Adverse Events of Pharmacologic Treatments of Major Depression in Older Adults

Elizabeth Salisbury-Afshar

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Feb 1, 2020 Issue

Implementing AHRQ Effective Health Care Reviews

Helping Clinicians Make Better Treatment Choices

Adverse Events of Pharmacologic Treatments of Major Depression in Older Adults

ELIZABETH SALISBURY-AFSHAR, MD, MPH, American Institutes for Research, Chicago, Illinois

Am Fam Physician. 2020 Feb 1;101(3):179-181.

Author disclosure: No relevant financial affiliations.

Key Clinical Issue

What are the adverse events of antidepressants prescribed to treat major depressive disorder in adults 65 years and older?

Evidence-Based Answer

Selective serotonin reuptake inhibitors (SSRIs) cause adverse events at a similar frequency to placebo and have lower discontinuation rates than tricyclic antidepressants during up to 12 weeks of treatment. (Strength of Recommendation [SOR]: B, based on inconsistent or limited-quality patient-oriented evidence.) Serotonin-norepinephrine reuptake inhibitors (SNRIs) cause more adverse events and greater discontinuation of therapy during up to 12 weeks of treatment compared with placebo. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Duloxetine increases the risk of falls over 12 to 24 weeks of treatment compared with placebo.1 (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.)

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CLINICAL BOTTOM LINE

Comparative Adverse Events of Antidepressants vs. Each Other: Summary Statements Based on Findings and Statistical Significance*

Comparison (study design)	Acute phase (< 12 weeks)	Continuation phase (12 to 48 weeks)	Maintenance phase (> 48 weeks)
SSRI vs. SSRI (RCT)	Adverse events similar with sertraline or escitalopram vs. fluoxetine ●●○ Withdrawal due to adverse events similar with paroxetine, sertraline, or escitalopram vs. fluoxetine ●○○ Insufficient evidence: mortality	No data	Adverse events similar with paroxetine vs. fluoxetine ●●○ Serious adverse events similar with paroxetine vs. fluoxetine ●●○ Insufficient evidence: mortality
SSRI vs. SSRI (observational)	No data	Hospitalization similar with escitalopram vs. other SSRI or SNRI ●○○	No data
SNRI vs. SSRI (RCT)	Adverse events similar with venlafaxine vs. fluoxetine ●●○ Withdrawals due to adverse events similar with venlafaxine vs. fluoxetine ●○○	Adverse events similar with venlafaxine vs. citalopram ●●○ Serious adverse events similar with venlafaxine vs. citalopram ●●○ Withdrawals due to adverse events similar with venlafaxine vs. citalopram ●●○ Inconclusive: falls, fractures, mortality	No data
SSRI vs. tricyclic antidepressant (RCT)	Adverse events fewer with paroxetine and citalopram vs. amitriptyline ●○○, NNT = 6 (95% CI, 4 to 11) Withdrawals due to adverse events fewer with paroxetine, citalopram, and sertraline vs. amitriptyline and nortriptyline ●○○, NNT = 13 (95% CI, 7 to 100) Inconclusive: cognitive impairment, hospitalization, mortality, and serious adverse events	No data	No data
Mirtazapine vs. paroxetine (RCT)	Adverse events similar with mirtazapine ●●○ Serious adverse events similar with mirtazapine ●○○ Withdrawals due to adverse events fewer with mirtazapine ●○○, NNT = 9 (95% CI, 5 to 72) Inconclusive: hospitalization	Adverse events similar with mirtazapine ●○○	No data
Vortioxetine vs. duloxetine (RCT)	Adverse events fewer with vortioxetine ●●●, NNT = 6 (95% CI, 4 to 17) Serious adverse events similar with vortioxetine ●●○ Withdrawals due to adverse events similar with vortioxetine ●●○ Inconclusive: fractures	No data	No data

Strength of evidence scale

●●● High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.

●●○ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.

●○○ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.

○ ○ ○ Insufficient: Evidence either is unavailable or does not permit a conclusion.

NNT = number needed to treat; RCT = randomized controlled trial; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor.

*—Conclusions based on statistical significance may miss small differences from insufficient studies.

Adapted from Sobieraj DM, Baker WL, Martinez BK, et al. Adverse effects of pharmacologic treatments of major depression in older adults. Comparative Effectiveness Review No. 215. (Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. 290-2015-00012- I.) AHRQ Publication No. 19-EHC011-EF. Rockville, Md.: Agency for Healthcare Research and Quality; March 2019. Accessed May 15, 2019. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-215-depression-older-adults-executive-summary.pdf

CLINICAL BOTTOM LINE

Comparative Adverse Events of Antidepressants vs. Each Other: Summary Statements Based on Findings and Statistical Significance*

Comparison (study design)	Acute phase (< 12 weeks)	Continuation phase (12 to 48 weeks)	Main

Address correspondence to Elizabeth Salisbury-Afshar, MD, MPH, at elizabeth.salisbury@gmail.com. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

References

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1. Sobieraj DM, Baker WL, Martinez BK, et al. Adverse effects of pharmacologic treatments of major depression in older adults. Comparative Effectiveness Review No. 215. (Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. 290-2015-00012- I.) AHRQ Publication No. 19-EHC011-EF. Rockville, Md.: Agency for Health-care Research and Quality; March 2019. Accessed May 15, 2019. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-215-depression-older-adults-executive-summary.pdf...

2. Centers for Disease Control and Prevention. CDC promotes public health approach to address depression among older adults. Accessed May 25, 2019. https://www.cdc.gov/aging/pdf/cib_mental_health.pdf

3. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. American Psychiatric Association; 2010. Accessed December 3, 2019. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf

4. Nelson JC, Delucchi K, Schneider LS. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry. 2008;16(7):558–567.

5. The 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674–694.

6. Coupland C, Dhiman P, Morriss R, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ. 2011;343:d4551.

7. Robinson M, Oakes TM, Raskin J, et al. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatr Psychiatry. 2014;22(1):34–45.

8. Boyce RD, Hanlon JT, Karp JF, et al. A review of the effectiveness of anti-depressant medications for depressed nursing home residents. J Am Med Dir Assoc. 2012;13(4):326–331.

9. Hewett K, Chrzanowski W, Jokinen R, et al. Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder. J Psychopharmacol. 2010;24(4):521–529.

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based on the review. AHRQ's summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions.

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This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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