Bayesian model of Hamilton Depression Rating Score (HDRS) with memantine augmentation in bipolar depression

Jasper Stevens, Robert Bies, Anantha Shekhar, Amit Anand

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 5mgweek-1 to 20mg) in a randomized, double-blind, parallel group, 8week 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 (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). Conclusions: This pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.

Original languageEnglish
Pages (from-to)791-798
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Volume75
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Memantine
Bipolar Disorder
Confidence Intervals
Depression
Placebos
Bayes Theorem
Antidepressive Agents
Outpatients
Therapeutics
Pharmaceutical Preparations
Population

Keywords

  • Bayesian analysis
  • Bipolar depression
  • Lamotrigine
  • Mathematical model
  • Memantine
  • Population dynamics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Bayesian model of Hamilton Depression Rating Score (HDRS) with memantine augmentation in bipolar depression. / Stevens, Jasper; Bies, Robert; Shekhar, Anantha; Anand, Amit.

In: British Journal of Clinical Pharmacology, Vol. 75, No. 3, 03.2013, p. 791-798.

Research output: Contribution to journalArticle

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abstract = "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 5mgweek-1 to 20mg) in a randomized, double-blind, parallel group, 8week 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 (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). Conclusions: This pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.",
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