Twists, Turns, and Tapers: Navigating the Benzodiazepine Ride

The discovery of benzodiazepines (BZDs) was part science, part fortunate coincidence. Frank Berger initially found mephenesin had calming effects but poor duration of action and potency.¹ He later developed a longer-acting compound, meprobamate. Roche Pharmaceuticals then tasked Leo Sternbach with creating a similar drug. While studying methylene blue dye, Sternbach shifted focus to its sedative properties and eventually synthesized chlordiazepoxide in 1955—the first BZD. By the 1970s, BZDs became widely prescribed, but long-term use led to dependence and increased risk of adverse effects.

Today, nearly 1 in 20 people fill a BZD prescription annually, with about 1.7% misusing BZDs or related sedatives (e.g., Z-drugs).² BZDs act by enhancing GABA-A receptor activity, increasing chloride ion influx and causing neuronal hyperpolarization, leading to CNS depression (Figure 1).³ Unlike barbiturates, BZDs rely only on endogenous GABA and increase the frequency—not duration—of channel opening. This mechanism has proven beneficial in treating conditions such as insomnia, seizures, anxiety, panic attacks, muscle spasticity, alcohol withdrawal, and amnesia induction. However, despite their clinical utility, the American Geriatrics Society Beers Criteria® recommends avoiding BZDs in older adults due to increased risks of misuse, addiction, delirium, falls, fractures, and motor vehicle crashes.⁴

To address inappropriate BZD use, the 2025 Joint Clinical Practice Guideline on Benzodiazepine Tapering offers a framework for tapering strategies that prioritize patient safety and shared decision-making.⁵ Experts highlight challenges such as drug-drug interactions and/or use of other CNS depressants. Before initiating a taper, it is essential to assess the patient’s physical and mental stability to determine if outpatient management is appropriate. Clinicians should weigh risks versus benefits, especially if BZDs have shown limited efficacy or worsened comorbidities. When discussing tapers with patients, an important message to convey is the goal of successful discontinuation—not rapid discontinuation. Tapering may take months to years, particularly for long-term and high-dose users, and must be done safely and collaboratively.

The guideline encourages patients to be involved in selecting their tapering strategy from several available options:⁵

• Reduce by ~5% weekly
• Reduce by ~10% every other week
• Reduce by ~20% over a longer interval
• Reducing number of total pills and allowing the patient to choose which doses to skip

Initial dose reductions of 5-10% every 6-8 weeks are generally recommended with close monitoring for withdrawal symptoms. Starting at the lower end (5%) and increasing based on patient response may allow for a gentler transition. If physical dependence (see Table 1) is unlikely, consider 10-25% dose reductions—but do not exceed >25% BZD reductions every two weeks to control withdrawal.

For patients taking short-acting BZDs, switching to a long-acting agent, such as diazepam, can facilitate a smooth taper when transitioned over 1-2 weeks.⁵ With a half-life ~200 hours, diazepam allows a more gradual blood level decline.⁶ However, BZD conversions are approximate due to differing pharmacologic profiles (e.g., potency and duration of action). For example, lorazepam has less hypnotic activity than diazepam, which may cause somnolence at equivalent doses. A BZD equivalence calculator may be beneficial, but with consideration of a patient’s age and comorbidities.

Ultimately, BZD tapering should not be punitive—even in cases of diversion. Engage patients in shared decision-making, monitor for withdrawal symptoms every 2 weeks, and continue follow-up after discontinuation. A safe, individualized taper with close monitoring is essential for success.

REFERENCES

1. Mendelson WB. Benzodiazepines: The Accidental Tranquilizers. Psychology Today. 2020. Accessed October 27, 2025. https://www.psychologytoday.com/us/blog/psychiatry-a-history/202006/benzodiazepines-the-accidental-tranquilizers?msockid=16f8555b192563581b6a43dc1864626e

2. SAMHSA. 2024 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality. 2024. Accessed October 27, 2025.

3. Bounds CG, Nelson VL. Benzodiazepines. National Library of Medicine. Published January 30, 2024. Accessed October 27, 2025. https://www.ncbi.nlm.nih.gov/books/NBK470159/

4. 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372. Accessed on October 27. 2025.

5. Brunner E, Chen CA, Klein T, et al. Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits. J Gen Intern Med. 2025;40(12):2814-2859. doi:10.1007/s11606-025-09499-2. Accessed on October 27. 2025.

6. Ashton CH. “Benzodiazepines: How They Work and How to Withdraw (The Ashton Manual).” Institute of Neuroscience, Newcastle University. 2002. Accessed December 16, 2025.