CITALOPRAM-LITHIUM COMBINATION TREATMENT OF ELDERLY DEPRESSED-PATIENTS - A PILOT-STUDY

Fourteen elderly depressive patients (age 67-88 yr), phenotyped with dextromethorphan and mephenytoin before and during the trial, were treated for 4 weeks with citalopram (final dose 20-30 mg/day, except one patient 60 mg/day). The clinical state of the patients was recorded weekly using the Hamilton Depression Rating Scale, the CGI (psychopathology) scale, the VAS and the UKU scale for side-effects. As assessed by the Hamilton Depression Rating Scale, nine patients improved by more than 50% and continued with their citalopram treatment. The treatment of the five non-responders was then continued for another 2 weeks by addition of lithium (target plasma levels 0.4-0.8 mmol/l) to the ongoing citalopram medication. After 1 week, one patient had to be withdrawn for non-response, three were responders, while the fifth patient was a responder only after 2 weeks of lithium addition. Due to side-effects, the lithium dose had to be decreased in one patient who had responded to the combination therapy. Plasma levels of citalopram were within 145-459 nmol/l after 4 weeks of citalopram treatment. All patients were extensive metabolizers of dextromethorphan, and all but possibly one also of mephenytoin. After 4 weeks of citalopram, there was a highly significant correlation between the ratios of S/R-mephenytoin in urine and citalopram/desmethylcitalopram in plasma, which suggests a common mechanism in the metabolism of these drugs. The preliminary finding that a citalopram-li combination therapy may be useful in elderly depressive patients resistant to citalopram alone needs to be replicated by a controlled double-blind study.