Implementing AHRQ Effective Health Care Reviews
Helping Clinicians Make Better Treatment Choices
Second-Generation Antidepressants for Depression in Adults
Am Fam Physician. 2013 Nov 15;88(10):687-689.
See the the full review, clinician summary, consumer summary, and CME activity.
Author disclosure: No relevant financial affiliations.
Key Clinical Issue
What are the comparative effectiveness and adverse effects of second-generation antidepressants for treating depression in adults?
Evidence-Based Answer
Second-generation antidepressants (antidepressants other than tricyclics and monoamine oxidase inhibitors) used to treat major depressive disorder in adults have similar effectiveness. However, some clinically significant differences among individual drugs exist with respect to onset of action and adverse effects, which may affect treatment choices. For example, mirtazapine has a faster onset of action, but is associated with greater weight gain. Also, bupropion has fewer sexual adverse effects than many comparators. More research is needed to evaluate whether the benefits or adverse effects of second-generation antidepressants differ in subgroups or in populations with accompanying symptoms such as anxiety, insomnia, or chronic pain. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
Clinical Bottom Line: Second-Generation Antidepressants for Depression in Adults
Comparative benefits | |
Major depressive disorder
| |
Dysthymia or subsyndromal depression
| |
Depression with accompanying symptoms
| |
Comparative adverse effects | |
| |
Strength of evidence scale | |
High: ●●● There are consistent results from good-quality studies. Further research is very unlikely to change the conclusions. | |
Moderate: ●●○ Findings are supported, but further research could change the conclusions. | |
Low: ●○○ There are very few studies, or existing studies are flawed. | |
Insufficient: ○○○ Research is either unavailable or does not permit estimation of a treatment effect. |
NOTE: Second-generation antidepressants (therapeutic classification): bupropion (other); citalopram (SSRI); desvenlafaxine (SNRI); duloxetine (SSNRI); escitalopram (SSRI); fluoxetine (SSRI); fluvoxamine (SSRI); mirtazapine (other); nefazodone (other); paroxetine (SSRI); sertraline (SSRI); trazodone (other); venlafaxine (SNRI)
SNRI = serotonin–norepinephrine reuptake inhibitor; SSNRI = selective serotonin and norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor.
Adapted from the Agency for Healthcare Research and Quality, Effective Health Care Program. Second-generation antidepressants for treating adult depression: An update. Clinician research summary. Rockville, Md.: Agency for Healthcare Research and Quality; July 2012. http://effectivehealthcare.ahrq.gov/ehc/products/210/1143/sec_gen_anti_dep_clin_fin_to_post.pdf. Accessed August 5, 2013.
Clinical Bottom Line: Second-Generation Antidepressants for Depression in Adults
Comparative benefits | |
Major depressive disorder
| |
Dysthymia or subsyndromal depression
| |
Depression with accompanying symptoms
| |
Comparative adverse effects | |
| |
Strength of evidence scale | |
High: ●●● There are consistent results from good-quality studies. Further research is very unlikely to change the conclusions. | |
Moderate: ●●○ Findings are supported, but further research could change the conclusions. | |
Low: ●○○ There are very few studies, or existing studies are flawed. | |
Insufficient: ○○○ Research is either unavailable or does not permit estimation of a treatment effect. |
NOTE: Second-generation antidepressants (therapeutic classification): bupropion (other); citalopram (SSRI); desvenlafaxine (SNRI); duloxetine (SSNRI); escitalopram (SSRI); fluoxetine (SSRI); fluvoxamine (SSRI); mirtazapine (other); nefazodone (other); paroxetine (SSRI); sertraline (SSRI); trazodone (other); venlafaxine (SNRI)
SNRI = serotonin–norepinephrine reuptake inhibitor; SSNRI = selective serotonin and norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor.
Adapted from the Agency for Healthcare Research and Quality, Effective Health Care Program. Second-generation antidepressants for treating adult depression: An update. Clinician research summary. Rockville, Md.: Agency for Healthcare Research and Quality; July 2012. http://effectivehealthcare.ahrq.gov/ehc/products/210/1143/sec_gen_anti_dep_clin_fin_to_post.pdf. Accessed August 5, 2013.
