Dataset Information

Changes in brain Glx in depressed bipolar patients treated with lamotrigine: A proton MRS study.

ABSTRACT:

Background

Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response.

Methods

We studied 21 bipolar patients who received lamotrigine treatment for a current episode of depression. Before starting lamotrigine and after 10-12 weeks treatment, patients underwent proton magnetic resonance spectroscopy (MRS) scanning at 3 Tesla where levels of glutamate (measured as Glx) were determined in anterior cingulate cortex (ACC).

Results

Overall, lamotrigine treatment had no significant effect on Glx levels in ACC. However, in patients who responded clinically to lamotrigine treatment Glx concentrations were significantly increased. Baseline levels of Glx did not predict response to lamotrigine.

Limitations

The main limitation of the study was the modest sample size. Most patients were medicated which may have modified the effect of lamotrigine on glutamate activity. MRS at 3T cannot give a reliable estimate of glutamate separate from its main metabolite, glutamine, and thus changes in Glx may not give a precise estimate of effects of lamotrigine on glutamate itself.

Conclusion

Lamotrigine does not appear to have a direct effect on glutamate levels in ACC in bipolar patients. However, therapeutic improvement during lamotrigine was associated with increased Glx, suggesting that alterations in glutamatergic activity might be related to recovery from bipolar depression.

SUBMITTER: Godlewska BR

PROVIDER: S-EPMC6368663 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Changes in brain Glx in depressed bipolar patients treated with lamotrigine: A proton MRS study.

Godlewska Beata R BR Emir Uzay E UE Masaki Charles C Bargiotas Theodoras T Cowen Philip J PJ

Journal of affective disorders 20181225

<h4>Background</h4>Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response.<h4>Methods</h4>We studied 21 bipolar patients who ...[more]

PMID: 30599363

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Project description:Background and purposeProton radiotherapy has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation necrosis among these patients. Our aim was to evaluate the incidence, timing, clinical significance, risk factors, and imaging patterns of radiation necrosis in pediatric patients with brain tumors treated with proton radiation therapy.Materials and methodsA retrospective study was performed on 60 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation necrosis was assessed by examining serial MRIs and clinical records to determine the incidence, timing, risk factors, imaging patterns, and clinical significance associated with the development of radiation necrosis in these patients. Radiation necrosis was defined as areas of new enhancement within an anatomic region with previous exposure to proton beam therapy with subsequent decrease on follow-up imaging without changes in chemotherapy.ResultsThirty-one percent of patients developed radiation necrosis with a median time to development of 5.0 months (range, 3-11 months). Risk factors included multiple chemotherapy agents (>3 cytotoxic agents) and atypical teratoid rhabdoid tumor pathology (P = .03 and P = .03, respectively). The most common imaging patterns were small (median, 0.9 cm) and multifocal (63% of patients) areas of parenchymal enhancement remote from the surgical site. The median time to complete resolution on imaging was 5.3 months (range, 3-12 months). Among patients with imaging findings of radiation necrosis, 25% demonstrated severe symptoms with medical intervention indicated.ConclusionsPediatric patients with brain tumors treated with proton radiation therapy demonstrate a high incidence of radiation necrosis and a short time to development of necrosis. Multiple small areas of necrosis are frequently identified on imaging. Exposure to multiple chemotherapy agents was a significant risk factor associated with radiation necrosis in these patients.

Project description:BACKGROUND:Depression in people with bipolar disorder is a major cause of long-term disability, possibly leading to early mortality and currently, limited safe and effective therapies exist. Although existing monotherapies such as quetiapine have limited proven efficacy and practical tolerability, treatment combinations may lead to improved outcomes. Lamotrigine is an anticonvulsant currently licensed for the prevention of depressive relapses in individuals with bipolar disorder. A double-blinded randomized placebo-controlled trial (comparative evaluation of Quetiapine-Lamotrigine [CEQUEL] study) was conducted to evaluate the efficacy of lamotrigine plus quetiapine versus quetiapine monotherapy in patients with bipolar type I or type II disorders. OBJECTIVE:Because the original CEQUEL study found significant depressive symptom improvements, the objective of this study was to reanalyze CEQUEL data and determine an unbiased classification accuracy for active lamotrigine versus placebo. We also wanted to establish the time it took for the drug to provide statistically significant outcomes. METHODS:Between October 21, 2008 and April 27, 2012, 202 participants from 27 sites in United Kingdom were randomly assigned to two treatments; 101: lamotrigine, 101: placebo. The primary variable used for estimating depressive symptoms was based on the Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16). The original CEQUEL study findings were confirmed by performing t test and linear regression. Multiple features were computed from the QIDS-SR16 time series; different linear and nonlinear binary classifiers were trained to distinguish between the two groups. Various feature-selection techniques were used to select a feature set with the greatest explanatory power; a 10-fold cross-validation was used. RESULTS:From weeks 10 to 14, the mean difference in QIDS-SR16 ratings between the groups was -1.6317 (P=.09; sample size=81, 77; 95% CI -0.2403 to 3.5036). From weeks 48 to 52, the mean difference was -2.0032 (P=.09; sample size=54, 48; 95% CI -0.3433 to 4.3497). The coefficient of variation (?/?) and detrended fluctuation analysis (DFA) exponent alpha had the greatest explanatory power. The out-of-sample classification accuracy for the 138 participants who reported more than 10 times after week 12 was 62%. A consistent classification accuracy higher than the no-information benchmark was obtained in week 44. CONCLUSIONS:Adding lamotrigine to quetiapine treatment decreased depressive symptoms in patients with bipolar disorder. Our classification model suggested that lamotrigine increased the coefficient of variation in the QIDS-SR16 scores. The lamotrigine group also tended to have a lower DFA exponent, implying a substantial temporal instability in the time series. The performance of the model over time suggested that a trial of at least 44 weeks was required to achieve consistent results. The selected model confirmed the original CEQUEL study findings and helped in understanding the temporal dynamics of bipolar depression during treatment. TRIAL REGISTRATION:EudraCT Number 2007-004513-33; https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004513-33/GB (Archived by WebCite at http://www.webcitation.org/73sNaI29O).

Dataset Information

Changes in brain Glx in depressed bipolar patients treated with lamotrigine: A proton MRS study.

Background

Methods

Results

Limitations

Conclusion

Publications

Changes in brain Glx in depressed bipolar patients treated with lamotrigine: A proton MRS study.

Similar Datasets

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