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Treating Depression in Later Life: Beyond Antidepressants

Two papers were published this past Spring pertaining to treatments for major depression among older adults using treatments other than antidepressants. An open trial of a novel form of psychotherapy targeting reward exposure showed comparable results to a problem-solving therapy although with much less training time, and a meta-analysis did not show improvement of depressive symptoms associated with B-12 and folate supplementation in randomized controlled trials.

Investigators from New York and California developed a form of psychotherapy called “Engage” aimed at treating patients with late-life depression. The therapy is based on principles from Problem-Solving therapy (PST), but places most of its emphasis on reward exposure with the goal of targeting positive valence systems that are hypothesized to be disrupted in patients with depression. The intervention involves facilitating meaningful rewarding activities, and when needed, also includes strategies for addressing negativity bias (such as examining alternate thoughts), apathy (such as checklists and reminders), and emotional dysregulation (such as relaxation exercises). Community social workers and research therapists were trained by having them read a manual, attend two 45 minute education sessions, engage in a role-play exercise and work with practice cases on which they had to achieve a set score. Audiotapes were examined to establish fidelity to the model. The therapy was provided to 39 patients in 9 weekly sessions, and the outcomes of scores on the Hamilton Depression Rating Scale (HAM-D) and the World Health Organization Disability Assessment Schedule (WHODAS) were assessed, in comparison to a historical cohort of 97 patients that received PST. The authors found comparable reductions in Ham-D and WHODAS scores in both groups, and remission rates of 41% for Engage compared with 35% for PST (ns). The training took less than 1/3 the time with Engage compared with PST, and fidelity on the audiotapes was stronger in the Engage group as well (p<0.0001).

The study was set up as a non-inferiority trial, and may be the first of this design testing psychotherapies in older adults. Since the point of comparison was a historical cohort exposed to 9 weeks of PST, the authors appropriately consider this a proof of concept trial, and plan a prospective randomized comparison. The mean HAM-D score at baseline for Engage was 3-points lower than in the PST group, and the MMSE score at baseline was one-point higher. The results were the same when repeated in a sample restricted to those with comparable HAM-D scores at baseline. There did not appear to be a minimum severity score on the Ham-D for this trial, and co-treatment with psychotropic medication was allowed but not described. Nonetheless, the ease of training and applicability of the model to less-experienced therapists makes Engage a potentially helpful psychotherapy modality that may address system-related barriers to care in older adults.

Alexopoulos, G.S., Raue, P.J., Kiosses, D.N., Seirup, J.K., Banerjee, S., Arean, P.A., Comparing Engage with PST in late-life major depression: A preliminary report. Am J Geriatric Psychiatry 2015, 23(5): 506-513.

Investigators from Australia assessed whether the association between folate and B12 deficiencies in observational studies translates to an improvement associated with supplementation with these vitamins in mood in randomized placebo-controlled trials. The authors screened 269 manuscripts identified in a search of 4 databases and identified 11 randomized controlled trials. Six studies assessed changes in depression scale scores among patients without mood disorder diagnoses, and 4 studies did the same in patients with major depressive episode (MDE) diagnoses who were concurrently treated with antidepressants. In a meta-analysis, there was no significant difference between the vitamin and placebo groups for either population, although the results were heterogeneous for the studies with patients with MDE. Similarly, although one of the three studies that examined clinically significant response to vitamin treatment among patients with MDE co-treated with antidepressants was positive, the meta-analysis of these three studies was negative with significant heterogeneity. They identified two “indicated prevention” trials of B vitamins, one in patients with hypertension and the other in patients post-stroke. Pooling these two studies yielded a homogeneous finding favouring B-vitamins over placebo (RR=0.65, 95% CI 0.43-0.98, p=0.04, I2=0). They identified an additional solitary study, from their own group last year showing reduction of relapse risk after remission of MDE associated with folate and B12 supplementation relative to placebo. In that study from 2014, the “BVitage study”, they also found that the vitamins improved response to antidepressant treatment over 52 weeks in those with high plasma homocysteine.

It is important to note that the quality of the studies in this systematic review was variable, with 10 of the 11 studies rated as having at least one domain of uncertain or high risk of bias, and that the age-range of the participants in the included trials was not restricted to older adults (and is incompletely characterized in the manuscript). The authors conclude that the beneficial role of folate and B12 in the literature to date seems to be restricted to relapse prevention and prevention of emergence of significant depressive symptoms in certain high risks groups, although they acknowledge that those studies need to be replicated.

Almeida, O.P., Ford, A.H., & Flicker, L., Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. International Psychogeriatrics 2015, 27(5): 727-737.

Mark J. Rapoport, MD, FRCPC; Associate Professor, Department of Psychiatry, University of Toronto; Staff Psychiatrist, Sunnybrook Health Sciences Centre, Canada

Excerpted article as reprint from IPA’s newsletter, the IPA Bulletin, Volume 32, Number 3

Acknowledgements

Acadia Pharmaceuticals Otsuka Pharmaceuticals Cambridge University Press Avanir Pharmaceuticals
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