Treatment Options for Depression in Dementia

Pharmacological Treatment

Evidence for improvement in symptoms of depression in patients with dementia on antidepressant treatment, although suggestive, do not definitively confirm efficacy. Many trials have been carried out on small numbers of patients and are hence underpowered to detect differences, resulting in inconclusive findings. Variable trial methods, comorbid conditions and differences in the administered antidepressants further confound findings. Most studies showed a trend towards antidepressants being effective on depressive symptoms in patients with dementia, but the recent meta-analysis by Nelson and Devanand [70] could not confirm efficacy. A Cochrane review on antidepressants for treating depression in dementia, conducted by Bains et al. 2009 [71], came to the conclusion that it is not that antidepressants are necessarily ineffective, but rather that there is not much evidence to support their efficacy. Given that they may produce serious side effects, clinicians should therefore prescribe with due caution. In the light of large trials that have failed to detect efficacy, a Norwegian study in 52 nursing homes attracts interest. The study evaluated the effect of controlled treatment discontinuation of selective serotonin reuptake inhibitors (SSRIs) (e.g. escitalopram, citalopram, sertraline and paroxetine) in patients who were diagnosed with AD, vascular dementia or a mixture of both, who were prescribed SSRIs for at least 3 months. After 25 weeks, the discontinuation led to a statistically significant as well as clinically relevant increase in depressive symptoms, compared with those patients who continued with treatment [72].

Current practice is to use antidepressants, preferably selective serotonin reuptake inhibitors (SSRI), as a first-line treatment for depression in dementia, based on recommendations of several guidelines. In the UK, the National Institute for Health and Clinical Excellence (NICE) advocates antidepressants for major depression in dementia. Additionally, NICE advises that treatment should be started by staff with specialist training, who should follow the guidelines for depression after a careful risk-benefit assessment [73] . The American Psychiatric Association (APA) [74] recommends a trial of an antidepressant to treat clinically significant, persistent depressed mood in patients with dementia, and SSRIs may be preferred because they appear to be better tolerated than other antidepressants. Alternative agents to SSRIs are mentioned, including venlafaxine, mirtazapine and bupropion. The APA publication is the only guideline which refers to electroconvulsive therapy (ECT) as a possible treatment and considers it appropriate for patients with moderate to severe depression that is life threatening or refractory to other treatments. There is evidence from some trials for ECT as an effective and well-tolerated option for treating depression in people with dementia. The Hausner et al. study reported improvement in depressive symptoms with ECT with any cognitive deficits arising during therapy being transient [75]. All guidelines advise against antidepressant drugs with anticholinergic effects because of their potential to adversely affect cognition. Although SSRIs have a favourable side effect profile, a population-based cohort study [76] found that SSRIs and newer non-SSRI antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants (TCAs). Hence this widely held belief of better tolerated SSRIs should be open to critical consideration and each patient treated after giving careful consideration to the risks like hyponatremia, gastrointestinal bleeding or falls versus benefits.

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