A systematic review of anterior lumbar interbody fusion (ALIF) versus posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), posterolateral lumbar fusion (PLF).

PURPOSE: The rate of elective lumbar fusion has continued to increase over the past two decades. However, there remains to be a consensus on the optimal fusion technique. This study aims to compare stand-alone anterior lumbar interbody fusion (ALIF) with posterior fusion techniques in patients with spondylolisthesis and degenerative disc disease through a systematic review and meta-analysis of the available literature. METHODS: A systematic review was performed by searching the Cochrane Register of Trials, MEDLINE, and EMBASE from inception to 2022. In the two-stage screening process, three reviewers independently reviewed titles and abstracts. The full-text reports of the remaining studies were then inspected for eligibility. Conflicts were resolved through consensus discussion. Two reviewers then extracted study data, assessed it for quality, and analysed it. RESULTS: After the initial search and removal of duplicate records, 16,435 studies were screened. Twenty-one eligible studies (3686 patients) were ultimately included, which compared stand-alone ALIF with posterior approaches such as posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), and posterolateral lumbar fusion (PLF). A meta-analysis showed surgical time and blood loss was significantly lower in ALIF than in TLIF/PLIF, but not in those who underwent PLF (p = 0.08). The length of hospital stay was significantly shorter in ALIF than in TLIF, but not in PLIF or PLF. Fusion rates were similar between the ALIF and posterior approaches. The Visual Analogue Scale (VAS) scores for back and leg pain were not significantly different between the ALIF and PLIF/TLIF groups. However, VAS back pain favoured ALIF over PLF at one year (n = 21, MD - 1.00, CI - 1.47, - 0.53), and at two years (2 studies, n = 67, MD - 1.39, CI - 1.67, - 1.11). The VAS leg pain scores (n = 46, MD 0.50, CI 0.12 to 0.88) at two years significantly favoured PLF. The Oswestry Disability Index (ODI) scores at one year were not significantly different between ALIF and the posterior approaches. At two years, ODI scores were also similar between the ALIF and the TLIF/PLIF. However, the ODI scores at two years (2 studies, n = 67, MD - 7.59, CI - 13.33, - 1.85) significantly favoured ALIF over PLF (I2 = 70%). The Japanese Orthopaedic Association Score (JOAS) for low back pain at one year (n = 21, MD - 0.50, CI - 0.78) and two years (two studies, n = 67, MD - 0.36, CI - 0.65, - 0.07) significantly favoured ALIF over PLF. No significant differences were found in leg pain at the 2-year follow-up. Adverse events displayed no significant differences between the ALIF and posterior approaches. CONCLUSIONS: Stand-alone-ALIF demonstrated a shorter operative time and less blood loss than the PLIF/TLIF approach. Hospitalisation time is reduced with ALIF compared with TLIF. Patient-reported outcome measures were equivocal with PLIF or TLIF. VAS and JOAS, back pain, and ODI scores mainly favoured ALIF over PLF. Adverse events were equivocal between the ALIF and posterior fusion approaches.

Resistance decay in individuals after antibiotic exposure in primary care: a systematic review and meta-analysis.

BACKGROUND: Antibiotic resistance is an urgent global problem, but reversibility is poorly understood. We examined the development and decay of bacterial resistance in community patients after antibiotic use. METHODS: This was a systematic review and meta-analysis. PubMed, EMBASE and CENTRAL (from inception to May 2017) were searched, with forward and backward citation searches of the identified studies. We contacted authors whose data were unclear, and of abstract-only reports, for further information. We considered controlled or times-series studies of patients in the community who were given antibiotics and where the subsequent prevalence of resistant bacteria was measured. Two authors extracted risk of bias and data. The meta-analysis used a fixed-effects model. RESULTS: Of 24,492 articles screened, five controlled and 20 time-series studies (total 16,353 children and 1461 adults) were eligible. Resistance in Streptococcus pneumoniae initially increased fourfold after penicillin-class antibiotic exposure [odds ratio (OR) 4.2, 95% confidence interval (CI) 3.5-5.4], but this fell after 1 month (OR 1.7, 95% CI 1.3-2.1). After cephalosporin-class antibiotics, resistance increased (OR 2.2, 95%CI 1.7-2.9); and fell to (OR 1.6, 95% CI 1.2-2.3) at 1 month. After macrolide-class antibiotics, resistance increased (OR 3.8, 95% CI 1.9-7.6) and persisted for 1 month (OR 5.2, 95% CI 2.6-10.3) and 3 months (OR 8.1, 95% CI 4.6-14.2, from controlled studies and OR 2.3, 95% CI 0.6-9.4, from time-series studies). Resistance in Haemophilus influenzae after penicillins was not significantly increased (OR 1.3, 95% CI 0.9-1.9) initially but was at 1 month (OR 3.4, 95% CI 1.5-7.6), falling after 3 months (OR 1.0, 95% CI 0.5-2.2). Data were sparse for cephalosporins and macrolides. Resistance in Enterobacter increased post-exposure (OR 3.2, 95% CI 0.9-10.8, from controlled studies and OR 7.1, 95% CI 4.2-12, from time-series studies], but was lower after 1 month (OR 1.8, 95% CI 0.9-3.6). CONCLUSIONS: Resistance generally increased soon after antibiotic use. For some antibiotic classes and bacteria, it partially diminished after 1 and 3 months, but longer-term data are lacking and urgently needed. TRIAL REGISTRATION: PROSPERO CRD42015025499 .

Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: 1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years). SEARCH METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people who left the studies early had no improvement. MAIN RESULTS: There are 10 included trials (N = 261) published between 1973 and 2010; eight are new from the 2015 and 2017 update searches. Forty-eight studies are excluded. Participants were mostly chronically mentally ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks) duration. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment and generation of the sequence. Studies were also not clearly blinded and we are unsure if data are incomplete or selectively reported, or if other biases were operating.One small, three-arm trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low-quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality evidence) may lead to a clinically important improvement in tardive dyskinesia symptoms compared with placebo after 2 weeks' treatment, but found no evidence of a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19 to 1.86; very low quality evidence). Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment and found no evidence of a difference on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR 0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on adverse events.For remaining outcomes there was no evidence of a difference between any of the interventions: alpha-methyldopa versus placebo for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence), celiprolol versus placebo for leaving the study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very low quality evidence), alpha-methyldopa versus reserpine for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events; very low quality evidence), reserpine or carbidopa/levodopa versus placebo for deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI 0.35 to 3.99; very low quality evidence), oxypertine versus placebo for deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride, oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6 RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1 RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00). AUTHORS' CONCLUSIONS: Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.

Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere. OBJECTIVES: To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention. 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 (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'. AUTHORS' CONCLUSIONS: This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia.

BACKGROUND: Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation. OBJECTIVES: To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established. SEARCH METHODS: We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement. MAIN RESULTS: We included 13 RCTs with 711 participants; eight of these studies were newly included in this 2017 update. One trial is ongoing.There was low-quality evidence of a clear difference on no clinically important improvement in TD favouring switch to risperidone compared with antipsychotic cessation (with placebo) (1 RCT, 42 people, RR 0.45 CI 0.23 to 0.89, low-quality evidence). Because evidence was of very low quality for antipsychotic dose reduction versus antipsychotic maintenance (2 RCTs, 17 people, RR 0.42 95% CI 0.17 to 1.04, very low-quality evidence), and for switch to a new antipsychotic versus switch to another new antipsychotic (5 comparisons, 5 RCTs, 140 people, no meta-analysis, effects for all comparisons equivocal), we are uncertain about these effects. There was low-quality evidence of a significant difference on extrapyramidal symptoms: use of antiparkinsonism medication favouring switch to quetiapine compared with switch to haloperidol (1 RCT, 45 people, RR 0.45 CI 0.21 to 0.96, low-quality evidence). There was no evidence of a difference for switch to risperidone or haloperidol compared with antipsychotic cessation (with placebo) (RR 1 RCT, 48 people, RR 2.08 95% CI 0.74 to 5.86, low-quality evidence) and switch to risperidone compared with switch to haloperidol (RR 1 RCT, 37 people, RR 0.68 95% CI 0.34 to 1.35, very low-quality evidence).Trials also reported on secondary outcomes such as other TD symptom outcomes, other adverse events outcomes, mental state, and leaving the study early, but the quality of the evidence for all these outcomes was very low due mainly to small sample sizes, very wide 95% CIs, and risk of bias. No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes that we designated as being important to patients. AUTHORS' CONCLUSIONS: Limited data from small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration to fully investigate this area.

