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Nausea and Vomiting Associated With Selective Serotonin Reuptake Inhibitors

Incidence, Mechanisms and Management

  • Adverse Effects
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Summary

Nausea and vomiting are common adverse effects of therapeutic drugs. Such symptoms are more often due to CNS effects than to direct toxic effects on the gastrointestinal tract (GIT). Drugs may cross the blood-brain barrier and activate the chemoreceptor trigger zone in the brainstem, which contains cells that are responsive to cholinergic, dopaminergic and serotonergic stimulation.

Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are effective and well tolerated in the treatment of major affective disorders, but their usefulness is sometimes limited by adverse effects, particularly gastrointestinal effects. SSRIs exert their beneficial effects in depressive syndromes by increasing brain serotonin levels. They also increase serotonin levels in other tissues, particularly the GIT, which contains 90% of the body’s store of serotonin and large numbers of serotonin-responsive cells. Increased serotonergic neurotransmission causes anorexia, nausea, vomiting and diarrhoea in other settings, such as carcinoid syndrome, so gastrointestinal adverse effects are not unexpected with drugs that increase tissue serotonin levels. SSRI-induced nausea and vomiting are probably due to effects on the GIT as well as on the CNS.

There are complex interactions between serotonin receptor subtypes. Drugs antagonising one receptor subtype may act as agonists at another receptor. The pharmacotherapy of SSRI-induced nausea and vomiting requires an understanding of the actions and interactions of these receptors and their agonists/antagonists. The most effective drug for the treatment of SSRI-related adverse effects on the GIT is ondansetron, a serotonin 5-HT3 receptor antagonist that blocks the effects of serotonin in the brain and GIT. However, this drug has a high acquisition cost. Thus, the drug of choice may be cisapride which, although a weak 5-HT3 receptor antagonist, has the potential to reduce or abolish SSRI-induced nausea. Many patients with mild adverse effects will not require specific pharmacotherapy, as the nausea tends to abate with prolonged treatment with SSRIs because of gradual desensitisation of 5-HT3 receptors.

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Authors and Affiliations

  1. Department of Neurology and Division of Medicine, Nepean Hospital, University of Sydney, Sydney, New South Wales, Australia

    Philip G. McManis

  2. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia

    Nicholas J. Talley

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  1. Philip G. McManis
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  2. Nicholas J. Talley
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Correspondence to Philip G. McManis.

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McManis, P.G., Talley, N.J. Nausea and Vomiting Associated With Selective Serotonin Reuptake Inhibitors. CNS Drugs 8, 394–401 (1997). https://doi.org/10.2165/00023210-199708050-00005

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