Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Relationship to plasma levels and treatment outcome

Israel Hanin, Stephen H. Koslow, James H. Kocsis, Charles L. Bowden, David Brunswick, Alan Frazer, Juanita Carl, Eli Robins

Research output: Contribution to journalArticle


Fifty-five (55) depressed patients were treated with amitriptyline (AMI) or imipramine (IMI). Concentrations of AMI, IMI, and their metabolites, nortriptyline (NT) and desmethylimipramine (DMI), were measured in cerebrospinal fluid (CSF) and plasma at steady state by gas chromatography mass spectrometry (GC/MS). Highly significant correlations between CSF and plasma levels of AMI, NT, IMI, and DMI were found (r > 0.75; P < 0.0001 in all cases). There were no significant sex, diagnostic subgroup, or geographic difference in any of the drug parameters measured. An evaluation of the relationship between CSF levels of drug variables and clinical response showed essentially no significant correlations between these various parameters. The results obtained do not support the concept of a 'therapeutic window' for levels of plasma NT in AMI-treated patients. Furthermore, the highly significant correlations between CSF and plasma compartments in terms of drug and metabolite levels would argue against the need to measure CSF levels of these parameters in clinical practice. Plasma level measurements should be equally informative, and simpler to obtain.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalJournal of Affective Disorders
Issue number1
Publication statusPublished - 1985
Externally publishedYes


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