Sleep aid taken by 2 million people ‘significantly’ impairs next-day function, world-first study finds
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 drag into the next day.
The antipsychotic drug quetiapine, sold as Seroquel, is approved to treat schizophrenia, but it is frequently prescribed off-label for insomnia. About 75 percent of patients who take quetiapine receive it for sleep-related issues, not for its approved uses.
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 found 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 US 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.
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’s a growing belief that low-dose quetiapine is a relatively harmless way to help people sleep,’ Dr Cricket Fauska, lead author of the study from Flinders University, said. ‘Our results show it’s not that simple.’
Quetiapine (sold as Seroquel) is approved for schizophrenia and bipolar disorder, but it’s prescribed off-label for insomnia in about 75 percent of patients (stock image)
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.
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 a disorder called 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.
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.
Earlier studies have found that using antipsychotic drugs off-label for insomnia or minor sleep problems can cause unpleasant next-day effects, such as shallow breathing and impaired work performance
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 — known as 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.
Each line represents one participant. The left end shows their steering deviation after placebo; the right end after quetiapine. Lines angling upward mean driving got worse. The purple arrow marks the average for healthy drivers, about 30–40 cm. Quetiapine worsened average steering by 24 cm (72 vs. 96), but individual results varied widely
Each line represents a person in the study The left end of the line shows their reaction time after taking placebo. The right end shows their reaction time after taking quetiapine. On a 10-minute reaction time test, participants who took quetiapine were significantly slower to respond than those who took a placebo — 382 milliseconds versus 336 milliseconds. The wide range of results also suggests some people are far more impaired than others
‘What was particularly concerning is that some people didn’t 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’re 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.
