Evidence-Based Reviews

Depression in older adults: How to treat its distinct clinical manifestations

Current Psychiatry. 2010 August;9(8):39-46

References

1. Lyketsos CG, Lee HB. Diagnosis and treatment of depression in Alzheimer’s disease. A practical update for the clinician. Dement Geriatr Cogn Disord. 2004;17(1-2):55-64.

2. Alexopoulos G. Late-life mood disorders. In: Sadavoy J, Jarvik LF, Grossberg GT, et al, eds. Comprehensive textbook of geriatric psychiatry. 3^rd ed. New York, NY: W.W. Norton and Company; 2004:609-653.

3. Shanmugham B, Karp J, Drayer R, et al. Evidence-based pharmacologic interventions of geriatric depression. Psychiatr Clin North Am. 2005;28(4):821-835,viii.

4. Alexopoulos GS, Katz IR, Reynolds CF, III, et al. The expert consensus guidelines series. Pharmacotherapy of depressive disorders in older patients. Postgrad Med. 2001; Spect No Pharmacolotherapy:1–86.

5. American Psychiatric Association practice guidelines for the treatment of psychiatric disorders. Arlington, VA: American Psychiatric Association; 2006:793–794.

6. Bartels SJ, Dums AR, Oxman TE, et al. Evidence-based practice in geriatric mental health care. Psychiatr Serv. 2002;53(11):1419-1431.

7. Bartels SJ, Dums AR, Oxman TE, et al. Evidence-based practices in geriatric mental health care: an overview of systematic reviews and meta-analyses. Psychiatr Clin North Am. 2003;26(4):971-990,x–xi.

8. Raskin J, Wiltse CG, Siegal A, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry. 2007;164(6):900-909.

9. Alexopoulos GS, Young RC, Abrams RC. ECT in the high-risk geriatric patient. Convuls Ther. 1989;5(1):75-87.

10. Young RC, Gyulai L, Mulsant BH, et al. Pharmacotherapy of bipolar disorder in old age: review and recommendations. Am J Geriatr Psychiatry. 2004;12:342-357.

11. Vieta E, Calabrese JR, Goikolea JM, et al. Quetiapine monotherapy in the treatment of patients with bipolar I or II depression and a rapid-cycling disease course: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2007;9(4):413-425.

12. Corya SA, Perlis RH, Keck PE, Jr, et al. A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression. J Clin Psychiatry. 2006;67(5):798-806.

13. Sajatovic M, Gyulai L, Calabrese JR, et al. Maintenance treatment outcomes in older patients with bipolar I disorder. Am J Geriatr Psychiatry. 2005;13(4):305-311.

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16. Starkstein SE, Mizrahi R, Power BD. Antidepressant therapy in post-stroke depression. Expert Opin Pharmacother. 2008;9(8):1291-1298.

17. Rush AJ, Trivedi MH, Wisniewski SR, et al. and STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354(12):1231-1242.

18. Trivedi MH, Fava M, Wisniewski SR, et al. and the STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243-1252.

19. McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1531-1541.

20. Appelberg BG, Syvälahti EK, Koskinen TE, et al. Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry. 2001;62(6):448-452.

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Although optimal mood stabilizer and antidepressant dosing for this population has not been adequately assessed, pharmacotherapy that has been effective generally should be continued without modification for at least 6 to 12 months.¹⁰ After the patient achieves remission, gradually discontinue antidepressants while maintaining the mood stabilizer.¹⁰

Algorithm 2: Bipolar depression: Options for combination therapy

ECT: electroconvulsive therapy; SSRIs: selective serotonin reuptake inhibitors

Depression in dementia

Managing depression in dementia patients is similar to treatment in older adults without dementia,^5,14 although pharmacologic agents must be carefully selected because of increased risk of side effects (Algorithm 3). American Psychiatric Association practice guidelines recommend considering antidepressants for depressed patients with dementia even if their mood disturbances do not meet DSM-IV-TR criteria for MDD.⁵

Clinical Point

ECT for depressed patients with dementia often is modified to twice-a-week, unilateral stimulus because of increased delirium risk

SSRIs’ lower side effect profile make them the preferred treatment; the selective serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine is a second-line option.^4,14 Avoid TCAs and other agents with anticholinergic side effects because of potential cardiovascular complications and cognitive side effects, unless SSRIs or SNRIs are ineffective or contraindicated.¹⁴ Recently clinicians have been reluctant to use antipsychotics in patients with dementia, because of the FDA’s “black-box” warning regarding the increased mortality risk associated with their use in this population.

