[alpha-beta L-aspartate magnesium in treatment of chronic benzodiazepine abuse: controlled and double-blind study versus placebo]

Abstract

Objective: To evaluate the efficacy of alpha-beta L-Aspartate Magnesium (Asp Mg) in discontinuation of long-term benzodiazepine use and to search for a predictive model of success for BZD cessation.

Method: Using a double-blind procedure, 144 patients selected as chronic users of one of 3 BZD lorazepam, alprazolam or bromazepam (duration of use > 6 months; regular dose > or = 3 mg lorazepam equivalent) and with clinical remission (score on Hamilton-Anxiety < 14; Raskin-Depression < 6) had entered a controlled study (versus placebo) and were randomized in two parallel groups. The trial was conducted on 3 consecutive phases (co-administration of Asp Mg or placebo with BZD during 1 month; gradual taper of BZD during 1 month; follow-up during a third month after complete BZD discontinuation, with urinary BZD control on d75 and d90).

Results: The intent-to-treat analysis showed at the endpoint an overall rate of 80% of "BZD discontinuation" and of 35.4% of "BZD cessation without withdrawal" in the total population (no significant intergroup differences were observed on these rates). However, there were some tendencies to positive differences between Asp Mg versus placebo on the following: 1) prolonged delay of BZD use if reintake (30 days vs 20 days, p [log-rank] = 0.5); 2) reduction of withdrawal intensity: 11% of important difficulties during BZD cessation versus 23% with placebo (p = 0.2) and on Benzodiazepine Withdrawal Symptoms Questionnaire (BWSQ) (final score 4.0 vs 4.8, p = 0.10); 3) lower modification of anxiety during BZD tapering and discontinuation (rate of increase on HAM-A between d30-d90 of 6% vs 23% in placebo group, p = 0.10). Moreover, 3 predictive factors of "success" (BZD cessation without withdrawal phenomenon) were identified by uni- and multivariate analysis with logistic regression: chronicity of anxiety disorder (p = 0.04) and amplitude of BWSQ change during tapering phase (p < 0.0001) as negative factors; and initial score of Speilberger Anxiety Inventory "Anxiety-Trait" (p = 0.002) as positive factor. A predictive model is constructed according to these 3 parameters. Further clinical trials are needed to explore the benefits of alpha-beta L-Aspartate Magnesium in different criteria of prescription (dosage, duration of treatment, repetitive cures...).