect on their engagement with these types of interventions. Personal support was valued very highly as a major component of the success of DHIs. The main reason for this was the way it enabled individual personalization of care. CONCLUSIONS: Findings from the systematic review have implications for the design of future DHIs to improve uptake, retention, and outcomes in DHIs for depression, anxiety, and somatoform disorders. DHIs need to be personalized to the specific needs of the individual. Future research should explore whether the findings could be generalized to other health conditions.

Pharmacy-based management for depression in adults.

BACKGROUND: It is common for peoples not to take antidepressant medication as prescribed, with around 50% of people likely to prematurely discontinue taking their medication after six months. Community pharmacists may be well placed to have a role in antidepressant management because of their unique pharmacotherapeutic knowledge and ease of access for people. Pharmacists are in an ideal position to offer proactive interventions to people with depression or depressive symptoms. However, the effectiveness and acceptability of existing pharmacist-based interventions is not yet well understood. The degree to which a pharmacy-based management approach might be beneficial, acceptable to people, and effective as part of the overall management for those with depression is, to date, unclear. A systematic review of randomised controlled trials (RCTs) will help answer these questions and add important knowledge to the currently sparse evidence base. OBJECTIVES: To examine the effects of pharmacy-based management interventions compared with active control (e.g. patient information materials or any other active intervention delivered by someone other than the pharmacist or the pharmacy team), waiting list, or treatment as usual (e.g. standard pharmacist advice or antidepressant education, signposting to support available in primary care services, brief medication counselling, and/or (self-)monitoring of medication adherence offered by a healthcare professional outside the pharmacy team) at improving depression outcomes in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR) to June 2016; the Cochrane Library (Issue 11, 2018); and Ovid MEDLINE, Embase, and PsycINFO to December 2018. We searched theses and dissertation databases and international trial registers for unpublished/ongoing trials. We applied no restrictions on date, language, or publication status to the searches.  SELECTION CRITERIA: We included all RCTs and cluster-RCTs where a pharmacy-based intervention was compared with treatment as usual, waiting list, or an alternative intervention in the management of depression in adults over 16 years of age. Eligible studies had to report at least one of the following outcomes at any time point: depression symptom change, acceptability of the intervention, diagnosis of depression, non-adherence to medication, frequency of primary care appointments, quality of life, social functioning, or adverse events.  DATA COLLECTION AND ANALYSIS: Two authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment (including GRADE). We discussed disagreements within the team until we reached consensus. Where data did not allow meta-analyses, we synthesised results narratively.  MAIN RESULTS: Twelve studies (2215 participants) met the inclusion criteria and compared pharmacy-based management with treatment as usual. Two studies (291 participants) also included an active control (both used patient information leaflets providing information about the prescribed antidepressant). Neither of these studies reported depression symptom change. A narrative synthesis of results on acceptability of the intervention was inconclusive, with one study reporting better acceptability of pharmacy-based management and the other better acceptability of the active control. One study reported that participants in the pharmacy-based management group had better medication adherence than the control participants. One study reported adverse events with no difference between groups. The studies reported no other outcomes. Meta-analyses comparing pharmacy-based management with treatment as usual showed no evidence of a difference in the effect of the intervention on depression symptom change (dichotomous data; improvement in symptoms yes/no: risk ratio (RR), 0.95, 95% confidence interval (CI) 0.86 to 1.05; 4 RCTs, 475 participants; moderate-quality evidence; continuous data: standard mean difference (SMD) -0.04, 95% CI -0.19 to 0.10; 5 RCTs, 718 participants; high-certainty evidence), or acceptability of the intervention (RR 1.09, 95% CI 0.81 to 1.45; 12 RCTs, 2072 participants; moderate-certainty evidence). The risk of non-adherence was reduced in participants receiving pharmacy-based management (RR 0.73, 95% CI 0.61 to 0.87; 6 RCTs, 911 participants; high-certainty evidence). We were unable to meta-analyse data on diagnosis of depression, frequency of primary care appointments, quality of life, or social functioning. AUTHORS' CONCLUSIONS: We found no evidence of a difference between pharmacy-based management for depression in adults compared with treatment as usual in facilitating depression symptom change. Based on numbers of participants leaving the trials early, there may be no difference in acceptability between pharmacy-based management and controls. However, there was uncertainty due to the low-certainty evidence.

