Depression

Depression refers to a state of low mood that can be accompanied with loss of interest in activities that the individual normally perceived as pleasurable, altered appetite and sleep/wake balance. Its severe form, major depression is classified as a mood disorder.

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  • News and Views |

    Matta et al. report that men with prostate cancer who underwent surgery or radiotherapy, but not active surveillance, had greater odds of receiving antidepressants than controls. However, methodological limitations preclude the interpretation of a psychological benefit for men on active surveillance. Screening for distress and referral to evidence-based intervention should be a priority.

    • Suzanne K. Chambers
    •  & Peter Heathcote
  • News |

    Researchers are developing wristbands and apps to predict moods — but the technology has pitfalls as well as promise.

    • Matt Kaplan
    Nature 563, 20-22
  • News | | open

    The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallel-comparison design. Efficacy was measured using the Montgomery–Åsberg Depression Rating Scale (MADRS). FORWARD-5 achieved the primary endpoint and demonstrated that adjunctive BUP/SAM 2 mg/2 mg was superior to placebo (average difference change from baseline to week 3 through end of treatment [EOT] in MADRS-6 and −10 versus placebo: −1.5, P = 0.018; −1.9, P = 0.026, respectively). FORWARD-4 did not achieve the primary endpoint (change from baseline in MADRS-10 at week 5 versus placebo: –1.8, P = 0.109), although separate analyses showed significant treatment differences at other timepoints using traditional, regulatory-accepted endpoints such as reduction in MADRS-10 at EOT. The pooled analysis of the two studies demonstrated consistently greater reduction in MADRS-10 scores from baseline for BUP/SAM 2 mg/2 mg versus placebo at multiple timepoints including EOT and average change from baseline to week 3 through EOT (–1.8, P = 0.010; –1.8, P = 0.004, respectively). The overall effect size (Hedges’ g) in the pooled analyses for MADRS-10 change from baseline to EOT was 0.22. Overall, BUP/SAM was generally well tolerated, with most adverse events (AEs) being mild or moderate in severity. The most common AEs, occurring in ≥5% of patients in the BUP/SAM 2 mg/2 mg treatment group, which was more frequently than the placebo group, included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by AEs or objective measures. This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.

    • Maurizio Fava
    • , Michael E. Thase
    • , Madhukar H. Trivedi
    • , Elliot Ehrich
    • , William F. Martin
    • , Asli Memisoglu
    • , Narinder Nangia
    • , Arielle D. Stanford
    • , Miao Yu
    •  & Sanjeev Pathak