Quetiapine

Is quetiapine safe?

For its approved uses, quetiapine is an effective and widely prescribed medicine, but it is not a mild one. Sold as Seroquel and Seroquel XR, it is an atypical antipsychotic used for schizophrenia and for the manic and depressive phases of bipolar disorder. The extended-release form is also approved in the US as an add-on for major depression.

It carries two boxed warningsBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary, often causes sleepiness and weight gain, and shifts blood sugar and lipids in some people. Much of its use today is off-label, especially at low doses for sleep and anxiety, where those trade-offs are harder to justify. We score it 55, close to lithium at 51 and below trazodone, another sedating drug used off-label for sleep, at 67.

Weight, blood sugar and other metabolic effects

These are the side effects that shape long-term health. The Seroquel label reports these rates of weight gain of 7% or more of body weight:

Trial group	Quetiapine	Placebo
Schizophrenia, up to 6 weeks	23%	6%
Bipolar mania, up to 12 weeks	21%	7%
Bipolar depression, up to 8 weeks	8%	2%

Fasting glucose moved from normal to diabetic levels in 2.4% of people on quetiapine against 1.4% on placebo in short trials, and lipids rose too. The label asks prescribers to check weight, fasting glucose and lipids before and during treatment. Over years, that combination raises the risk of diabetes and heart disease, so the checks matter more than the short-term numbers suggest.

Sedation, falls and the heart

Sleepiness is the most common effect: 57% of people in the bipolar depression trials reported it, against 15% on placebo. Quetiapine also lowers blood pressure on standing, especially in the first days, and the label warns about falls. It can lower thyroid hormone levels, cause cataracts in long-term use and, rarely, lower white blood cells.

On heart rhythm, the label is cautious rather than alarming. Trials found no persistent QT increase, but cases of QT prolongationQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary have been reported in overdose and in people taking other QT drugs. The label says to avoid combining it with antiarrhythmics such as amiodarone, other antipsychotics and some antibiotics. Tardive dyskinesia (involuntary movements that may be permanent) and neuroleptic malignant syndrome are rare but serious risks shared with other antipsychotics.

The two boxed warnings

The first concerns older people with dementia. In 17 placebo-controlled trials of antipsychotics in dementia-related psychosis, the death rate over about 10 weeks was 4.5% on the drug against 2.6% on placebo, mostly from heart failure, sudden death or pneumonia. Quetiapine is not approved for this use.

The second is the antidepressant class warning: because quetiapine is approved for bipolar depression, it carries the warning about suicidal thoughts and behaviour in children, teenagers and young adults. Seroquel is not approved for children under 10.

Off-label use for sleep and misuse

Quetiapine at doses well below the antipsychotic range is widely prescribed for insomnia, partly because it is not a controlled substanceControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary like zolpidem or benzodiazepines. A 2021 review in the Cleveland Clinic Journal of Medicine found scant evidence for this use and pointed to weight gain, metabolic effects and abuse as reasons for caution.

Misuse is real, though less common than with controlled drugs. US emergency visits involving quetiapine rose from 35,581 in 2005 to 67,497 in 2011, and in Victoria, Australia, quetiapine-related deaths rose 7.4-fold between 2006 and 2016 as prescriptions grew. Most harm comes from overdose, often with alcohol or other drugs. In the label's trials, people survived overdoses of up to 30 g, but one person died after 13.6 g of quetiapine alone.

Who should be careful

Talk to your doctor or pharmacist before starting quetiapine, or before adding another medicine, if you:

• are older, have dementia, or are at risk of falls
• have diabetes, high cholesterol, obesity or heart disease
• have a heart rhythm problem or take other QT-prolongingQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary drugs
• take antifungals, HIV medicines, carbamazepine, phenytoin or St John's wort, which change quetiapine levels a lot
• drink alcohol regularly or take other sedatives or opioids
• have a history of seizures, low white cell count, glaucoma or urinary retention
• are under 25 or have had thoughts of self-harm

Do not stop quetiapine suddenly: in XR trials, 12.1% had discontinuation symptoms such as insomnia, nausea and vomiting. A lower score is no reason to stop a medicine that keeps a serious illness under control; talk to your prescriber first. For an overdose, call Poison Help on 1-800-222-1222 in the US or 999 in the UK.

How we scored it

Track record (88) is solid. Regulatory warnings (35) reflect the two boxed warningsBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary, and serious side effects (45) the frequent weight gain, metabolic changes and sedation. Interactions (50) are driven by large CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary effects and sedative combinations, and dependence (65) by documented misuse despite no controlled status.