Classification of all pharmacological interventions tested in trials relevant to people with schizophrenia: A study-based analysis.

BACKGROUND: Systematic reviewing is a time-consuming and resource-intensive process. Information specialists are maintaining study-based registers to facilitate efficient conduct of systematic reviews. Classification of study-level meta-data -such as interventions -can result in much more accurate searches, saving time in the early steps of systematic reviewing. OBJECTIVE: To classify all pharmacological interventions from all schizophrenia trials. METHODS: We used Cochrane Schizophrenia's Study-based Register as the source of trials, Emtree and MeSH for synonyms, AdisInsight and CT.gov for research drugs and WHO ATC for marketed drugs. RESULTS: One third of tested interventions on patients with schizophrenia are pharmacological (816; belonging to 106 clinical classes) with antipsychotic drugs being the most researched (15.1%). Only 528 of these medications are listed in WHO ATC. Around one third of these drug interventions are seen only in research (236; from 21 pharmacological/biochemical classes). Within the pharmacological interventions, we identified 28 'qualifiers' including dose, route and timing of drug delivery. CONCLUSION: Identification and classification of pharmacological interventions from trials require use of many sources of information none of which are inclusive of all drugs. Limitations of each source are helpful to understand. Classification of non-pharmacological interventions is now a priority for clinical and information scientists and professionals.

Rapid tranquillisation in a psychiatric emergency hospital in Lebanon: TREC-Lebanon - a pragmatic randomised controlled trial of intramuscular haloperidol and promethazine v. intramuscular haloperidol, promethazine and chlorpromazine.

BACKGROUND: Agitated patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians differ in opinion and practice. In Lebanon, the use of the triple therapy haloperidol plus promethazine plus chlorpromazine (HPC) is frequently used but no studies involving this combination exists. METHOD: A pragmatic randomised open trial (September 2018-July 2019) in the Lebanese Psychiatric Hospital of the Cross in Beirut Lebanon involving 100 people requiring urgent intramuscular sedation due to aggressive behaviour were given intramuscular chlorpromazine 100 mg plus haloperidol 5 mg plus promethazine 25 mg (HPC) or intramuscular haloperidol 5 mg plus promethazine 25 mg. RESULTS: Primary outcome data were available for 94 (94%) people. People allocated to the haloperidol plus promethazine (HP) group showed no clear difference at 20 min compared with patients allocated to the HPC group [relative risk (RR) 0.84, 95% confidence interval (CI) 0.47-1.50]. CONCLUSIONS: Neither intervention consistently impacted the outcome of 'calm', or 'asleep' and had no discernible effect on the use of restraints, use of additional drugs or recurrence. If clinicians are faced with uncertainty on which of the two intervention combinations to use, the simpler HP is much more widely tested and the addition of chlorpromazine adds no clear benefit with a risk of additional adverse effects.

Electroconvulsive therapy for treatment-resistant schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long-term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment. OBJECTIVES: Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment-resistant schizophrenia.Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well-defined treatment-resistant schizophrenia as opposed to less rigorously defined treatment-resistant schizophrenia (who would be expected to have a greater affective component to their illness). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies. SELECTION CRITERIA: Randomised controlled trials investigating the effects of ECT in people with treatment-resistant schizophrenia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed-effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework. MAIN RESULTS: We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment-resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.The included trials reported useable data for four comparisons: ECT plus standard care compared with sham-ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.For the comparison ECT plus standard care versus sham-ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI -3.69 to 10.89; participants = 25; studies = 1; very low-quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low-quality evidence).When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low-quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short-term BPRS; MD -5.20, 95% CI -7.93 to -2.47; participants = 162; studies = 1; very low-quality evidence).When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate-quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low-quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low-quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD -11.18, 95% CI -12.61 to -9.76; participants = 345; studies = 2; low-quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low-quality evidence).For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium-term BPRS; MD -0.93, 95% CI -6.95 to 5.09; participants = 30; studies = 1; very low-quality evidence); general functioning scores were also similar between groups (medium-term Global Assessment of Functioning; MD -0.66, 95% CI -3.60 to 2.28; participants = 30; studies = 1; very low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence indicates that relative to standard care, ECT has a positive effect on medium-term clinical response for people with treatment-resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham-ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good-quality evidence is needed before firm conclusions can be made.

