Advances in the Management of Major Depressive Disorder - Episode 1

Limitations of Current Treatment Options for Depression

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Dr Greg Mattingly shares his view on major challenges in the management of Major Depressive Disorder and limitations of medications currently used.


The clinicians identify major challenges in diagnosing and managing depression, including inadequately addressing symptoms like anhedonia, cognition, and motivation that drive disability. Current antidepressants like SSRIs often don't improve these hard-to-treat symptoms. SSRIs also worsen cognition by decreasing dopamine. Another limitation of SSRIs is their delayed therapeutic benefit, taking 4-6 weeks to relieve symptoms despite increasing serotonin right away. This delay contributes to increasing depression rates and disability.

Additionally, SSRI side effects can limit long-term treatment adherence. While patients tolerate short-term side effects, ongoing effects like weight gain and sexual dysfunction often lead patients to discontinue treatment.

Given these SSRI limitations, Drs. Cutler and Mattingly emphasize the need for faster-acting antidepressants that provide “pan-symptom improvement” beyond mood, including motivation and cognition. Promising options may target glutamate signaling or activate overall neural networks more rapidly.

In summary, while SSRIs are the standard depression treatment, they fail to address all symptoms and have a slow, limited response plus troublesome side effects for many patients. More effective, rapid-onset antidepressants with better side effect profiles are critically needed.

Summary was AI-generated and edited for clarity.