CRD summary: This review assessed the effects of acute tryptophan depletion (ATD) on declarative episodic memory. Secondary objectives included investigating the effects of gender, age and serotonergic vulnerability. The authors concluded that delayed recall and immediate recall is affected by ATD, and that ATD affects females more than males. An unclear analysis, lack of reported methodology, and uncertain quality of the primary studies limit interpretation of the results. CRD commentary: The review question was clearly supported in terms of the treatment, outcome and study design. Two electronic databases were searched, but the search terms were not reported and it was not clear whether the search was restricted by language. The authors did not describe the procedures undertaken to select papers and extract the data, therefore it is not possible to assess the likelihood of reviewer error or bias being introduced at these stages. Only double-blind studies were included but no other aspect of validity was assessed, which limits interpretation of the results. The results were based on an ANOVA model but the data were not pooled on a within-study basis. Since the results were based on a single treatment dose in a small number of diverse participants, the authors' main conclusions should be interpreted with caution.

CRD summary: This review, which determined the efficacy of cognitive- behavioural therapy (CBT) for obsessive-compulsive disorder in children and adolescents, concluded that CBT gives promising results particularly when combined with medication, but additional studies are needed to clarify its benefits. Given the small datasets with few high-quality studies, the author's conclusion seems appropriate. CRD commentary: The review question was clear and supported by detailed inclusion and exclusion criteria. The search involved appropriate electronic databases and was not restricted by language. The author did not report whether steps were taken to minimise reviewer bias and errors in relation to the study selection and data extraction processes. Validity was assessed using an aggregate quality scoring system and summary results were reported. Standard statistical methods were used to pool the data and potential sources of heterogeneity were explored. Given the small datasets with few high-quality studies, the author's conclusion that, whilst results are promising, additional studies are required to clarify the benefits of CBT, seems appropriate.

• Data on the use of antidepressants in patients with ischaemic heart disease are limited. • SSRIs are the agents of choice in patients with persisting mild depression and underlying medical conditions. Although there is limited data on their use in patients with cardiac disease, they have not been found to have an adverse cardiovascular effect profile. • Sertraline is considered the SSRI of choice in patients with IHD and is recommended first line by NICE guidance in those patients with a recent MI or unstable angina. • Tricyclic antidepressants have the most data on their use in depression but are known to have adverse cardiovascular effects such as increasing heart rate, inducing orthostatic hypotension and having antiarrhythmic activity. • Tricyclic antidpressants are advised to be used with caution in patients with IHD, ventricular arrhythmias, angina and hypertension and are contraindicated in patients who have had a recent MI. • NICE recommends that where a tricyclic antidepressant is chosen, lofepramine is a reasonable choice due to its relative lack of cardiotoxicity. • Venlafaxine is not recommended in patients with pre-existing heart disease.

Objectives: To determine if, in the short term, depressed adolescents attending routine NHS Child and Adolescent Mental Health Services (CAMHS), and receiving ongoing active clinical care, treatment with selective serotonin reuptake inhibitors (SSRIs) plus cognitive behaviour therapy (CBT) compared with SSRI alone, results in better healthcare outcomes. Design: A pragmatic randomised controlled trial (RCT) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention (BII) prior to randomisation. Setting: Six English CAMHS participated in the study. Participants: A total of 208 patients aged between 11 and 17 years were recruited and randomised. Interventions: All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT. Main outcome measures: The duration of the trial was a 12-week treatment phase, followed by a 16-week maintenance phase. Follow-up assessments were at 6, 12 and 28 weeks. The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). Secondary outcome measures were self-report depressive symptoms, interviewer-rated depressive signs and symptoms, interviewer-rated psychosocial impairment and clinical global impression of response to treatment. Information on resource use was collected in interview at baseline and at the 12- and 28-week follow-up assessments using the Child and Adolescent Service Use Schedule (CA-SUS). Results: Of the 208 patients randomised, 200 (96%) completed the trial to the primary end-point at 12 weeks. By the 28-week follow-up, 174 (84%) participants were re-evaluated. Overall, 193 (93%) participants had been assessed at one or more time points. Clinical characteristics indicated that the trial was conducted on a severely depressed group. There was significant recovery at all time points in both arms. The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point. This lack of difference held when baseline and treatment characteristics where taken into account (age, sex, severity, co-morbid characteristics, quality and quantity of CBT treatment, number of clinic attendances). The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group (p = 0.057) and no more cost-effective. Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline. There was no significant increase in disinhibition, irritability and violence compared with levels at baseline. Around 20% (n = 40) of patients in the trial were non-responders. Of these, 17 (43%) showed no improvement by 28 weeks and 23 (57%) were considered minimally (n = 10) or moderately to severely worse (n = 13). Conclusions: For moderately to severely depressed adolescents who are non-responsive to a BII, the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective. SSRIs (mostly fluoxetine) are not likely to result in harmful adverse effects. The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression. Modification is advised for those presenting with moderate (6–8 symptoms) to severe depressions (>8 symptoms) and in those with either overt suicidal risk and/or high levels of personal impairment. In such cases, the time allowed for response to psychosocial interventions should be no more than 2–4 weeks, after which fluoxetine should be prescribed. Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention, determining the characteristics of patients with severe depression who are non-responsive to fluoxetine, relapse prevention in severe depression and i