Droperidol for psychosis-induced aggression or agitation.

BACKGROUND: People experiencing acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone antipsychotic, has been used for this purpose in several countries. OBJECTIVES: To estimate the effects of droperidol, including its cost-effectiveness, when compared to placebo, other 'standard' or 'non-standard' treatments, or other forms of management of psychotic illness, in controlling acutely disturbed behaviour and reducing psychotic symptoms in people with schizophrenia-like illnesses. SEARCH METHODS: We updated previous searches by searching the Cochrane Schizophrenia Group Register (18 December 2015). We searched references of all identified studies for further trial citations and contacted authors of trials. We supplemented these electronic searches by handsearching reference lists and contacting both the pharmaceutical industry and relevant authors. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) with useable data that compared droperidol to any other treatment for people acutely ill with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode. DATA COLLECTION AND ANALYSIS: For included studies, we assessed quality, risk of bias and extracted data. We excluded data when more than 50% of participants were lost to follow-up. For binary outcomes, we calculated standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI). We created a 'Summary of findings' table using GRADE. MAIN RESULTS: We identified four relevant trials from the update search (previous version of this review included only two trials). When droperidol was compared with placebo, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 227, RR 1.18, 95% CI 1.05 to 1.31, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for the droperidol group (1 RCT, N = 227, RR 0.55, 95% CI 0.36 to 0.85, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 227, RR 0.34, 95% CI 0.01 to 8.31, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 227, RR 0.62, 95% CI 0.15 to 2.52, low-quality evidence) than placebo. For 'being ready for discharge', there was no clear difference between groups (1 RCT, N = 227, RR 1.16, 95% CI 0.90 to 1.48, high-quality evidence). There were no data for mental state and costs.Similarly, when droperidol was compared to haloperidol, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 228, RR 1.01, 95% CI 0.93 to 1.09, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for participants in the droperidol group (2 RCTs, N = 255, RR 0.37, 95% CI 0.16 to 0.90, high-quality evidence). There was no evidence that droperidol caused more cardiovascular hypotension (1 RCT, N = 228, RR 2.80, 95% CI 0.30 to 26.49,moderate-quality evidence) and cardiovascular hypotension/desaturation (1 RCT, N = 228, RR 2.80, 95% CI 0.12 to 67.98, low-quality evidence) than haloperidol. There was no suggestion that use of droperidol was unsafe. For mental state, there was no evidence of clear difference between the efficacy of droperidol compared to haloperidol (Scale for Quantification of Psychotic Symptom Severity, 1 RCT, N = 40, mean difference (MD) 0.11, 95% CI -0.07 to 0.29, low-quality evidence). There were no data for service use and costs.Whereas, when droperidol was compared with midazolam, for the outcome of tranquillisation or asleep by 30 minutes we found droperidol to be less acutely tranquillising than midazolam (1 RCT, N = 153, RR 0.96, 95% CI 0.72 to 1.28, high-quality evidence). As regards the 'need for additional medication by 60 minutes after initial adequate sedation, we found an effect (1 RCT, N = 153, RR 0.54, 95% CI 0.24 to 1.20, moderate-quality evidence). In terms of adverse effects, we found no statistically significant differences between the two drugs for either airway obstruction (1 RCT, N = 153, RR 0.13, 95% CI 0.01 to 2.55, low-quality evidence) or respiratory hypoxia (1 RCT, N = 153, RR 0.70, 95% CI 0.16 to 3.03, moderate-quality evidence) - but use of midazolam did result in three people (out of around 70) needing some sort of 'airway management' with no such events in the droperidol group. There were no data for mental state, service use and costs.Furthermore, when droperidol was compared to olanzapine, for the outcome of tranquillisation or asleep by any time point, we found no clear differences between the older drug (droperidol) and olanzapine (e.g. at 30 minutes: 1 RCT, N = 221, RR 1.02, 95% CI 0.94 to 1.11, high-quality evidence). There was a suggestion that participants allocated droperidol needed less additional medication after 60 minutes than people given the olanzapine (1 RCT, N = 221, RR 0.56, 95% CI 0.36 to 0.87, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 221, RR 0.32, 95% CI 0.01 to 7.88, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 221, RR 0.97, 95% CI 0.20 to 4.72, low-quality evidence) than olanzapine. For 'being ready for discharge', there was no difference between groups (1 RCT, N = 221, RR 1.06, 95% CI 0.83 to 1.34, high-quality evidence). There were no data for mental state and costs. AUTHORS' CONCLUSIONS: Previously, the use of droperidol was justified based on experience rather than evidence from well-conducted and reported randomised trials. However, this update found high-quality evidence with minimal risk of bias to support the use of droperidol for acute psychosis. Also, we found no evidence to suggest that droperidol should not be a treatment option for people acutely ill and disturbed because of serious mental illnesses.

