Depression involves a wide range of biological changes, from gene variations to epigenetic modifications, not only serotonergic mechanisms. Therapy response to antidepressants is linked to epigenetic regulation of genes in the serotonergic system. Persistent depressive symptoms may involve stable molecular adaptations in the brain at the epigenetic level. Responses to psychotherapy for mood disorders correlate with epigenetic alterations, including in genes regulating the serotonergic and glutamatergic systems and the HPA axis. Ketamine's antidepressant effects may be linked to epigenetic alterations, and further exploration of BDNF's relation with ketamine in epigenetic signaling is warranted. Understanding these mechanisms may help gauge therapy efficacy and duration.
Patients with mental illnesses should have the same access to promising experimental therapies, including psychedelics, as patients with other conditions. The principle of early access to experimental treatments, advanced by activist Larry Kramer during the AIDS pandemic, is now standard in medicine for diseases like cancer and infectious diseases. Psychiatry has failed to provide similar expanded access during public health emergencies, psychological crises, and pandemics, despite patient preferences and community needs. The field must align with the rest of medicine and let patient preferences guide policy and law on unapproved medications such as psychedelics.
A client with treatment-resistant PTSD stemming from racism and childhood sexual abuse showed significant symptom reduction after four ketamine administrations over 13 days combined with mindfulness-based cognitive therapy and functional analytic psychotherapy. Gains were maintained at a 4-month follow-up. The case demonstrates ketamine as an effective adjunct to psychotherapy for treatment-resistant PTSD.