fluvoxamine and Alcohol-Amnestic-Disorder

The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration > or = 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms.

Topics: Aged; Alcohol Amnestic Disorder; Cognition; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Time Factors; Treatment Outcome

Eight patients suffering from the alcoholic Korsakoff syndrome (AKS) were entered in a double-blind cross-over trial of fluvoxamine 200 mg per day for 4 weeks versus matched placebo for 4 weeks. At the end of each phase, patients were assessed using a detailed neuropsychological test battery. Verbal fluency performance was significantly impaired following fluvoxamine treatment. No significant differences emerged on any of the other cognitive test measures when fluvoxamine was compared with placebo. However, two of the patients developed a major depressive episode while receiving fluvoxamine.

Topics: Affect; Aged; Alcohol Amnestic Disorder; Cognition; Cross-Over Studies; Double-Blind Method; Fluvoxamine; Humans; Memory; Verbal Behavior; Wechsler Scales

Ten patients with alcoholic chronic organic brain disease were categorized as having alcohol amnestic disorder, or Korsakoff's psychosis (n = 6), dementia associated with alcoholism (n = 3), or compensated alcoholic liver disease (n = 1). All patients had severe deficits in memory for recently acquired information (episodic memory). Patients with alcohol dementia also showed global intellectual decline, including decreased performance on measures of semantic (knowledge) memory and reduction in levels of cerebrospinal fluid somatostatin. In a 4-week double-blind crossover design, the serotonin-uptake blocker fluvoxamine maleate (100 to 200 mg/d) was found to improve episodic memory in only the patients with alcohol amnestic disorder. These improvements in memory were significantly correlated with reductions in levels of cerebrospinal fluid 5-hydroxyindoleacetic acid, suggesting that facilitation of serotonergic neurotransmission may ameliorate the episodic memory failure in patients with alcohol amnestic disorder.

Topics: Aged; Alcohol Amnestic Disorder; Clinical Trials as Topic; Double-Blind Method; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Male; Memory; Middle Aged; Oximes; Psychoses, Alcoholic; Serotonin Antagonists; Somatostatin; Wechsler Scales

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clinically useful agent in the treatment of this syndrome.

Topics: Aged; Alcohol Amnestic Disorder; Dementia; Double-Blind Method; Ethanol; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Middle Aged; Oximes; Substance-Related Disorders

Topics: Alcohol Amnestic Disorder; Amnesia; Animals; Fluvoxamine; Humans; Memory Disorders; Oximes; Serotonin; Serotonin Antagonists