Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response.
An analysis of the literature on tricyclic antidepressant level in blood using receiver operating characteristics curves as the primary statistical tool was performed. For nortriptyline, a significant curvilinear relationship between therapeutic response and nortriptyline was observed that ranged from 58 to 148 ng/ml. The sensitivity and specificity for the nortriptyline therapeutic window were 78 and 61%, respectively. The response rate within the therapeutic range was 66% versus 26% outside the therapeutic range. For desipramine, a significant linear relationship between therapeutic response and desipramine concentration in plasma was observed. The threshold concentration in plasma for therapeutic response was 116 ng/ml. The sensitivity and specificity for the desipramine threshold level in blood were 81 and 59%, respectively. The response rate above the threshold level was 51% versus 15% below the therapeutic threshold concentration. For imipramine, a significant curvilinear relationship between therapeutic response and total imipramine (imipramine+desipramine) concentration in plasma was observed between 175 and 350 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 52 and 74%, respectively. The response rate within the therapeutic range was 67% versus 39% outside the therapeutic range. For amitriptyline, a significant curvilinear relationship between therapeutic response and total amitriptyline (amitriptyline+nortriptyline) concentration in plasma was observed between 93 and 140 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 37 and 80%, respectively. The response rate within the therapeutic range was 50% versus 30% outside the therapeutic range.
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City 52246.
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Perry
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Zeilmann
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Arndt
D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D003891:Desipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012372:ROC Curve; D012680:Sensitivity and Specificity
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D009661:Nortriptyline; D007099:Imipramine; D003891:Desipramine