There is a lack of data on participants displaying suicidality in antidepressant clinical trials, according to study data published in the Journal of Clinical Psychiatry. Of all the antidepressant efficacy trials conducted between 1991 and 2013, just 1 explicitly included patients who presented with suicidality. As such, antidepressant safety and efficacy data from these trials may not be applicable to patients with more severe depression.
Investigators assessed the inclusion and exclusion criteria of antidepressant efficacy trials for US Food and Drug Administration (FDA)-approved drugs between 1991 and 2013. The relevant efficacy trials were identified by reading FDA labels. For drugs approved after 1998, labels were publicly available on the FDA website. For drugs approved prior to 1998, a Freedom of Information Act request was filed, after which drug label information was supplied. The trials described on the FDA labels were identified via a PubMed search using drug and trial names as keywords. Publications were classified into 4 categories: (1) trials which did not mention suicidality in inclusion or exclusion criteria; (2) trials which excluded patients with suicidality but did not report use of a suicidality metric; (3) trials which excluded patients with suicidality and reported use of at least 1 instrument to assess suicidality; and (4) trials which explicitly included patients with suicidality. Qualifying instruments included the Montgomery-Asberg Depression Rating Scale, Hamilton Depression Rating Scale, Columbia-Suicide Severity Rating Scale, and Mini-International Neuropsychiatric Interview.
A total of 36 publications were associated with drugs approved between 1991 and 2000. Of these, 26 did not mention suicidality in the inclusion or exclusion criteria, 7 excluded patients with suicidality but did not describe assessing suicidality with an instrument, and 2 excluded patients with suicidality following the use of an instrument. Just 1 study reported including patients with suicidality. For drugs approved from 2000 through 2013, 28 publications were identified. Of these, 4 did not mention suicidality in the inclusion or exclusion criteria, 12 excluded patients with suicidality and did not report measuring suicidality with an instrument, and 12 excluded patients with suicidality and reported measuring suicidality with an instrument. None of the 28 studies reported including patients with suicidality.
The apparent increase in the use of validated instruments to measure suicidality may represent the “use of more rigorous, systematic exclusion criteria” in clinical trials, the investigators wrote. While improvements in scientific rigor are important, the consistent exclusion of patients with suicidality limits data generalizability. Safety and efficacy data abstracted from these trials may not be applicable to patients with more severe depression. While exclusion of patients can be warranted in some scenarios, investigators should “offer…robust justification for exclusion,” the researchers wrote. Further, to reduce health inequities, trial designs should seek to accommodate all patient subgroups so that medication safety and efficacy data can be extrapolated to as many persons as possible.
Disclosure: One study author declared affiliations with the pharmaceutical industry.
Please see the original reference for a full list of authors’ disclosures.
Iltis AS, McCall WV, Deria R. Suicidality, depression, and the FDA: health inequities and the ethical conduct of research. J Clin Psychiatry. 2020;81(2).