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Dosing of antidepressants--the unknown art
1Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
Journal of Clinical Psychopharmacology
|December 1, 1995
Summary
Tricyclic antidepressant doses, like amitriptyline and nortriptyline, were reduced in older patients, but this did not align with their drug kinetics. Therapeutic drug monitoring improved amitriptyline levels but not nortriptyline levels.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Drug Metabolism
Background:
- Tricyclic antidepressants (TCAs) like amitriptyline and nortriptyline are widely prescribed.
- Individualized dosing is crucial due to significant inter-individual variability in drug kinetics.
- Optimal therapeutic drug monitoring (TDM) strategies are essential for maximizing efficacy and minimizing toxicity.
Purpose of the Study:
- To analyze factors influencing prescribed daily doses of amitriptyline and nortriptyline.
- To evaluate plasma concentrations in relation to established therapeutic ranges.
- To assess the impact of TDM on achieving therapeutic drug levels.
Main Methods:
- Retrospective analysis of 2,393 observations from 1,606 patients receiving TCAs.
- Evaluation of prescribed daily doses and achieved plasma concentrations.
- Comparison of drug levels against recommended therapeutic ranges.
Main Results:
- Prescribed doses of amitriptyline and nortriptyline significantly decreased with increasing age, irrespective of age's minor role in drug kinetics.
- Concomitant medication interactions were not adequately addressed by dose adjustments.
- TDM improved the proportion of plasma concentrations within the therapeutic range for amitriptyline but not for nortriptyline.
Conclusions:
- Age-related dose reduction for TCAs may not be pharmacokinetically justified.
- Current individualized dosing practices for TCAs may be based on incorrect assumptions.
- Optimized TDM protocols are necessary to improve therapeutic outcomes for nortriptyline and potentially other TCAs.