Journal of Clinical Outcomes Management. 2017 March;24(3)
References
Studies have demonstrated antidepressants to be superior to placebo in the treatment of geriatric depression. Table 3 summarizes commonly prescribed anti-depressants and usual geriatric doses. A large meta-analysis of 51 double-blind randomized controlled trials with depressed patients age 55 and older without comorbid dementia found antidepressants to be superior to placebo in achieving both response (48%) and remission (33.7%) [55]. Response was defined as greater than 50% decrease on depression rating scales such as the Hamilton Depression Rating Scale (HAM-D) or the Montgomery Åsberg Depression Rating Scale (MADRS), both of which are considered gold standards in antidepressant clinical trials [56,57]. Remission was defined as a score less than 7 or 10 on the HAM-D (depending on the version used) or less than 12 on the MADRS. This study found no difference in response and remission rates between tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and other antidepressants (serotonin norepinephrine reuptake inhibitors [SNRIs], bupropion, mirtazapine, nefazodone, trazodone, and several other antidepressants not available in the United States) [55]. Similar results regarding efficacy were found by Mukai and Tampi in a systematic review comparing older patients with major depression prescribed SSRIs or dual-acting agents (SNRIs and TCAs). This study also found similar efficacy between single- and dual-acting antidepressants [58].
While cognitive impairment may affect antidepressant efficacy, age does not appear to be a determinant. Gildengers et al examined antidepressant response in young, middle, and older-old patients and found no significant difference in response rates [59]. Early onset versus late onset of first depressive episode also does not predict antidepressant response in patients age 55 and over [60]. There is scant evidence for efficacy of antidepressants in depressed patients with neurocognitive disorders. A 2002 Cochrane review with 4 studies in the meta-analysis ( n = 137) concluded that there was weak support for antidepressant efficacy in this population [61]. A 2011 meta-analysis with 330 participants also yielded inconclusive results [62]. The paucity of evidence for antidepressant efficacy in depressed patients with neurocognitive disorders should prompt careful consideration of potential benefits versus adverse effects.
Antidepressants are generally well tolerated in older adults. Side effects vary by medication and contribute to discontinuation in up to 25% of new users (versus 22% for new users who discontinue for reasons other than side effects) [63]. Potential adverse effects shared by most SSRIs and SNRIs include GI disturbance (nausea, diarrhea or constipation), sexual dysfunction, headache, and sleep disturbance [64,65]. In addition, abrupt discontinuation can precipitate serotonin withdrawal syndrome characterized by sensory disturbance (paresthesia, tremor, and irritability) as well as headache, lightheadedness, diaphoresis, insomnia, and agitation. Other medication-specific side effects include risk of seizure with bupropion and sedation with mirtazapine [65].
Despite superiority of antidepressants to placebo in treating depression, up to one-third of patients may not respond to a trial of antidepressants. Sequential treatment protocols such as switching to a different antidepressant or augmentation can increase the proportion of antidepressant responders [66–68]. Studies have found particularly favorable response to augmentation with lithium, with one study achieving a 33% remission rate in treatment- resistant geriatric depression [67,69]. Other pharmacologic augmentation strategies include the addition of mood stabilizers such as lamotrigine, antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone), and psychostimulants [70–73]. Electroconvulsive therapy (ECT) is a nonpharmacologic option for treatment-resistant depression that will be reviewed later.
