A Systematic Review of Treatments for Refractory Depression in Older People

Abstract

Objective: The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older). Method: The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies. Results: All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI542-62; N5381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI521-65; N557). Only two studies included comparison groups receiving no additional treatment, and none of the participants in these groups responded. In single randomized studies, extended-release venlafaxine was more efficacious than paroxetine, lithium augmentation more than phenelzine, and selegiline more than placebo.Conclusions: Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people. The only treatment for which there was replicated evidence was lithium augmentation. Double-blind randomized controlled trials for management of treatment-refractory depression in older people, encompassing pharmacological and nonpharmacological therapies and populations that reflect the levels of physical and cognitive impairment present in the general older population with depression, are needed.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

“…Half of the participants responded to a switch or augmentation strategy, with lithium augmentation demonstrating the most consistent data for all approaches. 144 Of all studies included in the analysis, a sequential treatment strategy provided the highest response rates. 145 For LLD, RCT data generally only assess an individual step in an algorithmic or stepwise approach.…”

Dépression du sujet âgé : données épidémiologiques, aspects cliniques et approches thérapeutiques spécifiques

“…Là encore, à l'inverse du sujet adulte non âgé pour lequel on dispose de recommandations issues de données robustes, comme l'étude STAR*D [24], très peu de données sont exploitables pour le sujet âgé. La revue de Cooper et al [25] …”

Non-Response to Initial Antidepressant Therapy

“…Onset of depression in patients >60 years has been associated with a greater likelihood of psychotic symptoms and vascular brain changes that may increase the risk to develop to resistance (Kornstein et Schneider, 2001) Similar efficacy rates for antidepressant and psychological therapies have been reported in older adults and those under the age of 60 (Goldberg et al, 1998). TRD is clearly understudied in the elderly, because late-life depression has higher rates of physical and cognitive comorbidity and agerelated pharmacodynamic/pharmacokinetic changes add greatly to the complexity of monitoring TRD (Cooper et al, 2011) …”