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2. Benzodiazepines for GAD
David N. Osser, MD
Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System
General Editor - Psychopharmacology Algorithm Project
Harvard South Shore Residency Training Program

3. Benzodiazepines for GAD
Most prescribed
anxiolytic agents
Alprazolam:
FDA-approved
for GAD
BZs
work rapidly
(clonazepam
+ SSRI)
Effective
for somatic and
psychic symptoms
Hoffman, E. J., & Mathew, S. J. (2008). Anxiety disorders: a comprehensive review of pharmacotherapies. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, 75(3),
Bandelow, B., Boerner, R., Kasper, S., Linden, M., Wittchen, H. U., & Möller, H. J. (2013). The diagnosis and treatment of generalized anxiety disorder. Deutsches Ärzteblatt International, 110(17), 300.
Lydiard, R. B., Rickels, K., Herman, B., & Feltner, D. E. (2010). Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. International Journal of Neuropsychopharmacology, 13(2),

4. Sedation Car accidents Memory impairment Falls
Olfson, M., King, M., & Schoenbaum, M. (2015). The Popularity of Benzodiazepines, Their Advantages, and Inadequate Pharmacological Alternatives—Reply. JAMA psychiatry, 72(6),
Rapoport, M. J., Lanctôt, K. L., Streiner, D. L., Bédard, M., Vingilis, E., Murray, B., ... & Herrmann, N. (2009). Benzodiazepine use and driving: a meta-analysis.
Abejuela, H. R., & Osser, D. N. (2016). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an algorithm for generalized anxiety disorder. Harvard review of psychiatry, 24(4),

5. Observational study (Pariente et al)
Long-term use and permanent cognitive impairment
OR: 1.5 (50 % increase in risk)
Observational study (Gray et al)
No association
Pariente, A., de Gage, S. B., Moore, N., & Bégaud, B. (2016). The benzodiazepine–dementia disorders link: current state of knowledge. CNS drugs, 30(1), 1-7.
Gray, S. L., Dublin, S., Yu, O., Walker, R., Anderson, M., Hubbard, R. A., ... & Larson, E. B. (2016). Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. bmj, 352, i90.

6. Psychomotor dysfunction Falls (elderly) Increased car accidents
Olfson, M., King, M., & Schoenbaum, M. (2015). The Popularity of Benzodiazepines, Their Advantages, and Inadequate Pharmacological Alternatives—Reply. JAMA psychiatry, 72(6),

7. Tolerance / dependence (40%)
Other
Rebound withdrawal
Respiratory depression
(contraindicated in sleep apnea)
American Psychiatric Association. (1990). Benzodiazepine dependence, toxicity, and abuse: a task force report of the American Psychiatric Association. American Psychiatric Pub.
Soldatos, C. R., Dikeos, D. G., & Whitehead, A. (1999). Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. International Clinical Psychopharmacology, 14(5),
Huh, J., Goebert, D., Takeshita, J., Lu, B. Y., & Kang, M. (2011). Treatment of generalized anxiety disorder: a comprehensive review of the literature for psychopharmacologic alternatives to newer antidepressants and benzodiazepines. The Primary Care Companion to CNS Disorders, 13(2).
Ioachimescu, O. C., & Collop, N. A. (2012). Sleep-disordered breathing. Neurologic clinics, 30(4),

8. Avoid benzodiazepines in patients with substance use disorders.
Abejuela, H. R., & Osser, D. N. (2016). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an algorithm for generalized anxiety disorder. Harvard review of psychiatry, 24(4),

9. Benzodiazepines: Relative Abuse Liability
Diazepam
Lorazepam
Alprazolam
Clorazepate
Oxazepam
Chlordiazepoxide 20 40 60 80
100
Griffiths, R. R., & Wolf, B. (1990). Relative abuse liability of different benzodiazepines in drug abusers. Journal of clinical psychopharmacology.

10. Key Points
SSRIs are first line but many patients might prefer to choose one of
the lesser-evidenced options discussed due to side effects
Options: duloxetine, buspirone, hydroxyzine, pregabalin or
gabapentin, bupropion (surprise!)
Avoid benzodiazepines as an option for first-line use

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