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PubMed Clinical Q&A [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2008-2013.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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PubMed Clinical Q&A [Internet].

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Comparing Antidepressants

, MD.

Created: .

Depressive disorders are common, and treatment often includes medication. The newer, second-generation antidepressants lack many of the severe health risks that are associated with the older, first-generation drugs. The newer drugs are also used to treat a variety of conditions other than depression, including anxiety disorders, obsessive-compulsive disorder, and panic disorder.

It is not entirely clear how antidepressants work, but they are thought to affect the levels of neurotransmitters such as serotonin, norepinephrine, or dopamine in the central nervous system. For example, drugs in the largest class of second-generation antidepressants block the uptake of serotonin. They are known as the selective serotonin reuptake inhibitors (SSRIs) and include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

The "Drug Class Review on Second-generation Antidepressants" compares the safety and effectiveness of twelve drugs. A summary of the findings is below.

How do newer antidepressants compare in depression?

Overall, all of newer antidepressants are similarly effective in treating major depressive disorder in adults. Although there are some differences in efficacy, the differences are small and unlikely to be clinically relevant.

For major depressive disorder in children, the strength of the comparative evidence is poor. Compared to placebo, only fluoxetine and escitalopram appear to have some benefit and may outweigh the risks of treatment, such as the increased risk of suicidal thoughts.

Evidence is also limited to how newer antidepressants compare in other depressive disorders, such as dysthymic disorder, subsyndromal depression, and seasonal affective disorder. [full review]

How do newer antidepressants compare in anxiety disorders?

For anxiety disorders, the strength of evidence is fair for some comparative trials, but poor for most of them. Overall, there are no relevant differences in efficacy among the following drugs:

  • Generalized anxiety disorder - fluoxetine vs. sertraline and paroxetine vs. escitalopram or venlafaxine
  • Obsessive-compulsive disorder - paroxetine vs. escitalopram, sertraline, or venlafaxine; and venlafaxine vs. duloxetine or escitalopram
  • Panic disorder - sertraline vs. citalopram, nefazodone, or venlafaxine
  • Post-traumatic stress disorder - sertraline vs. citalopram, nefazodone, or venlafaxine
  • Social anxiety disorder - paroxetine vs. escitalopram or venlafaxine ER [full review]

How do the newer antidepressants compare in safety?

The newer antidepressants share a similar overall rate of adverse events. However, the frequencies of some adverse events differ among drugs. These include:

  • Mirtazapine causes higher weight gains
  • Venlafaxine leads to higher rates of nausea and vomiting than other SSRIs
  • Sertraline has an increased risk of diarrhea
  • Paroxetine has higher rates of sexual dysfunction (bupropion has the lowest)

For serious adverse events, fair evidence suggests no difference in the risk of sudden cardiac death among citalopram, fluoxetine, and venlafaxine. Less comparative evidence exists for other adverse events, such as suicidality and seizures. [full review]

Does age, gender or other factors influence the safety or effectiveness of the newer antidepressants?

Fair evidence suggests that the efficacy and tolerability of antidepressants does not differ in adults over the age of 60. And although there are some exceptions, in general, antidepressants have a similar effect in women and men.

Evidence is lacking on how newer antidepressants compare in the presence of other illnesses, or in adults with different ethnic backgrounds. [full review]

Drugs included in this review

Generic NameTrade Names
Wellbutrin SR
Wellbutrin XL
Prozac Weekly
Paxil CR
Effexor XR

Further Information

Image th-antidep11.jpgThis PubMed Clinical Q&A was reviewed by Gerald Gartlehner, MD, MPH.

For the full report and evidence tables, please see:
Gartlehner G, Hansen RA, Reichenpfader U, Kaminski A, Kien C, Strobelberger M, Van Noord M, Thieda P, Thaler K, Gaynes B. Drug Class Review on Second-generation Antidepressants [Internet]. Portland (OR): Oregon Health & Science University; 2011 March. Available at


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