Assessment and Treatment of Late-Life Depression
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.
Psychotherapeutic and Psychosocial Interventions
Psychotherapeutic interventions have demonstrated efficacy in the treatment of geriatric depression, including but not limited to cognitive behavioral therapy (CBT), interpersonal therapy (IPT), problem-solving therapy (PST), reminiscence and life review, and brief psychodynamic psychotherapy [74]. Some older adults may prefer psychotherapy to pharmacologic treatment (57% vs. 43%) [75]. Potential benefits of psychotherapy include ability to directly address psychosocial stressors that may precipitate or perpetuate depressive symptoms. In addition, psychotherapy is associated with few to no side effects and avoids drug interactions. Barriers to employing psychotherapy may include cost and access to trained psychotherapists [76]. Efficacy of several psychotherapeutic approaches in the care of older depressed adults has been examined. CBT, brief psychodynamic psychotherapy, and IPT will be briefly reviewed here.
CBT. Cognitive therapy was first described by Aaron Beck in the 1960s [77]. It is a highly structured therapy built on the premise that beliefs and assumptions an individual holds can influence emotions and behavior. CBT aims to identify maladaptive belief systems, test the validity of these cognitive distortions, and help individuals formulate more realistic cognitions [78]. Symptom improvement results from addressing these cognitive aspects as well as integration of behavioral activation and skills training to overcome maladaptive behavioral patterns [78]. CBT approaches have been applied to older adults with depression and results show acceptability [79] and efficacy in this population [80–82]. A 2008 Cochrane review (n = 153) found CBT to be superior to waitlist controls [82].
Brief psychodynamic psychotherapy. Brief psychodynamic psychotherapy, unlike highly structured CBT, aims to alter behavior by examining how past experiences and unresolved conflicts influence current emotions and behavior. While studies on application to the treatment of geriatric depression are scarce, limited data demonstrate efficacy in treating geriatric depression [81] and no significant difference in outcomes when compared to CBT [82].
IPT. Like CBT, IPT is a structured time-limited psychotherapeutic treatment approach first developed in the late 1960s by Klerman and Weissman [83]. IPT focuses on the impact of interpersonal relationships on depressive symptoms and examines 4 domains: interpersonal conflict, interpersonal deficits, role transitions, and grief [74].
Studies have shown efficacy of IPT in reducing depressive symptoms in the elderly when compared to usual care [84]. Reynolds et al found IPT combined with nortriptyline (a tricyclic antidepressant) to be superior to either nortriptyline alone or IPT alone in preventing recurrent depressive episodes [85]. Interestingly, a similar study investigating the efficacy of IPT in combination with paroxetine (an SSRI) failed to show added benefit of IPT in preventing recurrence, suggesting that further studies are needed [86].
Psychosocial interventions are integral in the care of the elderly depressed patient. Studies have shown positive benefits of aerobic exercise on depressive symptoms [87]. Yoga, Tai Chi, and other mindfulness-based exercises can increase sense of emotional and physical wellbeing [88–90]. Spirituality, religious beliefs, and involvement with a faith group may be protective against development of mental illness while at the same time provide avenues for increased social connectedness [91]. These and other avenues for socialization should be encouraged as part of the treatment plan for older depressed patients [92]
Electroconvulsive Therapy
ECT is indicated for the treatment of mood and psychotic disorders and has demonstrated efficacy in the treatment of severe depression [93]. It is typically initiated when patients fail to respond to pharmacotherapy and psychotherapy. Circumstances in which ECT can be considered first-line treatment include situations that require a rapid response (severe inanition, weight loss, or suicidality), situations where risks of ECT are lower than that of alternative treatments, previous positive response to ECT, or strong patient preference [94]. ECT is performed under general anesthesia and involves the induction of a generalized tonic-clonic seizure, which is theorized to enhance serotonergic, noradrenergic, and dopaminergic neurotransmission. A typical course of ECT involves treatments 3 times a week for an average of 6 to 12 treatments in total [95]. Elderly patients and those suffering from severe depression with psychotic features respond more robustly to ECT [93,96]. Estimated remission rates after an ECT series have been higher than 80% [93], making this modality the most effective treatment for severe depression to date.
Conclusion
As the population continues to age, clinicians are increasingly likely to encounter patients with late-life depression. A thorough evaluation includes not only assessment of depressive symptoms, but also cognitive, functional, and suicide assessment. Treatment options include pharmaco-therapy, psychotherapy, and in some cases electroconvulsive therapy. Utilization of assessment and treatment nuances unique to the geriatric population, with a multidisciplinary and collaborative approach involving primary care, mental health, and other ancillary providers, will serve to ultimately enhance patient care.
Corresponding author: Corresponding author: Juliet Glover, MD, Dept. of Neuropsychiatry and Behavioral Science, Univ. of South Carolina School of Medicine, 15 Medical Park, Suite 301, Columbia, SC 29203, Juliet.Glover@uscmed.sc.edu.
Financial disclosures: None reported.
Author contributions: conception and design, JAG, SS; drafting of article, JAG, SS; critical revision of the article, JAG, SS.
