A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder

Sylvia, Louisa G.; Gold, Alexandra K.; Stange, Jonathan P.; Peckham, Andrew; Deckersbach, Thilo; Calabrese, Joseph R.; Weiss, Roger D.; Perlis, Roy H.; Nierenberg, Andrew A.; Ostacher, Michael J.

doi:10.1111/ajad.12346

Cited by 27 publications

(17 citation statements)

References 13 publications

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“… 8 Unfortunately, treatment research for co-occurring BD and AD is remarkably limited. Only seven double-blind, placebo-controlled studies of medications for BD+AD have been conducted to date, 9 , 10 , 11 , 12 , 13 , 14 , 15 and only one of these studies demonstrated a medication (that is, valproate) effect on drinking. 12 Better understanding the mechanisms that give rise to co-occurring BD and AD could help to identify differences in genetic risk, prevention strategies and novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence

et al. 2017

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Bipolar disorder (BD) and alcohol dependence (AD) frequently co-occur, and co-occurring BD and AD are associated with devastating public health costs. Minimal neurobiological research exists to guide the development of effective treatments for this treatment-resistant population. We believe the present study represents the first investigation of prefrontal gamma-aminobutyric acid (GABA) and glutamate levels in co-occurring BD and current AD. The participants were 78 individuals who met DSM-IV criteria for BD I/II and current AD (n=20), BD I/II alone (n=19), current AD alone (n=20) or no diagnosis (n=19). The participants completed a baseline diagnostic visit, then returned approximately 4 days later for a two-dimensional J-resolved proton magnetic resonance spectroscopy (1H-MRS) acquisition in dorsal anterior cingulate cortex (dACC). All participants were required to demonstrate ⩾1 week of abstinence from alcohol/drugs via serial biomarker testing before 1H-MRS. A 2 × 2 factorial analysis of variance of cerebrospinal fluid (CSF)-corrected GABA/water concentrations demonstrated a significant BD × AD interaction (F=2.91, P<0.05), signifying uniquely low levels of GABA in BD+AD; this effect doubled when the sample was restricted to individuals who consumed alcohol within 2 weeks of 1H-MRS. There were no overall effects of BD/AD on CSF-corrected glutamate/water levels. However, the BD × AD interaction, signifying uniquely low levels of glutamate in BD+AD, approached statistical significance (F=3.83, P=0.06) in individuals who consumed alcohol within 2 weeks of 1H-MRS. The dACC GABA levels were significantly, negatively associated with Barratt Impulsiveness Scale (r=−0.28, P=0.02) and Obsessive Compulsive Drinking Scale (r=−0.35, P<0.01) scores. If replicated, these results may suggest that future treatment studies should preferentially evaluate therapeutics in BD+AD known to increase prefrontal GABA and glutamate levels.

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Section: Introductionmentioning

confidence: 99%

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence

et al. 2017

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“…A single study has investigated the effects of the anticonvulsant medication, Topiramate, on symptoms of bipolar disorder and co‐occurring alcohol dependence . Participants received either placebo or Topiramate (150 mg/d) in a 12‐week, randomized, proof of concept trial.…”

Section: Resultsmentioning

confidence: 99%

Pharmacotherapies for co‐occurring substance use and bipolar disorders: A systematic review

2019

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Objectives Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co‐occurring SUDs in bipolar illness have not been well‐developed and may be an important practical reason for the reduced effectiveness of these medications in community practice. Methods We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co‐occurring bipolar disorders and SUDs. Results Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co‐occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open‐label designs and of modest sample sizes. Conclusions Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co‐morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co‐morbidity is clearly needed.

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“…Quality assessment results are summarized in Supplemental Table 1. Ten studies were assessed as having a strong quality rating, 25,28,31,38,40,43,48,[53][54][55] 15 were assessed as having a moderate quality rating, 24,26,27,29,30,33,[35][36][37]44,46,49,50,52,56 and 7 were assessed as having a weak quality rating. 34,39,41,42,45,47,51 The Funnel plot (see Supplemental Figure 1) was asymmetrical suggesting that studies without statistically significant effects remain unpublished, particularly those with small participant sample sizes and those that investigated…”

Section: Quality and Bias Assessmentmentioning

confidence: 99%

Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L’humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse

et al. 2020

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Objective: Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity. Methods: A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects. Results: A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = −0.15; 95% confidence interval [95% CI], −0.29 to −0.02; P = 0.03) but not BD depressive symptoms (SMD = −0.09; 95% CI, −0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = −0.23; 95% CI, −0.39 to −0.06; P = 0.008) but not BD depressive symptoms (SMD = −0.07; 95% CI, −0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = −0.16; 95% CI, −0.30 to −0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = −0.58; 95% CI, −1.03 to −0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = −0.06; 95% CI, −0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence. Conclusions: Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI’s for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.

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A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder

Cited by 27 publications

References 13 publications

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence

Pharmacotherapies for co‐occurring substance use and bipolar disorders: A systematic review

Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L’humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse

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