Coenzyme Q10 for heart failure.

BACKGROUND: Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014. OBJECTIVES: To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection. MAIN RESULTS: We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision. AUTHORS' CONCLUSIONS: The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.

Haloperidol discontinuation for people with schizophrenia.

BACKGROUND: Schizophrenia is a disabling serious mental illness that can be chronic. Haloperidol, one of the first generation of antipsychotic drugs, is effective in the treatment of schizophrenia but can have adverse side effects. The effects of stopping haloperidol in people with schizophrenia who are stable on their prescription are not well researched in the context of systematic reviews. OBJECTIVES: To review the effects of haloperidol discontinuation in people with schizophrenia who are stable on haloperidol. SEARCH METHODS: On 20 February 2015, 24 May 2017, and 12 January 2019, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers. SELECTION CRITERIA: We included clinical trials randomising adults with schizophrenia or related disorders who were receiving haloperidol, and were stable. We included trials that randomised such participants to either continue their current treatment with haloperidol or discontinue their haloperidol treatment. We included trials that met our selection criteria and reported usable data. DATA COLLECTION AND ANALYSIS: We independently checked all records retrieved from the search and obtained full reports of relevant records for closer inspection. We extracted data from included studies independently. All usable data were dichotomous, and we calculated relative risks (RR) and their 95% confidence intervals (95% CI) using a fixed-effect model. We assessed risk of bias within the included studies and used GRADE to create a 'Summary of findings' table. MAIN RESULTS: We included five randomised controlled trials (RCTs) with 232 participants comparing haloperidol discontinuation with haloperidol continuation. Discontinuation was achieved in all five studies by replacing haloperidol with placebo. The trials' size ranged between 23 and 87 participants. The methods of randomisation, allocation concealment and blinding were poorly reported.Participants allocated to discontinuing haloperidol treatment were more likely to show no improvement in global state compared with those in the haloperidol continuation group (n = 49; 1 RCT; RR 2.06, 95% CI 1.33 to 3.20; very low quality evidence: our confidence in the effect estimate is limited due to relevant methodological shortcomings of included trials). Those who continued haloperidol treatment were less likely to experience a relapse compared to people who discontinued taking haloperidol (n = 165; 4 RCTs; RR 1.80, 95% CI 1.18 to 2.74; very low quality evidence). Satisfaction with treatment (measured as numbers leaving the study early) was similar between groups (n = 43; 1 RCT; RR 0.13, 95% CI 0.01 to 2.28; very low quality evidence).No usable mental state, general functioning, general behaviour or adverse effect data were reported by any of the trials. AUTHORS' CONCLUSIONS: This review provides limited evidence derived from small, short-term studies. The longest study was for one year, making it difficult to generalise the results to a life-long disorder. Very low quality evidence shows that discontinuation of haloperidol is associated with an increased risk of relapse and a reduction in the risk of 'global state improvement'. However, participant satisfaction with haloperidol treatment was not different from participant satisfaction with haloperidol discontinuation as measured by leaving the studies early. Due to the very low quality of these results, firm conclusions cannot be made. In addition, the available studies did not report usable data regarding the adverse effects of haloperidol treatment.Considering that haloperidol is one of the most widely used antipsychotic drugs, it was surprising that only a small number of studies into the benefit and harm of haloperidol discontinuation were available. Moreover, the available studies did not report on outcomes that are important to clinicians and to people with schizophrenia, particularly adverse effects and social outcomes. Better designed trials are warranted.

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.

Coenzyme Q10 for heart failure.

BACKGROUND: Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted. OBJECTIVES: To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers. MAIN RESULTS: We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution. AUTHORS' CONCLUSIONS: No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.

Anticholinergic medication for non-clozapine neuroleptic-induced hypersalivation in people with schizophrenia.

BACKGROUND: Treatment of schizophrenia depends heavily on neuroleptic drugs. Hypersalivation is a common side effect when people with schizophrenia are treated with neuroleptic drugs. Hypersalivation can be an embarrassing and stigmatising problem, can affect quality of life and can result in discontinuation of neuroleptic treatment. It can also be difficult to treat. OBJECTIVES: To summarise the best available evidence of the effects of anticholinergic drugs in the treatment of non-clozapine neuroleptic-induced hypersalivation in people with schizophrenia. Clozapine-induced hypersalivation has been addressed in another Cochrane review. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (15 November 2012) and inspected references of all identified studies for further relevant studies. We were to contact the first author of each included study for information regarding unpublished trials. SELECTION CRITERIA: All randomised controlled trials comparing an anticholinergic drug with placebo, no treatment, another anticholinergic drug or any other intervention. DATA COLLECTION AND ANALYSIS: We inspected the results of the search to identify relevant studies. We were to extract data onto standard, simple forms. Disagreements were resolved through discussion. The risk of bias was to be assessed using the Cochrane risk assessment tool. For binary outcomes, we were to calculate a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we were to estimate the mean difference between groups. MAIN RESULTS: The search resulted in four potential studies; after inspection, all were excluded. Three studies were excluded because they involved people with clozapine-induced hypersalivation - a topic covered in another Cochrane review. The fourth study was excluded because it involved people with schizophrenia, mood disorders or other mental disorders who were suffering from clozapine- and non-clozapine induced hypersalivation and were treated with Chinese medicines with unknown anticholinergic properties. People in the control group received an anticholinergic drug (artane) or an antihistamine (phenergan). It was not possible to separate clozapine- from non-clozapine-treated people in the intervention group, or to separate artane-treated people from phenergan-treated people in the control group. AUTHORS' CONCLUSIONS: We have been unable to locate any studies addressing the question raised in this review. Accordingly, this empty review points out an important clinical problem that needs to be investigated via well-designed and well-conducted randomised trials. Clinicians and patients are likely to continue with their current dependence on clinical judgement and personal experience. Policy makers have no trial-based evidence upon which to base guidelines for the treatment of hypersalivation induced by neuroleptics other than clozapine. They are likely to continue to rely on opinion and habit when making recommendations. Funders of studies may wish to make this important subgroup of people a priority in future research.

Preventive interventions for postnatal psychosis.

BACKGROUND: Postnatal psychosis is a worldwide life-threatening condition that affects one to two in every 1000 new mothers. It has an abrupt onset within a month of childbirth. Affected new mothers rapidly develop frank psychosis, cognitive impairment, and disorganised behaviours. Factors that increase the risk of postnatal psychosis include primiparous mothers who are single, women who are older, or with a past psychiatric history and family history of affective psychosis, prenatal depression and autoimmune thyroid dysfunction. The risk of a future postnatal recurrence is 25% to 57%. Preventive interventions for postnatal psychosis aim at identifying women with risk factors, early recognition of imminent psychosis through screening, and preventive drug therapy. Mood stabilisers, antipsychotic drugs and hormone therapy may be beneficial in the prevention of postnatal psychotic episodes in women at risk. OBJECTIVES: To investigate the best available evidence for interventions aimed at preventing postnatal psychosis. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in October 2012 using the search strategy of the Cochrane Schizophrenia Group. SELECTION CRITERIA: All randomised controlled trials relevant to the prevention of postnatal psychosis. DATA COLLECTION AND ANALYSIS: Two review authors inspected all citations to ensure reliable selection. If we had included relevant trials, we planned to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors would have independently extracted data. For homogenous dichotomous data, we planned to calculate the risk ratio (RR), 95% confidence interval (CI), and the number needed to treat to benefit/harm (NNTB/NNTH) on an intention-to-treat basis. MAIN RESULTS: There are no included studies in this review. The electronic search produced three relevant references, among which we identified two old planned trials that seem never to have started, and one which we excluded a study because it was a report of a case series. AUTHORS' CONCLUSIONS: This is not an empty review - it is a review full of unanswered questions. Despite growing interest in women's mental health, the literature in the area of postnatal psychosis is still very limited. It seems that clinicians have no choice but to continue with their current practices guided solely by varied clinical judgement. Women at risk of postnatal psychosis and their relatives are justified to be disappointed in the medical/research fraternity. A post hoc PubMed topic (not methodology-specific) search identified mainly case series. Policy makers have no trial-based evidence upon which to base their guidelines. Certainly, preventive interventions for postnatal psychosis are difficult to justify with confidence without well-designed, well-conducted, and well-reported randomised studies. Available publications suggest that such studies are possible and funders of research may wish to make this work a priority.

