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As companies race to develop fast-acting antidepressants, they are grappling with how to design clinical trials for a type of drug that doesn’t yet exist.

There’s no shortage of interest in the idea: Janssen (JNJ) is testing an esketamine nasal spray, which, when combined with an oral antidepressant, has shown promise in quickly curbing symptoms of serious depression and is also being tested in patients at risk of suicide. Allergan (AGN) is developing its own experimental rapid-acting antidepressant, rapastinel, for patients with major depression and those at high risk of suicide. Both act on the brain’s NMDA receptor, which is involved in learning and memory.

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