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Depression, a complex and varied condition, continues to challenge treatment efforts despite existing medications and therapies. With the global market for depression treatments expected to exceed $16 billion by 2027, attention is turning to psychedelic drugs as a promising frontier.

Currently, selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Zoloft, combined with psychotherapy, form the standard treatment regimen. However, up to 30 percent of patients with major depressive disorder do not respond adequately to these treatments, a condition known as treatment-resistant depression (TRD). GH Research, focusing on 5-MeO-DMT, highlights that less than 15% of TRD patients achieve remission with current treatments.

Johnson & Johnson's approval of Spravato (esketamine) in 2019 marked a significant step, though it's not classified as a classic psychedelic due to its non-hallucinogenic effects. Dr. Carlene MacMillan of Osmind noted superior outcomes in depression symptom improvement with Spravato compared to traditional methods in clinical trials.

Companies like GH Research and Compass Pathways are advancing with psilocybin and 5-MeO-DMT, emphasizing their hallucinogenic properties. Psilocybin, currently in Phase III trials by Compass, shows promise in altering brain connectivity, potentially offering new perspectives on depression treatment.

"The psychedelics allow you to teach an old dog new tricks," MacMillan told Biospace. "Psychedelics, particularly psilocybin, have shown great promise at helping people who are not traditionally helped, and faster."

Compass' COMP360, administered with psychological support, demonstrated significant reduction in depressive symptoms in Phase IIb trials. Similarly, GH Research is progressing with GH001, focusing on the rapid-acting nature of 5-MeO-DMT compared to longer-acting psychedelics like psilocybin.

Dr. MacMillan noted the rapid onset and potential efficacy of psychedelics in treating TRD, contrasting them with traditional serotonin-targeting medications. However, she cautioned about the intensity and risk profile of psychedelics like 5-MeO-DMT, emphasizing the need for rigorous safety protocols.

While psychedelics offer promising avenues for difficult-to-treat depression, Dr. MacMillan stressed the importance of broader treatment options like neuromodulation therapies. She emphasized the need for a balanced approach to mental health treatment, incorporating both traditional and emerging methods.

"I think it's important that we see broadly treatments for TRD and not get overly focused on psychedelics being the only way, because it's just a different time in our field now," she said.