Pacing for drug-refractory or drug-intolerant hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance for which negative inotropes are the most widely used initial therapies. Observational studies and small randomised trials have suggested symptomatic and functional benefits using pacing and several theories have been put forward to explain why. Pacing, although not the primary treatment for HCM, could be beneficial to patients with relative or absolute contraindications to surgery or alcohol ablation. Several randomised controlled trials comparing pacing to other therapeutic modalities have been conducted but no Cochrane-style systematic review has been done. OBJECTIVES: To assess the effects of pacing in drug-refractory or drug-intolerant hypertrophic cardiomyopathy patients. SEARCH METHODS: We searched the following on the 14/4/2010: CENTRAL (The Cochrane Library 2010, Issue 1), MEDLINE OVID (from 1950 onwards ), EMBASE OVID (from 1980 onwards ), Web of Science with Conference Proceedings (from 1970 onwards). No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of either parallel or crossover design that assess the beneficial and harmful effects of pacing for hypertrophic cardiomyopathy were included. When crossover studies were identified, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS: Data from included studies were extracted onto a pre-formed data extraction paper by two authors independently. Data was then entered into Review Manager 5.1 for analysis. Risk of bias was assessed using the guidance provided in the Cochrane Handbook. For dichotomous data, relative risk was calculated; and for continuous data, the mean differences were calculated. Where appropriate data were available, meta-analysis was performed. Where meta-analysis was not possible, a narrative synthesis was written. A QUROUM flow chart was provided to show the flow of papers. MAIN RESULTS: Five studies (reported in 10 papers) were identified. However, three of the five studies provided un-usable data. Thus the data from only two studies (reported in seven papers) with 105 participants were included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption.When comparing active pacing versus placebo pacing on exercise capacity, one study showed that exercise time decreased from (13.1 ± 4.4) minutes to (12.6 ± 4.3) minutes in the placebo group and increased from (12.1 ± 5.6) minutes to (12.9 ± 4.2) minutes in the treatment group (MD 0.30; 95% CI -1.54 to 2.14). Statistically significant data from the same study showed that left ventricular outflow tract obstruction decreased from (71 ± 32) mm Hg to (52 ± 34) mm Hg in the placebo group and from (70 ± 24) mm Hg to (33 ± 27) mm Hg in the active pacing group (MD -19.00; 95% CI -32.29 to -5.71). This study was also able to show that New York Heart Association (NYHA) functional class decreased from (2.5 ± 0.5) to (2.2 ± 0.6) in the inactive pacing group and decreased from (2.6 ± 0.5) to (1.7 ± 0.7) in the placebo group (MD -0.50; 95% CI -0.78 to -0.22).When comparing active pacing versus trancoronary ablation of septal hypertrophy (TASH), data from one study showed that NYHA functional class decreased from (3.2 ± 0.7) to (1.5 ± 0.5) in the TASH group and decreased from (3.0 ± 0.1) to (1.9 ± 0.6) in the pacemaker group. This study also showed that LV wall thickness remained unchanged in the active pacing group compared to reduction from (22 ± 4) mm to (17 ± 3) mm in the TASH group (MD 0.60; 95% CI -5.65 to 6.85) and that LV outflow tract obstruction decreased from (80 ± 35.5) mm Hg in the TASH group to (49.3 ± 37.7) mm Hg in the pacemaker group. AUTHORS' CONCLUSIONS: Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.

Antipsychotic drug treatment for elderly people with late-onset schizophrenia.

