The Role of Captodiamine in the Withdrawal From Long-Term Benzodiazepine Treatment

C. Mercier-Guyon; J. P. Chabannes; P. Saviuc

Disclosures

Curr Med Res Opin. 2004;20(9) 

In This Article

Results

Eighty-three subjects were included. Two subjects withdrew prematurely from the study, one at inclusion and the other after one day of treatment; the intention-to-treat analysis thus included the 81 remaining subjects (40 women and 41 men). Forty subjects were random ised to the captodiamine treatment group and 41 to the placebo group.

The two groups were comparable for all baseline characteristics ( Table 1 ). The mean age of the included subjects was 40.5 years and men and women were equally represented. Baseline scores on the Tyrer BWSQ and on the HARS were 1.06 and 6.4 respectively. All patients reported having discontinued benzodiazepines early in the two week discontinuation period. In both groups, all urinary screening tests performed at D14, D21, D45 and D60 were negative, indicating good subject compliance with benzodiazepine discontinuation.

During the two week weaning phase when benzo diazepines were discontinued, withdrawal symptoms emerged in both treatment groups. Analysis of the primary outcome criterion, the Tyrer BWSQ score, revealed a statistically significant difference ( p < 0.0001; ANCOVA with repeated measures) between the two study groups in favour of captodiamine attesting to a decrease in the number and intensity of withdrawal symptoms (Figure 2). Over the assessment period, BSWQ scale scores progressively declined to return to baseline levels at the end of the post-treatment phase (D60). The difference in BSWQ scores between the two study groups remained statistically significant ( p < 0.0001; Mann-Whitney U-test) at all study times.

Evolution of Tyrer Benzodiazepine Withdrawal Symptom Scale scores over the study period. BWSQ: Benzodiazepine withdrawal symptom scale. l: captodiamine treatment group; : placebo group. The asterisk indicates a significant difference between the two treatment groups (p < 0.0001; Mann-Whitney U-test). NS: not significant.

Visual analogue scales were used throughout the study to allow self-assessment by subjects of the impact of treatment on their degree of tension, drowsiness, physical and mental slowness and level of anxiety. Findings were essentially similar for all five scales. Two profiles for the anxiety and drowsiness scales are illustrated in Figure 3.

Visual analogue scale scores for anxiety and drowsiness in the two treatment groups during the study. VAS: visual analogue scale. l: captodiamine treatment group; : placebo group. The asterisk indicates a significant difference between the two treatment groups (p < 0.001; Mann-Whitney U-test). NS: not significant

For the anxiety scale, the self-reported anxiety scores rose in the placebo group during the weaning and assess ment phases before returning to baseline at the end of the post-treatment period. In contrast, in the capto diamine treatment group, anxiety scores evolved little during the weaning phase and then fell during the assessment phase. There was a significant difference in scores between the two treatment groups at all observation points during the experimental phases of the study. For the drowsiness score, the scores for the placebo group remained stable during the weaning phase and then declined slightly, whereas they declined from D0 for the captodiamine group. Again, all inter-group differences were statistically significant during the experimental phases of the study. The data for the remaining scales, which are essentially similar, are presented in Table 2 .

Anxiety was also assessed by the investigator at D14 and D45 using the Hamilton Anxiety Rating Scale (Figure 4). In the placebo group, mean anxiety rating scores rose by a factor of nearly two during benzodi azepine discontinuation, and then fell somewhat during the following month of the assessment phase, at the end of which they were still significantly elevated compared to the baseline period. In the captodiamine treatment group, the increase in anxiety scores during the discon tinuation phase was modest and not statistically signif icant. At the end of the assessment phase, anxiety scores fell to below baseline levels. At both the D14 and D45 evaluation points, anxiety scores were significantly lower in the captodiamine treatment group compared to the placebo group.

Hamilton anxiety rating score in the two treatment groups during the study. HARS: Hamilton anxiety rating score. l: captodiamine treatment group; : placebo group. The asterisk indicates a significant difference between the two treatment groups (p < 0.001; Mann-Whitney U-test). NS: not significant. Note that the Y-axis does not begin at zero.

Similarly, analysis of the Spiegel quality of sleep score revealed a clear and significant difference between the two groups at all study points, with patients in the placebo group having better sleep quality; a mean difference in improvement of between 1.8 and 1.6 units was observed at D14 and D45 respectively ( Table 3 ).

Visual reaction time increased ( p < 0.001; Student's t-test) from baseline to D45 by an average of 0.6 msec, with no significant difference between the two treatment groups. Similar improvements were observed in the two parameters of the DADS, with a significant decrease in numbers of errors and lapses between D0 and D45 and no difference between the two treatment groups. Patient satisfaction was significantly greater in the captodiamine treated group compared to the placebo groups at all observation point, by a factor of around 1.2 on a five-point scale ( Table 3 ).

No adverse effects were observed other than those related to benzodiazepine withdrawal symptoms and anxiety symptoms, which were taken into account in the efficacy analysis. No clinically significant changes in heart rate or arterial blood pressure were observed.

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