Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with meta-analysis.

Posttraumatic Stress Disorder Symptoms During the First Six Months After Traumatic Brain Injury

Psychological therapies for the treatment of mental disorders in low- and middle-income countries affected by humanitarian crises.

Alpha-2 Agonists for Attention-Deficit/Hyperactivity Disorder in Youth: A Systematic Review and Meta-Analysis of Monotherapy and Add-On Trials to Stimulant Therapy

Attention deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder of childhood onset, which may persist into adulthood. ADHD has a significant impact on a child's daily life, affecting relationships and academic performance. Its core symptoms include developmentally inappropriate levels of inattention, hyperactivity, and impulsive behaviour. Tricyclic antidepressants (TCAs) are sometimes used as second line of treatment in the reduction of ADHD symptoms in children and adolescents with ADHD. However, their efficacy is not yet known. To assess the efficacy of TCAs in the reduction of ADHD symptoms within the broad categories of hyperactivity, impulsivity, and inattentiveness in young people aged 6 to 18 years with established diagnoses of ADHD. On 26 September 2013, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, CINAHL, seven other databases, and two trials registers. We also searched the reference lists of relevant articles, and contacted manufacturers and known experts in the field to determine if there were any ongoing trials or unpublished studies available. Randomised controlled trials (RCTs), including both parallel group and cross-over study designs, of any dose of TCA compared with placebo or active medication in children or adolescents with ADHD, including those with comorbid conditions. Working in pairs, three review authors independently screened records, extracted data, and assessed trial quality. We calculated the standardised mean differences (SMD) for continuous data, the odds ratio (OR) for dichotomous data, and 95% confidence intervals (CIs) for both. We conducted the meta-analyses using a random-effects model throughout. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of each included trial and the GRADE approach to assess the quality of the body evidence. We included six RCTs with a total of 216 participants. Five of the six trials compared desipramine with placebo; the remaining trial compared nortriptyline with placebo. One trial compared desipramine with clonidine and placebo, and another compared two TCAs (desipramine and clomipramine) with methylphenidate and placebo. Of the six trials, one RCT primarily assessed the efficacy of TCA in children with ADHD and comorbid tic or Tourette disorder, and another one trial was in children with comorbid tic disorder. RCTs that met our inclusion criteria varied both in design and quality, and none were free of bias. The quality of the evidence was low to very low according to our GRADE assessments.TCA outperformed placebo regarding the proportions of patients achieving a predefined improvement of core ADHD symptom severity (OR 18.50, 95% CI 6.29 to 54.39, 3 trials, 125 participants, low quality evidence). In particular, there was evidence that desipramine improved the core symptoms of ADHD in children and adolescents as assessed by parents (SMD -1.42, 95% CI -1.99 to -0.85, 2 trials, 99 participants, low quality evidence), teachers (SMD -0.97, 95% CI -1.66 to -0.28, 2 trials, 89 participants, low quality evidence), and clinicians (OR 26.41, 95% CI 7.41 to 94.18, 2 trials, 103 participants, low quality evidence). Nortriptryline was also efficacious in improving the core symptoms of ADHD in children and adolescents as assessed by clinicians (OR 7.88, 95% CI 1.10 to 56.12). Desipramine and placebo were similar on "all-cause treatment discontinuation" (RD -0.10, 95% CI -0.25 to 0.04, 3 trials, 134 participants, very low quality evidence). Desipramine appeared more efficacious than clonidine in reducing ADHD symptoms as rated by parents (SMD -0.90, 95% CI -1.40 to -0.40, 1 trial, 68 participants, very low quality evidence) in participants with ADHD and comorbid tics or Tourette syndrome.Although this Cochrane Review did not identify serious adverse effects in patients taking TCAs, it did identify mild increases in diastolic blood pressure and pulse rates. Also, patients treated with desipramine had significantly higher rates of appetite suppression compared to placebo whilst nortriptyline resulted in weight gain. Other reported adverse effects included headache, confusion, sedation, tiredness, blurred vision, diaphoresis, dry mouth, abdominal discomfort, constipation, and urinary retention. Most evidence on TCAs relates to desipramine. Findings suggest that, in the short term, desipramine improves the core symptoms of ADHD, but its effect on the cardiovascular system remains an important clinical concern. Thus, evidence supporting the clinical use of desipramine for the treatment of children with ADHD is low.

Internet-based cognitive and behavioural therapies for post-traumatic stress disorder (PTSD) in adults.

