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.

Women with epilepsy: clinically relevant issues.

Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population.

A case of Parry-Romberg syndrome and alien hand.

Parry-Romberg syndrome (PRS) is a rare condition characterised by progressive hemi-facial atrophy. Here we present a PRS case with alien-hand syndrome, which has not previously been described in adult onset disease. On the basis of the presumed auto-immune pathology of PRS we justify the treatment strategy we successfully used in this patient. A review of the literature was extensively done for understanding the history of alien hand sign over the years.

Aripiprazole versus other atypical antipsychotics for schizophrenia.

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first-line drug treatments for people with schizophrenia. In this review, we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To review the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2012), inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study and used GRADE approach to rate quality of evidence. MAIN RESULTS: We now have included 174 trials involving 17,244 participants. Aripiprazole was compared with clozapine, quetiapine, risperidone, ziprasidone and olanzapine. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with clozapine, there were no significant differences for global state (no clinically significant response, n = 2132, 29 RCTs, low quality evidence); mental state (BPRS, n = 426, 5 RCTs, very low quality evidence); or leaving the study early for any reason (n = 240, 3 RCTs, very low quality evidence). Quality of life score using the WHO-QOL-100 scale demonstrated significant difference, favouring aripiprazole (n = 132, 2 RCTs, RR 2.59 CI 1.43 to 3.74, very low quality evidence). General extrapyramidal symptoms (EPS) were no different between groups (n = 520, 8 RCTs,very low quality evidence). No study reported general functioning or service use.When compared with quetiapine, there were no significant differences for global state (n = 991, 12 RCTs, low quality evidence); mental state (PANSS positive symptoms, n = 583, 7 RCTs, very low quality evidence); leaving the study early for any reason (n = 168, 2 RCTs, very low quality evidence), or general EPS symptoms (n = 348, 4 RCTs, very low quality evidence). Results were significantly in favour of aripiprazole for quality of life (WHO-QOL-100 total score, n = 100, 1 RCT, MD 2.60 CI 1.31 to 3.89, very low quality evidence). No study reported general functioning or service use.When compared with risperidone, there were no significant differences for global state (n = 6381, 80 RCTs, low quality evidence); or leaving the study early for any reason (n = 1239, 12 RCTs, very low quality evidence). Data were significantly in favour of aripiprazole for improvement in mental state using the BPRS (n = 570, 5 RCTs, MD 1.33 CI 2.24 to 0.42, very low quality evidence); with higher adverse effects seen in participants receiving risperidone of general EPS symptoms (n = 2605, 31 RCTs, RR 0.39 CI 0.31 to 0.50, low quality evidence). No study reported general functioning, quality of life or service use.When compared with ziprasidone, there were no significant differences for global state (n = 442, 6 RCTs, very low quality evidence); mental state using the BPRS (n = 247, 1 RCT, very low quality evidence); or leaving the study early for any reason (n = 316, 2 RCTs, very low quality evidence). Weight gain was significantly greater in people receiving aripiprazole (n = 232, 3 RCTs, RR 4.01 CI 1.10 to 14.60, very low quality evidence). No study reported general functioning, quality of life or service use.When compared with olanzapine, there were no significant differences for global state (n = 1739, 11 RCTs, very low quality evidence); mental state using PANSS (n = 1500, 11 RCTs, very low quality evidence); or quality of life using the GQOLI-74 scale (n = 68, 1 RCT, very low quality of evidence). Significantly more people receiving aripiprazole left the study early due to any reason (n = 2331, 9 RCTs, RR 1.15 CI 1.05 to 1.25, low quality evidence) and significantly more people receiving olanzapine gained weight (n = 1538, 9 RCTs, RR 0.25 CI 0.15 to 0.43, very low quality evidence). None of the included studies provided outcome data for the comparisons of 'service use' or 'general functioning'. AUTHORS' CONCLUSIONS: Information on all comparisons is of limited quality, is incomplete and problematic to apply clinically. The quality of the evidence is all low or very low. Aripiprazole is an antipsychotic drug with an important adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerge from ongoing larger, independent pragmatic trials.

Aripiprazole versus other atypical antipsychotics for schizophrenia.

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review. AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials.

Aripiprazole versus placebo for schizophrenia.

