Novel Targets to Treat Depression: Opioid-Based Therapeutics.

@article{Browne2020NovelTT,
  title={Novel Targets to Treat Depression: Opioid-Based Therapeutics.},
  author={Caroline A Browne and Moriah L. Jacobson and Irwin Lucki},
  journal={Harvard Review of Psychiatry},
  year={2020}
}
LEARNING OBJECTIVES After participating in this activity, learners should be better able to:• Identify the effects of dysregulated opioid signalling in depression• Evaluate the use of opioid compounds and ketamine in patients with depression ABSTRACT: Major depressive disorder (MDD) remains one of the leading causes of disability and functional impairment worldwide. Current antidepressant therapeutics require weeks to months of treatment prior to the onset of clinical efficacy on depressed mood… 
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References

SHOWING 1-10 OF 220 REFERENCES
Targeting opioid dysregulation in depression for the development of novel therapeutics.
Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants
TLDR
Preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine.
Opioid modulation of cognitive impairment in depression.
Endogenous opioid system dysregulation in depression: implications for new therapeutic approaches
TLDR
The development of safe and effective agents to treat MDD-associated endogenous opioid dysregulation may represent a distinct and currently underappreciated means of addressing treatment resistant depression with the potential to attenuate the on-going opioid crisis.
Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments
TLDR
Ketamine and other potentially novel glutamate-based treatments for treatment-resistant depression are reviewed, including N-methyl-D-aspartate receptor antagonists, glycine binding site ligands, metabotropic glutamate receptor modulators, and other glutamatergic modulators.
Kappa Opioid Receptor Antagonists as Potential Therapeutics for Stress-Related Disorders.
TLDR
The preclinical evidence illustrating the induction of behaviors relevant to the endophenotypes of MDD and KOR antagonist activity in stress-naïve and stress-exposed animals is evaluated, highlighting the emergent literature supporting the pursuit of KOR antagonists as novel therapeutics for MDD.
Identifying fast-onset antidepressants using rodent models
TLDR
This review discusses and assesses the validity of seven rodent models currently used to assess antidepressant onset, as well as six treatments that possess fast-onset antidepressant effects in the clinic: electroconvulsive shock therapy, sleep deprivation, ketamine, scopolamine, GLYX-13 and pindolol used in conjunction with classical antidepressants.
Evaluation of Opioid Modulation in Major Depressive Disorder
TLDR
A combination of BUP and SAM showed antidepressant activity in subjects with MDD, and Balanced agonist–antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.
A randomized, placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression
TLDR
Results suggest that AZD2327 has larger potential anxiolytic than antidepressant efficacy, and additional research with DOR agonists should be considered.
The Role of Eukaryotic Elongation Factor 2 Kinase in Rapid Antidepressant Action of Ketamine
...
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2
3
4
5
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