Calcium channel blockers for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. OBJECTIVES: To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. DATA COLLECTION AND ANALYSIS: We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. MAIN RESULTS: Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. AUTHORS' CONCLUSIONS: Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.

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

BACKGROUND: Aggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast-acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis-induced aggression or agitation. OBJECTIVES: To examine whether oral risperidone alone is an effective treatment for psychosis-induced aggression or agitation. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' tables. MAIN RESULTS: The review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome, specific behaviour - agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI -2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone versus quetiapineOne trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low-quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial.Risperidone versus risperidone + oxcarbazepineOne trial (n = 68) measured agitation using the Positive and Negative Syndrome Scale - Excited Component.(PANSS-EC) endpoint score and found a clear difference, favouring the combination treatment at one week (MD 2.70, 95% CI 0.42 to 4.98; very low-quality evidence), but no effect was observed for global state using Clinical Global Impression - Improvement (CGI-I) endpoint score at one week (MD -0.20, 95% CI -0.61 to 0.21; very-low quality evidence). Incidence of extrapyramidal symptoms after 24 hours was similar between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very-low quality evidence).Risperidone versus risperidone + valproic acidTwo trials compared risperidone with a combination of risperidone plus valproic acid. No clear differences between the treatment groups were observed for aggression (MOAS endpoint score at three days: MD 1.07, 95% CI -0.20 to 2.34; participants = 54; studies = 1; very low-quality evidence) or incidence of akathisia after 24 hours: RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low-quality evidence). AUTHORS' CONCLUSIONS: Overall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under-sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis-induced aggression. High-quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis-induced aggression or agitation.

Managing acutely aggressive or agitated people in a psychiatric setting: a survey in Lebanon.

Background: Violent patients constitute 10% of all psychiatric admissions. Treatment options and clinical practice interventions vary across the globe and no survey of practice in a Middle Eastern setting exists. Surveying treatments in Lebanon will show treatment interventions used in this part of the world and, most importantly, provide the treatment options that could potentially be used for clinical trials pertaining to emergency psychiatry. Methods: A survey of clinicians' opinions and practice was conducted between July and August 2017 at the largest psychiatric hospital in Lebanon. Results: Five of seven experienced psychiatrists provided opinions when interviewed of their preferred intervention when dealing with an emergency psychiatric episode. Whilst this varied in detail, there was a consistent view that there should first be verbal control, then use of medications, and finally physical restrain of the patient. A total of 39 emergency episodes (28 people) occurred in the one month (64% men in their 30s). Bipolar disorder was the most frequent single diagnosis behind the aggression (n=16, 41%; 12 people 43%) but the combined schizophrenia-like illnesses underlay 18 of the 39 episodes (46%; 13/28 people 46%). In clinical life, we found evidence of high family involvement, but little attempts made at initial verbal control in the hospital. All 39 episodes involved administration of pharmacological interventions. Medications were used in 29 of cases (74%) and non-medication interventions used in the remaining 10/39 (26%). Conclusion: This survey provides some evidence that clinicians' preferences may not fully reflect clinical practice but also that experienced clinicians are using several clearly effective techniques to manage these very difficult situations. However, as for other parts of the world, treatment in Lebanon has limited or no underpinning by evidence from well-designed, conducted and reported evaluative studies.

Study protocol for a cluster randomised controlled trial to assess the effectiveness of user-driven intervention to prevent aggressive events in psychiatric services.

BACKGROUND: People admitted to psychiatric hospitals with a diagnosis of schizophrenia may display behavioural problems. These may require management approaches such as use of coercive practices, which impact the well-being of staff members, visiting families and friends, peers, as well as patients themselves. Studies have proposed that not only patients' conditions, but also treatment environment and ward culture may affect patients' behaviour. Seclusion and restraint could possibly be prevented with staff education about user-centred, more humane approaches. Staff education could also increase collaboration between patients, family members and staff, which may further positively affect treatment culture and lower the need for using coercive treatment methods. METHODS: This is a single-blind, two-arm cluster randomised controlled trial involving 28 psychiatric hospital wards across Finland. Units will be randomised to receive either a staff educational programme delivered by the team of researchers, or standard care. The primary outcome is the incidence of use of patient seclusion rooms, assessed from the local/national health registers. Secondary outcomes include use of other coercive methods (limb restraint, forced injection, and physical restraint), service use, treatment satisfaction, general functioning among patients, and team climate and employee turn-over (nursing staff). DISCUSSION: The study, designed in close collaboration with staff members, patients and their relatives, will provide evidence for a co-operative and user-centred educational intervention aiming to decrease the prevalence of coercive methods and service use in the units, increase the functional status of patients and improve team climate in the units. We have identified no similar trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02724748 . Registered on 25th of April 2016.

