Savvy Psychopharmacology

Do glutamatergic drugs have a role in treating depression?

Current Psychiatry. 2015 February;14(2):14-16, 27

References

1. Niciu MJ, Ionescu DF, Richards EM, et al. Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm. 2014;121(8):907-924.
2. Gaynes BN, Dusetzina SB, Ellis AR, et al. Treating depression after initial treatment failure: directly comparing switch and augmenting strategies in STAR*D. J Clin Psychopharmacol. 2012;32(1):114-119.
3. Curry SC, Mills KC, Ruha A, et al. Neurotransmitters and neuromodulators. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank’s toxicologic emergencies. 9th ed. New York, NY: McGraw-Hill; 2011:189-220.
4. Zarate C Jr, Machado-Vieira R, Henter I, et al. Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry. 2010;18(5):293-303.
5. Lapidus KA, Soleimani L, Murrough JW. Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013;9:1101-1112.
6. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134-1142.
7. Ibrahim L, Diazgranados N, Franco-Chaves J, et al. Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology. 2012;37(6):1526-1533.

Acamprosate, often used for treating alcohol abuse, is another a drug with glutamatergic activity that has been studied for possible use as an antidepressant.⁵

A review by Lapidus et al⁵ has a more extensive listing of current medications and investigational compounds that modulate glutamate transmission, and are of interest for their possible antidepressant activity. Given the relatively new “glutamatergic hypothesis” of depression, it is exciting that so many current and novel glutamatergic drug therapies are being evaluated.

Future of ketamine treatment
Glutamate has been shown to play an important part in the pathophysiology of depression. The rapid antidepressant efficacy of ketamine provides evidence that future medications with glutamate-modulating activity could be useful for patients who struggle to achieve symptom relief using available antidepressants. Several limitations exist regarding ketamine use, and more work in this important therapeutic area needs to be done. This last point is important to remember when speaking with patients such as Mrs. S. Although it is understandable for her to be excited about novel treatment options such as ketamine, stress to her that treating depression with ketamine at this time is strictly investigational, and that the drug needs to be thoroughly evaluated for safety and efficacy before it can be prescribed for this indication.

CASE CONTINUED
Mrs. S realizes that ketamine may not be the best next step for her, and she agrees to explore other approaches to treat her residual depressive symptoms.

Related Resources
• Machado-Vieira R, Ibrahim L, Henter ID, et al. Novel glutamatergic agents for major depressive disorder and bipolar disorder. Pharmacol Biochem Behav. 2012;100(4):678-687.
• Mathews DC, Henter ID, Zarate CA. Targeting the glutamatergic system to treat major depressive disorder: rationale and progress to date. Drugs. 2012;72(10):1313-1333.

Drug Brand Names
Acamprosate • Campral Duloxetine • Cymbalta
Aripiprazole • Abilify Ketamine • Ketalar
Bupropion • Wellbutrin, Zyban Riluzole • Rilutek

Disclosures
The authors report no financial relationships with any companies whose products are mentioned in this article or with manufacturers of competing products.

Do glutamatergic drugs have a role in treating depression?

References

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