COMPLETE AND PROLONGED SUPPRESSION OF SYMPTOMS AND CONSEQUENCES OF ALCOHOL-DEPENDENCE USING HIGH-DOSE BACLOFEN: A SELF-CASE REPORT OF A PHYSICIAN

Alcohol & Alcoholism Vol. 40, No. 2, pp. 147–150, 2005 Advance Access publication 13 December 2004 doi:10.1093/alcalc/agh130 CASE REPORT COMPLETE AND PROLONGED SUPPRESSION OF SYMPTOMS AND CONSEQUENCES OF ALCOHOL-DEPENDENCE USING HIGH-DOSE BACLOFEN: A SELF-CASE REPORT OF A PHYSICIAN OLIVIER AMEISEN* 23 rue du Départ BP37, 75014 Paris, France (Received 2 October 2004; first review notified 19 October 2004; in revised form 10 November 2004; accepted 11 November 2004) Abstract — Aims: To test whether the dose-dependent motivation-suppressing effect of baclofen in animals could be transposed to humans, and suppress craving and sustain abstinence. Methods: Neurologists safely use up to 300 mg/day (10 times the dosage currently used for alcohol dependence) of high-dose oral baclofen, to control spasticity, in order to avoid invasive therapy. I am a physician with alcohol dependence and comorbid anxiety. I self-prescribed high-dose baclofen, starting at 30 mg/day, with 20 mg increments every third day and an (optional) additional 20–40 mg/day for cravings. Results: Cravings became easier to combat. After reaching the craving-suppression dose of 270 mg/day (3.6 mg/kg) after 5 weeks, I became and have remained free of alcohol dependence symptoms effortlessly for the ninth consecutive month. Anxiety is well controlled. Somnolence disappeared with a dosage reduction to 120 mg/day, now used for the eighth consecutive month. Conclusions: High-dose baclofen induced complete and prolonged suppression of symptoms and consequences of alcohol dependence, and relieved anxiety. This model, integrating cure and well-being, should be tested in randomized trials, under medical surveillance. It offers a new concept: medication-induced, dosedependent, complete and prolonged suppression of substance-dependence symptoms with alleviation of comorbid anxiety. INTRODUCTION consume alcohol and attenuates self-administration of cocaine, alcohol, heroin, nicotine and D-amphetamine (Roberts and Andrews, 1997; Shoaib et al., 1998; Xi and Stein, 1999; Colombo et al., 2000, 2003; Fattore et al., 2002; Brebner et al., 2004). Effects are dose-dependent for each substance. For alcohol, up to 3 mg/kg are required. (iii) In multiple sclerosis, neurologists safely use long-term high-dose oral baclofen (270 mg/day), to control spasticity, in order to protect patients from risks of invasive intrathecal therapy (Smith et al., 1991). Given the safety record of baclofen since 1967, neurologists with experience in spasticity do not hesitate to use up to 300 mg/day of baclofen, as long as somnolence and/or muscular weakness do not limit treatment (John Schaefer, Cornell University Medical College, personal communication). In the highest recorded baclofen overdose (acute ingestion of 2 g), the patient survived (Gerkin et al., 1986). Alcohol dependence symptoms (craving, preoccupation) are defined as chronic (Morse and Flavin, 1992), and current therapeutic approaches are based on the idea that such symptoms can be attenuated but not suppressed. Therefore, medical trials set abstinence with lower-grade craving as the declared goal (Addolorato et al., 2000, 2002a; Pelc et al., 2002; Froehlich et al., 2003; Johnson et al., 2003, 2004). I am a physician diagnosed with alcohol dependence and comorbid anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSMIV) (American Psychiatric Association, 1994). I had been hospitalized for acute withdrawal seizures. Anxiety disorder had long preceded addiction. I had tried recommended dosages of medications proposed for promotion of abstinence and reduction of craving (see Patient and Methods). I had achieved prolonged abstinence with and without medications. But I had always experienced cravings and preoccupation with alcohol, and achieving abstinence in such conditions required daily planning as well as constant and full attention. Baclofen is a potent gamma-aminobutyric acid (GABAB) receptor agonist clinically used to control spasticity (Davidoff, 1985): I postulated the notion that dose-dependent suppressing effects could be transposed to humans and that by using baclofen in dose ranges used in animal studies, one might reach a critical dose at which craving and motivation to drink alcohol might be suppressed in alcoholics, thus substantially reducing relapse risk. Baclofen has also been used successfully in anxiety disorders (Breslow et al., 1989; Drake et al., 2003), and was shown to be effective in ameliorating some affective disturbances in alcoholic patients, including anxiety and depression (Krupitsky et al., 1993; Addolorato et al., 2002a,b). Anxiety is an overwhelmingly prevalent comorbidity of alcoholism (Grant et al., 2004), and efficacy on anxiety has not been shown for other agents used for alcohol dependence (disulfiram, naltrexone, acamprosate or topiramate). I had used baclofen for >1 year (2002–2003) to (i) In alcohol-dependent patients, low-dose baclofen at 30 mg/day (~0.5 mg/kg) was shown to be effective in promoting abstinence, reducing alcohol craving and consumption, with no limiting side-effects (Addolorato et al., 2000, 2002a,b). (ii) In rats, at doses up to 10 times higher (5 mg/kg), baclofen suppresses cocaine self-administration, motivation to *Correspondence: Tel: +33 675599914. E-mail: 147 Alcohol & Alcoholism Vol. 40, No. 2 © Medical Council on Alcohol 2005; all rights reserved 148 O. AMEISEN reduce anxiety. I had progressively increased the dosage to 180 mg/day, which improved personal and general well-being considerably, but did not suppress cravings and alcohol relapses. Being unaware then that higher dosages were safe, I had not exceeded 180 mg/day. By analysing the literature, I subsequently realized that baclofen was the only monotherapy that could, in theory, completely suppress cravings, while alleviating comorbid anxiety simultaneously. Although my doctors remained unconvinced, I decided to self-prescribe high-dose baclofen, choosing 300 mg/day (4 mg/kg) as the maximal daily dosage, as long as side-effects were not limiting. PATIENT AND METHODS On January 9, 2004, I was a 50-year-old white FrenchAmerican male physician with alcohol dependence and comorbid pre-existing anxiety disorder. Since 1997, there had been numerous emergency hospitalizations, emergency room visits, detoxifications, years of inpatient and outpatient rehabilitation treatments. I bear no medical sequelae. On a typical drinking day, I consumed ~750 ml of Scotch. Treatment had included 500 mg/day of disulfiram (I did drink while taking it). Thereafter, I had consecutively and for each medication been on 12–18 months of naltrexone (50 mg/day), acamprosate (2 g/day) and baclofen (180 mg/day). I have subsequently been on topiramate (300 mg/day) for 3 months. Naltrexone and acamprosate had been discontinued because there had been no perceptible effects on cravings or relapse reduction. During this time, I benefited (...truncated)