Fluphenazine (oral) versus placebo for schizophrenia.

BACKGROUND: Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades. OBJECTIVES: To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (23 July 2013, 23 December 2014, 9 November 2016 and 28 December 2017 ) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects. DATA COLLECTION AND ANALYSIS: For the effects of interventions, a review team inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. Economic studies were searched and reliably selected by an economic review team to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary. MAIN RESULTS: From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). For economic outcomes, we valued outcomes for relapse and presented them in additional tables. AUTHORS' CONCLUSIONS: The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.

Benzodiazepines for psychosis-induced aggression or agitation.

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.

Elective delivery versus expectant management for pre-eclampsia: a meta-analysis of RCTs.

PURPOSE: To evaluate the effectiveness and safety of elective delivery versus expectant management for women with pre-eclampsia (PE) and to assess neonatal outcomes before and after 34 weeks gestation. METHODS: We searched Biomed Central, CINAHL, Cochrane Library, Embase, HMIC, Medline, and WHO trial registry, British Nursing Index, ClinicalTrials.gov, Current Controlled Trials, and Web of Science on 16 March, 2016. 1704 citations were identified. Randomised controlled trials comparing elective delivery with expectant management for women with PE were included. Seven studies were included (n = 1501). There were no maternal deaths. RESULTS: Elective delivery lowered incidence of complications in women with PE or hypertension greater than 34 weeks gestation (n = 756; RR, 0.64; 95% CI 0.51-0.80). For women with severe PE less than 34 weeks gestation, elective delivery lowered the incidence of placental abruption (n = 483, 5 RCTs; RR, 0.43; 95% CI 0.19-0.98). For women with PE or hypertension greater than 34 weeks gestation, elective delivery also reduced the need for antihypertensive drug therapy. The need for ventilatory support and the risk of developing neonatal intraventricular hemorrhage or hypoxic ischemic encephalopathy may be increased in infants whose mothers undergo elective delivery for severe PE at less than 34 weeks gestation. However, there was no relevant evidence for women with severe PE over 34 weeks. CONCLUSIONS: In women with PE or gestational hypertension beyond 34 weeks gestation, elective delivery can decrease the incidence of complications, severe hypertension and the need for antihypertensive drug therapy. Elective delivery can also lower the risk of placental abruption in women before 34 weeks gestation with severe PE, however, may be associated with increased risk of neonatal complications.

Risperidone (depot) for schizophrenia.

BACKGROUND: Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. OBJECTIVES: To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies. SELECTION CRITERIA: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence). AUTHORS' CONCLUSIONS: Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.

Fluphenazine (oral) versus atypical antipsychotics for schizophrenia.

BACKGROUND: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. OBJECTIVES: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. SEARCH METHODS: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. DATA COLLECTION AND ANALYSIS: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. MAIN RESULTS: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness. AUTHORS' CONCLUSIONS: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

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.

Chlorpromazine versus atypical antipsychotic drugs for schizophrenia.