CRD summary: The authors concluded that adjunctive antipsychotic treatment is more effective than monotherapy with mood stabilisers for patients with acute bipolar mania who are already taking a mood stabiliser. A more cautious conclusion may have been more appropriate in view of the small number of studies with high drop-out rates and short-term follow-up. CRD commentary: The review addressed a clear question that was defined in terms of the participants, intervention and study design. Although inclusion criteria for the outcomes were not specifically defined, the outcomes of interest were clearly stated. Several relevant sources were searched and attempts were made to minimise language bias. It is not clear whether unpublished studies were eligible, so the potential for publication bias cannot be assessed. Methods were used to minimise reviewer error and bias in the selection of studies, but it is not clear whether similar steps were taken at the validity assessment and data extraction stages. Validity was assessed using specified criteria and the results of the assessment were reported. The studies were pooled, where appropriate, and the effects of individual drugs examined. The authors' conclusions appear to reflect the data presented, but the findings were based on a small number of studies with high drop-out rates and short-term follow-up (8 weeks or less) and a more cautious conclusion may therefore have been more appropriate. One of the authors is an employee of Sanofi-Aventis.

CRD summary: This review found that antipsychotic drugs added to antidepressants are more effective than antidepressants plus placebo for reducing symptoms in patients with treatment-resistant obsessive compulsive disorder. The conclusion reflects the evidence presented but is limited by the small number and size of the available trials. The authors' recommendation for further trials with more participants and using standard drug doses appears appropriate. CRD commentary: This review addressed a clear question and the inclusion and exclusion criteria were clear. The authors searched a reasonable range of sources without language restrictions. There was no systematic search for unpublished studies and the risk of publication bias was not assessed. Validity was assessed using a standard method and the results were used in a sensitivity analysis. Measures were taken to minimise reviewer errors and bias in the validity assessment and data extraction, although it is unclear whether similar methods were used at the study selection stage. Adequate details of the included studies were presented in the text and tables. The studies were combined by meta-analysis. Statistical heterogeneity was assessed and appropriate subgroup analyses were performed. The authors' conclusions and recommendations for practice are in line with the evidence presented, but should be treated with caution because of the small numbers of studies and patients involved. The authors' recommendations for further research appear appropriate.

CRD summary: This review concluded that valerian might improve sleep quality without producing negative side-effects. The limited number of small, varied and often poor-quality studies on which this conclusion relies suggests that the findings might not be reliable. CRD commentary: The review question was clearly stated, apart from participant eligibility. A wide range of sources was searched, but the authors made no attempts to locate unpublished data and evidence for publication bias was found when assessed. Appropriate review methods were used to reduce error and bias in the quality assessment and data extraction, but it is unclear whether similar methods were undertaken at the study selection stage. The variation in participant characteristics, valerian doses, preparations, length of treatment and outcome assessment might indicate that a narrative synthesis is most appropriate. The authors also highlighted a number of limitations, including the poor reporting of the severity of insomnia in the included participants. In addition, only 1 study used a standardised valerian extract and most studies did not have sufficient power to rule out even relatively common side-effects. Given these considerations, the authors' conclusion may be overstated.