Psychological therapies delivered remotely for the management of chronic pain (excluding headache) in adults (Review)

To determine the relations between obstructive sleep apnea (OSA) diagnosis, the likelihood of being diagnosed with a psychological condition, among obese veterans, after accounting for severity of obesity and the correlated nature of patients within facility. We hypothesized that (1) individuals with a diagnosis of OSA would be more likely to receive a diagnosis of a (a) mood disorder and (b) anxiety disorder, but not (c) substance use disorder. Cross-sectional retrospective database review of outpatient medical records between October 2009 and September 2010, conducted across all 140 Veterans Health Administration (VHA) facilities. The entire VA Health Care System. Population-based sample of veterans with obesity (N = 2,485,658). Physician- or psychologist-determined diagnosis of psychological conditions including mood, anxiety, and substance use disorders. Using generalized linear mixed modeling, after accounting for the correlated nature of patients within facility and the severity of obesity, individuals with a diagnosis of sleep apnea had increased odds of receiving a mood disorder diagnosis (OR = 1.85; CI = 1.71-1.72; p < 0.001), anxiety disorder diagnosis (OR = 1.82; CI = 1.77-1.84; p < 0.001), but not a diagnosis of substance use disorder. Among obese veterans within VA, OSA is associated with increased risk for having a mood and anxiety disorder, but not substance use disorder, with the strongest associations observed for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In addition, this relation remained after accounting for severity of BMI.

Primary-level worker interventions for the care of people living with mental disorders and distress in low- and middle-income countries.

Acupuncture for chronic nonspecific low back pain.

Motivational interviewing for substance use reduction.

ObjectiveTo investigate the effect of aquatic high-intensity interval training (AHIIT) on exercise capacity in people with chronic conditions.DesignSystematic review and meta-analysis.ParticipantsAdults (age ≥18 years) with any chronic conditions (long duration,...

People with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular death and morbidity. Several clinical studies suggested that aldosterone antagonists would be a promising treatment option for people undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for people with CKD on dialysis has yet to be determined. This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in people with CKD requiring haemodialysis (HD) or peritoneal dialysis (PD). We searched the Cochrane Kidney and Transplant Register of Studies up to 5 August 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included parallel randomised controlled trials (RCTs), cross-over RCTs, and quasi-RCTs (where group allocation is by a method that is not truly random, such as alternation, assignment based on alternate medical records, date of birth, case record number, or other predictable methods) that compared aldosterone antagonists with placebo or standard care in people with CKD requiring dialysis. Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I² statistic to measure heterogeneity among the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. We included 16 studies (14 parallel RCTs and two cross-over RCTs) involving a total of 1446 participants. Thirteen studies compared spironolactone to placebo or standard care and one study compared eplerenone to a placebo. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists probably reduced the risk of death (any cause) for people with CKD requiring dialysis (9 studies, 1119 participants: RR 0.45, 95% CI 0.30 to 0.67; I² = 0%; moderate certainty of evidence). Aldosterone antagonist probably decreased the risk of death due to cardiovascular disease (6 studies, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I² = 0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 studies, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I² = 0%; moderate certainty of evidence). While aldosterone antagonists probably increased risk of gynaecomastia compared with control (4 studies, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I² = 0%; moderate certainty of evidence), aldosterone antagonists may make little or no difference to the risk of hyperkalaemia (9 studies, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I² = 47%; low certainty of evidence). Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (8 studies, 633 participants: SMD -0.42, 95% CI -0.78 to 0.05; I² = 77%). In people with CKD requiring dialysis received aldosterone antagonists compared to control, there were 72 fewer deaths from all causes per 1000 participants (95% CI 47 to 98) with a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 10 to 21) and for gynaecomastia were 26 events per 1000 participants (95% CI 15 to 39) with a number need to treat for an additional harmful outcome (NNTH) of 38 (95% CI 26 to 68). Based on moderate certainty of the evidence, aldosterone antagonists probably reduces the risk of all-cause and cardiovascular death and probably reduces morbidity due to cardiovascular and cerebrovascular disease in people with CKD requiring dialysis. For the adverse effect of gynaecomastia, the risk was increased compared to control. For this outcome, the absolute risk was lower than the absolute risk of death. It is hoped the three large ongoing studies will provide better certainty of evidence.