BACKGROUND: First generation 'typical' antipsychotics such as chlorpromazine and haloperidol have been the mainstay of treatment up until the introduction of the second generation 'atypical' antipsychotics such as risperidone and olanzapine. Typical and atypical antipsychotics do provide a treatment response for most people with schizophrenia, whether a reduction in psychotic episodes or a lessening in the severity of their illness. However, a proportion of people still do not respond adequately to antipsychotic medication. Additionally, atypical and especially typical antipsychotics are associated with serious adverse effects, which can often compromise compliance with medication and therefore increase the incidences of relapse. In this review we examine the effects of aripiprazole compared with placebo. OBJECTIVES: To evaluate the effects of aripiprazole compared with placebo for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (January 2008) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. For this update, we carried out an initial search in May 2007 and a second search in August 2008. SELECTION CRITERIA: We included all randomised trials comparing aripiprazole with placebo in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a fixed-effect model. MAIN RESULTS: Despite the fact that 2585 people participated in nine randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. In general, study attrition was very large for all studies over four weeks' duration. There was high attrition in most of the included studies. Fewer people left the aripiprazole group compared with those in the placebo group (n = 2585, 9 RCTs, RR 0.73 CI 0.60 to 0.87). Compared with placebo, aripiprazole significantly decreased relapse in both the short (n = 310, 1 RCT, RR 0.59 CI 0.45 to 0.77) and medium term (n = 310, 1 RCT, RR 0.66 CI 0.53 to 0.81). It also produced better compliance with study protocol (n = 2275, 8 RCTs, RR 0.74 CI 0.59 to 0.93). Aripiprazole may decrease prolactin levels below those expected from placebo (n = 305, 2 RCT, RR 0.21 CI 0.11 to 0.37). Insomnia (˜23%) and headaches (˜15%) were commonly reported in both groups, with no significant difference. AUTHORS' CONCLUSIONS: Aripiprazole may be effective for the treatment of schizophrenia. Aripiprazole has a lower risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short-, medium- and long-term randomised controlled trials should be undertaken to determine its position in everyday clinical practice.

Aripiprazole versus other atypical antipsychotics for schizophrenia.

BACKGROUND: In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. 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 random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. MAIN RESULTS: The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side-effects such as cholesterol increase, weight gain, sedation and prolactin associated side-effects. Compared with risperidone there was no difference in efficacy (PANSS total score: n=372, 2 RCTs, MD 1.50 CI -2.96 to 5.96). Dystonia, QTc abnormalities, prolactin and cholesterol increase were less frequent in the aripiprazole group, while tremor was more frequent in the aripiprazole group compared with those allocated risperidone. AUTHORS' CONCLUSIONS: Aripiprazole may be somewhat less effective than olanzapine, but more tolerable in terms of metabolic effects and sedation. There is no evidence for a difference in efficacy compared to risperidone, but for better tolerability in terms of dystonias, cholesterol prolactin increase and QTc prolongation. Randomised evidence comparing aripiprazole with other second generation antipsychotic drugs is currently not available.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.

BACKGROUND: Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine. METHODS: Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. RESULTS: 64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02-2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. CONCLUSION: These findings would suggest that dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07752728.

Aripiprazole versus typical antipsychotic drugs for schizophrenia.

BACKGROUND: Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. 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 random effects 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 random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data. MAIN RESULTS: We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). AUTHORS' CONCLUSIONS: Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.

BACKGROUND: In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. METHODS/DESIGN: The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

Internet-based search of randomised trials relevant to mental health originating in the Arab world.

BACKGROUND: The internet is becoming a widely used source of accessing medical research through various on-line databases. This instant access to information is of benefit to busy clinicians and service users around the world. The population of the Arab World is comparable to that of the United States, yet it is widely believed to have a greatly contrasting output of randomised controlled trials related to mental health. This study was designed to investigate the existence of such research in the Arab World and also to investigate the availability of this research on-line. METHODS: Survey of findings from three internet-based potential sources of randomised trials originating from the Arab world and relevant to mental health care. RESULTS: A manual search of an Arabic online current contents service identified 3 studies, MEDLINE, EMBASE, and PsycINFO searches identified only 1 study, and a manual search of a specifically indexed, study-based mental health database, PsiTri, revealed 27 trials. CONCLUSION: There genuinely seem to be few trials from the Arab world and accessing these on-line was problematic. Replication of some studies that guide psychiatric/psychological practice in the Arab world would seem prudent.

Gross Domestic Product (GDP) and productivity of schizophrenia trials: an ecological study.

BACKGROUND: The 5000 randomised controlled trials (RCTs) in the Cochrane Schizophrenia Group's database affords an opportunity to research for variables related to the differences between nations of their output of schizophrenia trials. METHODS: Ecological study--investigating the relationship between four economic/demographic variables and number of schizophrenia RCTs per country. The variable with closest correlation was used to predict the expected number of studies. RESULTS: GDP closely correlated with schizophrenia trial output, with 76% of the total variation about the Y explained by the regression line (r = 0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of schizophrenia trials, exceeding their predicted output. All nations with no identified trial output had GDPs that predicted zero trial activity. Several nations with relatively small GDPs are, nevertheless, highly productive of trials. Some wealthy countries seem either not to have produced the expected number of randomised trials or not to have disseminated them to the English-speaking world. CONCLUSIONS: This hypothesis-generating study could not investigate causal relationships, but suggests, that for those seeking all relevant studies, expending effort searching the scientific literature of Germany, Italy, France, Brazil and Japan may be a good investment.