Current pharmacotherapies for depression: comparing serotonergic, glutamatergic, and GABA modulating agents
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Depression is the leading cause of disability in the world. The most common depression related diagnosis is major depressive disorder (MDD). Around 7% of the adult population in the United States have suffered at least one major depressive episode. MDD demonstrates a high economic burden and comorbidity as well. Depression is an incredibly complex disease in terms of cause, and patients can vary greatly in presentation as well as treatment outcomes. There are many proposed pathological mechanisms for the development of depression, but a common cause has not been found. Antidepressant medications, as well as psychotherapy, have been the main stay of depression treatment since the 1950s. These medications act by boosting serotonergic and/or adrenergic transmission. Selective serotonin reuptake inhibitors (SSRIs) are the most popular first-line antidepressant medications. However, only around 50% of MDD patients experience a response from first-line antidepressants. The purpose of this review is to compare an SSRI, escitalopram, to two recently approved depression medications which exhibit novel mechanisms of action. Esketamine acts on the glutamatergic system, while brexanolone acts on the GABAergic system. The pharmacological properties of these 3 drugs were compared, through analysis of clinical trials and reviews, in order to determine which mechanism warrants the greater focus in future antidepressant research. Both esketamine and brexanolone showed efficacy and safety in treating their respective depression subtype populations. The major difference between esketamine and brexanolone in comparison with escitalopram was a rapid antidepressant effect. The conclusion of this review indicates that future research should perhaps focus more on alternative mechanisms of action than serotonergic, like glutamatergic and GABAergic drugs. Future research should include studying the efficacy and safety of glutamatergic and GABAergic antidepressants in the MDD population.
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