BACKGROUND: Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a 'gold standard' to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources. OBJECTIVES: To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach. MAIN RESULTS: This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental state (4 RCTs, N = 245; MD 3.21, 95% CI -0.62 to 7.05,very low quality evidence). There were significantly more extrapyramidal symptoms experienced amongst people receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very low quality evidence). Quality of life ratings using the general quality of life interview (GQOLI) - physical health subscale were more favourable with people receiving olanzapine (1 RCT, N = 61; MD -10.10, 95% CI -13.93 to -6.27, very low quality evidence). There was no difference between groups for people leaving the studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality evidence). 2. Chlorpromazine versus risperidoneIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low quality of evidence), nor in average endpoint score using the BPRS for mental state 4 RCTs, N = 247; MD 0.90, 95% CI -3.49 to 5.28, very low quality evidence), or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI 0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL scale were significantly more favourable with people receiving risperidone (1 RCT, N = 100; MD -14.2, 95% CI -20.50 to -7.90, very low quality evidence). There was no difference between groups for people leaving the studies early (one RCT, N = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine versus quetiapineIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or quetiapine (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD -0.18, 95% CI -1.23 to 0.88, very low quality evidence). Quality of life ratings using the GQOL1-74 scale were significantly more favourable with people receiving quetiapine (1 RCT, N = 59; MD -6.49, 95% CI -11.30 to -1.68, very low quality evidence). Significantly more people receiving chlorpromazine experienced extrapyramidal adverse effects (8 RCTs, N = 644; RR 8.03, 95% CI 4.78 to 13.51, low quality of evidence). There was no difference between groups for people leaving the studies early in the short term (12 RCTs, N = 1223; RR 1.04, 95% CI 0.77 to 1.41,moderate quality evidence). AUTHORS' CONCLUSIONS: Most included trials included inpatients from hospitals in China. Therefore the results of this Cochrane review are more applicable to the Chinese population. Mostincluded trials were short term studies, therefore we cannot comment on the medium and long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy evidence suggests chlorpromazine causes more extrapyramidal adverse effects. However, all studiesused varying dose ranges, and higher doses would be expected to be associated with more adverse events.

Perphenazine for schizophrenia.

BACKGROUND: Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan. OBJECTIVES: To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We updated our original search using the Cochrane Schizophrenia Group's register (September 2013), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials. SELECTION CRITERIA: We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine. DATA COLLECTION AND ANALYSIS: Two review authors independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow-up was greater than 50% we considered results as 'prone to bias'. For dichotomous data, we calculated risk ratios (RR) and for continuous data we calculated mean differences (MD), both with the 95% confidence intervals (CI). We assessed quality of data using the GRADE (Grading of Recommendations Assessment, Development and Evaluationtool) and assessed risk of bias for included studies. MAIN RESULTS: Thirty-one studies fulfilled the inclusion criteria, with a total of 4662 participants (of which 4522 were receiving the drugs relevant to our comparison) and presented data that could be used for at least one comparison. The trial centres were located in Europe (especially Scandinavia), Japan and Northern America.When comparing perphenazine with placebo, for our primary outcome of clinical response, results favoured perphenazine with significantly more people receiving placebo rated as either 'no better or deterioration' for global state than people receiving perphenazine (1 RCT, n = 61 RR 0.32 CI 0.13 to 0.78, very low quality evidence). More people receiving placebo relapsed, although not a statistically significant number (1 RCT, n = 48, RR 0.14 CI 0.02 to 1.07, very low quality evidence). Death was not reported in the perphenazine versus placebo comparison. Experiences of dystonia were equivocal between groups (1 RCT, n = 48, RR 1.00 CI 0.07 to 15.08, very low quality evidence); other outcomes not reported in this comparison include serious adverse events, economic outcomes, and service use and hospitalisation.For the comparison of perphenazine versus any other antipsychotic drugs, no real differences in effect between the drugs were found. There was no significant difference between groups for those considered 'no better or deterioration' (17 RCTs, n = 1879, RR 1.04 CI 0.91 to 1.17, very low quality evidence). For mental state outcome of 'no effect' of the study drug, there was again no significant difference between groups (4 RCTs, n = 383, RR 1.24 CI 0.61 to 2.52, very low quality evidence). Death was not reported in any of the included studies. There was no significant difference in rates of dystonia with perphenazine versus any other antipsychotic drugs (4 RCTs, n = 416, RR 1.36 CI 0.23 to 8.16, very low quality evidence), nor was there a significant difference between groups for serious adverse events (2 RCTs, n = 1760, RR 0.98 CI 0.68 to 1.41, very low quality evidence). AUTHORS' CONCLUSIONS: Although perphenazine has been used in randomised trials for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes in this review were of very low quality evidence. At best we can say that perphenazine showed similar effects and adverse events as several of the other antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.

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.

Sulpiride versus placebo for schizophrenia.

