Evaluation of risk factors for elevated tricyclic antidepressant plasma concentrations.
OBJECTIVE
To quantify the effect of clinical and demographic factors on the risk of elevated and toxic tricyclic antidepressant (TCA) plasma concentrations (Cp) and to describe the rates of elevated and toxic TCA Cp.


METHODS
This matched, case-control study was conducted among adult patients enrolled in a group model HMO who had a TCA Cp laboratory measurement and purchased at least one TCA prescription for either amitriptyline or nortriptyline during the 70 days preceding the TCA Cp measurement. Predictive models of experiencing an elevated or toxic Cp were created using multivariate conditional logistic regression.


RESULTS
At least one Cp was drawn in 1057 unique patients with a TCA purchase. Of these, 18.4% (194/1057) patients (cases) had an elevated TCA Cp and were matched to 716 non-elevated Cp patients. Additionally, 27.3% (53/194) of the cases (matched to 196 controls) experienced a toxic TCA Cp. The best fitting model of an elevated TCA Cp included TCA dose category (daily doses >or=150 mg, OR = 4.08; doses of 50 to <100 mg, OR = 0.36; and doses <50 mg, OR = 0.18, p < 0.05 for all comparisons), female gender (OR = 1.78, p < 0.05) and concurrent use of fluoxetine or paroxetine (OR = 1.75, p < 0.05). The best fitting predictive model of a toxic TCA Cp included the same factors as for the predictive model of an elevated TCA Cp.


CONCLUSIONS
Recognizing and monitoring predictors of elevated or toxic TCA Cps, including increasing TCA dose, female gender, and concurrent use of fluoxetine or paroxetine, may reduce serious adverse drug reactions and deaths in the TCA-receiving patient population.
Billups
Sarah J
SJ
School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA. sarah.j.billups@kp.org
Delate
Thomas
T
Dugan
Daniel
D
D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D017374:Paroxetine / Q000008:administration & dosage / Q000494:pharmacology; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors
D000639:Amitriptyline; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D016642:Bupropion; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005473:Fluoxetine; D009661:Nortriptyline; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors