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  • 1
    In: World Psychiatry, Wiley, Vol. 20, No. 3 ( 2021-10), p. 387-396
    Abstract: Major depression is often a relapsing disorder. It is therefore important to start its treatment with therapies that maximize the chance of not only getting the patients well but also keeping them well. We examined the associations between initial treatments and sustained response by conducting a network meta‐analysis of randomized controlled trials (RCTs) in which adult patients with major depression were randomized to acute treatment with a psychotherapy (PSY), a protocolized antidepressant pharmacotherapy (PHA), their combination (COM), standard treatment in primary or secondary care (STD), or pill placebo, and were then followed up through a maintenance phase. By design, acute phase treatment could be continued into the maintenance phase, switched to another treatment or followed by discretionary treatment. We included 81 RCTs, with 13,722 participants. Sustained response was defined as responding to the acute treatment and subsequently having no depressive relapse through the maintenance phase (mean duration: 42.2±16.2 weeks, range 24‐104 weeks). We extracted the data reported at the time point closest to 12 months. COM resulted in more sustained response than PHA, both when these treatments were continued into the maintenance phase (OR=2.52, 95% CI: 1.66‐3.85) and when they were followed by discretionary treatment (OR=1.80, 95% CI: 1.21‐2.67). The same applied to COM in comparison with STD (OR=2.90, 95% CI: 1.68‐5.01 when COM was continued into the maintenance phase; OR=1.97, 95% CI: 1.51‐2.58 when COM was followed by discretionary treatment). PSY also kept the patients well more often than PHA, both when these treatments were continued into the maintenance phase (OR=1.53, 95% CI: 1.00‐2.35) and when they were followed by discretionary treatment (OR=1.66, 95% CI: 1.13‐2.44). The same applied to PSY compared with STD (OR=1.76, 95% CI: 0.97‐3.21 when PSY was continued into the maintenance phase; OR=1.83, 95% CI: 1.20‐2.78 when PSY was followed by discretionary treatment). Given the average sustained response rate of 29% on STD, the advantages of PSY or COM over PHA or STD translated into risk differences ranging from 12 to 16 percentage points. We conclude that PSY and COM have more enduring effects than PHA. Clinical guidelines on the initial treatment choice for depression may need to be updated accordingly.
    Type of Medium: Online Resource
    ISSN: 1723-8617 , 2051-5545
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2236130-3
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  • 2
    In: Psychiatry and Clinical Neurosciences, Wiley, Vol. 76, No. 9 ( 2022-09), p. 416-422
    Abstract: Brexpiprazole augmentation is an effective treatment strategy for antidepressant‐refractory depression, but its optimal dosage remains unclear. Aims To find the optimal dosage of brexpiprazole as augmentation of other antidepressants. Methods We searched multiple electronic databases (from inception to September 16th, 2021) to identify double‐blind, randomized placebo‐controlled fixed‐dose trials evaluating brexpiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder not adequately responding to one or more antidepressant treatment. Our outcomes of interest at 8 weeks (range 4–12 weeks) were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects) and acceptability (dropouts for any reason). We performed a random‐effects, one‐stage dose‐effect meta‐analysis with restricted cubic splines. Results Six studies met the inclusion criteria, including 1671 participants in total. The dose‐efficacy curve showed an increase up to doses around 2 mg (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12–2.06) and then a decreasing trend through the higher licensed dose up to 3 mg (OR 1.40, 95% CI 0.95–2.08). The shape of the dose‐tolerability curve was comparable to that of the efficacy and the dose‐acceptability curve showed a monotonic increasing trend but both had wide confidence bands. Conclusions One to two milligrams of brexpiprazole as augmentation treatment may achieve an optimal balance between efficacy, tolerability, and acceptability in the acute treatment of antidepressant‐refractory depression. However, the small number of included studies limit the reliability of the results. Further research is required to validate the findings.
    Type of Medium: Online Resource
    ISSN: 1323-1316 , 1440-1819
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2010264-1
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  • 3
    In: The British Journal of Psychiatry, Royal College of Psychiatrists, Vol. 221, No. 2 ( 2022-08), p. 440-447
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0007-1250 , 1472-1465
    RVK:
    Language: English
    Publisher: Royal College of Psychiatrists
    Publication Date: 2022
    detail.hit.zdb_id: 2021500-9
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