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

BACKGROUND: Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas. OBJECTIVES: To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest. MAIN RESULTS: We found nine new RCTs from the 2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21, very low-quality evidence).Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to 28.86, very low-quality evidence).Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI 0.91 to 1.43, very low-quality of evidence).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI 0.46 to 147.45, very low-quality of evidence).Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence). AUTHORS' CONCLUSIONS: Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are available, sole use of haloperidol for extreme emergency could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real-world practice.

Antipsychotic combinations for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with their initial antipsychotic drug treatment. Sometimes a second antipsychotic, in combination with the first, is used in these situations. OBJECTIVES: To examine whether:1. treatment with antipsychotic combinations is effective for schizophrenia; and2. treatment with antipsychotic combinations is safe for the same illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's register which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran searches in September 2010, August 2012 and January 2016. We checked for additional trials in the reference lists of included trials. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials comparing antipsychotic combinations with antipsychotic monotherapy for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data from the included studies. We analysed dichotomous data using risk ratios (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean difference (MD) with a 95% CIs. For the meta-analysis we used a random-effects model. We used GRADE to complete a 'Summary of findings' table and assessed risk of bias for included studies. MAIN RESULTS: Sixty-two studies are included in the review, 31 of these compared clozapine monotherapy with clozapine combination. We considered the risk of bias in the included studies to be moderate to high. The majority of trials had unclear allocation concealment, method of randomisation and blinding, and were not free of selective reporting.There is some limited evidence that combination therapy is superior to monotherapy in improving clinical response (RR 0.73, 95% CI 0.63 to 0.85; participants = 2364; studies = 29, very low-quality evidence), although subgroup analyses show that the positive result was due to the studies with clozapine in both the monotherapy and combination groups (RR 0.66, 95% CI 0.53 to 0.83; participants = 1127; studies = 17). Few studies reported on rate of relapse, most likely due to the short length of the studies. Overall, a combination of antipsychotics was not superior or inferior to antipsychotic monotherapy in preventing relapse (RR 0.63, 95% CI 0.31 to 1.29; participants = 512; studies = 3, very low-quality evidence), but the pooled data showed high heterogeneity (I² = 82%). A combination of antipsychotics was not superior or inferior to antipsychotic monotherapy in reducing the number of participants discontinuing treatment early (RR 0.89, 95% CI 0.73 to 1.07; participants = 3103; studies = 43, low-quality evidence). No difference was found between treatment groups in the number of participants hospitalised (RR 0.96, 95% CI 0.36 to 2.55; participants = 202; studies = 3, low-quality evidence) . We did not find evidence of a difference between treatment groups in serious adverse events or those requiring discontinuation (RR 1.05, 95% CI 0.65 to 1.69; participants = 2398; studies = 30, very low-quality evidence). There is as lack of evidence on clinically important change in quality of life, with only four studies reporting average endpoint or change data for this outcome on three different scales, none of which showed a difference between treatment groups. AUTHORS' CONCLUSIONS: Currently, most evidence regarding the use of antipsychotic combinations comes from short-term trials, limiting the assessment of long-term efficacy and safety. We found very low-quality evidence that a combination of antipsychotics may improve the clinical response. We also found low-quality evidence that a combination of antipsychotics is may make no difference at preventing participants from leaving the study early, preventing relapse and/or causing more serious adverse events than monotherapy.

Short Text Messages to Encourage Adherence to Medication and Follow-up for People With Psychosis (Mobile.Net): Randomized Controlled Trial in Finland.

