Chronic insomnia disorder is characterized by sleep continuity disturbance associated with considerable distress or impairments of daytime functioning. It occurs in 4% to 22% of the population in the US and is highly disabling.¹ It is associated with both physical and psychiatric comorbidities² and has a large economic burden.³ Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for chronic insomnia, based on its efficacy and safety profile.^4,5

Cognitive behavioral therapy for insomnia (CBT-I) has demonstrated efficacy for both insomnia and depression. With a tenfold increase in expected participant numbers, we aimed to update the systematic review and meta-analysis of CBT-I for major depressive disorders (MDD). Multiple databases were searched up to March 27th 2024 to include all randomized controlled trials examining CBT-I among adults with MDD. The certainty of evidence was evaluated using GRADE. The primary outcome was depression response at post-treatment. Secondary outcomes included insomnia remission and all-cause dropout at post-treatment. Frequentist random-effects pairwise meta-analyses were performed using odds ratio (OR) for dichotomous outcomes. This study was prospectively registered (https://osf.io/kcndz/). Nineteen trials with 4808 randomized participants were identified (mean age, 33.2 [standardized deviation 15.0] years, 73.2 % women. Mean Insomnia Severity Index 19.2 [5.4], median Patient Health Questionnaire-9 16 [range, 8-21]). CBT-I was more beneficial than control conditions for depression response (OR 2.28 [95 % Confidence Interval (CI), 1.67-3.12; GRADE certainty of evidence: moderate), insomnia remission (OR 3.57 [95%CI, 2.48-5.14]: moderate) but could lead to more dropout (OR 1.69 [95%CI, 0.98-2.89]: low). Depression improvement was seen beyond the sleep domain. With a control condition depression response rate of 17 % at post-treatment (median 8 weeks), CBT-I yielded a 32 % response rate (95 % CI, 26 %-39 %). This meta-analysis indicates that CBT-I has significant effects on depressive symptoms beyond the sleep domain among people with MDD. Despite higher dropout rates, these findings suggest CBT-I is an effective treatment for depression comorbid with insomnia.

Objectives To find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults. Design Systematic review and duration-effect meta-analysis. Data sources MEDLINE, Embase and CENTRAL through 25 August 2021. Eligibility criteria All randomised controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. Both outpatients and inpatients were included but not those admitted to intensive care units. We imposed no date, language or publication status restriction. Data extraction and synthesis Data extraction by two independent reviewers. We conducted a random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the prespecified non-inferiority margin of 10% examined against 10 days . The primary outcome was clinical improvement on day 15 (range 7–45 days). Secondary outcomes: all-cause mortality, serious adverse events and clinical improvement on day 30 (15–60 days). Results We included nine trials (2399 patients with a mean (SD) age of 61.2 (22.1); 39% women). The duration-effect curve was monotonic with longer duration leading to a lower probability of improvement, and shorter treatment duration (3–9 days) was likely to be non-inferior to 10-day treatment. Harmful outcome curves indicated no association. The weighted average percentage of the primary outcome in the 10-day treatment arms was 68%. Using that average, the absolute clinical improvement rates of the following durations were: 3-day treatment 75% (95% CI: 68% to 81%), 5-day treatment 72% (95% CI: 66% to 78%) and 7-day treatment 69% (95% CI: 61% to 76%). Conclusions Shorter treatment duration (3–5 days) probably offers the optimal balance between efficacy and treatment burden for treating CAP in adults if they achieved clinical stability. However, the small number of included studies and the overall moderate-to-high risk of bias may compromise the certainty of the results. Further research on the shorter duration range is required. PROSPERO registration number CRD 42021273357.

Background: We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT‐I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder.Methods: We searched multiple databases to December 27, 2023. We included trials in hypnotic‐free adults with chronic insomnia comparing at least two of CBT‐I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long‐term remission. Secondary outcomes included all‐cause dropout and self‐reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random‐effects network meta‐analyses (CRD42024505519).Findings: We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT‐I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15–2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88–3.30: moderate]) and no clear difference of CBT‐I against combination (1.07 [95% CI, 0.63–1.80: moderate]). CBT‐I was associated with fewer dropouts than pharmacotherapy. Short‐term outcomes favored CBT‐I over pharmacotherapy except total sleep time. Given the average long‐term remission rate in the pharmacotherapy‐initiating arms of 28%, CBT‐I resulted in a long‐term remission rate of 41% (95% CI, 31%–53%) and combination 40% (95% CI, 25%–56%).Interpretation: The current study found that starting with CBT‐I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT‐I alone.

Background: Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.Aims: To find the optimal dosage of aripiprazole augmentation.Method: Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose–effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4–12 weeks).Results: Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose–efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15–1.85) and 5 mg (OR = 1.93, 95% CI 1.33–2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52–2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.Conclusions: Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.