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.

Cannabis and schizophrenia.

BACKGROUND: Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. OBJECTIVES: To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. SELECTION CRITERIA: We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. 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 identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. AUTHORS' CONCLUSIONS: Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.

Chlorpromazine versus placebo for schizophrenia.

BACKGROUND: Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. OBJECTIVES: To review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed-effect model. MAIN RESULTS: We inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early ( n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43). AUTHORS' CONCLUSIONS: The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

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 estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared with placebo or antipsychotics, alone or in combination with antihistamines, to control disturbed behaviour and reduce psychotic symptoms. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's register (January 2012), inspected reference lists of included and excluded studies and contacted authors of relevant studies. SELECTION CRITERIA: We included all randomised clinical 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 with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality assessed them and extracted data. For binary outcomes, we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we calculated the mean difference (MD) between groups. If heterogeneity was identified, this was explored using a random-effects model. MAIN RESULTS: We included 21 trials with a total of n = 1968 participants. There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo, although there was a higher risk of no improvement in people receiving placebo 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). There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics (n = 308, 5 RCTs, RR 1.10, 95% CI 0.85 to 1.42, low quality evidence); however, people receiving benzodiazepines were less likely to experience extrapyramidal effects (EPS) in the medium term (n = 536, 8 RCTs, RR 0.15, 95% CI 0.06 to 0.39, moderate quality of evidence). Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results. 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 = 155, 3 RCTs, RR 1.27, 95% CI 0.94 to 1.70, very 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). However, more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine (n = 60,1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality evidence) or ziprasidone (n = 60, 1 RCT, RR 4.00, 95% CI 1.25 to 12.75 very low quality evidence). When haloperidol and midazolam were compared with olanzapine, there was some evidence the combination was superior in terms of improvement, sedation and behaviour. AUTHORS' CONCLUSIONS: The evidence from trials for the use of benzodiazepines alone is not good. There were relatively little good data and most trials are 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 needed in this area.

Haloperidol dose for the acute phase of schizophrenia.

BACKGROUND: Haloperidol is a benchmark, accessible antipsychotic drug against which the effects of newer treatments are gauged. OBJECTIVES: To determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (February 2010), which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: We selected studies if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes. DATA COLLECTION AND ANALYSIS: For this update, we inspected all citations and independently re-inspected a sample of citations in order to ensure reliable selection. We resolved any disagreement by discussion, and where doubt remained, we acquired the full-text article for further inspection. We then ordered papers, and reliably re-inspected and quality assessed the full reports, and extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR) with 95% confidence intervals (CI) on an intention-to-treat (ITT) basis. We assumed that people who left the study early or were lost to follow-up had a negative outcome. We calculated mean differences (MD) for continuous outcomes that reported ITT, last observation carried forward (LOCF) data. We excluded data if loss to follow-up was greater than 50%. MAIN RESULTS: We included 19 trials with 19 different randomised dose comparisons. No studies reported data on relapse rates or quality of life and only one compared low dose (> 1.5 to 3 mg/day) haloperidol to higher dose ranges. Using standard lower dose (> 3 to 7.5 mg/day) did not result in loss of efficacy (no clinically important improvement in global state, versus standard higher dose (> 7.5 to 15 mg/day, n = 48, 1 RCT, RR 1.09, 95% CI 0.7 to 1.8, very-low-quality evidence); versus high dose (> 15 to 35 mg/day, n = 81, 2 RCTs, RR 0.95, 95% CI 0.8 to 1.2, very-low-quality evidence). Doses of haloperidol in the range of > 3 to 7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus standard higher dose, n = 64, 2 RCTs, RR 0.12, 95% CI 0.01 to 2.1, very-low-quality evidence); versus high dose, n = 144, 3 RCTs, RR 0.59, 95% CI 0.5 to 0.8, very-low-quality evidence; versus very high dose (> 35 mg/day, n = 86, 2 RCTs, RR 0.70, 95% CI 0.5 to 1.1, very-low-quality evidence). None of the other comparisons between dose ranges yielded statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences. AUTHORS' CONCLUSIONS: Noresults were conclusive and all were based on small, short studies of limited quality. However, it would be understandable if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the lower dose ranges, especially > 1.5 to 3 mg/day.