BACKGROUND: A text messaging service (short message service [SMS]) has the potential to target large groups of people with long-term illnesses such as serious mental disorders, who may have difficulty with treatment adherence. Robust research on the impact of mobile technology interventions for these patients remains scarce. OBJECTIVE: The main objective of our study was to investigate the impact of individually tailored short text messages on the rate of psychiatric hospital readmissions, health care service use, and clinical outcomes. In addition, we analyzed treatment costs. METHODS: Between September 2011 and November 2012, we randomly assigned 1139 people to a tailored text message intervention (n=569) or usual care (n=570). Participants received semiautomated text messages for up to 12 months or usual care. The primary outcome, based on routinely collected health register data, was patient readmission into a psychiatric hospital during a 12-month follow-up period. Secondary outcomes were related to other service use, coercion, medication, adverse events, satisfaction, social functioning, quality of life, and economic factors (cost analysis). RESULTS: There was 98.24% (1119/1139) follow-up at 12 months. Tailored mobile telephone text messages did not reduce the rate of hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between hospitalizations (mean difference 7.0 days 95% CI -8.0 to 24.0; P=.37), time spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI -2.0 to 7.0; P=.35), or other service outcomes. People who received text messages were less disabled, based on Global Assessment Scale scores at the time of their readmission, than those who did not receive text messages (odds ratio 0.68; 95% CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS group than in the control group (mean €10,103 vs €9210, respectively, P<.001). CONCLUSIONS: High-grade routinely collected data can provide clear outcomes for pragmatic randomized trials. SMS messaging tailored with the input of each individual patient did not decrease the rate of psychiatric hospital visits after the 12 months of follow-up. Although there may have been other, more subtle effects, the results of these were not evident in outcomes of agreed importance to clinicians, policymakers, and patients and their families. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6rVzZrbuz).

Factors Associated With Dropout During Recruitment and Follow-Up Periods of a mHealth-Based Randomized Controlled Trial for Mobile.Net to Encourage Treatment Adherence for People With Serious Mental Health Problems.

BACKGROUND: Clinical trials are the gold standard of evidence-based practice. Still many papers inadequately report methodology in randomized controlled trials (RCTs), particularly for mHealth interventions for people with serious mental health problems. To ensure robust enough evidence, it is important to understand which study phases are the most vulnerable in the field of mental health care. OBJECTIVE: We mapped the recruitment and the trial follow-up periods of participants to provide a picture of the dropout predictors from a mHealth-based trial. As an example, we used a mHealth-based multicenter RCT, titled "Mobile.Net," targeted at people with serious mental health problems. METHODS: Recruitment and follow-up processes of the Mobile.Net trial were monitored and analyzed. Recruitment outcomes were recorded as screened, eligible, consent not asked, refused, and enrolled. Patient engagement was recorded as follow-up outcomes: (1) attrition during short message service (SMS) text message intervention and (2) attrition during the 12-month follow-up period. Multiple regression analysis was used to identify which demographic factors were related to recruitment and retention. RESULTS: We recruited 1139 patients during a 15-month period. Of 11,530 people screened, 36.31% (n=4186) were eligible. This eligible group tended to be significantly younger (mean 39.2, SD 13.2 years, P<.001) and more often women (2103/4181, 50.30%) than those who were not eligible (age: mean 43.7, SD 14.6 years; women: 3633/6514, 55.78%). At the point when potential participants were asked to give consent, a further 2278 refused. Those who refused were a little older (mean 40.2, SD 13.9 years) than those who agreed to participate (mean 38.3, SD 12.5 years; t1842=3.2, P<.001). We measured the outcomes after 12 months of the SMS text message intervention. Attrition from the SMS text message intervention was 4.8% (27/563). The patient dropout rate after 12 months was 0.36% (4/1123), as discovered from the register data. In all, 3.12% (35/1123) of the participants withdrew from the trial. However, dropout rates from the patient survey (either by paper or telephone interview) were 52.45% (589/1123) and 27.8% (155/558), respectively. Almost all participants (536/563, 95.2%) tolerated the intervention, but those who discontinued were more often women (21/27, 78%; P=.009). Finally, participants' age (P<.001), gender (P<.001), vocational education (P=.04), and employment status (P<.001) seemed to predict their risk of dropping out from the postal survey. CONCLUSIONS: Patient recruitment and engagement in the 12-month follow-up conducted with a postal survey were the most vulnerable phases in the SMS text message-based trial. People with serious mental health problems may need extra support during the recruitment process and in engaging them in SMS text message-based trials to ensure robust enough evidence for mental health care. CLINICALTRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6oHcU2SFp).

Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of Randomized Controlled Trials.

BACKGROUND: Understanding more about the efficacy and safety of oral second-generation antipsychotic medications in reducing the symptoms of acute agitation could improve the treatment of psychiatric emergencies. OBJECTIVE: The objective of this scoping review was to examine the evidence base underlying expert consensus panel recommendations for the use of oral second-generation antipsychotics to treat acute agitation in mentally ill patients. METHODS: The Cochrane Schizophrenia Group's Study-Based Register was searched for randomized controlled trials comparing oral second-generation antipsychotics, benzodiazepines, or first-generation antipsychotics with or without adjunctive benzodiazepines, irrespective of route of administration of the drug being compared. Six articles were included in the final review. RESULTS: Two oral second-generation antipsychotic medications were studied across the six included trials. While the studies had relatively small sample sizes, oral second-generation antipsychotics were similarly effective to intramuscular first-generation antipsychotics in treating symptoms of acute agitation and had similar side-effect profiles. CONCLUSIONS: This scoping review identified six randomized trials investigating the use of oral second-generation antipsychotic medications in the reduction of acute agitation among patients experiencing psychiatric emergencies. Further research will be necessary to make clinical recommendations due to the overall dearth of randomized trials, as well as the small sample sizes of the included studies.

Aggregator: a machine learning approach to identifying MEDLINE articles that derive from the same underlying clinical trial.

OBJECTIVE: It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. METHODS: We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression. RESULTS: Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial. DISCUSSION: Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial.

Chlorpromazine versus reserpine for schizophrenia.

BACKGROUND: In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of the very first antipsychotic drugs. Its irreversible pharmacological potency and adverse effects meant that it has been withdrawn in the UK and its role has been superceded by 'newer' compounds. The effects of reserpine are of historical interest although there are some reports of it still being used in highly specialist situations in psychiatry. Chlorpromazine is also an old drug but it is still used for treatment of people with schizophrenia. OBJECTIVES: To investigate the effects of two old medications (reserpine and chlorpromazine) for people with schizophrenia. Reserpine is now rarely used while chlorpromazine remains on the essential list of drugs of the World Health Organization (WHO). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (24 March 2016). SELECTION CRITERIA: We included randomised clinical trials focusing on chlorpromazine versus reserpine for schizophrenia that presented useable data. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: The review currently includes nine studies with an average 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962. When chlorpromazine was compared with reserpine for people with schizophrenia, improvement in global state was better at short term for those receiving chlorpromazine (n = 781, 6 RCTs, RR 'not improved' 0.75 95% CI 0.62 to 0.92, low-quality evidence). Short-term improvement in paranoid distortion was measured using the Multidimensional Scale for Rating Psychiatric Patients (MSRPP). Data showed no clear difference between treatment groups (n = 19, 1 RCT, RR 1.33 95% CI 0.62 to 2.89, very low-quality evidence). There was no difference in functioning: occupational adjustment, medium term (n = 40, 1 RCT, RR 0.83 95% CI 0.47 to 1.47, moderate-quality evidence) and general behaviour (n = 98, 1 RCT, RR 0.79 CI 0.41 to 1.53, moderate-quality evidence). Adverse events were poorly reported. For 'toxic reaction' there was, again, no obvious difference between the two compounds (n = 210, 3 RCTs, RR 1.68 95% CI 0.43 to 6.54, moderate-quality evidence), and this also applied to leaving the study early (n = 229, 4 RCTs, RR 1.16 95% CI 0.94 to 1.42, moderate-quality evidence). AUTHORS' CONCLUSIONS: Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity. Reserpine did have some effect on global state - but chlorpromazine did seem to perform better. Important issues regarding adverse effects were not really addressed by these trials. Chlorpromazine remains on the WHO list of essential drugs. Reserpine is now almost obsolete, although, probably as a result of evidence other than that reported in the pioneering trials used in this review.

