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

Jasper Stevens, Robert R. Bies, Anantha Shekhar, Amit Anand

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)791-798
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Issue number3
Publication statusPublished - Mar-2013
Externally publishedYes


  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants
  • Bayes Theorem
  • Bipolar Disorder
  • Dopamine Agents
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Memantine
  • Middle Aged
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Treatment Outcome
  • Triazines
  • Young Adult
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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