Stopping Benzos May Raise Mortality Risk

In a surprise finding, discontinuing long-term benzodiazepines was associated with higher death rates

STUDY: Maust DT et al, JAMA Netw Open 2023;6(12):e2348557

STUDY TYPE: Comparative effectiveness study with trial emulation

FUNDING: National Institute on Drug Abuse

Background

Stopping benzodiazepines is assumed to reduce harm. That assumption has driven FDA policy, prescriber guidelines, and deprescribing campaigns, but drug withdrawal comes with its own risks, and this large study suggests caution.

The Study

This trial emulation used US insurance claims data on 353,576 adults prescribed stable long-term benzodiazepines, defined as consistent use covering 90% of days over a year with no large dose fluctuations. Roughly 20% discontinued during a six-month window. Researchers tracked all-cause mortality, overdose, suicidal ideation, and emergency department visits over 12 months, stratifying by concurrent opioid use.

Across the board, discontinuation was associated with a higher mortality risk over a year (1.6-fold higher), even when the researchers narrowed the scope to those who would most likely benefit from discontuation: Older adults and those on opioids.

Emergency department visits were substantially higher among discontinuers (42.7% vs. 36.6% without opioids; 54.3% vs. 45.2% with opioids). Suicidal ideation was modestly increased; nonfatal overdose was slightly higher. Suicide attempts didn’t differ significantly between groups.

We don’t know the cause of these deaths. It is possible patients turned to street use when the prescriptions stopped, or that withdrawal effects led to suicide or other dangerous behavior.

Limitations: It is possible that clinicians decided to taper the benzodiazepine because these were high-risk patients to begin with. The study also couldn’t determine how discontinuation was done: rapid taper, slow taper, or abrupt stop.

Practice Implications

1. This study doesn’t say benzodiazepines are safe. It says that stopping them in stable long-term users may not be as straightforward as current policy assumes.
2. In balance, clinical trials find that sleep, cognition, and physical abilities improve after discontinuation, particularly in the elderly. Those are long-term benefits and they are gradual. At first, withdrawal can worsen sleep and anxiety.
3. We saw similar problems in large trials of opioid cessation.