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Antidepressant medications (ADMs) are widely used and long-term use is increasing. Given this extensive use and recommendation of ADMs in guidelines, one would expect ADMs to be universally considered effective. Surprisingly, that is not the case; fierce debate on their benefits and harms continues. This editorial seeks to understand why the controversy continues and how consensus can be achieved.
‘Position’ paper. Critical analysis and synthesis of relevant literature.
Advocates point at ADMs impressive effect size (number needed to treat, NNT = 6–8) in acute phase treatment and continuation/maintenance ADM treatment prevention relapse/recurrence in acute phase ADM responders (NNT = 3–4). Critics point at the limited clinically significant surplus value of ADMs relative to placebo and argue that effectiveness is overstated. We identified multiple factors that fuel the controversy: certainty of evidence is low to moderate; modest efficacy on top of strong placebo effects allows critics to focus on small net efficacy and advocates on large gross efficacy; ADM withdrawal symptoms masquerade as relapse/recurrence; lack of association between ADM treatment and long-term outcome in observational databases. Similar problems affect psychological treatments as well, but less so. We recommend four approaches to resolve the controversy: (1) placebo-controlled trials with relevant long-term outcome assessments, (2) inventive analyses of observational databases, (3) patient cohort studies including effect moderators to improve personalized treatment, and (4) psychological treatments as universal first-line treatment step.
Given the public health significance of depression and increased long-term ADM usage, new approaches are needed to resolve the controversy.
Consistent evidence suggests that face-to-face cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) may be equally effective depression treatments. Current clinical research focuses on detecting the best predictors-moderators of efficacy to guide treatment personalisation. However, individual moderator studies show inconsistent findings. This systematic review and meta-analysis aimed to compare the efficacy of CBT and IPT, including combined treatment with antidepressants for depression, and evaluate the predictive power of demographic, clinical presentation and treatment characteristics moderators for both therapies.
PsycArticles, PsycINFO, PubMed and Cochrane Library were systematically searched through December 2017 for studies that have assessed individuals with major depression receiving either CBT or IPT in a face-to-face format both at pre- and post-treatment. Random-effects moderator meta-analyses were conducted.
In total 168 samples from 137 studies including 11 374 participants qualified for the meta-analytic review. CBT and IPT were equally effective across all but one prespecified moderators. For psychotherapy delivered without concomitant antidepressant treatment [antidepressant medications (ADMs)], CBT was superior to IPT (g = 1.68, Qbetweenp = 0.037). Within-CBT moderator analyses showed that increased CBT efficacy was associated with lower age, high initial depression severity, individual format of administration and no adjunctive ADMs. Within-IPT analyses showed comparable efficacy across all moderators.
Clinical guidance around combined treatment (psychotherapy plus ADMs) should be reconsidered. CBT alone is superior to IPT alone and to combined treatment, while IPT alone is non-inferior to combined treatment. More research is needed to assess the moderating effect of older age and number of previous episodes on IPT efficacy.
As depression has a recurrent course, relapse and recurrence prevention is essential.
In our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/−AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.
Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.
Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/−AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/−AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/−AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/−AD.
Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/−AD will become cost-effective.
Declaration of interest
C.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents.
We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents).
These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected.
These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.
Currently only about half of the people who have major depressive disorder are detected during regular health care. Screening in high-risk groups might be a possible solution.
To evaluate the effectiveness of selective screening for major depressive disorder in three high-risk groups in primary care: people with mental health problems, people with unexplained somatic complaints and people who frequently attend their general practitioner.
Prospective cohort study among 2005 people in high-risk groups in three health centres in The Netherlands.
Of the 2005 people identified, 1687 were invited for screening and of these 780 participated. Screening disclosed 71 people with major depressive disorder: 36 (50.7%) already received treatment, 14 (19.7%) refused treatment and 4 individuals did not show up for an appointment. As a final result of the screening, 17 individuals (1% of 1687) started treatment for major depressive disorder.
Screening for depression in high-risk populations does not seem to be effective, mainly because of the low rates of treatment initiation, even if treatment is freely and easily accessible.
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