BACKGROUND: Sulpiride is a relatively old antipsychotic drug reputed to have a low incidence of adverse effects and an effect on the negative symptoms of schizophrenia. This relatively inexpensive antipsychotic drug has a similar neuropharmacological profile to several novel atypical drugs. OBJECTIVES: To evaluate the effects of sulpiride for schizophrenia and other similar serious mental illnesses in comparison with placebo. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (September 2008) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. We updated this search 7th November 2012. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing sulpiride with placebo for people with schizophrenia and other types of schizophrenia-like psychoses. The primary outcome of interest was clinically significant response in global state. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected and quality-assessed these. IMO and JW extracted data. We analysed dichotomous data using a random-effects risk ratio (RR) and estimated the 95% confidence interval (CI) around this. Where continuous data were included, we analysed these data using random-effects mean difference (MD) with a 95% CI. MAIN RESULTS: No new trials were included from the 2012 search. The review still includes two trials of short duration comparing sulpiride with placebo (total n = 113). No study reported our primary outcome of interest of 'global state: clinically significant response', nor our secondary outcomes of interest of 'quality of life', 'severe adverse effects', and 'safety assessments'. As regards mental state, there were no clear differences between groups for either positive or negative symptoms; measured positive symptoms using the Manchester scale were skewed and therefore not included in meta-analysis (n = 18, 1 RCT, very low quality evidence). Measured negative symptoms using the Manchester scale also demonstrated no clear difference (n = 18, 1 RCT, MD -3.0 CI -1.66 to 1.06, very low quality evidence). Few people left these studies by three months (n = 113, 2 RCTs, RR 1.00 CI 0.25 to 4.00). One subscore finding demonstrated a significant improvement in social behaviour using the Current Behaviour Schedule (CBS) when receiving placebo (n = 18, 1 RCT, MD -2.90 CI -5.60 to -0.20). There were no data for many important outcomes such as global outcomes, service use or adverse effects. AUTHORS' CONCLUSIONS: Sulpiride may be an effective antipsychotic drug but evidence of its superiority over placebo from randomised trials is very limited. Practice will have to use evidence from sources other than trials until better evidence is generated.

Family intervention (brief) for schizophrenia.

BACKGROUND: Supportive, positive family environments have been shown to improve outcomes for patients with schizophrenia in contrast with family environments that express high levels of criticism, hostility, or over-involvement, which have poorer outcomes and have more frequent relapses. Forms of psychosocial intervention, designed to promote positive environments and reduce these levels of expressed emotions within families, are now widely used. OBJECTIVES: To assess the effects of brief family interventions for people with schizophrenia or schizophrenia-like conditions. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2012), which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted authors of trials for additional information. SELECTION CRITERIA: All relevant randomised studies that compared brief family-oriented psychosocial interventions with standard care, focusing on families of people with schizophrenia or schizoaffective disorder were selected. 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). For continuous outcomes, we estimated a mean difference (MD) between groups and their 95% CIs. We used GRADE to assess quality of evidence for main outcomes of interest and created a 'Summary of findings' table. We assessed risk of bias for included studies. MAIN RESULTS: Four studies randomising 163 people could be included in the review. It is not clear if brief family intervention reduces the utilisation of health services by patients, as most results are equivocal at long term and only one study reported data for the primary outcomes of interest of hospital admission (n = 30, 1 RCT, RR 0.50, 95% CI 0.22 to 1.11, very low quality evidence). Data for relapse are also equivocal by medium term (n = 40, 1 RCT, RR 0.50, 95% CI 0.10 to 2.43, low quality evidence). However, data for the family outcome of understanding of family member significantly favoured brief family intervention (n = 70, 1 RCT, MD 14.90, 95% CI 7.20 to 22.60, very low quality evidence). No study reported data for other outcomes of interest including days in hospital; adverse events; medication compliance; quality of life or satisfaction with care; or any economic outcomes. AUTHORS' CONCLUSIONS: The findings of this review are not outstanding due to the size and quality of studies providing data; the analysed outcomes were also minimal, with no meta-analysis possible. All outcomes in the 'Summary of findings' table were rated low or very low quality evidence. However, the importance of brief family intervention should not be dismissed outright, with the present state of demand and resources available. The designs of such brief interventions could be modified to be more effective with larger studies, which may then have enough power to inform clinical practice.

Length of hospitalisation for people with severe mental illness.

