Clomipramine concentration as a predictor of delayed response: a naturalistic study.
OBJECTIVE
The aim of the present study was to characterise onset of response to clomipramine treatment in a naturalistic setting and to investigate the relationship between concentration and delayed response, postulated to reflect drug-specific response to antidepressant therapy.


METHODS
Ninety-eight depressed patients were prescribed clomipramine in an open flexible manner and followed for depressive symptoms (Montgomery-Asberg depression scale) over a maximum 12 weeks follow-up period. All patients had at least one concentration measurement for therapeutic drug monitoring purpose.


RESULTS
Firstly, survival analysis revealed a probability of 15.4% for patients not to show 50% improvement over baseline by week 12, and thus to be considered as non-responders. Median time to onset of response was 31 days for responders, indicating a relatively high probability of delayed response under routine treatment. Secondly, pattern analysis indicated a significant association between early and abrupt response on the one hand and delayed and gradual response on the other. A tendency towards an association between delayed and persistent response was also observed. Finally, receiver operating characteristics analysis allowed identification of a highly significant lower threshold of 230 ng x ml(-1) for the sum of clomipramine and desmethyl-clomipramine, as measured at week 3, with respect to response from week 3 onward. Predictive values were 68.8% and 81.0% for concentrations above and below this threshold to predict delayed response and non-response, respectively. Thresholds were 55 ng x ml(-1) for parent compound and 180 ng x ml(-1) for metabolite.


CONCLUSIONS
This approach supports the hypothesis that delayed response may be concentration dependent and thus may reflect true drug effect. As a consequence, monitoring clomipramine concentration about 3 weeks after initiation of therapy may valuably contribute to help clinicians decide about the adequacy of ongoing therapy.
Gex-Fabry
M
M
Department of Psychiatry, Geneva University Hospitals, Switzerland. gexfabry@cmu.unige.ch
Balant-Gorgia
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Balant
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D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000494:pharmacology; D002849:Chromatography, Gas; D002997:Clomipramine / Q000097:blood* / Q000494:pharmacology; D003863:Depression / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine