mise à jour du
15 juin 2003
  J Clin Psychiatry
1992; 53; 5
cas cliniques
 Fluoxetine induced yawning and anorgasmia
reversed by cyproheptadine treatment
Alan J Cohen
Oakland, California
Bâillements et dépression - Yawning and depression
Le bâillement: de la physiologie à la iatrogénie
Yawning: from physiology to iatrogenic effect
Fluoxetine, an effective antidepressant with highly selective serotonin reuptake inhibition, has been reported to cause sexual dysfuntion as well as yawning, clitoral engorgement, and orgasm. Cyproheptadine, a serotonin antagonist and antihistamine, has successfully reversed the anorgasmia caused by antidepressants including fluoxetine. Druginduced yawning bas been previously reported. However, this is the first case of fluoxetine-induced yawning and anorgasinia reversed by cyproheptadine treatment.

Case report. Mr. A, a 48-year-old Ethiopian, had a history of nonpsychotic major depression. He had symptoms of anxiety, insomnia, and loss of libido that responded to a trial of desipramine 150 mg q.h.s. and lorazepam 1 mg p.o. t.i.d. Physical examination and laboratory evaluation, including thyroid studies, thyroid-stimulating hormone, SMAC-20, CBC ' and liver function studies, revealed essentially normal findings (except for borderline elevated GGT due to a hepatitis A infection 20 years prior to treatment). Despite the resolution of his depressive symptoms, Mr. A requested a trial of fluoxetine due to intolerable dry mouth from desipramine. He did not report sexual dysfunction with the tricyclic. After a gradual taper and withdrawal of the desipramine, treatment with fluoxetine 20 mg q.a.m. was started. After 2 weeks, Mr. A reported an even more positive antidepressant response; he experienced increased energy, improved work performance, and brighter mood. He continued treatment with lorazepam 1 mg t.i.d.

One month into the treatment, he questioned me about the side effects of fluoxetine-reporting excessive daytime yawning despite adequate, restful sleep at night. In addition, he reported difficulty in achieving orgasm despite full erections. These symptoms seemed to have started about the same time in the therapy. Cyproheptadine 4 mg p.o. t.i.d. was prescribed for the anorgasmia. In 1 week, the anorgasmia was resolved. He also stated that the yawning was gone. The cyproheptadine was continued for 6 months al which time it was discontinued. Lorazepam and fluoxetine doses were held constant throughout the treatment course. Within 1 week of discontinuing cyproheptadine, Mr. A again reported excessive daytime yawning accompanied by anorgasmia. During this period, he did not describe any sleep disturbance nor daytime sedation. Reinitiation of cyproheptadine therapy again eliminated both the yawning and anorgasmia.

Fluoxetine-induced yawning and sexual dysfunction were reversed by cyproheptadine in this patient. It seems likely that serotonergic pathways were responsible for the adverse effects since fluoxetine selectively inhibits serotonin reuptake and cyproheptadine is a serotonergic antagonist. However, research in humans and rats suggests that sexual dysfunction and yawning are linked most closely to dopamine-2 reoftptor activity. Serotonergic neurons may have indirectly affected dopaminergic pathways resulting in yawning and anorgasmia by dopaminergic stimulation and inhibition, respectively. This dual action on dopamine pathways by serotonin reuptake blockers has been described. Cyproheptadine was able to counter both of these adverse reactions, presumably by antagonizing serotonin's effects on the dopaminergic pathways. This is the first known report of the reversal of drug-induced yawning by cyproheptadine.

  • McCormick S, Olin J, Brotman AW Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients. B Clin Psychiatry 1990;51:383-384
  • Sovner R. Treatment of tricyclic antidepressant-induced orgasmic inhibition with cyproheptadine. J Clin Psychopharmacol 1984;4:169
  • Lal S, Tesfaye Y, et al. Apomorphine: clinical studies on erectile impotence and yawning. Prog Neuropsychophamnacol Biol Psychiatry 1989; 13:329-339
  • Blin 0, Azulay JP, Masson G, et al. Apomorphine-induced yawning in migraine patients: enhanced responsiveness. Clin Neuropharmacol 199 1; 14:91-95
  • Delini-Stula A, Hunn C. Effects of single and repeated treatment with antidepressants on apomorphine-induced yawning in the rat: the implication of alpha1 adrenergic mechanisms in the D2 receptor furiction. Psychopharmacology 1990-,101:61-66
  • Lauterbach EC, Schweri MM. Ameliorafion of pseudobulbar affect by fluoxetine: possible alteration of doparnine-related pathophysiology by a selective serotonin reuptake inhibitor. J Clin Psychopharmacol 199 1; 11:392-393