Aniracetam treatment for lithium-produced cognitive deficits of bipolar patients

Aniracetam is considered to be a drug that can modulate the brain acetylcholine system. Administration of aniracetam (trade name: Referan, 1500 mg/day) has been reported to be effective in enhancing the cognitive function of patients with senile dementia of the Alzheimer type. It is the first time that aniracetam is being used to improve cognitive dysfunction in patients with bipolar affective disorder on lithium treatment. Cognitive dysfunction has been reported to be one of the most serious side effects of lithium salts. Our research purpose was to clarify the relationship among bipolar affective disorder, lithium treatment and cognitive deterioration of these patients.
 
In the present study, we administered aniracetam to bipolar patients who were being treated prophylactically and evaluated possible changes in the RANDT Memory Test, in the Benton Visual Retention Test and in the Mini Mental State Examination. The subjects were 128 patients suffering from bipolar affective disorder based on DSM-IV criteria, receiving litium treatment for at least 3 years and under a regular follow up in the mood disorders clinic of our hospital. 67 patients (33 males and 34 females) were complaining of cognitive deterioration and difficulty in coping with routine daily activities. Prior to administration of aniracetam and at 4, 8, 12, 16, 20 and 24 weeks after administration, evaluation of the patients' condition on the basis of the instruments quoted above was carried out. The recall time (reaction time) in both Randt and Benton tests and the overall scoring significantly improved after the 12th week, while 97% of the patients expressed subjective improvement. This effect could be due either to a positive amelioration of a sub-clinical depression or to a direct effect on the cognitive function of the patients.
 
The findings showed that aniracetam administration significantly improved the cognitive function of the patients. This change may have been due to improvement of the mental state of the patients (basically improvement of the patients' depressive state) but most likely explanation is that aniracetam has a direct effect on the mechanism by which litium produces memory dysfuntion in bipolar patients and most probably on intracellular second-messenger generating systems and in particular on reception-coupled hydrolysis of phosphati-dylinositol-4,5 biphosphate (PIP2).