Early intervention for psychosis.

BACKGROUND: Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness).Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. OBJECTIVES: To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). MAIN RESULTS: Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding.The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, -1.39 CI -2.8 to 0.1), neither were data for 'Not hospitalised' by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers 'not living independently' by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were 'not living independently' (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99).Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. AUTHORS' CONCLUSIONS: There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials.

Day hospital versus admission for acute psychiatric disorders.

BACKGROUND: Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders. It has been proposed that many of those currently treated as inpatients could be cared for in acute psychiatric day hospitals. OBJECTIVES: To assess the effects of day hospital versus inpatient care for people with acute psychiatric disorders. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (June 2010) which is based on regular searches of MEDLINE, EMBASE, CINAHL and PsycINFO. We approached trialists to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials of day hospital versus inpatient care, for people with acute psychiatric disorders. Studies were ineligible if a majority of participants were under 18 or over 65, or had a primary diagnosis of substance abuse or organic brain disorder. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and cross-checked data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data. We calculated weighted or standardised means for continuous data. Day hospital trials tend to present similar outcomes in slightly different formats, making it difficult to synthesise data. We therefore sought individual patient data so that we could re-analyse outcomes in a common format. MAIN RESULTS: Ten trials (involving 2685 people) met the inclusion criteria. We obtained individual patient data for four trials (involving 646 people). We found no difference in the number lost to follow-up by one year between day hospital care and inpatient care (5 RCTs, n = 1694, RR 0.94 CI 0.82 to 1.08). There is moderate evidence that the duration of index admission is longer for patients in day hospital care than inpatient care (4 RCTs, n = 1582, WMD 27.47 CI 3.96 to 50.98). There is very low evidence that the duration of day patient care (adjusted days/month) is longer for patients in day hospital care than inpatient care (3 RCTs, n = 265, WMD 2.34 days/month CI 1.97 to 2.70). There is no difference between day hospital care and inpatient care for the being readmitted to in/day patient care after discharge (5 RCTs, n = 667, RR 0.91 CI 0.72 to 1.15). It is likely that there is no difference between day hospital care and inpatient care for being unemployed at the end of the study (1 RCT, n = 179, RR 0.88 CI 0.66 to 1.19), for quality of life (1 RCT, n = 1117, MD 0.01 CI -0.13 to 0.15) or for treatment satisfaction (1 RCT, n = 1117, MD 0.06 CI -0.18 to 0.30). AUTHORS' CONCLUSIONS: Caring for people in acute day hospitals is as effective as inpatient care in treating acutely ill psychiatric patients. However, further data are still needed on the cost effectiveness of day hospitals.

Family intervention for schizophrenia.

BACKGROUND: People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. OBJECTIVES: To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. SEARCH STRATEGY: We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). SELECTION CRITERIA: We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. DATA COLLECTION AND ANALYSIS: We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). MAIN RESULTS: This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. AUTHORS' CONCLUSIONS: Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings.

Clozapine versus typical neuroleptic medication for schizophrenia.