CRD summary: This review concluded that selective serotonin re-uptake inhibitors may be effective and are generally well tolerated in adolescents and children with major depressive disorder. However, their use must be monitored closely as they may increase risk of suicide. The review was subject to probable publication bias, as well as methodological weaknesses, and therefore these conclusions might not be reliable. CRD commentary: The review question and inclusion criteria were clear, but the search covered only one database and studies might have been missed. The authors noted that many unpublished data were unavailable, thus publication bias is very likely. There was no description of how the studies were selected for inclusion or how the data were extracted, nor of any steps taken to minimise bias in the review process, such as multiple reviewers making decisions independently. There was also no indication that the validity of the primary studies was systematically assessed. However, the authors drew attention to the limited applicability of the included studies and their short follow-up times. The results were difficult to interpret because in most cases only statistically significant outcomes were reported in the review. Sometimes it was unclear how many measures had been applied in the individual studies and whether the outcomes reported were predetermined primary outcomes; thus there is a risk that the findings were subject to reporting bias. The abstract and introductory sections of the review were inconsistent with the main text and excluded three unpublished studies. The authors' conclusions and recommendations appear to derive partly from the findings of other systematic reviews and guidelines, rather than from the evidence of the included studies. Given the likelihood of publication bias, as well as methodological weaknesses in the review process, the conclusions of the review might not be reliable.

Background Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking. Objectives To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations. Search strategy The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data. Selection criteria To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers. Data collection and analysis Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants. Main results Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly more frequent in naltrexone depot groups compared to placebo. In alcohol dependent samples only, adverse effects appeared to be significantly more frequent in the low-dose naltrexone depot groups compared to placebo (RR 1.18, 95% CI 1.02 to 1.36, p=0.02). In the opioid dependent sample, group differences were not statistically significant. Reports on systematic assessment of side effects and adverse events were scarce. Authors' conclusions There is insufficient evidence to evaluate the effectiveness of sustained-release naltrexone for treatment of opioid dependence. For naltrexone injections, administration site-related adverse effects appear to be frequent, but of moderate intensity and time limited. For a harm-benefit evaluation of naltrexone implants, more data on side effects and adverse events are needed. -------------------------------------------------------------------------------- Plain language summary People with opioid dependence require substantial therapeutic effort to keep them drug free. Their use of illicit opioids can be reduced and retention in treatment improved with supervised agonist replacement therapy with methadone, which is a highly addictive drug. Naltrexone is a long-acting, opioid-antagonist that blocks heroin effects. It is used to prevent relapse of both opioid and alcohol dependence. Highly motivated people do best with naltrexone. Most opioid users are sceptical about treatment with naltrexone tablets and many drop out early on. Dropouts can be reduced with supervised tablet taking, offering incentives and using sustained-release naltrexone such as subcutaneous implants or depot injections. There is insufficient evidence from randomised controlled trials to evaluate the effectiveness of sustained-release naltrexone. In the one controlled study that met inclusion criteria, 60 outpatients were randomised to one of three gro

Background Depression is common, disabling, costly and under-treated. There are problems in the current first-line drug treatment, antidepressants, for moderate or severe depression. There is a body of research that has evaluated the effect of psychostimulants (PS) in the treatment of depression. This has not been reviewed systematically. Objectives To determine the effectiveness of PS in the treatment of depression and to assess adverse events associated with PS. Search strategy Databases CCDANCTR-Studies and CCDANCTR-References were searched on 21/6/2006. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and the National Health Service Research Register were searched. Selection criteria Randomised controlled trials (RCTs) assessing the effectiveness of PS were included. The trial population comprised adults of either sex with a diagnosis of depression. Data collection and analysis Two review authors extracted the data independently and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. The primary outcome was depression symptoms, based on a continuous outcome, using the standardised mean difference (SMD), or a dichotomous measure of clinical response, using odds ratios (OR), with 95% confidence intervals (CI). Main results Twenty-four RCTs were identified. The overall quality of the trials was low. Five drugs were evaluated; dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology is different to that of the other PS. PS were administered as a monotherapy, adjunct therapy, in oral or intravenous preparation and in comparison with a placebo or an active therapy. Most effects were measured in the short term (up to four weeks). Thirteen trials had some usable data for meta-analyses. Three trials (62 participants) demonstrated that oral PS, as a monotherapy, significantly reduced short term depressive symptoms in comparison with placebo (SMD -0.87, 95% CI -1.40, -0.33, with non-significant heterogeneity. A similar effect was found for fatigue. In the short term PS were acceptable and well tolerated. Tolerance and dependence were under evaluated. No statistically significant difference in depression symptoms was found between modafinil and placebo. Authors' conclusions There is some evidence that in the short-term, PS reduce symptoms of depression. Whilst this reduction is statistically significant, the clinical significance is less clear. Larger high quality trials with longer follow-up and evaluation of tolerance and dependence are needed to test the robustness of these findings and, furthermore, to explore which PS may be more beneficial and in which clinical situations they are optimal. -------------------------------------------------------------------------------- Plain language summary Psychostimulants for depression Depression is common and under-treated. The current first-line drug treatment for moderate or severe depression is antidepressants, but there are problems with their use. This review evaluated the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of psychostimulants (PS) in the treatment of depression. Twenty-four RCTs were identified, of which 14 had data for meta-analysis. Five drugs were evaluated, including dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology differs from other PS. Three small trials of PS involving a total of 62 participants indicated that oral treatment with PS in the short term (up to four weeks) significantly reduced depressive symptoms when compared with placebo, however, the overall quality of the trials was poor, limiting confidence in the findings. Two trials involving 411 participants compared modafinil against placebo when combined with antidepressant treatment at 6-8 weeks, a

Background Bipolar disorder is a complex psychiatric disorder and is amongst the top thirty causes of worldwide disability. Mood stabilisers are the primary pharmacological intervention, both in the treatment of acute episodes and in prophylaxis. There is, however, mounting evidence that dietary supplementation with omega-3 fatty acids may be beneficial in psychiatric conditions, particularly those involving disturbances of mood. Objectives To review the efficacy of omega-3 fatty acids as either a monotherapy or an adjunctive treatment for bipolar disorder. Search strategy Electronic searches of the following databases were performed: CCDANCTR-Studies and CCDANCTR-References were searched on 12/2/2008, Supplementary searches were carried out on Biological Abstracts, CINAHL, The Cochrane Library, CCDAN Register, EMBASE, MEDLINE, and PsycINFO. The search strategy also included cited reference searching, personal contact with all authors of studies initially included and contact with the omega-3 producing pharmaceutical companies. Selection criteria All relevant randomised controlled trials were included in the review. Studies involving males and females of all ages with a diagnosis of bipolar disorder qualified for inclusion. Studies using any type or dose of omega-3 fatty acid treatment as monotherapy or in addition to standard pharmacotherapy were eligible. The primary outcome was symptom severity; and secondary outcomes were adverse effects, dropout and satisfaction with treatment. Data collection and analysis Two review authors independently inspected the citations identified from the search. Potentially relevant abstracts were identified and full papers ordered and reassessed for inclusion and methodological quality. All relevant data were extracted. The weighted mean difference (WMD) was used for continuous outcome data, with 95% confidence intervals (CI). Main results Five studies met inclusion criteria for the review, however, methodological quality was highly variable. Only one study, involving 75 participants, provided data for analysis, and showed a benefit of active treatment over control for depression symptom levels (WMD -3.93, 95% CI -7.00 to -0.86)and Clinical Global Impression scores (WMD -0.75, 95% CI -1.33 to -0.17) but not for mania (WMD -2.81, 95% CI -7.68 to 1.90). No serious adverse effects were reported in the five studies. The pattern of dropout was highly variable between studies. Authors' conclusions Results from one study showed positive effects of omega-3 as an adjunctive treatment for depressive but not manic symptoms in bipolar disorder. These findings must be regarded with caution owing to the limited data available. There is an acute need for well-designed and executed randomised controlled trials in this field. -------------------------------------------------------------------------------- Plain language summary Omega-3 fatty acids for bipolar disorder This systematic review investigated the efficacy of omega-3 fatty acids for bipolar disorder. Five randomised controlled trials met inclusion criteria for the review. Only one trial provided data that could be analysed, investigating ethyl-EPA as an adjunctive treatment in a mixed outpatient population. Some positive benefits were found for depressive symptoms but not for mania, and no adverse events were reported. There is currently insufficient evidence on which to base any clear recommendations concerning omega-3 fatty acids for bipolar disorder. However, given the general health benefits and safety of omega-3, the preliminary evidence from this review provides a strong case for well-powered, high-quality trials in specific index populations.

