Treatment of Alcohol Dependence With Low-Dose Topiramate

In This Article

Abstract and Introduction

Abstract

Background: GABAergic anticonvulsants have been recommended for the treatment of alcohol dependence and the prevention of relapse. Several studies have demonstrated topiramate's efficacy in improving drinking behaviour and maintaining abstinence. The objective of the present open-label controlled study was to assess efficacy and tolerability of low-dose topiramate as adjunctive treatment in alcohol dependence during the immediate post-detoxification period and during a 16-week follow-up period after alcohol withdrawal.
Methods: Following a 7–10 day inpatient alcohol detoxification protocol, 90 patients were assigned to receive either topiramate (up to 75 mg per day) in addition to psychotherapeutic treatment (n = 30) or psychotherapy alone (n = 60). Symptoms of depression and anxiety, as well as craving, were monitored for 4–6 weeks immediately following detoxification on an inpatient basis. Thereafter, both groups were followed as outpatients at a weekly basis for another 4 months in order to monitor their course and abstinence from alcohol.
Results: A marked improvement in depressive (p < 0.01), anxiety (p < 0.01), and obsessive-compulsive drinking symptoms (p < 0.01) was observed over the consecutive assessments in both study groups. However, individuals on topiramate fared better than controls (p < 0.01) during inpatient treatment. Moreover, during the 4-month follow up period, relapse rate was lower among patients who received topiramate (66.7%) compared to those who received no adjunctive treatment (85.5%), (p = 0.043). Time to relapse in the topiramate augmentation group was significantly longer compared to the control group (log rank test, p = 0.008). Thus, median duration of abstinence was 4 weeks for the non-medicated group whereas it reached 10 weeks for the topiramate group. No serious side effects of topiramate were recorded throughout the study.
Conclusions: Low-dose topiramate as an adjunct to psychotherapeutic treatment is well tolerated and effective in reducing alcohol craving, as well as symptoms of depression and anxiety, present during the early phase of alcohol withdrawal. Furthermore, topiramate considerably helps to abstain from drinking during the first 16-week post-detoxification period.

Cite this: Treatment of Alcohol Dependence with Low-dose Topiramate - Medscape - Mar 01, 2011.

Table 1. Sociodemographic characteristics and variables related to alcohol consumption of the sample (N = 85)
	Topiramate group (N = 30)	Control group* (N = 55)
Mean age, years (± SD)	43.8 ± 8.1	46.3 ± 11.0
Sex (M, F)	M: 27, F: 3	M: 48, F: 7
Family status (S, M, D)	S: 8, M: 16, D: 6	S: 10, M: 33, D: 12
Socioeconomic status (H, M, L)	H: 1, M: 25, L: 4	H: 2, M: 39, L: 14
Educational years	7.6 ± 3.1	8.3 ± 3.8
Age at onset, years (± SD)	24.1 ± 6.2	27.3 ± 9.6
Mean alcohol consumption (gr/day)	272 ± 115	284 ± 140
Mean (CIWA-Ar) during the first week	26.1 ± 6.7	25.7 ± 6.3

M, Male; F, Female; S, Single; M, Married; D, Divorced/separated/widowed; H, High; M, Middle; L, Low. CIWA-Ar, Clinical Institute Withdrawal Assessment for Alcohol, Revised
*All comparisons between groups were non-significant.

Table 2. Mean scores ± SD of the various measures of psychopathology and craving at the different time points of assessment (time 0 → time 2) in the control and the topiramate augmentation group
Variable (Mean ± SD)	Group	1^st Assessment (time 0)	2^nd Assessment (time 1)	3^rd Assessment (time 2)
HDRS
	Controls	38.7 ± 7.6	15.9 ± 8.6+	8.1 ± 6.6∞
	Topiramate	39.6 ± 5.5	12.5 ± 3.1*+	4.9 ± 3.1*∞
HARS
	Controls	30.5 ± 10.2	13.9 ± 6.7+	7.1 ± 6.2∞
	Topiramate	31.8 ± 5.3	10.9 ± 3.6*+	4.3 ± 3.8*∞
GAS
	Controls	46.7 ± 5.1	75.6 ± 9.3+	85.4 ± 8.5∞
	Topiramate	46.6 ± 4.7	74.3 ± 6.7+	84.3 ± 5.6∞
OCDS
	Controls	37.2 ± 8.3	17.3 ± 3.9+	13.3 ± 2.8∞
	Topiramate	37.6 ± 7.8	15.3 ± 3.9*+	10.3 ± 3.1**∞

Statistics: Between groups (independent samples t-test); within groups (RMANOVA)
*Significant difference between controls and topiramate augmentation group (< 0.05)
** Significant difference between controls and topiramate augmentation group (< 0.01)
+ Significant difference between 2^nd and 1^st assessment (< 0.01)
∞ Significant difference between 3rd and 2nd assessment (< 0.01)

Table 3. Reported adverse effects by study group
	Topiramate group N = 30 (%)	Control group N = 55 (%)
Dizziness	6 (20.0)	4 (7.2)
Somnolence	7 (23.3)	3 (5.4)*
Nervousness	2 (6.6)	7 (12.7)
Numbness/Paresthesias	3 (10.0)	3 (5.4)
Psychomotor slowness	4 (13.3)	2 (3.6)
Nausea	5 (16.6)	2 (3.6)

* Fisher's Exact Test (2-tailed sig.), p < 0.05

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