BACKGROUND: Long-term drug treatment of schizophrenia with typical antipsychotics has limitations: 25 to 33% of patients have illnesses that are treatment-resistant. Clozapine is an antipsychotic drug, which is claimed to have superior efficacy and to cause fewer motor adverse effects than typical drugs for people with treatment-resistant illnesses. Clozapine carries a significant risk of serious blood disorders, which necessitates mandatory weekly blood monitoring at least during the first months of treatment. OBJECTIVES: To evaluate the effects of clozapine compared with typical antipsychotic drugs in people with schizophrenia. SEARCH STRATEGY: For the current update of this review (March 2006) we searched the Cochrane Schizophrenia Group Trials Register. SELECTION CRITERIA: All relevant randomised clinical trials (RCTs). DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model. MAIN RESULTS: We have included 42 trials (3950 participants) in this review. Twenty-eight of the included studies are less than 13 weeks in duration, and, overall, trials were at significant risk of bias. We found no significant difference in the effects of clozapine and typical neuroleptic drugs for broad outcomes such as mortality, ability to work or suitability for discharge at the end of the study. Clinical improvements were seen more frequently in those taking clozapine (n=1119, 14 RCTs, RR 0.72 CI 0.7 to 0.8, NNT 6 CI 5 to 8). Also, participants given clozapine had fewer relapses than those on typical antipsychotic drugs (n=1303, RR 0.62 CI 0.5 to 0.8, NNT 21 CI 15 to 49). BPRS scores showed a greater reduction of symptoms in clozapine-treated patients, (n=1145, 16 RCTs, WMD -4.22 CI -5.4 to -3.1), although the data were heterogeneous (Chi(2) 0.0001, I(2) 66%). Short-term data from the SANS negative symptom scores favoured clozapine (n=196, 5 RCTs, WMD -5.92 CI -7.8 to -4.1). We found clozapine to be more acceptable in long-term treatment than conventional antipsychotic drugs (n=982, 16 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 15 CI 12 to 20). Blood problems occurred more frequently in participants receiving clozapine (3.2%) compared with those given typical antipsychotics (0%) (n=1031, 13 RCTs, RR 7.09 CI 2.0 to 25.6). Clozapine participants experienced more drowsiness, hypersalivation, or temperature increase, than those given conventional neuroleptics. However, clozapine patients experienced fewer motor adverse effects (n=1433, 18 RCTs, RR 0.58 CI 0.5 to 0.7, NNT 5 CI 4 to 6).The clinical effects of clozapine were more pronounced in participants resistant to typical neuroleptics in terms of clinical improvement (n=370, 4 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 4 CI 3 to 6) and symptom reduction. Thirty-four per cent of treatment-resistant participants had a clinical improvement with clozapine treatment. AUTHORS' CONCLUSIONS: Clozapine may be more effective in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse, than typical antipsychotic drugs - but data are weak and prone to bias. Participants were more satisfied with clozapine treatment than with typical neuroleptic treatment. The clinical effect of clozapine, however, is, at least in the short term, not reflected in measures of global functioning such as ability to leave the hospital and maintain an occupation. The short-term benefits of clozapine have to be weighed against the risk of adverse effects. Within the context of trials, the potentially dangerous white blood cell decline seems to be more frequent in children and adolescents and in the elderly than in young adults or people of middle-age.The existing trials have largely neglected to assess the views of participants and their families on clozapine. More community-based long-term randomised trials are needed to evaluate the efficacy of clozapine on global and social functioning as trials in special groups such as people with learning disabilities.

Cannabis and schizophrenia.

BACKGROUND: Many people with schizophrenia use cannabis and its effects on the illness are unclear. OBJECTIVES: To evaluate the effects of cannabis use on people with schizophrenia and schizophrenia-like illnesses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: We included all randomised trials involving cannabinoids and people with schizophrenia or schizophrenia-like illnesses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed effects model. We calculated the numbers needed to treat/harm (NNT/NNH). For continuous data, we calculated weighted mean differences (WMD) again based on a fixed effects model. MAIN RESULTS: We identified one randomised trial. No significant differences were found between the Cannabis and Psychosis Therapy (CAP) intervention group and the Psychoeducaton (PE) intervention for use of cannabis at three months assessment (n=47, RR 1.04 CI 0.6 to 1.7). BPRS-extended scale scores at three months assessment (n=47, WMD -3.60 CI -12.8 to 5.6) and nine months assessment (n=47, WMD 0.80 CI -7.5 to 9.1) were non-significant between CAP and PE. We found no significant improvement in social functioning in the CAP group compared with PE (at 3 months, n=47, WMD -0.80 CI -10 to 8.4) and (at 9 months, n=47, WMD -4.70 CI -14.5 to 5.1). AUTHORS' CONCLUSIONS: At present, there is insufficient evidence to support or refute the use of cannabis/cannabinoid compounds for people suffering with schizophrenia. This review highlights the need for well designed, conducted and reported clinical trials to address the potential effects of cannabis based compounds for people with schizophrenia.

Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review.

