AIM: Presynaptic and post-synaptic glutamatergic modulation is associated with antidepressant activity that takes several weeks to reach a maximal full effect. Limiting mood elevating effects after single drug administration may be the result of compensatory synaptic processes. Therefore, using augmentation treatment with agents having presynaptic and post-synaptic effects on the glutamatergic system, this study aims to evaluate the effect of augmentation therapy on the rate of change in mood elevation in patients with bipolar depression.
METHODS: In a pilot study, 29 outpatients with bipolar depression on a stable lamotrigine dose regimen received placebo or memantine pills daily (titrated up by 5 mg week⁻¹ to 20 mg) in a randomized, double-blind, parallel group, 8 week study. Patients were evaluated weekly using the 17-item Hamilton Depression Rating Score (HDRS) and all data were analyzed simultaneously. Linear, exponential, maximal effect, Gompertz and inverse Bateman functions were evaluated using a Bayesian approach population pharmacodynamic model framework. In these models, differences in parameters were examined across the memantine and placebo augmentation groups.
RESULTS: A Gompertz function with a treatment switch on the parameter describing the speed of HDRS decline (γ, 95% confidence interval [CI]) best described the data (γ(memantine) = 1.8, 95% CI 0.9, 3.6), γ(placebo) = 1.2, 95% CI 0.5, 3.5)). Between subject variability was identified on baseline HDRS (2.9, 95% CI 1.5, 4.4) and amplitude of score improvement (4.3, 95% CI 2.7, 6.5).
CONCLUSIONS: This pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.
|Number of pages||8|
|Journal||British Journal of Clinical Pharmacology|
|Publication status||Published - Mar-2013|
- Bayes Theorem
- Bipolar Disorder
- Dopamine Agents
- Double-Blind Method
- Drug Therapy, Combination
- Middle Aged
- Pilot Projects
- Psychiatric Status Rating Scales
- Severity of Illness Index
- Treatment Outcome
- Young Adult
- Journal Article
- Randomized Controlled Trial
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't