Piloerection induced by replacing fluvoxamine with milnacipran.
OBJECTIVE
To present a case of piloerection after replacing fluvoxamine maleate with milnacipran hydrochloride, and to analyse this effect based on receptor occupancy theory.


METHODS
A 40-year-old female with a 3-year history of panic disorder was prescribed fluvoxamine 50 mg day(-1) in addition to clorazepate dipotassium and sulpiride. Depression was not improved and she complained of fatigue, lack of energy and drowsiness. These symptoms worsened within a few days of an increase in the dose of fluvoxamine to 50 mg twice daily. Since an interaction between fluvoxamine and tizanidine, prescribed by another clinic, was suspected, fluvoxamine was replaced with milnacipran 50 mg day(-1). Although her drowsiness improved, she complained of piloerection throughout her body. This symptom gradually abated within a week and when the dosage of milnacipran was increased to 100 mg day(-1) at 2 months, no further piloerection occurred. We calculated the changes in alpha(1)-adrenoceptor occupancy by endogenous norepinephrine during treatment with the usual doses of milnacipran, fluvoxamine and imipramine by using pharmacokinetic and pharmacodynamic parameters obtained from the literature.


RESULTS
The ratios of alpha(1)-adrenoceptor occupancy by endogenous norepinephrine during the treatment with milnacipran, fluvoxamine and imipramine to that without drug were estimated to be 7.13, 1.00 and 4.12, respectively. The alpha(1)-adrenoceptor occupancy by endogenous norepinephrine was increased in a dose-dependent manner by milnacipran, whereas fluvoxamine had essentially no effect.


CONCLUSIONS
The piloerection observed after the replacement of fluvoxamine with milnacipran in this patient appears to have been due to an increase in the alpha(1)-adrenoceptor occupancy by endogenous norepinephrine induced by milnacipran.
Hori
Satoko
S
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Matsuo
Nobuko
N
Yamamoto
Akiko
A
Hazui
Tomomi
T
Yagi
Hiromi
H
Nakano
Marumi
M
Suzuki
Yuka
Y
Miki
Akiko
A
Ohtani
Hisakazu
H
Sawada
Yasufumi
Y
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D003521:Cyclopropanes / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000009:adverse effects* / Q000494:pharmacology; D000078764:Milnacipran; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism; D016584:Panic Disorder / Q000188:drug therapy*; D010863:Piloerection / Q000187:drug effects*
D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran; D016666:Fluvoxamine; D007099:Imipramine; D009638:Norepinephrine