Explore the vast range of titles available.

In a randomized trial involving 59 selected patients with depression, the change in depression scale scores from baseline to week 6 did not differ significantly between patients who received two doses of psilocybin and those who received daily escitalopram. Secondary outcomes generally favored psilocybin over escitalopram.

Electrical direct-current stimulation applied to the cranium was not shown to be noninferior to escitalopram for major depression. Direct current and escitalopram were superior to placebo, but the electrical treatment was associated with adverse events, including mania. Major depressive disorder is a highly prevalent condition. 1 There is interest in the effectiveness and safety of new and nonpharmacologic treatments for depression. In 2009, transcranial magnetic stimulation was approved by the Food and Drug Administration for the treatment of major depressive disorder. 2 The procedure has had mixed results in various trials, 3 is associated with a small risk of seizure, 4 and is costly. Transcranial direct-current stimulation (tDCS) is a noninvasive brain-stimulation technique that is less costly than transcranial magnetic stimulation and has not been associated with seizures. 5 In this procedure, weak, direct current is applied through electrodes that are placed . . .

Objectives To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. Design Double blind randomised placebo controlled trial. Setting 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. Participants 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. Interventions Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. Main outcome measures The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. Results The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. Conclusions Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

Over the past several decades, the number of electric vehicles (EVs) has continued to increase. Projections estimate that worldwide, more than 125 million EVs will be on the road by 2030. At the heart of these advanced vehicles is the lithium-ion (Li-ion) battery which provides the required energy storage. This paper presents and compares key components of Li-ion batteries and describes associated battery management systems, as well as approaches to improve the overall battery efficiency, capacity, and lifespan. Material and thermal characteristics are identified as critical to battery performance. The positive and negative electrode materials, electrolytes and the physical implementation of Li-ion batteries are discussed. In addition, current research on novel high energy density batteries is presented, as well as opportunities to repurpose and recycle the batteries.

Adult outpatients with a nonpsychotic major depressive disorder received sustained-release bupropion, sertraline, or extended-release venlafaxine after a lack of response to or an inability to tolerate the selective serotonin-reuptake inhibitor (SSRI) citalopram. Approximately one in four patients had a remission of symptoms after switching to another antidepressant. All these medications provided a reasonable second-step choice for depressed outpatients who did not have a remission with or could not tolerate the SSRI. Adult outpatients with a nonpsychotic major depressive disorder received bupropion, sertraline, or venlafaxine after a lack of response to or an inability to tolerate citalopram. Approximately one in four patients had a remission of symptoms after switching to another antidepressant. Major depressive disorder is associated with substantial morbidity, mortality, family burden, and health care costs. 1 Since no single treatment is uniformly effective, 2 – 4 subsequent interventions are often needed. Second-step treatments include augmenting the first agent with a second or discontinuing the first agent and beginning a second (switching). The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Trial used an equipoise, stratified, randomized design to evaluate the relative efficacy and tolerability of various antidepressant treatments for outpatients with nonpsychotic major depressive disorder who had a lack of remission or could not tolerate the selective serotonin-reuptake inhibitor (SSRI) citalopram (Celexa, Forest Pharmaceuticals) . . .

Abstract Study Objectives The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions’ effects relative to control in women with comparably severe insomnia symptoms and VMS. Methods We analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) ≥ 12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included the following: escitalopram 10–20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8–12 weeks of treatment. Results CBT-I produced the greatest reduction in ISI from baseline relative to control at −5.2 points (95% CI −7.0 to −3.4). Effects on ISI were similar for exercise at −2.1 and venlafaxine at −2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at −2.7 points (−3.9 to −1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol, and venlafaxine. Omega-3 supplements did not improve insomnia symptoms. Conclusions This study’s findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS.

The risks and benefits of standard antidepressants for patients with bipolar disorder are not well understood. In this randomized, placebo-controlled trial of patients with bipolar disorder, all of whom received a mood stabilizer, adjunctive treatment with an antidepressant did not reduce the symptoms of bipolar depression or increase the risk of mania. In patients with bipolar disorder, all of whom received a mood stabilizer, adjunctive treatment with an antidepressant did not reduce the symptoms of bipolar depression or increase the risk of mania. Bipolar disorder, the sixth-leading cause of disability worldwide, 1 is a chronic and recurrent psychiatric illness with a lifetime prevalence of just under 4% 2 and annual costs that exceed those of diabetes or recurrent (unipolar) major depressive disorder. 3 Although abnormal mood elevation is the cardinal diagnostic feature that distinguishes bipolar disorder from recurrent major depressive disorder, depression that alternates with manic episodes (bipolar depression) is the leading cause of impairment and death among patients with bipolar disorders. 4 – 6 Two main limitations related to standard antidepressant medications hamper their use in the treatment of bipolar depression. First, though these agents have proved . . .

Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder. We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D). The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates. Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.

Abstract Study Objective: To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design: A blinded, randomized split-plot experimental study. Setting: Two urban academic clinical centers. Participants: 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions: Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and Results: Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions: Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH’s sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I.

Rationale There is a substantial unmet need for biomarkers to predict treatment response in major depressive disorder (MDD). Evidence has converged on activation of the inflammatory response system as a fundamental mechanism underlying MDD. Objectives By investigating circulating leukocyte subsets quantified by fluorescence-activated cell sorting (FACS) analysis before treatment, we aim to predict antidepressant response. Methods Forty medication-free inpatients with melancholic, non-psychotic depression before treatment with either venlafaxine or imipramine and 40 age- and gender-matched healthy controls were included. Leukocyte subsets were quantified by FACS analysis using frozen peripheral blood mononuclear cells (PBMC) collected prior to and after 7 weeks of treatment with either venlafaxine (375 mg/day) or imipramine (blood level 200–300 ng/ml). Response was defined as at least 50 % reduction of the baseline Hamilton Rating Scale for Depression (HAM-D) score. Results Prior to treatment, MDD patients showed reduced percentages of CD4 + CD25 high Foxp3 + T regulatory (T reg ) cells when compared with controls (1.5 ± 0.6 vs. 1.8 ± 0.6, p  = .037). After treatment, robust rises in T reg cells were observed in patients (1.8 ± 0.7, p  < .001), yet T reg cells were not predictors of the clinical outcome of treatment. Antidepressant non-responders showed increased CD8 + cytotoxic T cell percentages (24.0 ± 8.6 vs. 15.9 ± 5.9, p  = .004) and decreased natural killer (NK) cell percentages (14.0 ± 6.9 vs. 21.4 ± 11.9, p  = .020) compared with responders before treatment. Both lymphocyte levels were not significantly modulated by treatment. Conclusion In melancholic MDD, FACS analysis of circulating leukocyte subpopulations might help to discriminate between patients with high or low responsiveness to antidepressant treatment.