Tricyclic antidepressant plasma levels in depression: A practical guide

Background Plasma levels can be used to monitor the clinical efficacy of tricyclic antidepressants (TCAs). In practice, the interpretation of plasma levels can be problematical, for several reasons: varying time-intervals between ingestion and blood sampling, the number of times per day a particular antidepressant is administered, the presence of active metabolites and the use of slow-release substances. aim To present realistic recommendations regarding the interpretation of plasma levels of tcas in clinical practice. method We studied the relevant literature. conclusion On the basis of the literature we make the following recommendations: - All the recommendations regarding TCA plasma levels are valid only if there is a steady-state situation (in practice, after a week). - In the case of nortriptyline the reference values are those of plasma levels determined after 10 to 24 hours. If this drug is administered three times a day, the plasma level should be determined be/ore the morning dose. The clinical efficacy of this drug deteriorates markedly when the plasma level is above 150 ng/ml. - In the case of amitriptyline, clomipramine or imipramine administered once a day, the reference values are those when the plasma level is measured after 10 to ïóhours. The same reference values hold when these drugs are administered three times a day, but then the plasma level should be determined before the morning dose. - In the case of the slow-release substances amitriptyline or clomipramine plasma levels can also best be measured after 10 to 16 hours. - If the TCA levels deviate markedly fiom the expected levels, one should consider the following as possible causes: non-compliance with the prescribed therapy, possible interaction with other medication or aberrant metabolising capacity of liver enzymes.

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