BACKGROUND: Schizophrenia is usually considered an illness of young adulthood. However, onset after the age of 40 years is reported in 23% of patients hospitalised with schizophrenia. At least 0.1% of the world's elderly population have a diagnosis of late-onset schizophrenia which seems to differ from earlier onset schizophrenia on a variety of counts including response to antipsychotic drugs. OBJECTIVES: To assess the effects of antipsychotic drugs for elderly people with late-onset schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (January 2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant authors of trials for additional information. SELECTION CRITERIA: All relevant randomised controlled trials that compared antipsychotic drugs with other treatments for elderly people (at least 80% older than 65 years) with a recent (within five years) diagnosis of schizophrenia or schizophrenia like illnesses. DATA COLLECTION AND ANALYSIS: For the 2010 search, two new review authors (AE, AG) inspected all citations to ensure reliable selection. We assessed methodological quality of trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions. AE and AG also independently extracted data. For homogenous dichotomous data, we planned to calculate the relative risk (RR) and 95% confidence interval (CI). MAIN RESULTS: There were no included studies in the original version of this review (2002 search). The 2010 search for the current update produced 211 references, among which we identified 88 studies. Only one study met the inclusion criteria and was of acceptable quality. This was an eight-week randomised trial of risperidone and olanzapine in 44 inpatients with late-onset schizophrenia. All participants completed the eight-week trial, indicating that both drugs were well tolerated. Unfortunately, this study provided little usable data. We excluded a total of 81 studies, 77 studies because they either studied interventions other than antipsychotic medication or because they involved elderly people with chronic - not late-onset - schizophrenia. We excluded a further four trials of antipsychotics in late-onset schizophrenia because of flawed design. Five studies are still awaiting classification, and one is on-going. AUTHORS' CONCLUSIONS: There is no trial-based evidence upon which to base guidelines for the treatment of late-onset schizophrenia. There is a need for good quality-controlled clinical trials into the effects of antipsychotics for this group. Such trials are possible. Until they are undertaken, people with late-onset schizophrenia will be treated by doctors using clinical judgement and habit to guide prescribing.

Calcium channel blockers for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Neuroleptic (antipsychotic) medications are the primary treatment for these disorders. Neuroleptic medications are associated with a variety of side 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) 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 STRATEGY: We updated previous searches in May 2010 by searching the Cochrane Schizophrenia Group Register using the Cochrane Schizophrenia Group search strategy. SELECTION CRITERIA: Randomised clinical 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. DATA COLLECTION AND ANALYSIS: We planned to extract and analyse data on an intention-to-treat (ITT) basis. We intended to calculate the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random-effects model, and, where possible, calculate the number needed to treat. We planned to calculate mean differences (MD) for continuous data. MAIN RESULTS: We did not include any trials in this review. We excluded 15 studies; eight were not randomised, one did not use calcium channel blockers, five small, randomised, studies reported no usable data and one did not include people with both tardive dyskinesia and schizophrenia. AUTHORS' CONCLUSIONS: 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 clinical trials.

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.

Use of M-CHAT for a multinational screening of young children with autism in the Arab countries.

There has been a decline in the mortality rate among infants and children under five years of age in the last decade in many developing countries. This has led to a shift in focus to look beyond survival to the prevention or reduction of impairment and promotion of children's health. With the apparent rise in the prevalence of autism spectrum disorders (ASD) in the Arab countries the development of an Arabic tool for early diagnosis and intervention was sought as part of an effort to better understand the prevalence of this disorder. The Modified Checklist for Autism in Toddlers (M-CHAT) was chosen. The study was conducted in nine Arabic speaking countries. The final analysis included 228 children (122 screened positive for ASD). The sensitivity (0.86), the specificity (0.80) and positive predictive value (0.88) were very similar to Robins et al. study (2001). Maternal health problems during pregnancy and labour were found to be more significant for ASD mothers than their control. In addition, child health problems were more evident among ASD subjects as reported by their parents with significant differences from controls. The limitation of the study is that the sample size is not large enough to generalize the results to all countries of the region. The strength of the study is that it is the first known study where Arab countries undertook a collaborative mental health study using the same tool for screening for a specific disorder.