Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial

Fava, Maurizio; Memişoğlu, Aslı; Thase, Michael E.; Bodkin, J. Alexander; Trivedi, Madhukar H.; Somer, Marc de; Du, Yangchun; Leigh-Pemberton, Richard; DiPetrillo, Lauren; Silverman, Bernard L.; Ehrich, Elliot W.

doi:10.1176/appi.ajp.2015.15070921

Cited by 159 publications

(160 citation statements)

References 40 publications

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“…Clinical evidence is supportive of this hypothesis; Alkermes have combined buprenorphine with the MOP antagonist samidorphan in a single sublingual tablet (ALKS5461) and in a 1:1 combination that provides KOP receptor antagonism and antagonism or extremely low stimulation at MOP receptors. ALKS5461 has been shown to have potential in the treatment of major depressive disorder [72,73] confirming the pre-clinical findings with buprenorphine-naltrexone and BU10119 [58,62].…”

Section: Mixed Kop/mop Antagonists Are Antidepressant In Animal Modelsmentioning

confidence: 53%

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Bailey

Husbands

2018

Neuronal Signaling

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The opioid receptors are a family of G-protein coupled receptors (GPCRs) with close structural homology. The opioid receptors are activated by a variety of endogenous opioid neuropeptides, principally β-endorphin, dynorphins, leu-and met-enkephalins. The clinical potential of targeting opioid receptors has largely focused on the development of analgesics. However, more recent attention has turned to the role of central opioid receptors in the regulation of stress responses, anhedonia and mood. Activation of the κ opioid receptor (KOP) subtype has been shown in both human and rodent studies to produce dysphoric and pro-depressive like effects. This has led to the idea that selective KOP antagonists might have therapeutic potential as antidepressants. Here we review data showing that mixed μ opioid (MOP) and KOP antagonists have antidepressant-like effects in rodent behavioural paradigms and highlight comparable studies in treatment-resistant depressed patients. We propose that developing multifunctional ligands which target multiple opioid receptors open up the potential for fine-tuning hedonic responses mediated by opioids. This alternative approach towards targeting multiple opioid receptors may lead to more effective treatments for depression.

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Section: Mixed Kop/mop Antagonists Are Antidepressant In Animal Modelsmentioning

confidence: 53%

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Bailey

Husbands

2018

Neuronal Signaling

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“…Clinical and pre-clinical studies have demonstrated the efficacy of buprenorphine and its novel analogues in the pharmacotherapy Review Danuta Szkutnik-Fiedler of depression [3,[71][72][73][74][75][76]. Ahmadi et al [73] suggest that a single high-dose of buprenorphine provides a safe, speedy and straightforward means of depression, especially in patients who are opioid dependent.…”

Section: Buprenorphine and Its New Analoguesmentioning

confidence: 99%

“…Vital signs and weight were stable, and the executive function and learning improved. Fava et al [72] studied the antidepressant activity of a combination of buprenorphine and a μ-opioid antagonist, samidorphan in patients with major depression. They showed significantly greater antidepressant effects for this combination compared to the placebo and concluded that it might be a promising candidate for the treatment of a major depressive disorder in patients who have an inadequate response to standard antidepressants.…”

Section: Buprenorphine and Its New Analoguesmentioning

confidence: 99%

“…The δ receptor-knockout mice exhibit increased depressive-like behaviors, so this receptor may also be a potential antidepressant target [3]. Due to the mechanisms of action of tramadol and buprenorphine [71][72][73][74][75][76], it may be concluded, that both drugs may enhance synaptic plasticity and achieve the purpose of antidepressant therapy by adjusting neurotransmitter systems [3]. Therefore, the treatment by tramadol or buprenorphine in relieving symptoms of depression may be involved in the inactivation of cycle pain-depression.…”

Section: The Role Of Tramadol and Buprenorphine In The Inactivation Omentioning

confidence: 99%

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Coexistence of Chronic Pain and Depression: A Short Review with a Focus on the Antidepressant Effect of Tramadol and Buprenorphine

Szkutnik-Fiedler¹,

Grześkowiak²

2018

Neuropsychiatry

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It is known that there is a strong relationship between chronic pain and depression, and both of these diseases can intensify each other. In addition to mental illnesses, there are also a number of somatic symptoms, including pain. While pain, especially chronic, is always associated with mental suffering, which can aggravate the symptoms of depression. Proper and timely identification of coexistence of these conditions allows for effective and safe pharmacotherapy.This article reviews the literature on the coexistence of chronic pain and depressive disorders. The common mechanisms of both these diseases and the frequency of their coexistence have been described. The results of studies on the problem of treatment of patients with chronic pain with concomitant depression and patients with depression declaring pain are presented. The role of tramadol and buprenorphine in relieving symptoms of depression, including severe and refractory to traditional treatment, has also been described.

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“…The results of a multicenter, randomized, double-blind, placebo-controlled study have shown that the modulation of the opiate system may be a novel treatment approach for treatment-resistant depression. 18 …”

Section: New Drugs Opioidsmentioning

confidence: 99%

Novel Treatment Options in Depression and Psychosis

Češková

2017

Clinical Therapeutics

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Abstract:In spite of tremendous development in central nervous system research, current treatment is suboptimal, especially in severe mental disorders. In medicine, there are two main methods of improving the health care provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring but also implementation of general trends in the clinical practice. New pharmacological options include new more sophisticated forms of monoaminergic drugs, old drugs rediscovered on the base of a better understanding of pathophysiology of mental illnesses, and drugs aimed at new treatment targets. In depression, treatment resistance to antidepressive pharmacotherapy represents one of the most important clinical challenges. Switching to monotherapy with new multimodal/multifunctional antidepressants and augmentation with new atypical antipsychotics (aripiprazole and brexpiprazole) may be promising options. Further, current evidence supports utility and safety of adjunctive treatment of nutraceuticals. Novel approaches being studied include ketamine and opioids. Recent advances in technology and emerging knowledge about dysfunctional brain circuits and neuroplasticity have led to the development of different new neuromodulation techniques usually used as add-on therapy. Antipsychotics are still the cornerstone of the current treatment of schizophrenia. Two new partial dopamine agonists, brexpiprazole and cariprazine, are now available in addition to aripiprazole. Although the mechanisms of action are similar, the two agents differ in terms of their pharmacodynamic profiles. Further, two new formulations of long-acting injections of second-generation antipsychotics (aripiprazole lauroxil and 3-month paliperidone palmitate) were introduced into clinical practice. New treatment options not yet available include cannabidiol, glutamate modulators, and nicotine receptors agonists.

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Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial

Abstract: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.

Cited by 159 publications

References 40 publications

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

Coexistence of Chronic Pain and Depression: A Short Review with a Focus on the Antidepressant Effect of Tramadol and Buprenorphine

Novel Treatment Options in Depression and Psychosis

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