BACKGROUND: In high-income countries, over the last three decades, the length of hospital stays for people with serious mental illness has reduced drastically although considerable variation remains. In lower-income countries this variation may be greater. Some argue that reduction in hospital stay leads to 'revolving door admissions' and worsening mental health outcomes despite apparent cost savings, whilst others suggest longer stays may be more harmful by institutionalising people to hospital care. OBJECTIVES: To evaluate the effect of short stay/brief admission hospital care with long stay/standard in-patient care in people with serious mental illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's register of trials, July 2007 and updated this search in May 2012. SELECTION CRITERIA: We included all randomised controlled trials comparing planned short/brief with long/standard hospital stays for people with serious mental illnesses. 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 basis based using a fixed-effect model. For continuous data, had we identified such data, we planned to calculate fixed-effect mean differences (MD). We assessed risk of bias for included studies and rated quality of evidence using GRADE. MAIN RESULTS: We included six relevant trials undertaken between 1969 and 1980. We found no significant difference in death (n = 175, 1 RCT, RR in the longer term 0.42, CI 0.10 to 1.83, very low quality evidence). In the long term, there was no difference in improvement of mental state (n = 61, 1 RCT, RR 3.39, CI 0.76 to 15.02, very low quality evidence). There was no difference in readmission to hospital (n = 651, 4 RCTs, RR by the long term 1.26, CI 1.00 to 1.57, low quality evidence). Data for leaving the study prematurely by the longer term showed no difference (n = 229, 2 RCTs, (RR 0.77, CI 0.34 to 1.77, low quality evidence). There was a significant difference favouring short stay (P = 0.01) in numbers of participants with delayed discharge from hospital exceeding the time planned in study (n = 404, 3 RCTs, RR in the longer term 0.54, CI 0.33 to 0.88, low quality evidence). There was no difference in numbers of participants lost to follow-up (n = 404, 3 RCTs, RR by the longer term 1.07, CI 0.70 to 1.62, low quality evidence). Finally, there was a significant difference favouring short-stay hospitalisation for social functioning, including unemployment, unable to housekeep, or unknown employment status (n = 330, 2 RCTs, RR by longer term 0.61, CI 0.50 to 0.76, very low quality evidence). AUTHORS' CONCLUSIONS: The effects of hospital care and the length of stay is important for mental health policy. We found limited low and very low quality data which were all over 30 years old. Outcomes from these studies do suggest that a planned short-stay policy does not encourage a 'revolving door' pattern of admission and disjointed care for people with serious mental illness. More large, well-designed and reported trials are justified especially where a short-stay policy is not routine care.

Horticultural therapy for schizophrenia.

BACKGROUND: Horticultural therapy is defined as the process of utilising fruits, vegetables, flowers and plants facilitated by a trained therapist or healthcare provider, to achieve specific treatment goals or to simply improve a person's well-being. It can be used for therapy or rehabilitation programs for cognitive, physical, social, emotional, and recreational benefits, thus improving the person's body, mind and spirit. Between 5% to 15% of people with schizophrenia continue to experience symptoms in spite of medication, and may also develop undesirable adverse effects, horticultural therapy may be of value for these people. OBJECTIVES: To evaluate the effects of horticultural therapy for people with schizophrenia or schizophrenia-like illnesses compared with standard care or other additional psychosocial interventions. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (Janurary 2013) and supplemented this by contacting relevant study authors, and manually searching reference lists. SELECTION CRITERIA: We included one randomised controlled trial (RCT) comparing horticultural therapy plus standard care with standard care alone for people with schizophrenia. DATA COLLECTION AND ANALYSIS: We reliably selected, quality assessed and extracted data. For continuous outcomes, we calculated a mean difference (MD) and for binary outcomes we calculated risk ratio (RR), both with 95% confidence intervals (CI). We assessed risk of bias and created a 'Summary of findings' table using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: We included one single blind study (total n = 24). The overall risk of bias in the study was considered to be unclear although the randomisation was adequate. It compared a package of horticultural therapy which consisted of one hour per day of horticultural activity plus standard care with standard care alone over two weeks (10 consecutive days) with no long-term follow-up. Only two people were lost to follow-up in the study, both in the horticultural therapy group (1 RCT n = 24,RR 5.00 95% CI 0.27 to 94.34, very low quality evidence). There was no clear evidence of a difference in Personal Wellbeing Index (PWI-C) change scores between groups, however confidence intervals were wide (1 RCT n = 22, MD -0.90 95% CI -10.35 to 8.55, very low quality evidence). At the end of treatment, the Depression Anxiety Stress Scale (DASS21) change scores in horticultural therapy group were greater than that in the control group (1 RCT n = 22, MD -23.70 CI -35.37 to - 12.03, very low quality evidence). The only included study did not report on adverse effects of interventions. AUTHORS' CONCLUSIONS: Based on the current very low quality data, there is insufficient evidence to draw any conclusions on benefits or harms of horticultural therapy for people with schizophrenia. This therapy remains unproven and more and larger randomised trials are needed to increase high quality evidence in this area.

Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders.

BACKGROUND: Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia. OBJECTIVES: To evaluate the effects of flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes. SEARCH METHODS: We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies. MAIN RESULTS: The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence). AUTHORS' CONCLUSIONS: In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.

Trifluoperazine versus placebo for schizophrenia.

BACKGROUND: Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses. OBJECTIVES: To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia. SEARCH METHODS: Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013. SELECTION CRITERIA: All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare trifluoperazine with placebo. DATA COLLECTION AND ANALYSIS: Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary. MAIN RESULTS: This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions. AUTHORS' CONCLUSIONS: Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.

Pimozide for schizophrenia or related psychoses.

BACKGROUND: Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained death. Electrocardiogram monitoring is now required before and during use. OBJECTIVES: To review the effects of pimozide for people with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.A secondary objective was to examine the effects of pimozide for people with delusional disorder. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Register (28 January 2013). SELECTION CRITERIA: We sought all relevant randomised clinical trials (RCTs) comparing pimozide with other treatments. DATA COLLECTION AND ANALYSIS: Working independently, we inspected citations, ordered papers and then re-inspected and assessed the quality of the studies and of extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and mean differences (MDs) for continuous data. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. MAIN RESULTS: We included 32 studies in total: Among the five studies that compared pimozide versus placebo, only one study provided data for global state relapse, for which no difference between groups was noted at medium term (1 RCT n = 20, RR 0.22 CI 0.03 to 1.78, very low quality of evidence). None of the five studies provided data for no improvement or first-rank symptoms in mental state. Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (1 RCT, n = 19, RR 5.50 CI 0.30 to 101.28, very low quality of evidence) or at medium term (1 RCT n = 25, RR 1.33 CI 0.14 to 12.82, very low quality of evidence), or for Parkinsonism (tremor) at medium term (1 RCT n = 25, RR 1 CI 0.2 to 4.95, very low quality of evidence). No data were reported for quality of life at medium term.Of the 26 studies comparing pimozide versus any antipsychotic, seven studies provided data for global state relapse at medium term, for which no difference was noted (7 RCTs n = 227, RR 0.82 CI 0.57 to 1.17, moderate quality of evidence). Data from one study demonstrated no difference in mental state (no improvement) at medium term (1 RCT n = 23, RR 1.09 CI 0.08 to 15.41, very low quality evidence); another study demonstrated no difference in the presence of first-rank symptoms at medium term (1 RCT n = 44, RR 0.53 CI 0.25 to 1.11, low quality of evidence). Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (6 RCTs n = 186, RR 1.21 CI 0.71 to 2.05,low quality of evidence) or medium term (5 RCTs n = 219, RR 1.12 CI 0.24 to 5.25,low quality of evidence), or for Parkinsonism (tremor) at medium term (4 RCTs n = 174, RR 1.46 CI 0.68 to 3.11, very low quality of evidence). No data were reported for quality of life at medium term.In the one study that compared pimozide plus any antipsychotic versus the same antipsychotic, significantly fewer relapses were noted in the augmented pimozide group at medium term (1 RCT n = 69, RR 0.28 CI 0.15 to 0.50, low quality evidence). No data were reported for mental state outcomes or for extrapyramidal symptoms (EPS). Data were skewed for quality of life scores, which were not included in the meta-analysis but were presented separately.Two studies compared pimozide plus any antipsychotics versus antipsychotic plus placebo; neither study reported data for outcomes of interest, apart from Parkinsonism at medium term and quality of life using the Specific Level of Functioning scale (SLOF); however, data were skewed.Only one study compared pimozide plus any antipsychotic versus antipsychotics plus antipsychotic; no data were reported for global state and mental state outcomes of interest. Data were provided for Parkinsonism (rigidity and tremor) using the Extrapyramidal Symptom Rating Scale (ESRS); however, these data were skewed. AUTHORS' CONCLUSIONS: Although shortcomings in the data are evident, enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with efficacy similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. No data support or refute its use for those with delusional disorder.

