Treatment-resistant depression (TRD) has historically had very limited options, but recent advances have expanded knowledge of effective interventions. Psychotherapy can help as an add-on but not alone. Adjunctive non-antidepressant drugs like buprenorphine and antipsychotics show little recent support; side effects and high discontinuation rates may outweigh benefits. Strong recent evidence supports interventional approaches: electroconvulsive therapy, ketamine/esketamine, and transcranial magnetic stimulation. Research on TRD should use internationally defined inclusion criteria for generalizable results.
Psilocybin is an emerging treatment for depression, but its effects on sleep are not well understood. Clinical trials show large improvements in depressive symptoms, but sleep quality or insomnia symptoms have not been directly studied. Preliminary data indicate that both depressive symptoms and sleep disturbances decreased significantly after psilocybin use, though sleep improvements were smaller than those for depression. More severe sleep disturbances at baseline were linked to a lower probability of depression remission, suggesting a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes and lead to more personalized treatment strategies.