Effectiveness of Social Media Interventions for People With Schizophrenia: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies have shown that people with serious mental disorders spend time online for the purposes of disclosure, information gathering, or gaming. However, coherent information on the effects of social media on treatment for people with schizophrenia is still lacking. OBJECTIVE: Our aim was to determine the effects of social media interventions for supporting mental health and well-being among people with schizophrenia. METHODS: A systematic review and meta-analysis were undertaken to determine the effects of social media interventions for supporting mental health and well-being among people with schizophrenia. Ten databases were searched, while search parameters included English-only manuscripts published prior to June 25, 2015. Study appraisals were made independently by 2 reviewers, and qualitative and quantitative syntheses of data were conducted. RESULTS: Out of 1043 identified records, only two randomized studies of moderate quality (three records, total N=331, duration 12 months) met the inclusion criteria. Participants were people with schizophrenia spectrum or an affective disorder. Social media was used as part of Web-based psychoeducation, or as online peer support (listserv and bulletin board). Outcome measures included perceived stress, social support, and disease-related distress. At 3 months, participants with schizophrenia in the intervention group reported lower perceived stress levels (P=.04) and showed a trend for a higher perceived level of social support (P=.06). However, those who reported more positive experiences with the peer support group also reported higher levels of psychological distress (P=.01). CONCLUSIONS: Despite using comprehensive searches from 10 databases, we found only two studies, whereas numerous reports have been published citing the benefits of social media in mental health. Findings suggest the effects of social media interventions are largely unknown. More research is needed to understand the effects of social media, for users with and without mental illness, in order to determine the impact on mental well-being ofsocial media use as well as its risks.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To review the effects of supportive therapy compared with standard care, or other treatments in addition to standard care for people with schizophrenia. SEARCH METHODS: For this update, we searched the Cochrane Schizophrenia Group's register of trials (November 2012). SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the risk ratio (RR) using a fixed-effect model with 95% confidence intervals (CIs). Where possible, we undertook intention-to-treat analyses. For continuous data, we estimated the mean difference (MD) fixed-effect with 95% CIs. We estimated heterogeneity (I(2) technique) and publication bias. We used GRADE to rate quality of evidence. MAIN RESULTS: Four new trials were added after the 2012 search. The review now includes 24 relevant studies, with 2126 participants. Overall, the evidence was very low quality.We found no significant differences in the primary outcomes of relapse, hospitalisation and general functioning between supportive therapy and standard care.There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (4 RCTs, n = 306, RR 1.82 CI 1.11 to 2.99, very low quality of evidence), clinical improvement in mental state (3 RCTs, n = 194, RR 1.27 CI 1.04 to 1.54, very low quality of evidence) and satisfaction of treatment for the recipient of care (1 RCT, n = 45, RR 3.19 CI 1.01 to 10.7, very low quality of evidence). For this comparison, we found no evidence of significant differences for rate of relapse, leaving the study early and quality of life.When we compared supportive therapy to cognitive behavioural therapy CBT), we again found no significant differences in primary outcomes. There were very limited data to compare supportive therapy with family therapy and psychoeducation, and no studies provided data regarding clinically important change in general functioning, one of our primary outcomes of interest. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies where we graded the evidence as very low quality. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Crisis intervention for people with severe mental illnesses.

