The role of captodiamine in the withdrawal from long-term benzodiazepine treatment.
OBJECTIVE
Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment. The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs.


METHODS
A controlled, randomised, double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine. Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine (150 mg/d) or placebo for 45 days from the beginning of the weaning period.


METHODS
The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Questionnaire. Secondary outcome criteria were; self-evaluation of tension, anxiety, drowsiness and slowing of physical and mental performance using visual analogue scales; quality of sleep using the Spiegel questionnaire; anxiety using the Hamilton Anxiety Rating Scale; and cognitive function using a driving stimulation test.


RESULTS
Analysis of the primary study criterion revealed a statistically significant difference (p < 0.0001) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two, six and eight weeks following initiation of therapy. These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures. The switch to captodiamine was associated with an improvement in vigilance, which may be an advantage for the overall safety of the anxiolytic treatment, for example with regard to road safety. Discontinuation of captodiamine was not associated with the emergence of rebound anxiety.


CONCLUSIONS
Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function. Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited.
Mercier-Guyon
C
C
Centre d'Etudes et de Recherches en Médecine du Trafic, Annecy, France. cermtcmg@wanadoo.fr
Chabannes
J P
JP
Saviuc
P
P
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001007:Anxiety / Q000175:diagnosis; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005021:Ethylamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000517:prevention & control*; D013440:Sulfides / Q000009:adverse effects / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D005021:Ethylamines; D013440:Sulfides; D001569:Benzodiazepines; C495502:captodiamine