Acamprosate inhibits the elevated glutamatergic neurotransmission evident in patients with alcohol dependence.6–11 Patients without withdrawal symptoms may not have sufficiently elevated glutamatergic neurotransmission for the drug to exert a therapeutic effect.10 The subjects enrolled in our study did require treatment for withdrawal symptoms, but because acamprosate administration began only after a period of inpatient treatment, glutamatergic activity was likely no longer elevated at this point. Although this aspect of study design is similar to the COMBINE study and the Australian study described above, subjects requiring treatment for withdrawal symptoms are also more likely to suffer occasional cravings even after prolonged periods of abstinence and are at risk of falling into a pattern of pathological consumption after relapse.38 The degree to which this latent tendency was present in our cohort may have influenced our findings.