BACKGROUND: A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis-intervention models of care were developed as a possible solution. OBJECTIVES: To review the effects of crisis-intervention models for anyone with serious mental illness experiencing an acute episode compared to the standard care they would normally receive. If possible, to compare the effects of mobile crisis teams visiting patients' homes with crisis units based in home-like residential houses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials. There is no language, time, document type, or publication status limitations for inclusion of records in the register. This search was undertaken in 1998 and then updated 2003, 2006, 2010 and September 29, 2014. SELECTION CRITERIA: We included all randomised controlled trials of crisis-intervention models versus standard care for people with severe mental illnesses that met our inclusion criteria. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: The update search September 2014 found no further new studies for inclusion, the number of studies included in this review remains eight with a total of 1144 participants. Our main outcomes of interest are hospital use, global state, mental state, quality of life, participant satisfaction and family burden. With the exception of mental state, it was not possible to pool data for these outcomes.Crisis intervention may reduce repeat admissions to hospital (excluding index admissions) at six months (1 RCT, n = 369, RR 0.75 CI 0.50 to 1.13, high quality evidence), but does appear to reduce family burden (at six months: 1 RCT, n = 120, RR 0.34 CI 0.20 to 0.59, low quality evidence), improve mental state (Brief Psychiatric Rating Scale (BPRS) three months: 2 RCTs, n = 248, MD -4.03 CI -8.18 to 0.12, low quality evidence), and improve global state (Global Assessment Scale (GAS) 20 months; 1 RCT, n = 142, MD 5.70, -0.26 to 11.66, moderate quality evidence). Participants in the crisis-intervention group were more satisfied with their care 20 months after crisis (Client Satisfaction Questionnaire (CSQ-8): 1 RCT, n = 137, MD 5.40 CI 3.91 to 6.89, moderate quality evidence). However, quality of life scores at six months were similar between treatment groups (Manchester Short Assessment of quality of life (MANSA); 1 RCT, n = 226, MD -1.50 CI -5.15 to 2.15, low quality evidence). Favourable results for crisis intervention were also found for leaving the study early and family satisfaction. No differences in death rates were found. Some studies suggested crisis intervention to be more cost-effective than hospital care but all numerical data were either skewed or unusable. We identified no data on staff satisfaction, carer input, complications with medication or number of relapses. AUTHORS' CONCLUSIONS: Care based on crisis-intervention principles, with or without an ongoing homecare package, appears to be a viable and acceptable way of treating people with serious mental illnesses. However only eight small studies with unclear blinding, reporting and attrition bias could be included and evidence for the main outcomes of interest is low to moderate quality. If this approach is to be widely implemented it would seem that more evaluative studies are still needed.

Fluphenazine decanoate (depot) and enanthate for schizophrenia.

BACKGROUND: Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects. OBJECTIVES: To assess the effects of fluphenazine decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. SELECTION CRITERIA: We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. DATA COLLECTION AND ANALYSIS: We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table. MAIN RESULTS: This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low.Compared with placebo, use of fluphenazine decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine decanoate with placebo reported clinically significant changes in global state or hospital admissions.Fluphenazine decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine decanoate with oral neuroleptics reported death or hospital admissions.No significant difference in relapse rates in the medium term between fluphenazine decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine decanoate and fluphenazine enanthate. No study comparing fluphenazine decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions. AUTHORS' CONCLUSIONS: There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.

First rank symptoms for schizophrenia.

BACKGROUND: Early and accurate diagnosis and treatment of schizophrenia may have long-term advantages for the patient; the longer psychosis goes untreated the more severe the repercussions for relapse and recovery. If the correct diagnosis is not schizophrenia, but another psychotic disorder with some symptoms similar to schizophrenia, appropriate treatment might be delayed, with possible severe repercussions for the person involved and their family. There is widespread uncertainty about the diagnostic accuracy of First Rank Symptoms (FRS); we examined whether they are a useful diagnostic tool to differentiate schizophrenia from other psychotic disorders. OBJECTIVES: To determine the diagnostic accuracy of one or multiple FRS for diagnosing schizophrenia, verified by clinical history and examination by a qualified professional (e.g. psychiatrists, nurses, social workers), with or without the use of operational criteria and checklists, in people thought to have non-organic psychotic symptoms. SEARCH METHODS: We conducted searches in MEDLINE, EMBASE, and PsycInfo using OvidSP in April, June, July 2011 and December 2012. We also searched MEDION in December 2013. SELECTION CRITERIA: We selected studies that consecutively enrolled or randomly selected adults and adolescents with symptoms of psychosis, and assessed the diagnostic accuracy of FRS for schizophrenia compared to history and clinical examination performed by a qualified professional, which may or may not involve the use of symptom checklists or based on operational criteria such as ICD and DSM. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for inclusion. Risk of bias in included studies were assessed using the QUADAS-2 instrument. We recorded the number of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) for constructing a 2 x 2 table for each study or derived 2 x 2 data from reported summary statistics such as sensitivity, specificity, and/or likelihood ratios. MAIN RESULTS: We included 21 studies with a total of 6253 participants (5515 were included in the analysis). Studies were conducted from 1974 to 2011, with 80% of the studies conducted in the 1970's, 1980's or 1990's. Most studies did not report study methods sufficiently and many had high applicability concerns. In 20 studies, FRS differentiated schizophrenia from all other diagnoses with a sensitivity of 57% (50.4% to 63.3%), and a specificity of 81.4% (74% to 87.1%) In seven studies, FRS differentiated schizophrenia from non-psychotic mental health disorders with a sensitivity of 61.8% (51.7% to 71%) and a specificity of 94.1% (88% to 97.2%). In sixteen studies, FRS differentiated schizophrenia from other types of psychosis with a sensitivity of 58% (50.3% to 65.3%) and a specificity of 74.7% (65.2% to 82.3%). AUTHORS' CONCLUSIONS: The synthesis of old studies of limited quality in this review indicates that FRS correctly identifies people with schizophrenia 75% to 95% of the time. The use of FRS to diagnose schizophrenia in triage will incorrectly diagnose around five to 19 people in every 100 who have FRS as having schizophrenia and specialists will not agree with this diagnosis. These people will still merit specialist assessment and help due to the severity of disturbance in their behaviour and mental state. Again, with a sensitivity of FRS of 60%, reliance on FRS to diagnose schizophrenia in triage will not correctly diagnose around 40% of people that specialists will consider to have schizophrenia. Some of these people may experience a delay in getting appropriate treatment. Others, whom specialists will consider to have schizophrenia, could be prematurely discharged from care, if triage relies on the presence of FRS to diagnose schizophrenia. Empathetic, considerate use of FRS as a diagnostic aid - with known limitations - should avoid a good proportion of these errors.We hope that newer tests - to be included in future Cochrane reviews - will show better results. However, symptoms of first rank can still be helpful where newer tests are not available - a situation which applies to the initial screening of most people with suspected schizophrenia. FRS remain a simple, quick and useful clinical indicator for an illness of enormous clinical variability.