When using ECT to treat depression in patients with dementia, the treatment protocol often is modified to twice-a-week, unilateral stimulus because of these patients’ increased risk of delirium.¹⁴ The safety of ECT to treat depression in patients with dementia has not been adequately assessed.¹⁴

Algorithm 3: Treating comorbid depression and dementia

ECT: electroconvulsive therapy; SNRI: selective serotoninnorepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor

Vascular depression

The “vascular depression hypothesis” proposes that accumulation of subcortical white matter hyperintensities can disrupt frontostriatal pathways, resulting in depressive symptoms.¹⁵ This hypothesis is supported by the confluence of depression and vascular risk factors.¹⁵ Sertraline, citalopram, nortriptyline,¹⁶ and trazodone¹⁵ have been shown to reduce depressive symptoms after a stroke.

Minor depression and dysthymia

Although the efficacy of antidepressants in minor depression—depression that does not meet criteria for MDD—is not well established, expert consensus guidelines recommend SSRIs and psychotherapy, separately or in combination, for minor depression and dysthymia in older adults (Algorithm 4).⁴ Depression in executive dysfunction responds poorly to SSRI treatment²; however, behaviorally oriented psychotherapeutic interventions such as problem-solving therapy (PST) show promise.²

Algorithm 4: Minor depression: SSRIs plus psychotherapy

SSRIs: selective serotonin reuptake inhibitors

Comorbid medical conditions

When an older adult has a medical problem that likely contributes to depression—such as hypothyroidism—treat the condition and prescribe antidepressants simultaneously.² However, if the medical problem likely causes depression—such as substance withdrawal—treat the condition first and prescribe antidepressants only if mood symptoms persist.²

Clinical Point

If a medical problem likely causes depression, treat the condition first and offer antidepressants if mood symptoms persist

Refractory depression

If your patient does not respond to an antidepressant trial of adequate dosage and duration, first make sure he or she is taking it correctly (Algorithm 5). After ruling out poor adherence, screen for comorbid psychiatric or medical conditions or psychosocial stressors and reassess the principal diagnosis.⁵

If these steps don’t address your patient’s depressive symptoms, expert consensus guidelines suggest switching to a different antidepressant:⁴

If you first prescribed an SSRI, consider venlafaxine XR or bupropion SR.^4,17
If your patient initially received a TCA or bupropion, an SSRI or venlafaxine XR would be appropriate.⁴
If venlafaxine XR was the first antidepressant, a SSRI is recommended.⁴

If your patient experienced a partial response but not full remission with the initial antidepressant, consider adding a second antidepressant or an augmenting agent:⁴

If your patient first received an SSRI, adding bupropion, lithium, or nortriptyline is recommended.
If the initial antidepressant was a TCA or bupropion, consider adding lithium or an SSRI.
Augmenting venlafaxine XR with lithium is recommended.⁴

The National Institutes of Mental Health-sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study of treatment-resistant depression in mixed-age groups reported that patients who do not attain remission with an initial SSRI may respond to switching to bupropion SR or venlafaxine XR.¹⁷ Augmenting an SSRI with bupropion SR has been shown to be effective.¹⁸ In addition, consider mirtazapine augmentation,¹⁹ especially if your patient experiences insomnia or anorexia. A combination of mirtazapine and venlafaxine have better efficacy and tolerability compared with the monoamine oxidase inhibitor tranylcypromine.¹⁹ Some studies have shown augmenting SSRIs with buspirone in patients with severe depression is efficacious and safe in younger adults,²⁰ but this practice is not well studied in older patients.