Background Paliperidone, risperidone's active metabolite, is now available in an oral formulation for daily use, and an intramuscular formulation for monthly administration may follow shortly. Objectives To compare effects of oral paliperidone with any other treatment for people with schizophrenia and schizophrenia-like illnesses. Search strategy We searched the Cochrane Schizophrenia Group's Register (December 2006), and inspected references of identified studies for further trials. We contacted the manufacturers of paliperidone, the Food and Drug Administration, and authors of relevant trials for additional material. Selection criteria We included all relevant randomised trials. Data collection and analysis We independently selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate, we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). We calculated Weighted Mean Differences (WMD) for continuous data. Main results Five studies compared paliperidone with placebo. Fewer people left the studies early if they were randomized to paliperidone (n=1647, 5 RCTs, RR 0.68 CI 0.61 to 0.76, NNT 7 CI 6 to 9) and those receiving any dose of paliperidone were significantly more likely to have an improvement in global state (n=1420, 4RCTs, RR 0.69 CI 0.63 to 0.75, NNT 5 CI 4 to 6). People randomised to paliperidone were less likely to experience a recurrence of psychosis (n=1638, 5 RCTs, RR 0.45 CI 0.31 to 0.66, NNT 16 CI 13 to 26) than those allocated to placebo. Adverse effect data were not well reported but paliperidone does seem to produce a greater incidence of tachycardia than placebo (n=1638, 5 RCTs, RR1.88 CI 1.28 to 2.76, NNH 21 CI 11 to 90) and a consistent, significant elevation in serum prolactin was found for both men (n=413, 3 RCTs, WMD 27.68 CI 23.66 to 31.69) and women (n=252, 3 RCTs, WMD 87.39 CI 74.27 to 100.51). People receiving paliperidone were more likely to experience extrapyramidal disorders (n=1638, 5 RCTs, RR 2.21 CI 1.26 to 3.88, NNH 28 CI 12 to 129) and weight gain (n=769, 4 RCTs, WMD 1.07 CI 0.65 to 1.49, I-squared 78%) compared with those allocated to placebo. When compared with 10 mg/day olanzapine we found no differences between paliperidone and olanzapine for leaving in the short term (n=1332, 3 RCTs, RR 1.04 CI 0.89 to 1.21; ˜40% in both groups left by six weeks). Those receiving any dose of paliperidone were no more likely to have a recurrence of psychotic symptoms than those receiving 10 mg/day olanzapine (n=1327, 3 RCTs, RR 0.1.07 CI 0.64 to 1.76). Data from all three studies found paliperidone was less likely to produce a weight change than olanzapine (n=660, 3 RCTs, WMD -0.88 CI -1.38 to -0.37). Results for various movement disorders all favoured olanzapine. There are no clear data relating to social functioning, services use, quality of life, satisfaction and cost. Authors' conclusions In short-term studies, oral paliperidone is an antipsychotic that is more efficacious than placebo. We found its adverse effects to be similar to those of its parent compound, risperidone, with movement disorders, weight gain, and tachycardia all more common with paliperidone than placebo. In addition, paliperidone is associated with substantial increases in serum prolactin that may be associated with sexual dysfunction, although sexual functioning outcomes were not reported. At doses greater than 3 mg per day, oral paliperidone appears comparable in efficacy to oral olanzapine 10 mg per day. Regarding the critical comparison of oral paliperidone to risperidone, we have no information and are thus unable to determine if paliperidone has any advantages or disadvantages compared to its well-known parent compound. -------------------------------------------------------------------------------- Plain language summary Paliperidone, 9-hydroxy-risperidone, is an active metabolite of r

