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Research · Medication

Benzodiazepines

Meta-analyses found benzodiazepines raised response in panic disorder, with about 4 people treated for one extra response, lowered generalized anxiety symptoms and added about an hour of sleep in short trials. Drowsiness was very common. FDA's boxed warnings cover use with opioids, addiction, dependence and withdrawal. Observational studies linked use to falls, hip fractures and road crashes.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US and Schedule IV controlled substances. FDA-approved uses differ by drug: alprazolam for generalized anxiety disorder and panic disorder, clonazepam for panic disorder and some seizure disorders, lorazepam for anxiety disorders and short-term relief of anxiety symptoms, and diazepam for anxiety, acute alcohol withdrawal, muscle spasm and seizure disorders. Every label carries an FDA boxed warning on use with opioids, on abuse, misuse and addiction, and on dependence and withdrawal.
Also called
benzos, alprazolam, Xanax, Xanax XR, clonazepam, Klonopin, lorazepam, Ativan, diazepam, Valium, anxiolytics, sedative-hypnotics
Taken for
anxiety, panic attacks, insomnia, sleep, social anxiety, alcohol withdrawal, seizures, muscle spasm, back pain

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks19

What people take it for, and what was found

Shown to help6

StrongVery common

Panic disorder

Shown to raise response in panic disorder, with about 4 treated for one extra response in short trials that reviewers rated low quality.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Response was more likely on a benzodiazepine than placebo (RR 1.65, 95% CI 1.39 to 1.96), a number needed to treat of 4 (95% CI 3 to 7). Remission was also more likely (RR 1.61, 95% CI 1.38 to 1.88), and fewer people dropped out than on placebo (RR 0.50, 95% CI 0.39 to 0.64) [1]. In a network meta-analysis, benzodiazepines raised remission against placebo (RR 1.47, 95% CI 1.36 to 1.60) and ranked first among drug classes for remission. Adverse events were also more frequent than on placebo (RR 1.76, 95% CI 1.50 to 2.06) [2]. In the clonazepam label trials, 74% on 1 mg a day were free of full panic attacks against 56% on placebo in one study, and 62% against 37% in the other [3].
Population
4,233 adults in 24 studies [1]; 12,800 participants in 87 studies of 12 drug classes [2]; adults with panic disorder in two trials of 6 to 9 weeks [3].
Sources
[1], [2], [3]
Caveats
The Cochrane review rated the evidence low quality and judged 20 of 24 studies at high risk of bias in at least one area [1]. Almost every study in the network analysis had some concern over bias [2]. Trials were short.
Strong

Generalized anxiety

Shown to reduce generalized anxiety symptoms more than placebo in short trials, with a moderate effect size of 0.50.

The numbers and sources
Effect
Across 23 trials, benzodiazepines lowered generalized anxiety symptoms against placebo with an effect size of 0.50, larger than for SSRIs (0.33) or SNRIs (0.36) [4]. In 23 trials of diazepam, lorazepam or alprazolam, fewer people stopped for lack of effect than on placebo (RR 0.29, 95% CI 0.18 to 0.45), while stopping for any reason did not clearly differ (RR 0.78, 95% CI 0.62 to 1.00) [5]. A network meta-analysis found benzodiazepines lowered anxiety scores more than placebo and had more dropouts than placebo [6].
Population
1,149 participants on benzodiazepines in 23 trials, within 56 studies of 12,655 adults [4]; 23 trials against placebo [5]; 25,441 adult outpatients in 89 trials [6].
Sources
[4], [5], [6], [7], [8]
Caveats
Effect sizes fell with later year of publication [4], and year of publication explained 74% of the variation between trials [5]. The trials were short. The lorazepam and diazepam labels state that use beyond 4 months has not been assessed [7][8].
Strong

Insomnia

Shown to lengthen sleep by about an hour and shorten the time to fall asleep by 4 to 20 minutes in short trials, with more daytime drowsiness.

