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Adverse Effects of Selective Serotonin Reuptake Inhibitors
Are there differences in adverse effects among the selective serotonin reuptake inhibitors (SSRIs)? How can adverse effects be managed?
Nausea.
Overall, the SSRIs have similar initial adverse effect profiles.1 Although specific head-to-head trials do show some differences in the incidence of different effects, clinicians should be prepared to encounter all the class-related adverse effects in any of the agents.
This is probably the most frequent adverse effect. About 25% to 50% of patients will experience some nausea in the first week. Tolerance generally develops over time. Dose reduction and/or taking the medication with meals for the first week is often helpful. In problem cases, short-term use of 5-HT3 blockers (such as ondansetron, 4 mg 2-3 times daily) can be helpful.
Agitation.
Although the SSRIs can be very effective in reducing the anxiety associated with depression, about 10% to 20% of patients may experience some increase in anxiety, sometimes with the first dose. The mechanism is not clear, although some cases seem similar in nature to the akathisia associated with neuroleptics. In these cases, low-dose  -blockers can be helpful. Temporary use of benzodiazepines (such as lorazepam or clonazepam) may be helpful.
Insomnia.
The SSRIs seem to increase light-stage sleep and frequency of awakenings, as evidenced by encephalography results, and may cause insomnia in some patients (about 20%). In such cases, adjunctive use of clonazepam or trazodone at bedtime may be helpful. Tolerance to this adverse effect generally does not develop.
Sedation.
Drowsiness is reported in about 20% of SSRI users. When noted, one solution may be to prescribe the medication at bedtime. Some clinicians recommend judicious use of morning caffeine.
Sexual Dysfunction.
All SSRIs may be associated with anorgasmia, impaired erection, and delayed ejaculation. These effects may respond to dose reduction, although antidepressant efficacy may also thereby be reduced. Other pharmacologic approaches include adjunctive use of bupropion (possibly through mild dopamine agonism), mirtazapine, or nefazodone (possibly through blocking 5-HT2 receptors). Finally, SSRI-induced erectile dysfunction may be improved by the use of sidenafil.
Richard J. Goldberg, MD
Providence, RI
1. Goldberg RJ. Selective serotonin reuptake inhibitors: infrequent medical adverse effects. Arch Fam Med. 1998;7:78-84.
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Arch Fam Med. 1999;8:196-197.
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