Am J Psychiatry 158:964-965, June 2001
© 2001 American Psychiatric
Association
Mania and Tramadol-Fluoxetine Combination
ANA
GONZALEZ-PINTO, M.D., HARKAITZ IMAZ, M.D., JOSE LUIS
PÉREZ DE HEREDIA, M.D., MIGUEL GUTIERREZ, M.D., and
JUAN ANTONIO MICÓ, M.D.
Vitoria, Spain
To the Editor: Tramadol is a centrally acting analgesic that
actives the mu opioid receptor and enhances the action of serotonin
and noradrenaline by interference with their uptake and release
mechanisms. It has been suggested (1)
that tramadol could be useful in the treatment of
obsessive-compulsive disorder associated with the use of selective
serotonin reuptake inhibitors (SSRIs). Discussion has included
possible pharmacological interaction, leading to side effects such as
serotonin syndrome. Also, tramadol-induced mania
in a patient with bipolar disorder has been reported (2),
but to our knowledge, there are no reports of tramadol-induced
mania in patients with unipolar disorder. We
present a report of a patient with serotonin syndrome and
mania who had no previous history of
manic episodes and was being treated with fluoxetine and
tramadol.
Ms. A was a 72-year-old woman who had been treated with
fluoxetine, 20 mg/day, for the last 10 years. She had had no cognitive
deficits, had never been hospitalized, and had had only one previous major
depressive episode, occurring 10 years before. She had been taking
acetaminophen for the last year for articular pain. She was planning to take a
trip, so her doctor prescribed tramadol to relieve the pain. After 18 days of
taking tramadol, 150 mg/day, and fluoxetine, 20 mg/day, Ms. A began to feel
nervous, had a temperature of 37.2°C, piloerection, and muscular contractions.
She stopped taking tramadol, and her physical symptoms disappeared by day
21. Nevertheless, she was agitated, euphoric, and hyperactive, slept less than
3 hours a day, and demonstrated rapid speech and paranoid ideation. She was
conscious and oriented at all times. Ms. A was hospitalized for 3 days and
stopped taking fluoxetine; haloperidol treatment was initiated at 5 mg/day.
The results of a physical examination were normal. After discharge, her
symptoms continued, so by day 31 she was hospitalized again. She then began
treatment with olanzapine, 10 mg/day. Two weeks later she was euthymic and was
discharged from the hospital while taking olanzapine, 10 mg/day.
This case of serotonin syndrome and mania
in the same patient could be due to the fluoxetine-tramadol treatment
combination. Tramadol contains a
mono-O-desmethyl metabolite that has less serotonergic
activity than tramadol. The rate of production of this metabolite is
influenced by the CYP2D6 system. Fluoxetine could previously have
inhibited CYP2D6 production, and, consequently, tramadol would have
accumulated in serum, conveying a greater risk of adverse
effects.
Also, preclinical reports have suggested an antidepressant effect
with tramadol therapy (3).
If this is the case, tramadol could induce mania
itself in a manner similar to that of antidepressants, although the
present episode probably was precipitated by coadministration of two
compounds with similar mechanisms of action. In conclusion, it is
important to consider the potential risk of inducing mania and serotonergic syndrome when
using tramadol combined with SSRIs.
References
- Goldsmith TB, Shapira NA, Keck PE Jr: Rapid remission of OCD with
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- Watts BV, Grady TA: Tramadol-induced mania (letter). Am J Psychiatry 1997; 154:1624[Free Full Text]
- Rojas-Corrales MO, Gibert-Rahola J, Mico JA: Tramadol induces
antidepressant-type effects in mice. Life Sci 1998; 63:175–180[CrossRef]
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