International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
Current Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
Abnormalities in glutamatergic neurotransmission are hypothesized to play a role in mood disorders, prompting investigation of NMDA receptor modulators for Major Depressive Disorder (MDD). Intranasal esketamine, an NMDA receptor antagonist, has been developed for treatment-resistant depression (TRD) and for rapidly reducing depressive symptoms, including suicidal ideation, in MDD patients at imminent suicide risk. A systematic review of literature up to October 2019 found that intravenous esketamine elicits rapid and sustained antidepressant effects in refractory patients. Phase II studies showed intranasal esketamine had rapid onset and persistent efficacy in TRD and MDD patients at suicide risk, though phase III data had discrepancies.
Human psychopharmacology
July 1, 2025
Maurizio Pompili, Maria Anna Trocchia, Ludovica Longhini et al.
3 citations
In a real-world outpatient setting, 21 patients with treatment-resistant depression received intranasal esketamine. Depressive symptoms, measured by clinician and self-report scales, decreased at 3-month and 6-month follow-ups. Suicidal ideation significantly declined between baseline and 6 months, and patients also reported reduced hopelessness over time. The findings suggest intranasal esketamine is associated with improvements in depressive symptoms, hopelessness, and suicidal ideation in treatment-resistant depression.
Annals of general psychiatry
March 17, 2025
Maurizio Pompili, Isabella Berardelli, Denise Erbuto et al.
Major depressive disorder (MDD) is a leading cause of disability globally, with prevalence twice as high in women as in men. Mental pain, distinct from depression, is a crucial framework in MDD that may precipitate suicide risk. According to Panksepp's emotional theory, the opioid system influences feelings tied to grief and separation, making it a renewed target for antidepressant treatment. Antidepressants with partial mu-opioid receptor agonism and kappa-opioid receptor antagonism could address unmet needs. The combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment for adults with MDD. It is hypothesized that this combination reduces mental pain by targeting the opioid system, potentially improving treatment outcomes.