Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis.

This systematic review and meta-analysis aimed to assess the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression. We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and ClinialTrials.gov from inception to July 3, 2023, identifying randomized controlled trials comparing SAMe with placebo or antidepressants (ADs). We synthesized data on reduced depressive symptoms (efficacy) and overall dropout rates (acceptability) using a random-effects model for pairwise frequentist meta-analysis. Our analysis included 23 trials (N = 2183) classified into three categories: 11 trials comparing SAMe and placebo, 5 trials comparing SAMe plus ADs and placebo plus ADs, and 7 trials comparing SAMe and ADs. Differences between experimental and control interventions in reducing depressive symptoms were observed: i) SAMe demonstrated significantly superior efficacy compared to placebo (SMD = -0.58, 95% CI = -0.93 to -0.23, I2 = 68%); ii) in conjunction with ADs, SAMe did not show a significant difference from placebo (SMD = -0.22, 95%CI = -0.63 to 0.19, I2 = 76%); and iii) SAMe did not exhibit a significant difference from ADs alone (SMD = 0.06, 95%CI = -0.06 to 0.18, I2 = 49%). No significant differences in dropout rates were observed across the three comparison categories. Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms. Considering its favorable acceptability profile, SAMe monotherapy should be considered as a treatment option for patients with depression. However, uncertainties regarding its efficacy as an adjunct to AD and its comparative efficacy with ADs remain unresolved.

Cross national comparison of medical students' attitudes and beliefs about medical cannabis and its application for pain management.

OBJECTIVES: To examine attitudes and beliefs about medical cannabis (MC), and specifically about its application for pain management, across medical students in Israel and Thailand. DESIGN: Cross-sectional survey which measured attitudes and beliefs about MC. Participants were additionally asked to rate the perceived efficacy of MC for different medical conditions that are related to pain (arthritis, chronic pain, fibromyalgia and multiple sclerosis). Pearson's Chi-squared test was used to compare between students from the participating universities. RESULTS: 430 medical students participated, 37.9 % (n = 163) from Israel and 62.1 % (n = 267) from Thailand. Personal cannabis use was reported by 55.6 % of the Israeli and only by 6.9 % of the Thai students (p < .001). Israeli secular students, compared to those from Thailand, were more likely to recommend MC for patient treatment, less concerned about serious physical and mental health risks, and more inclined to support legalization of recreational cannabis. Israeli students reported more permissive attitudes toward MC, but reported feeling less prepared to answer patient/client questions about MC than their Thai counterparts. CONCLUSIONS: The findings of this study accentuate the need for curriculum designed around MC use to promote students' preparedness to serve patients in pain or with other medical conditions that may benefit from MC use.

Is early-onset in major depression a predictor of specific clinical features with more impaired social function?

BACKGROUND: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. METHODS: In total, 547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. RESULTS: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. CONCLUSIONS: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment.

Efficacy, tolerability, and acceptability of bupropion for major depressive disorder: a meta-analysis of randomized-controlled trials comparison with venlafaxine.

BACKGROUND: Bupropion and venlafaxine are effective antidepressants with unique pharmacological profiles. OBJECTIVES: The purpose of this meta-analysis was to determine the efficacy, acceptability, and tolerability of bupropion and venlafaxine therapies for adults with major depressive disorder (MDD). The authors searched clinical trials with low risk of bias, performed from January 1985 to February 2013. DATA SOURCES: The searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Controlled Trials Register were conducted in February 2013. Included populations consisted of adult patients with MDD or major depression. Study eligible criteria participants and interventions: included studies were randomized controlled trials (rcts) comparing bupropion and venlafaxine in adult patients with MDD AND OFFERING ENDPOINT RESULTS RELEVANT TO: (1) severity of depression; (2) response rate; (3) remission rate; (4) overall discontinuation rate; or (5) discontinuation rate due to adverse events. Limitation of language was not utilized. STUDY APPRAISAL AND SYNTHESIS METHODS: The abstracts located from the electronic databases were reviewed. The completed reports from pertinent studies were examined, and essential data were extracted. Based on the Cochrane's bias assessment, risks of bias were assessed. Any study with two risks or more was excluded. Efficacious outcomes included the mean changed scores of rating scales for depression, overall response rates, and overall remission rates. Acceptability was determined by the overall discontinuation rates. The discontinuation rates due to adverse events were the measurement of tolerability. Relative risks (RR) and weighted mean differences or standardized mean differences with 95% confidence intervals (CI) were computed using a random effect model. RESULTS: A total of 1,117 participants in three RCTs were included. Depression rating scales used in one and two studies were the 17-item Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale, respectively. The pooled mean changed scores of the bupropion-treated group were comparable to those of the venlafaxine-treated group with standardized mean differences (95% CI) of 0.05 (-0.16 to 0.26). The overall response and remission rates were similar with the RRs (95% CI) of 0.92 (0.79-1.08) and 0.97 (0.75-1.24), respectively. The pooled overall discontinuation rate and discontinuation rate due to adverse events were not different between groups with the RRs (95% CI) of 1.00 (0.80-1.26) and 0.69 (0.44-1.10), respectively. LIMITATIONS: The small number of RCTs included in the meta-analysis. CONCLUSION: According to the limited data obtained from three RCTs, bupropion XL is as effective and tolerable as venlafaxine XR for adult patients with MDD. Further studies in this area should be conducted to confirm these findings.

Quetiapine versus typical antipsychotic medications for schizophrenia.

BACKGROUND: Quetiapine is a widely used atypical antipsychotic drug for schizophrenia that has been on the market for over a decade. However, It is not clear how the effects of quetiapine differ from typical antipsychotics. OBJECTIVES: To review the effects of quetiapine in comparison with typical antipsychotics in the treatment of schizophrenia and schizophrenia-like psychosis. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (March 2010), and inspected references of all identified studies. SELECTION CRITERIA: We included all randomised control trials comparing oral quetiapine with typical antipsychotic drugs in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated risk ratio (RR) and 95% confidence intervals (CI) using a random-effects model. We presented chosen outcomes in a 'Summary of findings' table and comparative risks where appropriate. For continuous data, we calculated mean differences (MD) based on a random-effects model. We assessed risk of bias for included studies. MAIN RESULTS: The review includes 43 randomised controlled trials (RCTs) with 7217 participants. Most studies were from China. The percentages of participants leaving the studies early were similar (36.5% in quetiapine group and 36.9% in typical antipsychotics group) and no significant difference between groups was apparent for leaving early due to any reason (23 RCTs n = 3576 RR 0.91 CI 0.81 to 1.01, moderate quality evidence), however, fewer participants in the quetiapine group left the studies early due to adverse events (15 RCTs, n = 3010, RR 0.48 CI 0.30 to 0.77).Overall global state was similar between groups (no clinically significant response; 16 RCTs, n = 1607, RR 0.96 CI 0.75 to 1.23, moderate quality evidence) and there was no significant difference in positive symptoms (PANSS positive subscore: 22 RCTs, n = 1934, MD 0.02 CI -0.39 to 0.43, moderate quality evidence). General psychopathology was equivocal (PANSS general psychopathology subscore: 18 RCTs, n = 1569, MD -0.20 CI -0.83 to 0.42) between those allocated to quetiapine and typical antipsychotics. However, quetiapine was statistically significantly more efficacious for negative symptoms (PANSS negative subscore: 22 RCTs, n = 1934, MD -0.82 CI -1.59 to -0.04, moderate quality evidence), however, this result was highly heterogeneous and driven by two small outlier studies with high effect sizes. Without these two studies, there was no heterogeneity and no statistically significant difference between quetiapine and typical antipsychotics.Compared with typical antipsychotics, quetiapine might cause fewer adverse effects (9 RCTs, n = 1985, RR 0.76 CI 0.64 to 0.90 number needed to treat to induce harm (NNTH) 10, CI 8 to 17), less abnormal ECG (2 RCTs, n = 165, RR 0.38 CI 0.16 to 0.92, NNTH 8, CI 4 to 55), fewer overall extrapyramidal effects (8 RCTs, n = 1,095, RR 0.17 CI 0.09 to 0.32, NNTH 3, CI 3 to 3, moderate quality evidence) and fewer specific extrapyramidal effects including akathisia, parkinsonism, dystonia and tremor. Moreover, it might cause lower prolactin level (4 RCTs, n = 1034, MD -16.20 CI -23.34 to -9.07, moderate quality evidence) and less weight gain compared with some typical antipsychotics in the short term (9 RCTs, n = 866, RR 0.52 CI 0.34 to 0.80, NNTH 8, CI 6 to 15).However, there was no significant difference between the two groups in suicide attempt, suicide, death, QTc prolongation, low blood pressure, tachycardia, sedation, gynaecomastia, galactorrhoea, menstrual irregularity and white blood cell count. AUTHORS' CONCLUSIONS: Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms and general psychopathology. There are no clear differences in terms of the treatment of negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain.

Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials.

AIM: The aim of this study was to systematically review the efficacy, acceptability and tolerability of bupropion in comparison to placebo. Only randomized-controlled trials were included in the meta-analysis. METHODS: MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in October 2010. Study populations comprised adults with any subtype of attention-deficit hyperactivity disorder, attention-deficit disorder, hyperkinetic disorder, minimal brain dysfunction, minimal cerebral dysfunction or minor cerebral dysfunction. Efficacy outcomes were pooled mean changed scores of the ADHD rating scale (ADHD-RS) and the overall response rates. The overall discontinuation rate was considered as the measure of acceptability. RESULTS: A total of 349 participants (n for bupropion treatment = 175) in five published randomized, controlled trials were included. Bupropion sustained- or extended-release was the experimental treatment in all studies. The pooled mean changed score of the ADHD-RS of the bupropion-treated group was greater than that of the placebo-treated group with a weighted mean difference (95%CI) of 5.08 (3.13-7.03). The overall response rate of the bupropion-treated group was significantly greater than that of placebo-treated groups with a relative risk (95%CI) of 1.67 (1.23-2.26). However, the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events were not significantly different between groups with a relative risk (95%CI) of 1.11 (0.71-1.72) and 0.87 (0.08-9.79), respectively. CONCLUSION: The evidence suggests that bupropion is superior to placebo and effective for the treatment of ADHD in adults. However, its acceptability and tolerability were not significantly higher than those of placebo.