Background and Aims Patients with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular mortality and morbidity. Several clinical trials suggested that aldosterone antagonists would be a promising treatment option for patients undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for patients with CKD on dialysis have yet to be determined. This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 14 trials (12 parallel RCTs and two cross-over trials) involving a total of 1,375 participants. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 participants: RR 0.45, 95% CI 0.30 to 0.67; I=0%; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I=0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I=0%; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I=0%; moderate certainty of evidence), the elevated risk of hyperkalaemia (9 trials, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I=47%; low certainty of evidence) and increase in serum potassium (7 trials, 519 participants: MD 0.21, 95% CI -0.06 to 0.47; I2=84%) due to aldosterone antagonists was uncertain. Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (7 trials, 562 participants: SMD -0.33, 95% CI -0.72 to 0.05; I2=76%). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis. Two ongoing studies will provide better certainty of evidence in the future.

Background People with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular death and morbidity. Several clinical studies suggested that aldosterone antagonists would be a promising treatment option for people undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for people with CKD on dialysis has yet to be determined. Objectives This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in people with CKD requiring haemodialysis (HD) or peritoneal dialysis (PD). Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 5 August 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria We included parallel randomised controlled trials (RCTs), cross-over RCTs, and quasi-RCTs (where group allocation is by a method that is not truly random, such as alternation, assignment based on alternate medical records, date of birth, case record number, or other predictable methods) that compared aldosterone antagonists with placebo or standard care in people with CKD requiring dialysis. Data collection and analysis Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I² statistic to measure heterogeneity among the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Main results We included 16 studies (14 parallel RCTs and two cross-over RCTs) involving a total of 1446 participants. Thirteen studies compared spironolactone to placebo or standard care and one study compared eplerenone to a placebo. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists probably reduced the risk of death (any cause) for people with CKD requiring dialysis (9 studies, 1119 participants: RR 0.45, 95% CI 0.30 to 0.67; I² = 0%; moderate certainty of evidence). Aldosterone antagonist probably decreased the risk of death due to cardiovascular disease (6 studies, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I² = 0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 studies, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I² = 0%; moderate certainty of evidence). While aldosterone antagonists probably increased risk of gynaecomastia compared with control (4 studies, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I² = 0%; moderate certainty of evidence), aldosterone antagonists may make little or no difference to the risk of hyperkalaemia (9 studies, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I² = 47%; low certainty of evidence). Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (8 studies, 633 participants: SMD -0.42, 95% CI -0.78 to 0.05; I² = 77%). In people with CKD requiring dialysis received aldosterone antagonists compared to control, there were 72 fewer deaths from all causes per 1000 participants (95% CI 47 to 98) with a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 10 to 21) and for gynaecomastia were 26 events per 1000 participants (95% CI 15 to 39) with a number need to treat for an additional harmful outcome (NNTH) of 38 (95% CI 26 to 68). Authors' conclusions Based on moderate certainty of the evidence, aldosterone antagonists probably reduces the risk of all-cause and cardiovascular death and probably reduces morbidity due to cardiovascular and cerebrovascular disease in people with CKD requiring dialysis. For the adverse effect of gynaecomastia, the risk was increased compared to control. For this outcome, the absolute risk was lower than the absolute risk of death. It is hoped the three large ongoing studies will provide better certainty of evidence.

This study examined the prevalence of lifetime traumatic events and current symptoms of posttraumatic stress disorder (PTSD) among treatment-seeking cocaine-dependent outpatients and compared patients with and without PTSD on current substance use, psychopathology, and sociodemographic characteristics. The subjects were 122 adult cocaine-dependent outpatients participating in a treatment outcome study of psychosocial therapy. In addition to standard self-report and interview measures of psychopathology and substance use, the subjects completed the Trauma History Questionnaire and the PTSD Checklist before entering treatment. These patients experienced a large number of lifetime traumatic events (mean = 5.7); men experienced more general disasters and crime-related traumas than women, and women experienced more physical and sexual abuse than men. According to self-report measures, 20.5% of the subjects currently met the DSM-III-R criteria for PTSD; the rate of PTSD was 30.2% among women and 15.2% among men. Patients with PTSD had significantly higher rates of co-occurring axis I and axis II disorders, interpersonal problems, medical problems, resistance to treatment, and psychopathology symptoms than patients without PTSD. Psychopathology symptoms represented the most consistent difference between the two groups and provided the best prediction of PTSD status in a logistic regression. However, the groups did not differ significantly in current substance use or sociodemographic characteristics. These findings underscore the value of screening substance abusers for PTSD, because it can identify a small but substantial number who might require additional treatment. Further studies of the relationship between PTSD and substance abuse appear warranted.