Voxel-based morphometry for separation of schizophrenia from other types of psychosis in first episode psychosis.

BACKGROUND: Schizophrenia is a psychiatric disorder which involves distortions in thought and perception, blunted affect, and behavioural disturbances. The longer psychosis goes unnoticed and untreated, the more severe the repercussions for relapse and recovery. There is some evidence that early intervention services can help, and diagnostic techniques that could contribute to early intervention may offer clinical utility in these situations. The index test being evaluated in this review is the structural magnetic resonance imaging (MRI) analysis technique known as voxel-based morphometry (VBM) that estimates the distribution of grey matter tissue volume across several brain regions. This review is an exploratory examination of the diagnostic 'potential' of VBM for use as an additional tool in the clinical examination of patients with first episode psychosis to establish whether an individual will progress on to developing schizophrenia as opposed to other types of psychosis. OBJECTIVES: To determine whether VBM applied to the brain can be used to differentiate schizophrenia from other types of psychosis in participants who have received a clinical diagnosis of first episode psychosis. SEARCH METHODS: In December 2013, we updated a previous search (May 2012) of MEDLINE, EMBASE, and PsycInfo using OvidSP. SELECTION CRITERIA: We included retrospective and prospective studies that consecutively or randomly selected adolescent and adult participants (< 45 years) with a first episode of psychosis; and that evaluated the diagnostic accuracy of VBM for differentiating schizophrenia from other psychoses compared with a clinical diagnosis made by a qualified mental health professional, with or without the use of standard operational criteria or symptom checklists. We excluded studies in children, and in adult participants with organic brain disorders or who were at high risk for schizophrenia, such as people with a genetic predisposition. DATA COLLECTION AND ANALYSIS: Two review authors screened all references for inclusion. We assessed the quality of studies using the QUADAS-2 instrument. Due to a lack of data, we were not able to extract 2 x 2 data tables for each study nor undertake any meta-analysis. MAIN RESULTS: We included four studies with a total of 275 participants with first episode psychosis. VBM was not used to diagnose schizophrenia in any of the studies, instead VBM was used to quantify the magnitude of differences in grey matter volume. Therefore, none of the included studies reported data that could be used in the analysis, and we summarised the findings narratively for each study. AUTHORS' CONCLUSIONS: There is no evidence to currently support diagnosing schizophrenia (as opposed to other psychotic disorders) using the pattern of brain changes seen in VBM studies in patients with first episode psychosis. VBM has the potential to discriminate between diagnostic categories but the methods to do this reliably are currently in evolution. In addition, the lack of applicability of the use of VBM to clinical practice in the studies to date limits the usefulness of VBM as a diagnostic aid to differentiate schizophrenia from other types of psychotic presentations in people with first episode of psychosis.