The numbers and sources
Effect
Against placebo, benzodiazepines increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Sleep latency on sleep records fell by 4.2 minutes, which was not significant, and by 14.3 minutes in patients' own estimates [9]. A later meta-analysis found sleep latency fell by 10.0 minutes on sleep-lab recordings (95% CI 3.4 to 16.6) and 19.6 minutes in sleep diaries, with a higher risk of harm than placebo (risk difference 0.15) [10]. A network meta-analysis found benzodiazepines among the drugs that beat placebo for acute insomnia, and among those with more side effects than placebo [11]. In people over 60, sedatives added 25.2 minutes of sleep and a small gain in sleep quality (effect size 0.14) [12].
Population
Randomized trials of benzodiazepines for insomnia [9]; 105 studies of drugs for chronic insomnia [10]; 44,089 participants in 154 trials of 30 drugs [11]; 2,417 people aged 60 and older in 24 studies [12].
Sources
[9], [10], [11], [12], [7]
Caveats
The pooled trials cover benzodiazepines as a class, including sleep drugs outside this page, and the abstracts do not break results down by drug. Of the four labels cited here, only lorazepam's mentions insomnia, as insomnia due to anxiety or passing stress [7]. Trials were short. See rebound insomnia under Risks.
Limited

Social anxiety

Small trials found response in social anxiety disorder about 4 times as likely on a benzodiazepine as on placebo, in 132 people.

The numbers and sources
Effect
In two studies, treatment response was more likely on a benzodiazepine than placebo (RR 4.03, 95% CI 2.45 to 6.65) [14].
Population
132 adults in 2 studies within a Cochrane review of 66 trials [14].
Sources
[14]
Caveats
Low-quality evidence from two small studies. The review authors asked readers to weigh the finding against the potential for abuse [14]. Not a labeled use of the four drugs on this page.
Moderate

Alcohol withdrawal

Shown to cut seizures during alcohol withdrawal, with a risk ratio of 0.16 against placebo in three studies.

The numbers and sources
Effect
Against placebo, benzodiazepines lowered the risk of withdrawal seizures (RR 0.16, 95% CI 0.04 to 0.69), with no significant difference on the other outcomes examined. No one benzodiazepine differed significantly from another [15].
Population
324 participants in 3 placebo-controlled studies, within a Cochrane review of 64 studies and 4,309 participants [15].
Sources
[15], [8]
Caveats
A supervised medical setting. Among the four drugs here, the label for diazepam lists acute alcohol withdrawal as a use [8].
Moderate

Stopping a prolonged seizure

Shown to stop prolonged seizures more often than placebo when given by vein in hospital, with lorazepam ahead of diazepam.

The numbers and sources
Effect
In status epilepticus, intravenous diazepam lowered the risk of seizures not stopping against placebo (RR 0.73, 95% CI 0.57 to 0.92), as did intravenous lorazepam (RR 0.52, 95% CI 0.38 to 0.71). Lorazepam did better than diazepam (RR 0.64, 95% CI 0.45 to 0.90) [16].
Population
2,755 participants in 18 studies of status epilepticus [16].
Sources
[16]
Caveats
Emergency treatment by injection, not the tablets most people are prescribed. Few studies used the same comparison [16].

Mixed results1

Moderate

Anxiety treatment beyond three months

Mixed results: in trials of 13 weeks or more, anxiety scores did not differ from placebo, while fewer people stopped a benzodiazepine than placebo.

The numbers and sources
Effect
In 8 studies lasting 13 weeks or more, the change in Hamilton Anxiety scores did not differ significantly between benzodiazepines and placebo. Fewer people discontinued a benzodiazepine than placebo, and constipation and dry mouth were more frequent. Among people who had responded in the first 8 weeks, benzodiazepines and antidepressants did not differ on any outcome [13].
Population
1,228 people with anxiety disorders in 8 randomized or maintenance studies [13].
Sources
[13]
Caveats
Few studies. The abstract gives no effect sizes [13].

Not shown to help1

Limited

Acute low back pain

One trial found diazepam added to naproxen did not improve acute low back pain or function more than placebo at one week or three months.

