A common medication taken by about two million Americans, often off-label as a sleep aid, has been shown to cause potentially dangerous side effects that persist into the next day. The antipsychotic drug quetiapine, sold as Seroquel, is approved to treat schizophrenia and bipolar disorder, but it is frequently prescribed off-label for insomnia. Approximately 75 percent of patients who take quetiapine receive it for sleep-related issues rather than its approved uses.
World-First Clinical Trial Reveals Lingering Effects
Now, a world-first clinical trial from Australia has found that in people who take quetiapine at bedtime, the drug's effects linger into the next morning, significantly reducing alertness and driving performance. Researchers at Flinders University discovered that while a low, 50-milligram dose of quetiapine modestly improved sleep quality and slightly reduced the severity of obstructive sleep apnea (OSA), it also caused notable next-day drowsiness and impaired driving ability.
In the United States alone, low-dose quetiapine is prescribed more than 10 million times each year. Previous research has shown that taking antipsychotic medications off-label for insomnia and milder sleep issues can lead to unpleasant morning-after effects, including reduced breathing and poor work performance.
Growing Concerns Over Safety
The new findings add to growing concerns about the drug's safety, particularly for people who drive or operate machinery the morning after taking it. 'There is a growing belief that low-dose quetiapine is a relatively harmless way to help people sleep,' said Dr. Cricket Fauska, lead author of the study from Flinders University. 'Our results show it is not that simple.'
He added that, even though participants experienced longer sleep duration and fewer nighttime awakenings, they showed slower reaction times and a clear decline in simulated driving performance the following morning.
How Quetiapine Works
Quetiapine is an atypical antipsychotic, meaning it belongs to a newer class of antipsychotic drugs that differ from older 'typical' antipsychotics in their receptor-binding profile and generally cause fewer movement-related side effects, such as tardive dyskinesia. At low doses, however, quetiapine is frequently prescribed off-label for insomnia due to its potent antihistamine effects. The drug works primarily by strongly blocking histamine H1 receptors in the brain, the same mechanism behind many first-generation antihistamines found in sleep aids.
By binding to and blocking these receptors, quetiapine reduces wakefulness and promotes sedation, helping people fall and stay asleep. However, this histamine blockade also explains the significant next-day sedation and cognitive impairment observed in studies, including this latest one, as the drug's effects can linger well beyond the sleep period. Unlike traditional sleep medications that target GABA receptors, quetiapine's broader receptor profile can also lead to side effects such as weight gain or metabolic changes, even at low doses.
Study Details and Findings
In the latest study, published in the Annals of the American Thoracic Society, researchers at Flinders University in Australia conducted a small but rigorous trial involving 15 people with both obstructive sleep apnea (OSA) and difficulty staying asleep. Each participant spent two separate nights in a sleep lab, about a week apart. Before bed on one night, they took a 50 mg dose of quetiapine; on the other night, they took a placebo pill. Neither the participants nor the researchers knew which pill was given on which night.
The next morning, about 8.5 to 9.5 hours after taking the medication, everyone completed a 10-minute reaction-time test and a 30-minute driving-simulator task designed to mimic a monotonous rural night drive.
The drug showed mixed effects. On the positive side, compared to placebo, quetiapine reduced the frequency of breathing pauses (the apnea-hypopnea index) by about 24 percent and improved sleep efficiency, meaning people spent more time actually asleep and less time awake during the night. However, the downsides were significant. The next morning, participants had slower reaction times on the vigilance test. On the driving simulator, their ability to stay centered in their lane worsened substantially, and they crashed nearly twice as often, with 55 crashes after quetiapine compared to 27 after placebo, though the crash increase was not statistically conclusive.
Safety Recommendations
'What was particularly concerning is that some people did not feel especially sleepy the next day, despite performing worse on objective tests,' Fauska said. 'That mismatch between how people feel and how they actually function poses a serious safety risk, especially when it comes to driving.'
The study's authors concluded that while a low dose of quetiapine may offer modest overnight benefits for sleep and breathing, it clearly impairs next-day alertness and driving ability. They warned that people should avoid driving or performing other safety-sensitive tasks for at least 9.5 hours after taking the drug.
'What we are learning is that treatment needs to be tailored – using the right approach, or combination of approaches, for the individual rather than defaulting to sedating medications,' said Flinders University sleep health professor and senior author Dr. Danny Ecker.
