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Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder

Molecular Psychiatry volume 20, pages 1142–1150 (2015)Cite this article

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Abstract

Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments—especially for treatment-resistant depression (TRD)—are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.

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Authors and Affiliations

  1. Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA

    G I Papakostas & D F Ionescu

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  1. G I Papakostas
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  2. D F Ionescu
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Correspondence to G I Papakostas.

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Competing interests

Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca, Avanir Pharmaceuticals, Brainsway, Bristol-Myers Squibb Company, Cephalon, Dey Pharma, Eli Lilly, GlaxoSmithKline, Evotec AG, H. Lundbeck A/S, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos and Wyeth. Dr Papakostas has received honoraria from Abbott Laboratories, Astra Zeneca, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Brainsway, Cephalon, Dey Pharma, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, H. Lundbeck A/S, Novartis Pharma AG, Otsuka Pharmaceuticals, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos, Titan Pharmaceuticals and Wyeth. Dr Papakostas has received research support from AstraZeneca, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB, Pfizer, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion Pharmaceuticals and Theracos. Dr Papakostas has served (not currently) on the speaker’s bureau for Bristol-Myers Squibb and Pfizer. Dr Ionescu has no conflict of interest to disclose, financial or otherwise.

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Re-submitted as an invited review to Molecular Psychiatry in March 2015.

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Papakostas, G., Ionescu, D. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Mol Psychiatry 20, 1142–1150 (2015). https://doi.org/10.1038/mp.2015.92

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