The numbers and sources
Effect
Disability scores improved by 11 points in both the diazepam and placebo groups at one week. Moderate or severe pain at one week was reported by 32% on diazepam and 22% on placebo, and at three months by 12% and 9%. Adverse events were reported by 21% on diazepam and 15% on placebo [17].
Population
114 emergency department patients with acute low back pain, all given naproxen [17].
Sources
[17], [8]
Caveats
One trial of 114 people. The diazepam label lists muscle spasm as an add-on use [8].

Doses studied

The alprazolam label lists 0.25 to 0.5 mg three times daily to start for generalized anxiety, up to 4 mg a day, and states that panic disorder trials used 1 to 10 mg a day with a mean of about 5 to 6 mg [18]. The clonazepam label describes a fixed-dose panic trial in which 1 mg a day did as well as 2, 3 or 4 mg with fewer adverse effects, and a flexible-dose trial with a mean of 2.3 mg a day [3]. The lorazepam label gives a usual range of 2 to 6 mg a day in divided doses [7]. The diazepam label lists 2 to 10 mg two to four times daily for anxiety [8].

In the abrupt discontinuation study, long-term users were taking a mean of 14.1 mg a day in diazepam equivalents [19].

Risks

Reported risks15

ModerateVery common

FDA boxed warning: dependence and withdrawal

FDA states continued use may lead to physical dependence, and abrupt stopping may bring life-threatening withdrawal. One study found withdrawal reactions in 58% to 100% of long-term users.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
The boxed warning states that the risks of dependence and withdrawal rise with longer treatment and higher daily dose, and that abrupt discontinuation or rapid dose reduction may precipitate acute withdrawal reactions, including seizures. The label also describes a protracted withdrawal syndrome lasting weeks to more than 12 months [18]. When long-term users were switched blind to placebo, 58% to 100% were judged to have a withdrawal reaction, depending on the criteria used, peaking at 2 days for short half-life drugs and 4 to 7 days for long half-life drugs [19]. FDA wrote that physical dependence can occur after several days to weeks of steady use, even as prescribed. In its series of 104 reports, about 80% described withdrawal, with symptoms lasting from weeks to years [22].
Population
57 people who had taken a benzodiazepine daily for more than a year, 47 switched to placebo [19]; 104 reports to FDA from 1968 to 2019 [22].
Sources
[18], [19], [22]
Caveats
The discontinuation study stopped the drug abruptly in people who had used it for over a year, so the band above applies to that setting. FDA described epidemiologic data on dependence and withdrawal as scarce, and no systematic review giving a pooled withdrawal rate was located. Withdrawal symptoms can be hard to tell from the return of the original condition [22].
ModerateVery common

Drowsiness and poor coordination

Shown to cause drowsiness, in 41% on alprazolam against 22% on placebo in anxiety trials, and impaired coordination in 40% against 18% in panic trials.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In alprazolam anxiety trials, drowsiness occurred in 41% against 22% on placebo. In its panic disorder trials, at higher doses, drowsiness occurred in 77% against 43%, impaired coordination in 40% against 18% and slurred speech in 23% against 6% [18]. In clonazepam panic trials, somnolence occurred in 37% against 10% and ataxia in 5% against 0 [3]. Among about 3,500 people treated with lorazepam, sedation was reported by 15.9%, dizziness by 6.9% and unsteadiness by 3.4%, rising with age [7]. In insomnia trials, daytime drowsiness and dizziness were more frequent than on placebo (OR 1.8, 95% CI 1.4 to 2.4) [9].
Population
565 adults on alprazolam and 505 on placebo in anxiety trials, 1,388 and 1,231 in panic trials [18]; 574 on clonazepam and 294 on placebo [3]; about 3,500 patients on lorazepam [7]; trials of benzodiazepines for insomnia [9].
Sources
[18], [3], [7], [9]
Caveats
The lorazepam figures have no placebo comparison. The labels state that these effects are dose dependent.
StrongVery common