Background The prevalence of opiate use among pregnant women ranges from 1% to 2% to as much as 21%. Heroin crosses the placenta and pregnant opiate dependent women experience a six fold increase in maternal obstetric complications such as low birth weight, toxaemia, 3rd trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neurobehavioral problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. Objectives To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on child health status, neonatal mortality, retaining pregnant women in treatment, and reducing use of substances Search strategy We searched Cochrane Drugs and Alcohol Group' Register of Trials (June 2007), PubMed (1966 - June 2007), CINAHL (1982- June 2007), reference lists of relevant papers, sources of ongoing trials, conference proceedings, National focal points for drug research. Authors of included studies and experts in the field were contacted. Selection criteria Randomised controlled trials enrolling opiate dependent pregnant women Data collection and analysis The authors assessed independently the studies for inclusion and methodological quality. Doubts were solved by discussion. Main results We found three trials with 96 pregnant women. Two compared methadone with buprenorphine and one methadone with oral slow morphine. For the women there was no difference in drop out rate RR 1.00 (95% CI 0.41 to 2.44) and use of primary substance RR 2.50 (95% CI 0.11 to 54.87) between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin RR 2.40 (95% CI 1.00 to 5.77) For the newborns in one trial buprenorphine performed better than methadone for birth weight WMD -530 gr (95% CI -662 to -397), this result is not confirmed in the other trial. For the APGAR score both studies didn't find significant difference . No differences for NAS measures used. Comparing methadone with oral slow morphine no differences for birth weight and mean duration of NAS. The APGAR score wasn't considered. Authors' conclusions We didn't find any significant difference betewen the drugs compared both for motheranf for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomized controlled trials. -------------------------------------------------------------------------------- Plain language summary Some women continue to use opiates when they are pregnant. Yet heroin readily crosses the placenta. Opiate dependent women experience a six-fold increase in maternal obstetric complications and give birth to low-weight babies. The newborn may experience narcotic withdrawal (neonatal abstinence syndrome), have development problems, increased neonatal mortality and a 74-fold increased risk of sudden infant death syndrome. Maintenance treatment with methadone provides a steady concentration of opiate in the pregnant woman's blood and so prevents the adverse effects on the fetus of repeated withdrawals. Buprenorphine is also used. They reduce illicit drug use, improve compliance with obstetric care and improve birth weight but are still associated with neonatal abstinence syndrome. The present review found few differences in newborn or maternal outcomes for pregnant opiate-addicted women who were maintained on methadone, buprenorphine or oral slow morphine from a mean gestational age of 23 weeks to delivery. Only three randomised controlled trials satisfied the criteria for the review, two from Austria (outpatients) and one from the USA (inpatients). The trials cont

Background Alzheimer's disease (AD) has become a major public health problem around the world due to its increasing prevalence, long duration, caregiver burden, and high financial cost of care. The degeneration of acetylcholine-containing neurons in the basal forebrain has been implicated in the symptoms of AD. Cholinesterase inhibitors may block the degradation of acetylcholine, thus increasing the efficacy of the remaining cholinergic neurons. Huperzine A is a linearly competitive, reversible inhibitor of acetyl cholinesterase that is said to have both central and peripheral activity with the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These properties might qualify Huperzine A as a promising agent for treating dementia (including AD). Objectives To assess the efficacy and safety of Huperzine A for the treatment of patients with AD. Search strategy The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 1 February 2006 using the search term: huperzin*. The CDCIG Specialized register contains records from all major health care databases (MEDLINE, EMBASE, PsycINFO, CINAHL, SIGLE, ISTP, INSIDE, LILACS) as well as from many trials databases and grey literature sources. In addition, the CBM and AMED databases and relevant websites were searched and some journals were hand-searched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references. Selection criteria All relevant randomized controlled trials (RCTs) studying the efficacy and safety of Huperzine A for AD. Data collection and analysis Data were extracted independently by two reviewers using a self-developed data extraction form and entered into RevMan 4.2.10 software. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardized differences in mean outcome measures were used due to the use of different scales and periods of treatment. Main results Six trials including a total of 454 patients met our inclusion criteria. The methodological quality of most included trials was not high. It was shown that compared to placebo, Huperzine A had beneficial effects on the improvement of general cognitive function measured by MMSE (WMD 2.81; 95% CI 1.87 to 3.76; P < 0.00001) and ADAS-Cog at six weeks (WMD 1.91; 95% CI 1.27 to 2.55) and at 12 weeks (WMD 2.51; 95% CI 1.74 to 3.28), global clinical assessment measured by CDR (WMD -0.80; 95% CI -0.95 to -0.65) and CIBIC-plus (OR 4.32, 95% CI 2.37 to 7.90), behavioral disturbance measured by ADAS-non-Cog at six weeks (WMD -1.33, 95%CI -2.12 to -0.54) and at 12 weeks (WMD -1.52, 95% CI-2.39 to -0.65), and functional performance measured by ADL (WMD = -7.17; 95% CI -9.13 to -5.22; P < 0.00001). However, Huperzine A was not superior to placebo in the improvement of general cognitive function measured by Hasegawa Dementia Scale (HDS) (WMD: 2.78; 95% CI -0.17 to 5.73, P = 0.06) and specific cognitive function measured by Weshler Memory Scale (WMS) (WMD = 6.64; 95% CI -3.22 to 16.50; P = 0.19). No data were available on quality of life and caregiver burden. The adverse events of Huperzine A were mild and there were no significant differences of adverse events between Huperzine A groups and control groups. Authors' conclusions From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD. However, only one study was of adequate quality and size. There is therefore inadequate evidence to make any recommendation about its use. Rigorous de