Signs of Irukandji syndrome (IS) suggest an underlying catecholamine storm with research demonstrating that Carukia barnesi venom causes a significant rise in adrenaline/noradrenaline serum levels. A systematic review was undertaken to ascertain the current evidence in treating IS with magnesium salts. A literature search was conducted using Scopus, Medline and ScienceDirect. Further articles were discarded via title description and/or abstract details. The remaining were read in full, and those identified as not having sufficient information regarding magnesium and patient outcomes were removed. Nine articles were identified. One article was a randomised controlled trial, which concluded that there appears to be no beneficial difference between those patients who received the magnesium sulphate (MgSO4 ) and those who received the placebo and recommended against the use of MgSO4 in IS. Of the remaining eight, one reported the failure of MgSO4 and the remaining seven were case series reporting varying success in its use. This systematic review found insufficient evidence to support any clear recommendation regarding the use of magnesium, but nor was there clear evidence to recommend against its use in IS. Two case series describe significant reduction in key symptoms and hypertension but are a non-randomised albeit prospective series with the limitations accompanying this. The reporting of recrudescence of symptoms with reduction of dose does suggest a dose-response relationship. The evidence for the use of MgSO4 is at best anecdotal, and further research is required to either confirm its benefit or confirm the randomised controlled trial.

Expediting citation screening using PICo-based title-only screening for identifying studies in scoping searches and rapid reviews.

BACKGROUND: Citation screening for scoping searches and rapid review is time-consuming and inefficient, often requiring days or sometimes months to complete. We examined the reliability of PICo-based title-only screening using keyword searches based on the PICo elements-Participants, Interventions, and Comparators, but not the Outcomes. METHODS: A convenience sample of 10 datasets, derived from the literature searches of completed systematic reviews, was used to test PICo-based title-only screening. Search terms for screening were generated from the inclusion criteria of each review, specifically the PICo elements-Participants, Interventions and Comparators. Synonyms for the PICo terms were sought, including alternatives for clinical conditions, trade names of generic drugs and abbreviations for clinical conditions, interventions and comparators. The MeSH database, Wikipedia, Google searches and online thesauri were used to assist generating terms. Title-only screening was performed by five reviewers independently in Endnote X7 reference management software using OR Boolean operator. Outcome measures were recall of included studies and the reduction in screening effort. Recall is the proportion of included studies retrieved using PICo title-only screening out of the total number of included studies in the original reviews. The percentage reduction in screening effort is the proportion of records not needing screening because the method eliminates them from the screen set. RESULTS: Across the 10 reviews, the reduction in screening effort ranged from 11 to 78% with a median reduction of 53%. In nine systematic reviews, the recall of included studies was 100%. In one review (oxygen therapy), four of five reviewers missed the same included study (median recall 67%). A post hoc analysis was performed on the dataset with the lowest reduction in screening effort (11%), and it was rescreened using only the intervention and comparator keywords and omitting keywords for participants. The reduction in screening effort increased to 57%, and the recall of included studies was maintained (100%). CONCLUSIONS: In this sample of datasets, PICo-based title-only screening was able to expedite citation screening for scoping searches and rapid reviews by reducing the number of citations needed to screen but requires a thorough workup of the potential synonyms and alternative terms. Further research which evaluates the feasibility of this technique with heterogeneous datasets in different fields would be useful to inform the generalisability of this technique.

Systematic review of the effects of care provided with and without diagnostic clinical prediction rules.

