Acetyl- l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects

Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl- l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms. Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3 g/day, 21 received ALC at a dosage of 1 g/day, and 20 were given placebo. ALC was given intravenously for 10 days, followed by 80 days of oral treatment plus a follow-up period of 45 days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith–Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech–Rafaelsen Melancholia Scale). The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p < 0.05) in both the ALC 3 g and ALC 1 g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1 g respect to placebo (p = 0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo. Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia. ► First trial to evaluate the efficacy of a drug for anhedonia in alcoholics. ► Robust anti-anhedonic efficacy after 10 days of intravenous treatment. ► ALC use is virtually free of side effects.