Letters to the Editor
Mirtazapine for Treatment of Nausea Induced by Selective Serotonin Reuptake Inhibitors
Dear Editor:
Nausea appears to be a dosage- related side effect in as many as 26% of patients treated with selective serotonin reuptake inhibitors (SSRIs) (1,2). SSRIs increase the concentration of serotonin (5-HT) at neuronal synapses. Emesis may result from subsequent activation of central or peripheral 5-HT3 receptors (2,3). Antagonism of 5-HT3 by drugs like ondansetron is known to reduce emesis in chemotherapy patients and may have some application in SSRI-induced nausea, but the effect is short-lived and the cost is prohibitive (2,3). The 5-HT antagonist cyproheptadine may have some efficacy for SSRI-induced nausea, but it has been associated with worsening of depressive symptoms when used to treat SSRI-induced sexual dysfunction (4). The antidepressant mirtazapine, an antagonist at presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors (where it enhances noradrenergic and serotonergic activity), is also a potent antagonist of 5-HT2 and 5-HT3 receptors (5). We report a case of SSRI-induced nausea successfully treated with mirtazapine.
Case Report
Ms K, aged 46 years, is a single white woman who has suffered for 10 years from a recurrent unipolar major depressive disorder associated with insomnia; she also suffers from obsessive–compulsive disorder (OCD). For the last 3 years, her symptoms have been partly controlled with sertraline 300 mg daily, bupropion slow release 150 mg twice daily, and trazodone 100 mg at bedtime. During treatment, she experienced recurring episodes of nausea associated with the administration of SSRIs. With sertraline, the nausea was partly controlled by her taking the dosage in 100 mg increments 3 times daily, approximately one-third of the way into a meal. Despite these efforts, her symptoms were occasionally sufficient to cause projectile vomiting, which forced her to reduce her total daily dosage. Attempts to decrease the sertraline dosage permanently increased her OCD symptoms.
To control her nausea, mirtazapine 15 mg at bedtime was substituted for trazodone. Nausea symptoms decreased the day after starting mirtazapine and completely disappeared within 4 days. However, she had difficulty sleeping and had to restart her trazodone. The combination of mirtazapine and trazodone left her with excess daytime sedation plus restless legs when falling asleep. Mirtazapine was subsequently discontinued, and her nausea returned within 4 days. Resumption of mirtazapine 15 mg at bedtime once more relieved all nausea. Replacement of trazodone with clonazepam 0.5 mg at bedtime allowed her to have a good sleep with no daytime sedation and no restless legs.
Discussion
We describe a patient who experienced resolution of SSRI-induced nausea with low- dosage mirtazapine. The use of this agent to control nausea associated with SSRIs was first discussed by Pedersen and others in 1997 (6). In their report, 3 patients experienced relief of nausea approximately 2 to 3 days after the addition of mirtazapine 15 mg daily. In 2 patients, nausea resumed when mirtazapine was discontinued and lessened when it was restarted. We observed a similar pattern in our case.
References
1. Trindale E, Menon D, Topfer LA, Coloma C. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis. CMAJ 1998;159:1245–52.
2. Bergeron R, Blier P. Cisapride for the treatment of nausea produced by selective serotonin reuptake inhibitors. Am J Psychiatry 1994;151:1084–6.
3. Coupland NJ, Bailey JE, Potokar JP, Nutt DJ. 5-HT3 receptors, nausea, and serotonin-reputake inhibition. J Clin Psychopharmacol 1997;17:142–3.
4. Woodrum ST, Brown CS. Management of SSRI-induced sexual dysfunction. Ann Pharmacother 1998;32:1209–15.
5. Bezchlibnyk-Butler K, Jeffries J, editors. Clinical handbook of psychotropic drugs. 13th ed. Toronto (ON): Hogrefe & Huber; 2003. p 30–2.
6. Pederesen L, Klysner R. Antagonism of selective serotonin reuptake inhibitor-induced nausea by mirtazapine. Int Clin Psychopharmacol 1997;12(1):59–60.
Efstratios V Caldis, MB, ChB, FRCPCP
Robert D Gair, BSc (Pharm)
Vancouver, British Columbia
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