SIR: The medical treatment of alcohol amnestic disorder (AAD) is a challenge. AAD follows Wernicke encephalopathy in about 80% of cases.1 Typical psychiatric features of AAD are short-term memory loss and disorientation to time, place, and person, but there is no damage to ultrashort memory, consciousness, or cognitive functions.2 Confabulations are typical but not necessary for diagnosis of AAD.
Only a few studies have been conducted in medical treatment of AAD, and each had a study population of 10 or fewer.
The theoretical basis for the treatment of AAD with an SSRI comes from the suggestion that enhancing serotonergic neurotransmission might play a potentially therapeutic role in AAD.3 Controversial results were reported by two research groups publishing four studies within the last 10 years.
In one of the first studies in this research area, 8 patients with AAD were treated with fluvoxamine in doses between 200 and 400 mg/day vs. control subjects in a double-blind crossover study over a period of 6 weeks.3,4 A significant improvement of memory function was observed in the treated group. Similar results were reported from a later study by this group,5 of 10 patients treated with fluvoxamine in doses up to 200 mg/day in a 4-week interval. However, in another study,6 no such improvement of memory function or cognitive or verbal performance was reported in 8 AAD patients treated with fluvoxamine in doses up to 200 mg/day.
A 51-year-old male patient had a history of chronic alcoholism for at least 20 years. He was admitted to our ward from an emergency unit with symptoms of Wernicke encephalopathy. He had severe disturbances of memory function and showed confabulations and disorientation to time and place. Psychomotor disturbances were seen, as well as neurologic symptoms, including ataxia and ophthalmoplegia. The patient's cranial computed tomography and nuclear magnetic resonance imaging showed cortical atrophy; basal brain structural damages, such as mammillary bodies; and enlargement of ventricles. With a thiamine treatment up to 400 mg/day iv, the neurological symptoms disappeared within days, but memory disturbances and disorientation in time and place persisted.
We started treatment with the SSRI paroxetine, with up to maximum dosage of 60 mg/day. Paroxetine instead of fluvoxamine was chosen for AAD treatment because of its shorter half-life, lack of active metabolites, and its supposedly fewer side effects compared with other SSRIs. A lower dosage can be administered, as well.7
A maximum paroxetine plasma-concentration of 387 ng/ml was found after 7 weeks of treatment. The plasma level was in the upper 5% of values from 1,302 inpatients from our hospital (level/dosage: 6.45; 95% confidence interval: level/dosage>5.54). The patient was tested before and retested with the same psychological tests after 7 weeks of medication. Improvement of memory function was observed; the patient recognized 5 pictures out of 12 (vs. l in the first testing); there was an improvement on the SKT (Syndrom Kurz Test8); and he showed a time improvement of 50% on the pathfinder test. However, despite improvement of memory function, disorientation persisted, and the patient was recommended for continued inpatient treatment.
In treatment studies, those patients with plasma fluvoxamine concentrations above 350 ng/ml showed the greatest improvements in memory function, whereas those with plasma concentrations below 150 ng/ml had negligible changes in memory function.4 The patient's paroxetine plasma levels observed in our case were higher than those of 95% of patients treated for depression in our hospital.
Paroxetine may contribute to improvement of memory function in AAD patients. However, larger studies with SSRIs in combination with memory training in AAD patients are needed to evaluate its use in alcohol-induced amnestic syndromes.