Successful Treatment of Severe Antidepressant-Induced Nausea with a Combination of Milnacipran and Olanzapine

Nausea is one of the most problematic side effects induced by newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). We report on a patient with obsessive-compulsive disorder and comorbid major depressive disorder who experienced severe nausea induced by SSRIs and an SNRI. She was successfully treated with a combination of milnacipran and olanzapine without nausea.

A 44-year-old female patient presented with the behavior of compulsively videotaping of entire TV programs on every channel. She recognized that this behavior was absurd and unnecessary, but its cessation made her anxious and irritable. When she could not record the TV programs herself, she asked her relatives to videotape them. When her relatives were not available, she asked video-recording companies to videotape the programs. Her room was filled with videotapes. She consulted a psychiatrist and was administered paroxetine. She could not continue this therapy, because a single paroxetine dose of 10 mg induced severe nausea. She visited several psychiatrists and was administered paroxetine, fluvoxamine, or milnacipran, with sulpiride as an antiemetic. However, the concomitant use of sulpiride could not suppress the severe nausea induced by antidepressants; a single dose of the smallest tablet resulted in intolerable nausea. After a psychiatrist told her that there was nothing to do for an obsessive-compulsive patient extremely sensitive to antidepressant-induced nausea, depressive symptoms appeared and gradually increased in severity. Finally, she was only able to videotape TV programs and spent most of the day in bed because of lassitude and loss of motivation. She visited our hospital on the advice of her relatives. She was administered a very low dose of milnacipran, because the incidence of nausea with milnacipran has been reported to be lower than that of SSRIs [5]. She was advised to buy a pill cutter and to try 1/8 of a 15-mg tablet once daily. This single low dose of milnacipran did not induce nausea. The number of doses per day and the amount of the dosage were gradually increased. She tolerated a dosage of 3.75 mg four times daily, but further increases in the daily dosage induced nausea. Because SSRI-induced nausea has been reported to be mediated via 5-HT₃ receptors [2], the concomitant administration of a drug with a 5-HT₃-inhibiting effect seemed to be appropriate. Olanzapine, an antipsychotic drug with a 5-HT₃-inhibiting effect, has been reported to be effective for obsessive-compulsive disorder in combination with SSRIs [1]. Therefore, a single dosage of 2.5 mg was added to the milnacipran treatment. After the administration of olanzapine, the daily dosage of milnacipran could be gradually increased. When the daily dosage of milnacipran reached 90 mg/day, her depressive symptoms began to ameliorate. It became possible for her to do household chores and go outside for shopping. At that time, however, her excessive videotaping remained unchanged. When the daily dosage of milnacipran reached 150 mg/day, her excessive videotaping began to ameliorate. It became possible for her to cease videotaping new serial dramas. Currently, she is taking milnacipran 200 mg/day and olanzapine 2.5 mg/day. No apparent side effects have emerged. Her consumption of videotapes has become less than 10% of that at the first visit to our hospital.

Individual differences in pharmacokinetics and pharmacodynamics, mediated mainly via genetic polymorphisms, can lead to individual differences in susceptibility to nausea and other side effects induced by antidepressants as well as the antidepressant effect itself [4]. This case suggests the way that patients who are extremely sensitive to antidepressant-induced nausea should be treated. First, the initiation of antidepressants at a very low dosage should be considered. Intolerance of a single dose of the smallest tablet does not necessarily mean complete intolerance of an antidepressant. Second, the concomitant use of a 5-HT₃-blocking agent should be considered. Dopamine antagonists, such as sulpiride and metoclopramide, seem to be frequently used as antiemetics with antidepressants in Japan. However, their antidopaminergic effect is indirect for antidepressant-induced nausea. If the use of olanzapine is undesirable, mianserin, a tetracyclic antidepressant may be useful as a 5-HT₃ inhibitor [3].

References

• 1 Bystritsky A, Ackerman DL, Rosen RM, Vapnik T, Gorbis E, Maidment KM. et al . Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial.  J Clin Psychiatry. 2004;  65 565-568
• 2 Coupland NJ, Bailey JE, Potokar JP, Nutt DJ. 5-HT₃ receptors, nausea, and serotonin reuptake inhibition.  J Clin Psychopharmacol. 1997;  17 142-143
• 3 Ferreri M, Lavergne F, Berlin I, Payan C, Puech AJ. Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone.  Acta Psychiatr Scand. 2001;  103 66-72
• 4 Malhotra AK, Murphy Jr GM, Kennedy JL. Pharmacogenetics of psychotropic drug response.  Am J Psychiatry. 2004;  161 780-796
• 5 Montgomery SA, Prost JF, Solles A, Briley M. Efficacy and tolerability of milnacipran: an overview.  Int Clin Psychopharmacol. 1996;  11 ((Suppl 4)) 47-51

Correspondence