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B ayesian model of H amilton D epression R ating S core ( HDRS ) with memantine augmentation in bipolar depression
Author(s) -
Stevens Jasper,
Bies Robert R.,
Shekhar Anantha,
Anand Amit
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2012.04398.x
Subject(s) - memantine , placebo , pharmacodynamics , bipolar disorder , population , glutamatergic , pharmacology , medicine , psychology , mood , nmda receptor , pharmacokinetics , psychiatry , receptor , glutamate receptor , alternative medicine , environmental health , pathology
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 H amilton D epression R ating S core ( HDRS ) and all data were analyzed simultaneously. Linear, exponential, maximal effect, G ompertz and inverse B ateman functions were evaluated using a B ayesian approach population pharmacodynamic model framework. In these models, differences in parameters were examined across the memantine and placebo augmentation groups. Results A G ompertz 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.