Treatment of alcohol dependence in patients with co-morbid major depressive disorder – predictors for the outcomes with memantine and escitalopram medication

Muhonen, Leea H.; Lahti, Jari; Sinclair, David; Lönnqvist, Jouko; Alho, Hannu

doi:10.1186/1747-597x-3-20

Cited by 35 publications

(20 citation statements)

References 54 publications

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“…Subsequently, a case report explored the antidepressant efficacy of repeat-dose ketamine followed by memantine; although this patient was eventually on seven psychotropic medications, she remained in remission for at least 13 weeks (124). Echoing the previous link between NMDA receptor antagonists and ketamine response, another randomized, non-placebo-controlled trial of memantine (20 mg/day) versus escitalopram (20 mg/day) in patients with MDD comorbid with alcohol dependence found that memantine had antidepressant and anxiolytic effects, improved psychosocial functioning, and decreased alcohol consumption (125, 126). …”

Section: Other Nmda Receptor Antagonistsmentioning

confidence: 99%

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Niciu

Henter

Luckenbaugh

et al. 2014

Annu. Rev. Pharmacol. Toxicol.

152

111

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The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine’s antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine’s antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine’s antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine’s adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine’s antidepressant effects.

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Section: Other Nmda Receptor Antagonistsmentioning

confidence: 99%

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Niciu

Henter

Luckenbaugh

et al. 2014

Annu. Rev. Pharmacol. Toxicol.

152

111

View full text Add to dashboard Cite

show abstract

“…Subsequently, a case report explored the antidepressant efficacy of repeat-dose ketamine followed by memantine; although this patient was eventually on many psychotropic medications, she remained in remission for at least approximately 3 months on memantine (Kollmar et al 2008). Another randomized, non-placebo-controlled trial of memantine (20 mg/day) versus escitalopram (20 mg/day) in patients with MDD comorbid with alcohol dependence found that memantine had antidepressant and anxiolytic effects, improved psychosocial functioning, and decreased alcohol consumption (Muhonen et al 2008a, b). …”

Section: Glutamatergic Medications In the Treatment Of Major Depressimentioning

confidence: 99%

Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder

et al. 2013

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Monoaminergic neurotransmitter (serotonin, norepinephrine and dopamine) mechanisms of disease dominated the research landscape in the pathophysiology and treatment of major depressive disorder (MDD) for more than 50 years and still dominate available treatment options. However, the sum of all brain neurons that use monoamines as their primary neurotransmitter is <20 %. In addition, most patients treated with monoaminergic antidepressants are left with significant residual symptoms and psychosocial disability not to mention side effects, e.g., sexual dysfunction. In the past several decades, there has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of MDD. Although several preclinical and human magnetic resonance spectroscopy studies had already implicated glutamatergic abnormalities in the human brain, it was rocketed by the discovery that the N-methyl-D-aspartate receptor antagonist ketamine has rapid and potent antidepressant effects in even the most treatment-resistant MDD patients, including those who failed to respond to electroconvulsive therapy and who have active suicidal ideation. In this review, we will first provide a brief introduction to glutamate and its receptors in the mammalian brain. We will then review the clinical evidence for glutamatergic dysfunction in MDD, the discovery and progress-to-date with ketamine as a rapidly acting antidepressant, and other glutamate receptor modulators (including proprietary medications) for treatment-resistant depression. We will finally conclude by offering potential future directions necessary to realize the enormous therapeutic promise of glutamatergic antidepressants.

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“…Therefore, the use of antidepressants as adjunctive therapy for AUD with comorbid depression might be considered since combining acamprosate and SSRIs such as escitalopram in theory could simultaneously downregulate glutamatergic and upregulate serotonergic neurotransmissions, in turn suppressing ethanol consumption. Clinical studies found SSRIs improved depressed mood and decrease alcohol use in some alcohol dependent individuals (Kranzler et al, 2012; Muhonen et al, 2011; Muhonen et al, 2008). Escitalopram is currently the most widely used SSRI (Owens et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

Qiu

Jia

et al. 2016

Alcohol Clin Exp Res

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Background Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). Since negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergist effect of FDA approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol consumption in stress-induced depressed mice. Methods Forty singly-housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and ethanol consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/day), escitalopram (5 mg/kg; twice/day), or their combination (n = 9–11/drug group/stress group). Two-bottle choice limited access drinking of 15% ethanol and tap water was performed 3 hours into dark phase for 2 hours immediately after the dark phase daily injection. Ethanol drinking was monitored for another 7 days without drug administration. Results Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their non-stressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher ethanol consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in ethanol consumption in non-stressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the post-drug administration period. Conclusions The combination of acamprosate and escitalopram suppressed ethanol intake in both non-stressed and stressed mice, hence this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use.

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Treatment of alcohol dependence in patients with co-morbid major depressive disorder – predictors for the outcomes with memantine and escitalopram medication

Cited by 35 publications

References 54 publications

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

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