Trazodone

Is trazodone safe?

It is reasonably safe for most adults, but it is not the gentle sleep aid its reputation suggests. Trazodone was approved in the US in 1981 as an antidepressant (brand Desyrel). Today it is the 20th most prescribed US medicine, with about 26.2 million prescriptions in 2024 (ClinCalc), and much of that use is low doses at bedtime for insomnia, which the FDA has never approved. We score it 67, below sertraline but well above zolpidem.

The appeal is real: 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, is rarely misused and does not cause the dependence seen with benzodiazepines and Z-drugs. The trade-off is a long label of uncommon but serious effects, from heart rhythm problems to priapism, and interactions with many common medicines.

Trazodone for sleep: what the evidence says

Trazodone makes people drowsy. In the label's trials, 41% of outpatients reported drowsiness against 20% on placebo, and 28% reported dizziness against 15%. Doctors use that side effect deliberately, usually at doses well below the antidepressant range.

Whether it helps insomnia over months is less clear. A 2018 Cochrane review pooled three trials of 370 people and found a moderate improvement in self-reported sleep quality, but rated the evidence low quality, and two lab studies showed little change in sleep efficiency. In 2017 the American Academy of Sleep Medicine suggested that clinicians not use trazodone for chronic insomnia. If you are taking trazodone for sleep, it is a fair question for your next review.

The serious side effects

• Heart rhythm. Trazodone lengthens the QT intervalQT 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. The label reports torsade de pointes, a dangerous arrhythmia, even at 100 mg or less, and says to avoid it in people with a history of arrhythmias, low potassium or magnesium, or congenital long QT, and in the early recovery phase after a heart attack.
• Priapism. Rare painful erections can permanently damage erectile tissue. An erection lasting more than 4 hours is an emergency. Men with sickle cell disease, multiple myeloma, leukaemia or Peyronie's disease need extra care.
• Low blood pressure and fainting. Dizziness on standing is common, and in older people it can mean falls, especially at night.
• Serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary. Agitation, fever, sweating, shaking and a racing heart can occur, mostly when trazodone is combined with other serotonergic drugs.
• Suicidal thoughts in young people. Like all antidepressants, trazodone carries a boxed warningBoxed 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. In pooled trials, antidepressants caused about 14 extra cases of suicidal thoughts or behaviour per 1,000 under-18s and 5 per 1,000 people aged 18 to 24, with fewer cases than placebo in older adults. Trazodone is not approved for children.

Interactions that matter

Trazodone is broken down by the liver enzyme 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 and affects serotonin, heart rhythm and alertness, so the interaction list is long.

Trazodone is often prescribed alongside an SSRI to help sleep. That combination is common and can be appropriate, but it is exactly where serotonin syndrome and QT effects add up, so both prescribers and the pharmacist should know about both drugs.

Who should be careful

• People with heart disease, a known long QT intervalQT 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, or low potassium or magnesium.
• Older adults, because of falls, low blood pressure and confusion.
• Anyone under 25, or with a history of bipolar disorder, which the label says to screen for before starting.
• People who drink alcohol regularly or take other sedatives.
• Anyone taking an MAOI, another antidepressant, an anticoagulant or a strong 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 inhibitor.

Do not drive until you know how trazodone affects you the next morning. If you want to stop, ask your doctor or pharmacist about tapering rather than stopping suddenly. Some people look at melatonin instead; it has its own evidence and limits.

How we scored it

Dependence (85) and track record (88) are trazodone's strengths, and it scores far better than zolpidem on misuse. Regulatory warnings (50) reflects the boxed warningBoxed 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, interactions (52) the serotonin, QT and 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 list, and serious side effects (62) the mix of rare but serious heart, priapism and fall risks against a backdrop of very common drowsiness.