Lithium and clozapine are the only two somatic treatments with high-quality evidence of reducing suicide risk, in mood disorders and schizophrenia respectively; stopping lithium increases that risk. Ketamine and esketamine may offer a small, immediate antisuicide effect, though a disproportionate number of suicides occurred in esketamine-treated subjects versus placebo (3 vs. 0 among over 3500 subjects), requiring ongoing evaluation. The evidence for electroconvulsive therapy's antisuicide effect is low-quality. Antidepressants' effect is unclear: direct evidence shows they may increase suicidal ideation and risk in young people over the short term, while indirect evidence suggests they reduce risk over the long term. Clinicians have an expanding pharmacopeia, but some agents may also increase suicidality under specific circumstances.
MDMA (Ecstasy) is a synthetic amphetamine analogue used recreationally for its mood-enhancing effects, and its use is increasing among young people in Western countries. Unlike traditional drugs of abuse, MDMA dependence and dose escalation are relatively uncommon. However, MDMA is neurotoxic, damaging serotonergic neurons and impairing memory and mood. There are few effective treatments for acute intoxication or the long-term consequences of use. The literature indicates MDMA has a wide range of adverse effects.
Higher baseline levels of anthranilic acid (AA), a metabolite in the kynurenine pathway, predicted remission in patients with treatment-resistant depression receiving intravenous ketamine. In an open-label trial of 74 patients, 52% achieved remission after three infusions. Composite ratios of AA to intercellular adhesion molecule-1 and AA to tryptophan improved predictive accuracy over AA alone. The findings suggest that immunometabolic biomarkers could guide personalized ketamine treatment.
Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.