Objective A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behaviour. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method Here, we examine this issue through two approaches: (i) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments; and (ii) by pooling data (N~6,000 participants) from cohorts from the ENIGMA-Major Depressive Disorder (ENIGMA-MDD) and ENIGMA-Suicidal Thoughts and Behaviour (ENIGMA-STB) working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behaviour. Results Our results suggested a pattern of moderate-to-high correlations between instruments, consistent with the wide range of correlations, r=0.22-0.97, reported in the literature. Two common complex instruments, the Columbia Suicide Severity Rating Scale (C-SSRS) and the Beck Scale for Suicidal Ideation (SSI), were highly correlated with each other (r=0.83), as were suicidal ideation items from common depression severity questionnaires. Conclusions Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behaviour, but share a core factor with single suicidal ideation items found in depression severity questionnaires. Multi-site collaborations including cohorts that used distinct instruments for suicide risk assessment should be feasible provided that they harmonise across instruments or focus on specific constructs of suicidal thoughts or behaviours.

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Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant effects as well as high remission rates, making them attractive therapeutic options. This chapter reviews the evidence for the antidepressant efficacy of several novel therapeutics, including ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine, as well as interventional techniques such as sleep deprivation. Notably, ketamine and esketamine also rapidly reduce suicidal thoughts, making them attractive solutions in an emergency setting. Because studying the rapid onset of antidepressant effects associated with these agents has also improved our understanding of the neurocircuitry and neural signaling systems underlying MDD, some pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed.