THE BROWN UNIVERSITY PSYCHOPHARMACOLOGY UPDATE
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Interaction of olanzapine and propranolol
Y. W. Francis Lam, Pharm.D., FCCP
It is well-known that atypical antipsy-
chotics increase the risk of several meta-
bolic conditions, such as glucose intoler-
ance and diabetes, weight gain, and hy-
perlipidemia. As with other psychotropic
medications, concurrent use of atypical an-
tipsychotics with some drugs used to treat
comorbid medical conditions can also lead
to drug-drug interactions. The following
report described a drug interaction with
olanzapine that resulted in the occurrence
A 47-year-old woman exhibited a spec-
trum of psychiatric symptoms, including
agitation and delusions, for two years. She
was admitted to a psychiatric ward for
worsening of her symptoms and deteriorat-
ing daily functioning, and was diagnosed
with paranoid schizophrenia.
While hospitalized, the patient was
treated with risperidone at doses of 2 to 6
mg/day for about four weeks. During this
time, the only side effects she experienced
were extrapyramidal effects. The patient
also received oxazepam 30 mg at bedtime
for insomnia and benzhexol (trihexypheni-
dyl; Artane®) 2 mg twice daily for extra-
pyramidal effects. Risperidone was even-
tually discontinued and olanzapine was
initiated at 20 mg nightly. The olanzapine
regimen was subsequently changed to 10
mg twice daily and continued for three
weeks. At the completion of this course
of treatment, the patient complained of
akathisia, for which propranolol 10 mg
twice a day was initiated.
On the first night of the patient’s con-
current propranolol and olanzapine, nurs-
ing staff reported that within two to three
hours of falling asleep, she began walking
around the psychiatric ward, and then
stood at the entry door quietly for about 20
minutes, apparently unknowingly wearing
another patient’s shoes. She subsequently
returned to her bed and continued sleep-
ing without any additional disturbance.
Upon awakening the next day, the patient
reportedly had no memory of any event the
Olanzapine was reduced to 10 mg/day,
while propranolol, which had improved the
akathisia, was maintained at 10 mg twice
daily. However, sleepwalking recurred,
and the patient became reluctant to take
olanzapine as a result. Thereafter, olan-
zapine was discontinued. The patient was
prescribed quetiapine 100 mg at bedtime
and aripiprazole 20 mg/day, in addition
to continuing on propranolol, oxazepam,
and benzhexol. There were no subsequent
reports of sleepwalking.
The patient described in this case did
not have a prior history of sleepwalk-
ing when taking various antipsychotics
(risperidone, olanzapine, quetiapine, and
aripiprazole). However, sleepwalking oc-
curred during concurrent therapy with
olanzapine and propranolol, and this
ceased after discontinuation of olanzapine.
The time course of sleepwalking occur-
rence and disappearance suggested that it
might be related to an interaction between
olanzapine and propranolol.
Both olanzapine and propranolol
monotherapy have been reported to pre-
cipitate sleepwalking, via their antagonis-
tic activities at 5-HT
and both beta-1 and
beta-2 receptors, respectively. Although
the mechanistic aspect of the interaction
was not evaluated, it could also be related
to propranolol and olanzapine competing
for the same metabolic enzymes for elimi-
nation, including CYP1A2, CYP2D6, and
the glucuronidation pathways for both
drugs, resulting in elevated concentrations
of one or both drugs. Clinicians should
The time course of sleepwalking in this patient suggests a possible interaction be-
tween olanzapine and propranolol. Clinicians should be mindful of the possibility for
this unusual interaction.
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