Nidotherapy for people with schizophrenia.

BACKGROUND: Nidotherapy is a therapeutic method that principally aims to modify the environment of people with schizophrenia and other serious mental illnesses, whilst working in conjunction with, or alongside other treatments. Rather than focusing on direct treatments or interventions, the aim is to help the individual identify the need for, and work to effect environmental change with the aim of minimising the impact of any form of mental disorder on the individual and society. OBJECTIVES: To review the effects of nidotherapy added to standard care, compared with standard care or no treatment for people with schizophrenia or related disorders. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (December 2011) and supplemented this by contacting relevant study authors, handsearching nidotherapy articles and manually searching reference lists. SELECTION CRITERIA: All randomised controlled trials (RCTs) that compared nidotherapy with standard care or no treatment. DATA COLLECTION AND ANALYSIS: We independently selected and quality assessed potential trials. We reliably extracted data. We calculated risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data. Scale data were only extracted from valid scales. For non-skewed continuous endpoint data, we estimated mean difference (MD) between groups. Skewed data have been presented in the Data and analyses as 'other data', with acknowledged means and standard deviations. We assessed risk of bias for the included study and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: We included only one study that compared nidotherapy-enhanced standard care with standard care alone (total 52 participants); this study was classified by its authors as a 'pilot study'. The duration of the included study was 18 months in total. The single study examined the short-term (up to six months) and medium-term (between six and 12 months) effects of nidotherapy-enhanced standard care versus standard care.Nidotherapy-enhanced standard care was favoured over standard care for social functioning in both the short term (n = 50, 1 RCT, MD -2.10, 95% CI -4.66 to 0.46) and medium term (n = 37, 1 RCT, MD -1.70, 95% CI -4.60 to 1.20, Very low quality); however, these results did not reach statistical significance. Results concerning engagement with non-inpatient services favoured the intervention group in both the short term (n = 50, 1 RCT, MD 2.00, 95% CI 0.13 to 3.87) and medium term (n = 37, 1 RCT, MD 1.70, 95% CI -0.09 to 3.49), with statistical significance evident in the short term, but not in the medium term. Results of people leaving the study early favoured the intervention in the short term (n = 52, 1 RCT, RR 0.86, 95% CI 0.06 to 12.98), with slight favour of the control group at medium term (n = 50, 1 RCT, RR 0.99, 95% CI 0.39 to 2.54); again, these results did not reach statistical significance. Results for the adverse effects/events of death (measured by 12 months) favoured the intervention (n = 52, 1 RCT, RR 0.29, 95% CI 0.01 to 6.74, Very low quality) but with no statistical significance. Skewed results were available for mental state, service use, and economic outcomes, and present a mixed picture of the benefits of nidotherapy. AUTHORS' CONCLUSIONS: Further research is needed into the possible benefits or harms of this newly-formulated therapy. Until such research is available, patients, clinicians, managers and policymakers should consider it an experimental approach.

Fluphenazine (oral) versus placebo for schizophrenia.

BACKGROUND: Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades. OBJECTIVES: To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. SEARCH METHODS: We updated searches of the Cochrane Schizophrenia Group's trials register, which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Central Register of Controlled Trials in The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile, 15 May, 2012. References of all identified studies were searched for further trial citations. SELECTION CRITERIA: We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects. DATA COLLECTION AND ANALYSIS: We inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. MAIN RESULTS: From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). AUTHORS' CONCLUSIONS: The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.