Major depressive disorder and patient satisfaction in relation to methadone pharmacokinetics and pharmacodynamics in stabilized methadone maintenance patients.

Many patients enrolled in methadone maintenance treatment experience significant interdose opioid withdrawal. Mood states have been related to patient satisfaction with treatment and may influence how methadone patients experience opioid withdrawal. The objective of this study was to investigate the influence of major depressive disorder on response to methadone in patients on methadone maintenance treatment. Seventeen methadone patients (7 depressed and 10 not depressed) had pharmacokinetic and pharmacodynamic assessments (opioid withdrawal, drug effects, and mood) over one 24-hour dosing interval. Subjects were also divided based on their satisfaction with methadone treatment: 12 holders and 5 nonholders. Depressed subjects experienced more dysphoric opioid effects as measured by the Addiction Research Centre Inventory (area under the effect versus time curve, 14 +/- 32 vs -31 +/- 47, P < 0.04) and had higher scores on the Subjective Opioid Withdrawal Scale (area under the effect versus time curve, 33 +/- 97 vs -74 +/- 67, P < 0.02) over the dosage interval. Hamilton Depression scores significantly correlated with trough subjective opioid withdrawal scale scores (r = 0.7, P < 0.004). Nonholders had significantly higher exposure to unbound (S)-methadone compared with holders, specifically: trough concentration (6.1 +/- 2.7 ng/mL vs 2.7 +/- 1.7 ng/mL, P < 0.01), average steady-state concentration (7.6 +/- 4.0 ng/mL vs 4.1 +/- 2.5 ng/mL, P < 0.05), maximum concentration (14.6 +/- 7.1 ng/mL vs 7.5 +/- 4.2 ng/mL, P < 0.04), and area under the curve (183 +/- 95 h*ng/mL vs 99 +/- 61 h*ng/mL, P < 0.05). Study findings suggest that (S)-methadone may relate to patients' dissatisfaction with methadone treatment. Depressed methadone patients may be more sensitive to negative opioid effects and opioid withdrawal.