Memory and thinking

Shown to impair memory in trials, in 33% on alprazolam against 22% on placebo, and linked to poorer cognition in long-term users.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In alprazolam panic trials, memory impairment was reported by 33% against 22% on placebo, and cognitive disorder by 29% against 21% [18]. In people over 60 taking sedatives for sleep, adverse cognitive events were 4.78 times as frequent as on placebo (95% CI 1.47 to 15.47) [12]. Long-term users performed worse than controls in every cognitive domain tested, with a mean weighted effect size of -0.74 [23]. An updated meta-analysis found deficits in working memory, processing speed, divided attention and recent memory in current users, and deficits that remained in people who had stopped [24].
Population
1,388 adults on alprazolam and 1,231 on placebo [18]; 2,417 people aged 60 and older in 24 studies [12]; long-term users with a mean of 9.9 years of use compared with controls [23]; studies of current and former long-term users [24].
Sources
[18], [12], [23], [24]
Caveats
The long-term comparisons are not randomized, so differences between users and controls may reflect the conditions being treated. The studies were small [23].
LimitedVery common

Rebound insomnia after stopping

The alprazolam label reports insomnia in 29.5% of people after discontinuation in its panic disorder studies, more than after placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Among 641 people who had received alprazolam for panic disorder, symptoms emerging on discontinuation included insomnia (29.5%), lightheadedness (19.3%), anxiety (19.2%), fatigue (18.4%), headache (17.0%), nausea or vomiting (16.5%) and sweating (14.4%). The label states each occurred more often than after placebo and does not give the placebo rates [18].
Population
641 patients in controlled and uncontrolled alprazolam studies [18].
Sources
[18]
Caveats
The data mix controlled and uncontrolled studies, and placebo rates are not shown.
ModerateVery common

Sexual side effects

Shown to raise reports of decreased libido, in 14% on alprazolam against 8% on placebo in panic trials, and of sexual dysfunction in 7% against 4%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In alprazolam panic disorder trials, decreased libido was reported by 14% against 8% on placebo, increased libido by 8% against 4%, sexual dysfunction by 7% against 4% and menstrual disorders by 11% against 9% [18].
Population
1,388 adults on alprazolam and 1,231 on placebo in trials of up to 10 weeks [18].
Sources
[18]
Caveats
One drug, at the higher doses used for panic disorder.
ModerateCommon

Low mood, disinhibition and paradoxical reactions

Shown to raise reports of depression, in 7% on clonazepam against 1% on placebo in panic trials. Labels also report rare agitation, rage and aggression.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In clonazepam panic trials, depression was reported by 7% against 1% on placebo, and led 4% against 1% to stop [3]. The alprazolam label states benzodiazepines may worsen depression and reports episodes of hypomania and mania in people with depression. It reports paradoxical reactions such as agitation, rage, irritability and aggressive behavior rarely [18]. The diazepam label states such reactions are more likely in children and older adults [8].
Population
574 adults on clonazepam and 294 on placebo in trials of 6 to 9 weeks [3].
Sources
[3], [18], [8]
Caveats
The labels give no rate for paradoxical reactions.
ModerateUncommon

Suicidal thoughts on clonazepam

The clonazepam label carries the antiepileptic class warning: suicidal thoughts or behavior occurred in 0.43% on these drugs against 0.24% on placebo.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In pooled analyses of 199 placebo-controlled trials of 11 antiepileptic drugs, the risk of suicidal thinking or behavior was about twice that on placebo (adjusted RR 1.8, 95% CI 1.2 to 2.7), with an incidence of 0.43% among 27,863 treated patients against 0.24% among 16,029 on placebo, over a median of 12 weeks [3].
Population
43,892 patients in 199 trials of 11 antiepileptic drugs [3].
Sources
[3]
Caveats
A class analysis that the label applies to clonazepam. The label does not say whether clonazepam was one of the 11 drugs.
ModerateHow often is not known