CRD summary: This review found that there is no evidence to support the suggestion that antidepressant drugs of the selective serotonin re-uptake inhibitor class that have a low milk-to-plasma ratio should be preferred for breast-feeding women. Although the review suffered from a number of limitations, the conclusions are supported by the data presented and are likely to be reliable. CRD commentary: The review addressed a focused question, but the selection criteria were only defined in terms of the intervention. However, it was clear that the population of interest was breast-feeding women and that broad criteria were applied to the outcomes and study design, as is appropriate for this type of objective. The search was adequate but did not include attempts to locate unpublished studies, thus the review might be subject to publication bias. Since very few details were reported about the review process, it is unclear whether appropriate steps were taken to minimise bias and error. A formal quality assessment was not undertaken but, given that this review aimed to assess adverse effects, this is not as much of a limitation as it would be for other types of review question. The narrative synthesis was appropriate given the nature of the data. The authors' conclusions are supported by the data presented and are likely to be reliable.

CRD summary: This review found that interventions that allow patient choice of medication and/or psychotherapy, combined with case management and community support, are associated with optimal clinical benefits for low-income minority women with depression. Treatment effectiveness varied across ethnic groups. Given the clinical variability of the studies and methodological limitations in the review process, the author's conclusions should be regarded as unreliable. CRD commentary: The author's objectives and inclusion criteria were wide and imprecise. A number of relevant sources were searched for eligible studies but no attempts were made to locate unpublished studies (other than ongoing studies), hence the review might be subject to publication bias. Since details of the review process were not reported, it is unclear whether methods were used to reduce the potential for reviewer bias and error at the study selection and data extraction stages. A formal quality assessment was not conducted, although the author referred to the Jadad criteria and reported some quality-related details in the tables. The overall validity of the included studies remains unclear. Most of the included studies failed to provide separate data on ethnic minority women and, therefore, appear unsuited to answer the clinical questions of the review. It was frequently unclear which findings were statistically significant and, where results were described as significant, no estimates of effect or p-values were reported. It was also unclear which comparisons were based on subgroup analysis and which on randomised comparisons. In addition, no attempts were made to synthesise findings across the studies. Given the clinical variability of the studies and the methodological limitations of the review process, the author's conclusions should be regarded as unreliable.

A New and Emerging Technology Briefing from the National Horizon Scanning Centre on the use of tarenflurbil (Flurizan®) for mild Alzheimer’s disease. Tarenflurbil is a first in class, selective amyloid-beta42 (Aß42) lowering agent (SALA), which acts by modulating the activity of gamma-secretase, an enzyme that converts amyloid precursor protein to amyloid-beta.

In its guidance on continuous positive airways pressure (CPAP) for the treatment of obstructive sleep apnoea/hypopnoea syndrome, NICE has recommended it as a possible treatment for adults with moderate or severe sleep apnoea. It may also be a possible treatment for people with mild sleep apnoea, but only if their symptoms affect their quality of life and ability to go about their daily activities, and lifestyle advice (e.g. weight loss, smoking cessation, cutting down on alcohol) and all other possible treatments have not worked or are not appropriate for that person. A person with sleep apnoea should be assessed and treated by a specialist in sleep disorders.