BACKGROUND: Diagnostic clinical prediction rules (CPRs) are worthwhile if they improve patient outcomes or provide benefits such as reduced resource use, without harming patients. We conducted a systematic review to assess the effects of diagnostic CPRs on patient and process of care outcomes. METHODS: We searched electronic databases and a trial registry and performed citation and reference checks, for randomised trials comparing a diagnostic strategy with and without a CPR. Included studies were assessed for risk of bias and similar studies meta-analysed. RESULTS: Twenty-seven studies evaluating diagnostic CPRs for 14 conditions were included. A clinical management decision was the primary outcome in the majority of studies. Most studies were judged to be at high or uncertain risk of bias on ≥3 of 6 domains. Details of study interventions and implementation were infrequently reported.For suspected Group A Streptococcus throat infection, diagnostic CPRs reduced symptoms (1 study) and antibiotic prescriptions (5 studies, RR 0.86, 95% CI 0.75 to 0.99). For suspected cardiac chest pain, diagnostic strategies incorporating a CPR improved early discharge rates (1 study), decreased objective cardiac testing (1 study) and decreased hospitalisations (1 study). For ankle injuries, Ottawa Ankle Rules reduced radiography when used with clinical examination (1 study) but had no effect on length of stay as a triage test (1 study). For suspected acute appendicitis, CPRs had no effect on rates of perforated appendix (1 study) or the number of non-therapeutic operations (5 studies, RR 0.68, 95% CI 0.43 to 1.08). For suspected pneumonia, CPRs reduced antibiotic prescribing without unfavourable outcomes (3 studies). For children with possible serious bacterial infection, diagnostic CPRs did not improve process of care outcomes (3 studies). CONCLUSION: There are few randomised trials of diagnostic CPRs, and patient outcomes are infrequently reported. Diagnostic CPRs had a positive effect on process outcomes in some clinical conditions; however, many studies were at unclear or high risk of bias and the results may be context specific. Future studies should seek to detail how the CPR might alter the diagnostic pathway, report effects on both patient and process outcomes, and improve reporting of the study interventions and implementation. TRIAL REGISTRATION: The protocol for this review was not registered with PROSPERO, the international prospective register of systematic review protocols. The review was conceived and protocol prepared prior to the launch of PROSPERO in February 2011.

A comparison of the performance of seven key bibliographic databases in identifying all relevant systematic reviews of interventions for hypertension.

BACKGROUND: Bibliographic databases are the primary resource for identifying systematic reviews of health care interventions. Reliable retrieval of systematic reviews depends on the scope of indexing used by database providers. Therefore, searching one database may be insufficient, but it is unclear how many need to be searched. We sought to evaluate the performance of seven major bibliographic databases for the identification of systematic reviews for hypertension. METHODS: We searched seven databases (Cochrane library, Database of Abstracts of Reviews of Effects (DARE), Excerpta Medica Database (EMBASE), Epistemonikos, Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Health and Turning Research Into Practice (TRIP)) from 2003 to 2015 for systematic reviews of any intervention for hypertension. Citations retrieved were screened for relevance, coded and checked for screening consistency using a fuzzy text matching query. The performance of each database was assessed by calculating its sensitivity, precision, the number of missed reviews and the number of unique records retrieved. RESULTS: Four hundred systematic reviews were identified for inclusion from 11,381 citations retrieved from seven databases. No single database identified all the retrieved systematic reviews for hypertension. EMBASE identified the most reviews (sensitivity 69 %) but also retrieved the most irrelevant citations with 7.2 % precision (Pr). The sensitivity of the Cochrane library was 60 %, DARE 57 %, MEDLINE 57 %, PubMed Health 53 %, Epistemonikos 49 % and TRIP 33 %. EMBASE contained the highest number of unique records (n = 43). The Cochrane library identified seven unique records and had the highest precision (Pr = 30 %), followed by Epistemonikos (n = 2, Pr = 19 %). No unique records were found in PubMed Health (Pr = 24 %) DARE (Pr = 21 %), TRIP (Pr = 10 %) or MEDLINE (Pr = 10 %). Searching EMBASE and the Cochrane library identified 88 % of all systematic reviews in the reference set, and searching the freely available databases (Cochrane, Epistemonikos, MEDLINE) identified 83 % of all the reviews. The databases were re-analysed after systematic reviews of non-conventional interventions (e.g. yoga, acupuncture) were removed. Similarly, no database identified all the retrieved systematic reviews. EMBASE identified the most relevant systematic reviews (sensitivity 73 %) but also retrieved the most irrelevant citations with Pr = 5 %. The sensitivity of the Cochrane database was 62 %, followed by MEDLINE (60 %), DARE (55 %), PubMed Health (54 %), Epistemonikos (50 %) and TRIP (31 %). The precision of the Cochrane library was the highest (20 %), followed by PubMed Health (Pr = 16 %), DARE (Pr = 13 %), Epistemonikos (Pr = 12 %), MEDLINE (Pr = 6 %), TRIP (Pr = 6 %) and EMBASE (Pr = 5 %). EMBASE contained the most unique records (n = 34). The Cochrane library identified seven unique records. The other databases held no unique records. CONCLUSIONS: The coverage of bibliographic databases varies considerably due to differences in their scope and content. Researchers wishing to identify systematic reviews should not rely on one database but search multiple databases.