The long-standing hypothesis that depression stems from a deficiency in monoamines (serotonin, norepinephrine, dopamine) has guided antidepressant development, but conventional treatments targeting these systems have limitations. The success of ketamine has revived interest in other substances, including the hallucinogen psilocybin (which targets serotonin 5HT2A receptors) and the neurosteroid brexanolone (a GABA-A receptor modulator). Unlike standard antidepressants, these modulators of glutamatergic, serotonergic, and GABAergic systems produce rapid antidepressant effects within 24 hours to a week. Beyond the search for a "miracle" molecule, these new targets may help identify biomarkers for rapid-acting antidepressants and reshape treatment strategies for mood disorders.
Nightmares affect an estimated 34-70% of individuals with psychiatric disorders and are linked to more severe psychopathology, including heightened depressive symptoms and suicidal ideation. Nightmares are independently associated with increased suicide risk, regardless of the underlying diagnosis, underscoring the need to include them in suicide risk assessments. A four-step diagnostic care algorithm is proposed: differentiating Nightmare Disorder from isolated nightmares; assessing the four core dimensions of the disorder; considering differential diagnoses; and identifying predisposing, precipitating, comorbid, and perpetuating factors. Imagery Rehearsal Therapy (IRT) currently stands as the first-line treatment for Nightmare Disorder, though more targeted and personalized therapeutic strategies are needed.