Woman patient having consultation with a psychiatrist.

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The treatment landscape for major depressive disorder (MDD) continues to diversify, and in the coming years, psychedelic options may be available, including COMPASS Pathways COMP360 and the deuterated psilocybin analog CYB003 from Cybin. CYB003 demonstrated a significant -14.08 point reduction in MADRS score, a 53.3% response rate, and a 20% remission rate at a 12mg dose in interim results from its phase 2 study.

The potential of faster-acting more effective therapies

While it is difficult to compare the results from disparate clinical trials, some broad patterns emerge when viewing data from current treatment options and drugs now in clinical development for MDD (see table below). In contrast, newer treatment options, especially psychedelic therapies such as CYB003 and COMP360, demonstrate potentially faster onset and greater magnitude of symptom reduction.

The promise of NMDA and dopamine receptor targeting

In addition, treatments targeting the NMDA receptor, such as J&J’s Spravato (esketamine) and the dextromethorphan component of Axsome Therapeutics’ Auvelity, offer rapid-acting effects, potentially providing relief within hours or days. This quick onset is a significant departure from traditional antidepressants, which typically require several weeks to show benefits.

Dopamine modulation could also be a promising dimension in the MDD treatment landscape, now that Vraylar (cariprazine) is FDA-approved as an adjunctive therapy for the condition. Emerging data indicate that Vraylar’s ability to target dopamine D3 receptors could improve anhedonia, which remains one of the most stubborn symptom of MDD. Conversely, traditional antidepressants primarily target serotonin and norepinephrine levels.

Clinical outcomes of MDD treatments summarized

The following table highlights the diversity of current and emerging treatments for MDD, and the potential for some patients with the condition to experience more rapid improvement. The growing availability of treatment options also point to a more personalized approach to treatment.

The table summarizes key clinical outcomes such as the reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS), response rates, remission rates, and time points at which these outcomes were measured: