Bayesian model of Hamilton Depression Rating Score (HDRS) with memantine augmentation in bipolar depression
Article first published online: 5 FEB 2013
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Special Issue: Nutraceuticals Themed Section
Volume 75, Issue 3, pages 791–798, March 2013
How to Cite
Stevens, J., Bies, R. R., Shekhar, A. and Anand, A. (2013), Bayesian model of Hamilton Depression Rating Score (HDRS) with memantine augmentation in bipolar depression. British Journal of Clinical Pharmacology, 75: 791–798. doi: 10.1111/j.1365-2125.2012.04398.x
- Issue published online: 5 FEB 2013
- Article first published online: 5 FEB 2013
- Accepted manuscript online: 30 JUL 2012 09:49PM EST
- Manuscript Accepted: 13 JUL 2012
- Manuscript Received: 9 APR 2012
- the Indiana Clinical and Translational Sciences Institute (CTSI)
- National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. Grant Number: TR000006
- Bayesian analysis;
- bipolar depression;
- mathematical model;
- population dynamics
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.
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.
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 (γmemantine = 1.8, 95% CI 0.9, 3.6), γplacebo = 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).
This pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.