FDA boxed warning: use with opioids

FDA states that taking benzodiazepines with opioids may cause profound sedation, slowed breathing, coma and death. Studies linked the combination to about twice the overdose risk.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states that concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma and death [18]. Among privately insured opioid users, also using a benzodiazepine was associated with an emergency visit or admission for opioid overdose (adjusted OR 2.14, 95% CI 2.05 to 2.24) [20]. Among veterans receiving opioids, a current benzodiazepine prescription was associated with death from drug overdose (HR 3.86, 95% CI 3.49 to 4.26), rising with benzodiazepine dose [21]. FDA reported that 55% of overdose deaths involving benzodiazepines from 2013 to 2017 also involved prescription opioids [22].
Population
US privately insured opioid users from 2001 to 2013 [20]; US veterans receiving opioid analgesics, 112,069 of them also prescribed benzodiazepines [21]; US death records summarized by FDA [22].
Sources
[18], [20], [21], [22]
Caveats
Observational studies. The sources give relative risks and counts, not the rate among people taking both.
LimitedHow often is not known

FDA boxed warning: abuse, misuse and addiction

FDA states that benzodiazepine use exposes people to abuse, misuse and addiction, which can lead to overdose or death. It calls the exact addiction risk uncertain.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states that abuse and misuse commonly involve other medicines, alcohol or illicit substances, which is associated with more serious outcomes [18]. FDA's review reported that an estimated 5.4 million people in the US aged 12 and older misused benzodiazepines in 2018, and that about half a million adults were estimated to have a benzodiazepine use disorder in 2015 to 2016. Overdose deaths involving benzodiazepines rose from 1,298 in 2010 to 11,537 in 2017, and 2.7% of the 2017 deaths involved benzodiazepines alone [22].
Population
US national surveys, poison center data and death records summarized by FDA [22].
Sources
[18], [22]
Caveats
Population counts, not rates among people prescribed the drugs. FDA wrote that the exact risk of addiction with benzodiazepine use is uncertain [22].
StrongHow often is not known

Falls and fractures

Linked to about 1.4 to 1.6 times the odds of falls in older adults and 1.5 times the risk of hip fracture in observational studies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In older adults, benzodiazepine use was associated with falls at an odds ratio of 1.57 (95% CrI 1.43 to 1.72), or 1.41 (95% CrI 1.20 to 1.71) in the adjusted estimate [25]. A later meta-analysis found an odds ratio of 1.42 (95% CI 1.22 to 1.65), with 1.81 for long-acting and 1.27 for short-acting drugs [26]. For hip fracture, the relative risk was 1.52 (95% CI 1.37 to 1.68), and 2.40 (95% CI 1.88 to 3.05) with short-term use [27].
Population
79,081 older participants in 22 studies of 9 drug classes [25]; 248 studies of psychotropic drugs and falls [26]; studies of benzodiazepines and hip fracture in older people [27].
Sources
[25], [26], [27]
Caveats
Observational, with substantial heterogeneity. Prescribing bias could not be accounted for [26]. The sources give no absolute rates.
ModerateHow often is not known

Road crashes and driving

Linked to a 60% to 80% higher risk of traffic accidents in observational studies, and to impaired driving in experimental studies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Benzodiazepine use was associated with traffic accidents in case-control studies (OR 1.59, 95% CI 1.10 to 2.31) and cohort studies (rate ratio 1.81, 95% CI 1.35 to 2.43), and with being responsible for the accident (OR 1.41). The association was weaker in drivers over 65 (OR 1.13) than in younger drivers (OR 2.21). In experimental studies, anxiolytics taken in the daytime impaired driving performance whatever their half-life [28].
Population
Epidemiological and experimental studies of benzodiazepines and driving [28].
Sources
[28]
Caveats
One meta-analysis. The accident studies are observational and give no absolute rate.
LimitedHow often is not known

