Cases of completed suicides and attempted suicides with the insomnia drug Belsomra have raised concerns with the Institute for Safe Medication Practices (ISMP) in its QuarterWatch review. The organization monitors Food and Drug Administration (FDA) MedWatch adverse event reports each quarter.
Belsomra was approved by the FDA in 2014. It contains the active ingredient suvorexant, which works by blocking two newly discovered neurotransmitters called orexins. Neurons that emit orexin send wakefulness signals to the complex neural circuits that regulate sleep and waking cycles. Belsomra was developed under the idea that blocking these wakeful signals at night would help people sleep.
During clinical trials testing the drug’s safety and effectiveness, the FDA required the use of a specialized assessment tool to systematically query every Phase 3 study participant in order to more accurately assess the risk of suicidal thoughts and behavior. At a higher-than-approved dose, eight cases of suicidal ideation was identified compared to none in a group taking a placebo. Based on this and other clinical trial results, the FDA required a warning about suicidal ideation and depression be added to the drug.
During its most recent analysis of 12 months of the FDA’s adverse event data, ISMP found evidence that not only confirmed the suicidal ideation risk with Belsomra, but also extended it. Among 2,290 adverse event reports linked to the drug, there were eight completed suicides, 11 attempted suicides, and 19 reports of suicidal ideation.
ISMP reported, “In a case examined in detail later and reported to the FDA MedWatch program, a 56-year-old IT specialist became aggressive and hostile to his wife soon after receiving free 20 mg suvorexant sample packs from his physician. This behavior was not typical for him. Relations were severely strained after he struck her without provocation one weekend night, something he had never done before. A few days later he committed suicide with a gun in a shed behind the house.”
After further review, it was found that missing doses may contribute to this risk. “Because of FDA concerns that suvorexant could impair next-day alertness, patients were warned not to take suvorexant unless they could remain in bed for at least 7 hours. The patient in this suicide case frequently missed doses because of his job, and told his doctor his emotional problems appeared on days he didn’t take suvorexant. He assaulted his wife on a day after he had skipped his dose. In addition, the FDA reviews describe two clinical trial cases of suicidal ideation that also occurred after treatment was interrupted.”
Because of the small number of cases, the risk of suicidal ideation with a missed dose or discontinuation of Belsomra should be a warning flag worth investigating further, ISMP noted. “If this is an important event feature, it is likely to have been underestimated in clinical studies because patients were encouraged to take the drug without interruption during the treatment period.”