Amitriptyline plasma-concentration and clinical effect. A World Health Organisation Collaborative Study

Area of Science:

• Pharmacology
• Psychiatry
• Clinical Therapeutics

Background:

• Depression treatment often involves managing antidepressant medication.
• Understanding the relationship between plasma drug levels and treatment efficacy is crucial.

Purpose of the Study:

• To investigate the correlation between steady-state plasma levels of amitriptyline (AT) and its metabolite nortriptyline (NT) and therapeutic response in depressed inpatients.
• To examine the relationship between plasma levels, therapeutic outcome, and corrected side effects.

Main Methods:

• 54 inpatients with depression (Hamilton rating scale >= 16) participated.
• Patients received amitriptyline (75 mg for 3 days, then 150 mg daily for 6 weeks).
• Plasma samples and clinical ratings were collected at baseline and at 2, 4, and 6 weeks.

Main Results:

• No significant correlations were found between steady-state plasma levels of AT or NT and therapeutic outcome.
• No significant correlations were observed between plasma levels and corrected side effects.
• Corrected side effects showed a negative correlation with therapeutic outcome.

Conclusions:

• Routine monitoring of plasma amitriptyline and nortriptyline levels appears to offer little advantage in predicting therapeutic response or side effects.
• Variations in plasma drug levels do not explain the considerable variability in treatment outcomes for depression.