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Do urinary MHPG and plasma drug levels correlate with response to amitriptyline therapy?
Abstract:
Twenty-nine inpatients with primary affective disorder were treated with 150 mg amitriptyline (AT) daily for 28 days. Pretreatment urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in two or three 24-h urine samples. Plasma levels of AT and nortriptyline (NT) were determined after 14, 21, and 28 days of treatment. MHPG excretion was significantly correlated with clinical response to treatment. Responders defined by two different methods showed higher pretreatment MHPG excretion than nonresponders. Correspondingly, high MHPG excretors (median split) showed significantly more improvement than low excretors. These relationships were even more apparent when possibly incomplete urine samples (creatinine excretion below 1000 mg/24h) were excluded. The high and low MHPG subgroups did not significantly differ from each other in their plasma levels of AT, NT, or AT plus NT. A significant rank correlation between clinical response and plasma levels of AT and/or NT did not exist, but there was a trend towards lower levels in responders.
Insights
Higher pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion predicted better response to amitriptyline (AT) treatment in patients with primary affective disorder. MHPG levels did not correlate with plasma AT or nortriptyline (NT) levels.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Primary affective disorder impacts mood regulation.
- Amitriptyline (AT) is a common antidepressant.
- Biomarkers for treatment response are crucial.
Purpose of the Study:
- To investigate the relationship between pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion and clinical response to amitriptyline (AT).
- To explore correlations between MHPG levels, plasma AT, and nortriptyline (NT) levels in patients with affective disorder.
Main Methods:
- Twenty-nine inpatients with primary affective disorder received 150 mg AT daily for 28 days.
- Pretreatment urinary MHPG excretion was measured.
- Plasma levels of AT and NT were determined at multiple time points.
Main Results:
- Higher baseline MHPG excretion significantly correlated with better clinical response to AT.
- Patients with high MHPG excretion showed significantly more improvement than low excretors.
- No significant differences in plasma AT or NT levels were found between high and low MHPG groups.
Conclusions:
- Pretreatment MHPG excretion may serve as a predictive biomarker for amitriptyline treatment response in primary affective disorder.
- MHPG levels appear independent of plasma concentrations of AT and NT in this patient cohort.