Advances in Pharmacotherapy of Late-Life Depression
Purpose of Summary
This paper reviews recent research on late-life depression (LLD) pharmacotherapy, focusing on updated information for monotherapy and augmentation treatments. We then review new research on moderators of clinical response and how to use the information for improved efficacy.
A recent review shows that sertraline, paroxetine, and duloxetine were superior to placebo for the treatment of LLD. There is concern that paroxetine could have adverse outcomes in the geriatric population due to anticholinergic properties; however, studies show no increases in mortality, dementia risk, or cognitive measures. Among newer antidepressants, vortioxetine has demonstrated efficacy in LLD, quetiapine has demonstrated efficacy especially for patients with sleep disturbances, and aripiprazole augmentation for treatment resistance in LLD was found to be safe and effective. Researchers have also been identifying moderators of LLD that can guide treatment. Researchers are learning how to associate moderators, neuroanatomical models, and antidepressant response.
SSRI/SNRIs remain first-line treatment for LLD. Aripiprazole is an effective and safe augmentation for treatment resistance. Studies are identifying actionable moderators that can increase treatment response.
KeywordsLate-life depression Pharmacotherapy Treatment response moderators
Compliance with Ethical Standards
Conflict of Interest
Kim G. Johnson declares no conflict of interest. John L. Beyer has received grants from Allergan, Forest, Janssen, Takeda, and Sunovion.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329–35.Google Scholar
- 3.Zhang Y, Chen Y, Ma L. Depression and cardiovascular disease in elderly: current understanding. J. Clin. Neurosci. 2017;Google Scholar
- 6.Miller MD, Frank E, Cornes C, Houck PR, Reynolds CF 3rd. The value of maintenance interpersonal psychotherapy (IPT) in older adults with different IPT foci. Am J Geriatr Psychiatry. 2003;11(1):97–102.Google Scholar
- 8.Wilson KC, Mottram PG, Vassilas CA. Psychotherapeutic treatments for older depressed people. Cochrane Database Syst Rev. 2008;1:CD004853.Google Scholar
- 12.• Bali V, Chatterjee S, Johnson ML, Chen H, Carnahan RM, Aparasu RR. Risk of mortality in elderly nursing home patients with depression using paroxetine. Pharmacotherapy. 2017;37(3):287–96. This study shows there is no increased risk of mortality with use of paroxetine in nursing home patients. CrossRefPubMedGoogle Scholar
- 13.• Bali V, Chatterjee S, Carnahan RM, Chen H, Johnson ML, Aparasu RR. Risk of dementia among elderly nursing home patients using paroxetine and other selective serotonin reuptake inhibitors. Psychiatr Serv. 2015;66(12):1333–40. This study shows there is no increased risk of dementia with use of paroxetine in nursing home patients. CrossRefPubMedGoogle Scholar
- 14.• Bali V, Chatterjee S, Johnson ML, Chen H, Carnahan RM, Aparasu RR. Risk of cognitive decline associated with paroxetine use in elderly nursing home patients with depression. Am J Alzheimers Dis Other Demen. 2016;31(8):678–86. This study shows there is no increased risk of cognitive decline with use of paroxetine in nursing home patients CrossRefPubMedGoogle Scholar
- 21.•• Robinson M, Oakes TM, Raskin J, Liu P, Shoemaker S, Nelson JC. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatr Psychiatry. 2014;22(1):34–45. This study shows no increased efficacy for treatment of depression of duloxetine over placebo for the primary endpoint at 12 weeks but it did separate from placebo at weeks 4,8,16 and 20 weeks. There was also a significant beneficial effect on pain at all weeks of the study. CrossRefPubMedGoogle Scholar
- 22.•• Kerner N, D’Antonio K, Pelton GH, et al. An open treatment trial of duloxetine in elderly patients with dysthymic disorder. SAGE open medicine. 2014;2. Duloxetine decreased dythymic symptoms and somatic symptoms in the geriatric population. Google Scholar
