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.
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