Do beta blockers cause sleep problems? Insomnia, nightmares and night waking: what the studies show

Yes, and their leaflets say so: with bisoprolol, sleep disorders are classed as “uncommon” and nightmares as “rare”¹. Most people on treatment sleep without difficulty, but insomnia that appears with treatment is not imagined.

The bisoprolol summary of product characteristics spells out what these words mean. An uncommon effect affects between 1 in 1,000 and 1 in 100 people, a rare effect between 1 in 10,000 and 1 in 1,000. The same section lists depression among uncommon effects, and hallucinations, along with nightmares, among rare effects¹.

Double-blind trials make it possible to separate what is due to the drug from what would have happened on placebo. In 2021, a team at the Charité in Berlin pooled 285 such trials, covering 53,533 patients. Depression, although the most frequently reported psychiatric effect with 1,600 cases, was no more frequent on beta blockers than on placebo (odds ratio 1.02). Among the other psychiatric effects, only unusual dreams, insomnia and sleep disorders appeared possibly linked to treatment. The authors rate the risk of bias as high in 79% of the included trials².

Several studies have measured a fall in the melatonin produced at night after taking certain beta blockers. The pineal gland makes this hormone mainly at night, in response to stimulation of beta-1 and alpha-1 adrenergic receptors, and beta blockers block the former³.

In 1999, a team in Graz gave 15 healthy volunteers a single dose of different drugs at 6 pm, in random order and double-blind. It measured the main breakdown product of melatonin in overnight urine. Mean excretion reached 26 µg on placebo, compared with 5 µg with the active form of propranolol (−80%) and 4 µg with that of atenolol (−86%). The inactive forms of the same molecules changed nothing. Carvedilol, which blocks both alpha and beta receptors, did not significantly lower melatonin (−10%)³.

In 2006, the same team compared three beta blockers prescribed for heart failure in 16 healthy men, for one week each. Bisoprolol reduced night-time melatonin release by 44%, whereas nebivolol and carvedilol had no measurable effect⁴. The Boston team that ran the melatonin trial in patients on beta blockers points out that the pineal gland lies outside the barrier that protects the brain: a beta blocker with low fat solubility can therefore act on it as much as a lipophilic one⁵.

Small studies have linked nightmares and restless nights on beta blockers with lower night-time melatonin, without being able to establish that this fall is the cause.

In 1987, Swedish researchers compared six patients who had nightmares or hallucinations on beta blockers with six patients on the same treatment without these symptoms. Night-time melatonin excretion was lower in all the symptomatic patients⁶. The following year, the same team followed hypertensive patients for four weeks. All the beta blockers tested reduced melatonin excretion, but the fall was significant only with metoprolol (13 patients, 197 mg a day on average). Disturbed nights were more common in this group, their proportion tracked the size of the fall in melatonin, and severe effects such as nightmares affected only patients on metoprolol (21% of them), always with low melatonin⁷.

An Australian study set out to see whether the phenomenon could be reversed. In 8 young men, a single 100 mg dose of atenolol lengthened time spent awake and shortened deep sleep and REM sleep. Taking melatonin (5 mg in total) after the atenolol corrected these changes. In a second part, in 10 young men, atenolol lengthened the time taken to fall asleep, and 3 mg of melatonin brought it back to its baseline value⁸. These volunteers were young and healthy, and each test covered only one night.

Current data do not allow beta blockers to be reliably ranked by risk of insomnia, and the data that concern bisoprolol directly remain thin.

The most widespread hypothesis concerns lipophilicity, that is, a molecule’s ability to dissolve in fats and cross the barrier surrounding the brain. Propranolol and metoprolol are lipophilic, atenolol is hydrophilic. In a 1987 double-blind trial, 30 healthy men took four beta blockers and a placebo in turn, for one week each. The number of awakenings recorded in the sleep laboratory was 6.3 on propranolol and 7.2 on metoprolol, compared with 3.6 on atenolol and 3.9 on placebo⁹. A 1990 review of all the studies comparing these molecules found the same order: nervous system effects that were mild overall, rarer with atenolol, more frequent with propranolol, with metoprolol in between. Its two authors worked for the company that marketed atenolol¹⁰.

Other results qualify this ranking. In the 1988 Swedish study, the fall in melatonin was significant only with metoprolol, and nightmares affected only patients on metoprolol, none on propranolol, although it is more lipophilic, even though the two groups differed in size and protocol⁷. A meta-analysis of 15 large trials found no difference in fatigue, depressive symptoms or sexual problems according to how fat-soluble the beta blocker was¹¹. Bisoprolol reduces night-time melatonin in the Graz study⁴, and its leaflet lists sleep disorders among uncommon effects¹. These findings do not say whether it disturbs sleep more or less often than another molecule.

Insomnia, repeated waking or nightmares that appear after starting treatment or after a dose increase are worth mentioning to the doctor or pharmacist, even if they seem minor.

The doctor has several levers that only they can use: the dose, the molecule, sometimes another class of drug depending on the condition being treated. The studies cited above show that not all beta blockers act in the same way on night-time melatonin³⁴. It helps them to know when the problems started, whether they affect falling asleep or rather the second half of the night, and whether other medicines or supplements have been added in the meantime.

Some signs warrant prompt medical advice. The bisoprolol leaflet lists among rare effects hallucinations and nightmares, and among uncommon effects depression¹. A darkening mood, visions at night or unusual daytime drowsiness should be reported without waiting for the next appointment.

No: a beta blocker is never stopped abruptly and never without medical advice, even when it is blamed for sleepless nights.

The bisoprolol leaflet states that treatment must not be stopped suddenly, particularly in coronary heart disease, as stopping can lead to a temporary worsening of the disease. When stopping is decided, the dose is reduced gradually¹. A US case-control study of 248 hypertensive patients with a first episode of coronary heart disease and 737 controls measured a relative risk of 4.5 (95% confidence interval: 1.1 to 18.5) in patients who had recently stopped renewing their beta blocker regularly. This increase was transient and specific to beta blockers; it did not occur with diuretics¹².

The melatonin route, for its part, has been tested in a randomised trial in hypertensive patients on atenolol or metoprolol: three weeks of melatonin in the evening lengthened their sleep by 36 minutes compared with placebo⁵. This trial, its doses and its limitations are covered in a separate article. Any decision, whether to change treatment or to add a supplement on top, is made with the doctor or pharmacist.