- 28.•• Katila H, Mezhebovsky I, Mulroy A, Berggren L, Eriksson H, Earley W, et al. Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder. Am J Geriatr Psychiatry. 2013;21(8):769–84. This study showed quetiapine has efficacy in geriatric depression especially for patients with sleep disturbances. CrossRefPubMedGoogle Scholar
- 30.•• Thorlund K, Druyts E, Wu P, Balijepalli C, Keohane D, Mills E. Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults: a network meta-analysis. J Am Geriatr Soc. 2015;63(5):1002–9. This review shows that sertraline, paroxetine and duloxetine are superior to placebo among the SSRI and SNRI's. CrossRefPubMedGoogle Scholar
- 31.•• Lenze EJ, Mulsant BH, Blumberger DM, Karp JF, Newcomer JW, Anderson SJ, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(10011):2404–12. Aripiprazole is a safe and effective augmentation to venlafaxine for treatment resistant depression. Side effects include akithisia and parkinsonism. CrossRefPubMedPubMedCentralGoogle Scholar
- 32.•• Lavretsky H, Reinlieb M, St Cyr N, Siddarth P, Ercoli LM, Senturk D. Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2015;172(6):561–9. The citalopram plus methylphenidate group showed the highest improvement in depression severity and faster treatment response than citalopram plus placebo and methylphendate plus placebo. CrossRefPubMedPubMedCentralGoogle Scholar
- 33.• Omranifard V, Shirzadi E, Samandari S, Afshar H, Maracy MR. Memantine add on to citalopram in elderly patients with depression: a double-blind placebo-controlled study. J Res Med Sci. 2014;19(6):525–30. There was no difference in efficacy for geriatric depression between the citalopram plus memantine group and the citalopram plus placebo group PubMedPubMedCentralGoogle Scholar
- 34.Almeida OP, Ford AH, Hirani V, Singh V, vanBockxmeer FM, McCaul K, et al. B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Br J Psychiatry. 2014;205(6):450–7.CrossRefPubMedGoogle Scholar
- 35.Alexopoulos GS, Katz IR, Reynolds CF 3rd, Carpenter D, Docherty JP, Ross RW. Pharmacotherapy of depression in older patients: a summary of the expert consensus guidelines. J Psychiatr Pract. 2001;7(6):361–76.Google Scholar
- 36.FDA. Drug Safety Announcement Posted 3/28/2012. Accessed 11/12/2017; https://www.fda.gov/Drugs/DrugSafety/ucm297391.htm.
- 40.MacQueen GM, Frey BN, Ismail Z, et al. Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. Can J Psychiatr. 2016;61(9):588–603.CrossRefGoogle Scholar
- 46.Small GW, Hamilton SH, Bystritsky A, Meyers BS, Nemeroff CB. Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression. Fluoxetine Collaborative Study Group. Int Psychogeriatr 1995;7 Suppl:41–53, 7.Google Scholar
- 53.• Alexopoulos GS, Manning K, Kanellopoulos D, McGovern A, Seirup JK, Banerjee S, et al. Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant. Psychol Med. 2015;45(14):3111–20. Study of cognitive dysfunction in LLD suggesting that differentiating types of cognitive impairment may identify treatment responsiveness. CrossRefPubMedPubMedCentralGoogle Scholar
- 55.• Kaneriya SH, Robbins-Welty GA, Smagula SF, Karp JF, Butters MA, Lenze EJ, et al. Predictors and moderators of remission with aripiprazole augmentation in treatment-resistant late-life depression: an analysis of the IRL-GRey randomized clinical trial. JAMA Psychiatry. 2016;73(4):329–36. Post-hoc analysis of LLD treatment response to pharmacotherapy based on neurocognitive testing. CrossRefPubMedPubMedCentralGoogle Scholar
- 56.Smagula SF, Wallace ML, Anderson SJ, Karp JF, Lenze EJ, Mulsant BH, et al. Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder. J Psychiatr Res. 2016;81:112–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 59.• Joel I, Begley AE, Mulsant BH, Lenze EJ, Mazumdar S, Dew MA, et al. Dynamic prediction of treatment response in late-life depression. Am J Geriatr Psychiatry. 2014;22(2):167–76. Study looked at predictors of treatment response in LLD with suggested recommendations for making decisions to continue or change therapy based on these factors. Google Scholar