Alcohol and other sedating drugs

Linked to a 7.7 times higher accident risk when benzodiazepines and alcohol were taken together. The label states their sedating effects add up.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Taking benzodiazepines and alcohol together was associated with a 7.7-fold increase in traffic accident risk (OR 7.69, 95% CI 4.33 to 13.65) [28]. The label states that benzodiazepines produce additive central nervous system depressant effects with other depressants, naming alcohol, psychotropic medicines, anticonvulsants and antihistamines [18].
Population
Epidemiological studies of drivers [28].
Sources
[28], [18]
Caveats
Observational. The estimate does not separate the effect of alcohol alone from the combination.
LimitedHow often is not known

Long-term use

FDA reported that about half of people dispensed a benzodiazepine in 2018 received it for two months or longer. Labels state use beyond 4 months has not been assessed.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
FDA estimated that 50% of patients dispensed oral benzodiazepines in 2018 received them for two months or longer [22]. The lorazepam and diazepam labels state that use beyond 4 months has not been assessed in systematic studies [7][8]. The alprazolam label states that spontaneous reports suggest dependence is more likely and more severe at doses above 4 mg a day and beyond 12 weeks, and describes anxiety returning between doses in people on maintenance treatment [18]. In trials of 13 weeks or more, anxiety scores did not differ from placebo [13].
Population
US prescription data summarized by FDA [22]; 1,228 people in 8 longer trials [13].
Sources
[22], [7], [8], [18], [13]
Caveats
Prescription data show how long people take the drugs, not what happened to them. The dependence, memory and dementia findings are in their own blocks.
LimitedHow often is not known

Breathing in people with lung disease

The alprazolam label reports deaths in people with severe lung disease shortly after starting treatment. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states there have been reports of death in patients with severe pulmonary disease shortly after the initiation of alprazolam, and describes respiratory depression, hypoventilation and apnea as signs to watch for in people with impaired respiratory function [18].
Population
Reports summarized in labeling [18].
Sources
[18]
Caveats
No denominator.
LimitedHow often is not known

Raised alprazolam levels with other medicines

The label reports alprazolam blood levels rising about 4 times with ketoconazole and 2.7 times with itraconazole, and lists such strong enzyme blockers as contraindicated.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Ketoconazole raised plasma alprazolam concentrations 3.98-fold and itraconazole 2.70-fold. The label lists strong CYP3A inhibitors, with ketoconazole, itraconazole and the antibiotic clarithromycin as examples, as contraindicated. It names the antidepressants nefazodone and fluvoxamine, cimetidine and the antibiotic erythromycin as weaker inhibitors that may raise levels, and carbamazepine and phenytoin as drugs that lower them [18].
Population
Drug interaction studies described in labeling [18].
Sources
[18]
Caveats
The block is for alprazolam. Changes in drug levels, with no rate of harm.

Mixed results4

ModerateVery common

Weight and appetite

Mixed results: in alprazolam panic trials weight gain, 27% against 18% on placebo, and weight loss, 23% against 17%, were both reported more often.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In alprazolam panic disorder trials, weight gain was reported by 27% against 18% on placebo, weight loss by 23% against 17%, increased appetite by 33% against 23% and decreased appetite by 28% against 24% [18].
Population
1,388 adults on alprazolam and 1,231 on placebo in trials of up to 10 weeks [18].
Sources
[18]
Caveats
Reported events with no measured change in kilograms, from one drug at panic disorder doses.
ModerateStudied in pregnancyCommon

