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Clinical Pharmacokinetics

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01.09.2002 | Review Articles

Comprehensive Survey of the Relationship Between Serum Concentration and Therapeutic Effect of Amitriptyline in Depression

verfasst von: Dr Sven Ulrich, Jürgen Läuter

Erschienen in: Clinical Pharmacokinetics | Ausgabe 11/2002

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Abstract

The relationship between serum concentration (C_s) of amitriptyline and its therapeutic effect in depression has been investigated frequently over the last 3 decades; however, the results were controversial and no consensus was reached. Therefore, we have performed a comprehensive survey and meta-analysis of the subject. All relevant literature was included, and the design of studies on the serum concentration-therapeutic effect relationship (SCTER) of amitriptyline was evaluated. Pooled original data from SCTER studies with adequate design were analysed by various statistical methods: regression analysis of therapeutic effect and C_s; comparison of the mean therapeutic effect in various ranges of C_s; dichotomisation of outcome and analysis according to sensitivity of receiver operation curves; frequency of responders and nonresponders in ranges determined by points of sensitivity; analysis of the distribution of C_s in responders and nonresponders; logistic regression of responders and nonresponders with C_s and other independent variables; calculation of effect size (g) and mean effect size (gm).

Forty-five SCTER studies of amitriptyline were identified, and 27 studies met the minimum criteria of adequate study design. Inadequate study design predicted the finding of no SCTER. Analysis of the pooled data from studies with adequate design confirmed a therapeutic window of the sum of C_s of amitriptyline and its active metabolite nortriptyline of about 80 to 200 µg/L. A moderate and significant positive gm (0.538, 95% confidence interval 0.167 to 0.909) was calculated for treatment with C_s within the therapeutic window in comparison with treatment with Cs outside the therapeutic window (19 studies with adequate design and original data available, n = 583).

In conclusion, the evidence for a biphasic SCTER of amitriptyline in depression is considerably improved, and the results may help to find a consensus in the future. However, the clinical benefit of therapeutic drug monitoring of amitriptyline can only be demonstrated in a controlled and randomised study. Furthermore, the results provide further evidence that antidepressants at optimum C_s are superior to placebo in the treatment of depression.

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Titel: Comprehensive Survey of the Relationship Between Serum Concentration and Therapeutic Effect of Amitriptyline in Depression
verfasst von: Dr Sven Ulrich
Jürgen Läuter
Publikationsdatum: 01.09.2002
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 11/2002
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200241110-00004

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Comprehensive Survey of the Relationship Between Serum Concentration and Therapeutic Effect of Amitriptyline in Depression

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Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

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