Olanzapine is a new atypical antipsychotic drug with proven efficacy in
several psychiatric conditions such as schizophrenia and autism. In a
pharmacovigilance study of Olanzapine in 8858 patients in the UK, the
main adverse effects were: somnolence with sedative effect,
extra-pyramidal signs, weight gain, lassitude, agitation, liver
abnormalities…[3]
In a study based on cases reported to the WHO International Drug
Monitoring Collaboration, Mannesse and all found that Olanzapine was the
second most common atypical antipsychotic associated with
hyponatremia/ISADH, after risperidone [4].
In animal models, it has been shown that Dopamine has an inhibitory
effect on ADH secretion. This effect can be blocked by dopamine receptor
antagonists. Olanzapine is a selective monoaminergic antagonist with a
high affinity for dopamine receptors and causes SIADH through its
antagonism to them [5,6].
The association between Olanzapine use and rhabdomyolysis and CPK
elevation has also been reported in the literature [7–9]. The exact
mechanism associating them remains to be elucidated, however some
authors suggest the existence of an important role for serotonin (5-HT),
as Olanzapine would have a more potent activity than antagonists of the
serotonin receptors of Dopamine. 5-HT is believed to be toxic to
skeletal muscle, which contains high-affinity receptors in the
sarcolemma, and the cell membrane [10,11].
In our patient, the elevation of CPK and LDH associated with the
existence of hyperkaliemia made it possible to retain the diagnosis of
rhabdomyolysis, the search for myoglobinuria was not performed. The
questioning and clinical examination did not reveal any signs of muscle
lysis other than toxic, thus allowing Olanzapine to be considered the
direct cause.
The chronology of the symptoms that appeared and worsened concomitantly
with the untimely intake of Olanzapine, as well as the improvement and
correction of the hyponatremia and rhabdomyolysis following the
cessation of the said drug and therapeutic measures, without recurrence,
support our diagnostic hypothesis.