Practice Pointers
All second-generation antidepressants, have similar effectiveness for treatment of major depressive disorder, with a 60% overall response rate.1 Therefore, it is reasonable to make the initial choice of a second-generation antidepressant for depression based on known adverse effect profiles, as recommended in current guidelines from the American Psychiatric Association2 and the American College of Physicians.3 For example, paroxetine (Paxil) is associated with more sexual adverse effects, and mirtazapine (Remeron) with more weight gain. Trazodone causes increased somnolence, and may be a good choice in patients with difficulty sleeping. Formulation (e.g., daily vs. weekly dosing, immediate vs. controlled release) does not impact clinical effectiveness.1
For patients with resistant depression, a large randomized trial showed no difference in response rates among sustained-release bupropion (Wellbutrin SR), sertraline (Zoloft), and extended-release venlafaxine (Effexor XR).4 Some lower-quality studies suggest venlafaxine may be slightly superior to fluoxetine (Prozac), mirtazapine, paroxetine, sertraline, and citalopram (Celexa).5 No studies have compared second-generation antidepressants for relapsed depression.
Evidence from 31 studies in the AHRQ review suggests that most second-generation antidepressants are effective for preventing relapse. No particular second-generation antidepressant is superior at maintaining remission based on existing head-to-head studies.1 No evidence currently exists to help guide patients in switching from one second-generation antidepressant to another.
Evidence from seven fair-quality head-to-head trials in the AHRQ review suggests that antidepressants do not differ substantially in effectiveness for patients with major depressive disorder and comorbid anxiety symptoms. Five trials included in the AHRQ review showed no substantial differences in effectiveness among second-generation antidepressants for treatment of major depressive disorder with accompanying insomnia.1
Overall, second-generation antidepressants have similar adverse effects; these occur in 63% of patients and include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual dysfunction, and somnolence. Nausea and vomiting are the most common reasons for discontinuation.6 Venlafaxine has a higher incidence of nausea than the selective serotonin reuptake inhibitors.
A good systematic review indicates that paroxetine and venlafaxine have the highest rates of antidepressant discontinuation syndrome, whereas fluoxetine has the lowest.7 More information on antidepressant discontinuation syndrome can be found at https://www.aafp.org/afp/2006/0801/p449.html. There is insufficient evidence on the comparative risks of second-generation antidepressants on the most serious adverse effects: suicidality, hyponatremia, cardiovascular events, seizures, hepatotoxicity, and serotonin syndrome.
REFERENCES
show all references1. Gartlehner G, Hansen RA, Morgan LC, et al. Second-generation antidepressants in the pharmacologic treatment of adult depression: An update of the 2007 Comparative Effectiveness Review. Rockville, Md.: Agency for Healthcare Research and Quality; December 2011. http://effectivehealthcare.ahrq.gov/ehc/products/210/863/CER46_Antidepressants-update_20111206.pdf. Accessed January 6, 2013....
2. Gelenberg AJ, Freeman MP, Markowitz JC, et al.; Work Group on Major Depressive Disorder. Practice guideline fo r the treatment of patients with major depressive disorder. Third edition. http://psychiatryonline.org/pdfaccess.ashx?ResourceID=243261&PDFSource=6. Accessed February 28, 2013.
3. Qaseem A, Snow V, Denberg TD, Forciea MA, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians [published correction appears in Ann Intern Med. 2009;150(2):148]. Ann Intern Med. 2008;149(10):725–733.
4. Kozel FA, Trivedi MH, Wisniewski SR, et al. Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report. Am J Geriatr Psychiatry. 2008;16(1):58–64.
5. Mackay FR, Dunn NR, Martin RM, Pearce GL, Freemantle SN, Mann RD. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract. 1999;49(448):892–896.
6. Trivedi MH, Fava M, Wisniewski SR, et al.; STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243–1252.
7. Expert Working Group of the Committee on Safety of Medicines. Report of the CSM Expert Working Group on the safety of selective serotonin reuptake inhibitor antidepressants. December 2004. http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf. Accessed October 11, 2013.
The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to organize knowledge and make it available to inform decisions about health care. A key clinical question based on the AHRQ Effective Health Care Program review is presented, followed by an evidence-based answer and an interpretation that will help guide clinicians in making treatment decisions.
A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at https://www.aafp.org/afp/ahrq.
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