Pregnancy and newborns

Mixed results: birth defects were not clearly raised, while miscarriage, preterm birth and newborn intensive care were linked to exposure in observational studies.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Congenital malformations occurred in 222 of 5,195 exposed pregnancies and 64,335 of 2,082,467 unexposed (OR 1.13, 95% CI 0.99 to 1.30). The odds ratio was 1.40 (95% CI 1.09 to 1.80) when a benzodiazepine was taken together with an antidepressant [34]. Exposure was associated with spontaneous abortion (OR 1.86, 95% CI 1.43 to 2.42), preterm birth (OR 1.96), low birth weight (OR 2.24) and newborn intensive care admission (OR 2.61, 95% CI 1.64 to 4.14) [35]. In a Quebec cohort, early pregnancy exposure was associated with spontaneous abortion after adjustment for mood and anxiety disorders (OR 1.85, 95% CI 1.61 to 2.12) [36]. The label states that use late in pregnancy can cause sedation and withdrawal symptoms in the newborn [18].
Population
8 studies of malformations [34]; studies of 9 pregnancy and delivery outcomes [35]; 442,066 pregnancies, 27,149 ending in spontaneous abortion [36].
Sources
[34], [35], [36], [18]
Caveats
Observational, with significant heterogeneity for most delivery outcomes, and confounding by the conditions being treated cannot be ruled out [35]. The band above is the malformation count in exposed pregnancies, about 4 in 100 against about 3 in 100 unexposed.
ModerateUncommon

Death from any cause

Mixed results: a meta-analysis linked benzodiazepine use to 1.6 times the death rate, while a large matched cohort found no rise at six months.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Across 10 cohort studies, benzodiazepine users had higher mortality than non-users (HR 1.60, 95% CI 1.03 to 2.49) [32]. In a matched cohort of people starting a benzodiazepine, deaths over six months occurred at 9.3 per 1,000 person-years against 9.4 in people not starting one (HR 1.00, 95% CI 0.96 to 1.04), with increases of 4% to 9% in some longer and subgroup analyses [33].
Population
2,350,093 patients in 25 studies of anxiolytics and hypnotics [32]; matched US adults starting or not starting a benzodiazepine, with about 5,000 deaths in each group [33].
Sources
[32], [33]
Caveats
Observational, with significant heterogeneity in the meta-analysis [32]. The cohort authors judged that leftover confounding likely explains part of any small increase [33].
ModerateHow often is not known

Dementia

Mixed results: two meta-analyses linked benzodiazepine use to 1.4 to 1.5 times the dementia risk, while a prospective cohort found none at the highest exposure.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Ever use was associated with dementia at an odds ratio of 1.39 (95% CI 1.21 to 1.59), and 1.30 (95% CI 1.14 to 1.48) in studies that ignored use in the 5 or more years before diagnosis [29]. An earlier meta-analysis found a risk ratio of 1.49 (95% CI 1.30 to 1.72) for ever users [30]. In a prospective cohort, the hazard ratio was 1.25 (95% CI 1.03 to 1.51) at the lowest level of use and 1.07 (95% CI 0.82 to 1.39) at the highest, and higher use was not associated with faster cognitive decline [31].
Population
159,090 cases in 15 studies [29]; 45,391 participants in 6 studies [30]; a population cohort followed a mean 7.3 years, 797 of whom developed dementia [31].
Sources
[29], [30], [31]
Caveats
Observational. Early dementia can cause anxiety and poor sleep, so use may follow the disease. The cohort authors concluded their results did not support a causal link [31].

Claims tested and not found

  1. That diazepam speeds recovery from acute low back pain. In 114 emergency department patients given naproxen, adding diazepam did not improve function or pain over adding placebo at one week or three months [17].
  2. That benzodiazepines keep lowering anxiety more than placebo over the long term. In studies of 13 weeks or more, the change in anxiety scores did not differ significantly from placebo [13].
  3. That heavier benzodiazepine use means a higher dementia risk. In a prospective cohort, the highest level of use was not associated with dementia (HR 1.07, 95% CI 0.82 to 1.39) or with faster cognitive decline [31].
  4. That benzodiazepines in pregnancy clearly raise birth defects. Across 8 studies the association was not statistically significant (OR 1.13, 95% CI 0.99 to 1.30) [34].
  5. That starting a benzodiazepine sharply raises the risk of death. In a matched cohort, mortality over six months was the same in people starting and not starting one (HR 1.00, 95% CI 0.96 to 1.04) [33].

Sources

  1. Breilmann J, Girlanda F, Guaiana G, et al. Benzodiazepines versus placebo for panic disorder in adults. Cochrane Database of Systematic Reviews. 2019. https://doi.org/10.1002/14651858.CD010677.pub2
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