Background Cocaine dependence is a major public health problem that is characterized by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence none exists currently for cocaine dependence despite two decades of clinical trials primarily involving antidepressant, anti convulsivant and dopaminergic medications. There has been extensive consideration of optimal pharmacological approaches to the treatment of cocaine dependence with consideration of both dopamine antagonists and agonists. Anticonvulsants have been candidates for the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. Objectives To evaluate the efficacy and the acceptability of anticonvulsants for cocaine dependence Search strategy We searched the Cochrane Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE (1966 - march 2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007) Selection criteria All randomised controlled trials and controlled clinical trials which focus on the use of anticonvulsants medication for cocaine dependence Data collection and analysis Two authors independently evaluated the papers, extracted data, rated methodological quality Main results Fifteen studies (1066 participants) met the inclusion criteria for this review: the anticonvulsants drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate, valproate. No significant differences were found for any of the efficacy measures comparing any anticonvulsants with placebo. Placebo was found to be superior to gabapentin in diminishing the number of dropouts, two studies, 81 participants, Relative Risk (RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for side effects, two studies, 56 participants RR 2.12 (95% CI 1.08 to 4.17). All the other single comparisons are not statistically significant. Authors' conclusions Although caution is needed when assessing results from a limited number of small clinical trials at present there is no current evidence supporting the clinical use of anticonvulsants medications in the treatment of cocaine dependence. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, we need to improve the primary research in the field of addictions in order to make the best possible use out of a single study and to investigate the efficacy of other pharmacological agent. -------------------------------------------------------------------------------- Plain language summary Cocaine is an illicit drug used as a powder for intranasal or intravenous use or smoked as crack. Short and long-term use of this drug spreads infectious diseases (for example AIDS, hepatitis and tuberculosis), crime, violence and prenatal drug exposure. Cocaine dependence has medical and psychosocial complications and is a major public health problem. No proven pharmacological treatment exists for cocaine dependence. Antidepressant, anticonvulsants and dopaminergic medications have all been trialled. The present review looked at the efficacy and safety of anticonvulsant drugs for treating cocaine dependence, as a class and individually. The review authors identified 17 randomised controlled trials involving 1194 participants, 80% male, with a mean age of 36 years. The mean duration of the trials was 11 weeks (range 1 to 24 weeks). All the trials were conducted in USA, 16 as outpatients. Very limited evidence can be drawn from the included trials. No significant differences were found between a placebo and any anticonvulsant in reducing the number of dropouts from treatment, use of cocaine, craving, and severity of dependence, depression or anxiety. Placebo was superior to gabapentin in reducing the number of dropouts from treatment (two studies) and use of cocaine. Gabapentin (one study

CRD summary: The authors concluded that psychotherapy and pharmacology appear to be equally efficacious for depression in the short-term, but psychotherapy is associated with lower relapse rates at follow-up. The conclusions regarding the similar short-term efficacy of psychotherapy and pharmacotherapy appear reliable, but limitations of the follow-up data suggest that the conclusions about longer term effects might not be definitive. CRD commentary: The review addressed a clear question and included clearly- defined inclusion and exclusion criteria for the participants, intervention, outcomes and study design. The strict inclusion criteria sought to minimise clinical heterogeneity between studies. Several relevant sources were searched but no specific attempts to minimise publication bias were reported; this could have resulted in the omission of other relevant studies. It is unclear whether any language restrictions were applied. Methods were used to minimise reviewer error and bias in the selection of studies and assessment of validity, but it is not clear whether similar steps were taken in the extraction of data. Validity was assessed using specified criteria but the results of the assessment were not reported. Adequate details of each included study were given. The studies were appropriately pooled using meta-analysis; statistical heterogeneity was assessed and specified subgroup analyses were conducted to examine treatment differences for different populations. In their discussion, the authors advised caution when interpreting the results on relapse in the follow-up period. The follow-up data were generally observational rather than part of RCTs, so this advice seems appropriate. Despite uncertainties surrounding the data extraction, the conclusions regarding the similar short-term efficacy of psychotherapy and pharmacotherapy appear reliable. However, limitations of the follow-up data suggest that the follow-up results might not be definitive.