Nightmares and panic disorder associated with carvedilol overdose.
OBJECTIVE
To report a case of nightmares and sleep disorder associated with improper use of carvedilol, an alpha/beta-blocker, and to model the time course of receptor occupancy in this patient.


METHODS
A 41-year-old man with panic disorder had been treated with alprazolam 1.2 mg/d (3 times daily), carvedilol 10 mg/d (once in the morning), and etizolam 0.5 mg (for anxiety attack). Although the physical and psychological symptoms gradually improved, he reported nightmares and panic attacks. An interview revealed that he had been taking carvedilol 5 mg twice a day after lunch and dinner on his own initiative, in addition to the prescribed dosage. The patient was asked to take carvedilol 10 mg only after breakfast, as had been advised. Consequently, the sleep disorder and nightmares disappeared.


METHODS
We calculated the time courses of beta(2)-adrenoceptor binding occupancy in the central nervous system after oral administration of carvedilol with the ordinary and improper regimens by using pharmacokinetic/pharmacodynamic parameters obtained from the literature.


RESULTS
Compared with the ordinary dose of carvedilol 10 mg once a day, the improper regimen (10 mg after breakfast followed by 5 mg after lunch and dinner) increases the beta(2)-adrenoceptor binding occupancy at night (2300) to as high as the mean beta(2)-adrenoceptor binding occupancy after an ordinary dose of propranolol.


CONCLUSIONS
The sleep disorder and nightmares experienced by this patient had been induced by elevation of central beta(2)-adrenoceptor binding occupancy at night as the result of improper use of carvedilol.
Maebara
Chiharu
C
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ohtani
Hisakazu
H
Sugahara
Hideyo
H
Mine
Kazunori
K
Kubo
Chiharu
C
Sawada
Yasufumi
Y
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077261:Carvedilol; D004325:Dreams / Q000187:drug effects*; D062787:Drug Overdose; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced*; D011237:Predictive Value of Tests; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol