Harvard Mental Health Letter

In Brief: Comparing the antidepressants

In Brief

Comparing the antidepressants

A review suggests that the many antidepressant drugs introduced since the mid-1980s are all about equally effective.

The survey covers 46 head-to-head comparisons between antidepressants. Most of the drugs included are selective serotonin reuptake inhibitors (SSRIs): citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). Also tested were several drugs that have a different mechanism of action, inhibiting the reuptake of norepinephrine alone or various combinations of neurotransmitters: bupropion (Wellbutrin), venlafaxine (Effexor), duloxetine (Cymbalta), and mirtazapine (Remeron). About half of the trials compared two SSRIs, and the rest compared an SSRI with one of the newer drugs. More than 90% of the trials showed no more than a chance difference in effectiveness between the two drugs. When several studies directly compared two drugs, the investigators combined the results for a meta-analysis. In these calculations, sertraline and venlafaxine proved to be slightly more effective than fluoxetine. Mirtazapine consistently, and venlafaxine in a few studies, produced a slightly faster response than SSRIs.

To examine side effects (which were usually not reported systematically in these studies), the researchers added 24 purely observational studies and trials in which a drug was compared with a placebo. All the drugs produced about the same rate of side effects, but not the same ones. Venlafaxine was most likely to cause dizziness and nausea, bupropion and sertraline most likely to cause headaches. Insomnia was most common with bupropion and sertraline. The risk of headache was lowest with venlafaxine, the risk of dizziness lowest with fluoxetine, and the risk of nausea and insomnia lowest with mirtazapine. Bupropion was least likely and sertraline, paroxetine, and mirtazapine most likely to cause sexual problems. Among SSRIs, paroxetine caused the most weight gain, but the non-SSRI mirtazapine caused even more. In one trial, patients taking bupropion lost weight.

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