Next Steps for Patients with Social Anxiety Disorders Who Don't Respond to Pharmacotherapy

Summary and Comment |
January 9, 2014

Next Steps for Patients with Social Anxiety Disorders Who Don't Respond to Pharmacotherapy

  1. Joel Yager, MD

Augmentation with a benzodiazepine showed some positive results, but remission rates remained low. Psychotherapy might be a more useful alternative.

  1. Joel Yager, MD

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy for social anxiety disorder (SAD), but up to three quarters of patients fail to achieve remission after initial therapy. To determine the most effective next-step pharmacotherapy for these patients, investigators conducted a multisite, randomized, controlled, double-blind, two-phase study funded by the National Institute of Mental Health.

The initial 397 patients with SAD were not receiving psychotherapy and were given the SSRI sertraline (≤200 mg/day). After 10 weeks, 181 nonresponders were randomized to one of three 12-week treatments: augmentation of sertraline with the benzodiazepine clonazepam (≤3 mg/day; mean dose, 1.5 mg/day), a switch to the serotonin–norepinephrine reuptake inhibitor venlafaxine (extended release; ≤225 mg/day; mean dose, 168 mg/day), or continuation of sertraline (mean dose, 180 mg/day) plus placebo.

Overall, 46% of patients met response criteria. On several measures, patients receiving sertraline plus clonazepam (but not those receiving venlafaxine) achieved greater response than those receiving sertraline plus placebo. Only 21% of all patients remitted; remission rates were not significantly different with sertraline plus clonazepam (27%), venlafaxine (19%), or sertraline plus placebo (17%).


No patients received any of the psychotherapies shown to assist those with social anxiety disorder. For practicing clinicians, prudent initial or second steps would involve starting with cognitive-behavioral therapy or psychodynamic psychotherapy (NEJM JW Psych Jun 3 2013) with or without SSRIs or subsequently adding psychotherapy to medication. This study finally substantiates a popular practice never before backed by data: Augmentation with clonazepam is an option for patients who fail to respond and for whom the potential benefits of benzodiazepines outweigh the risks. Where benzodiazepines are to be avoided, a serotonin–norepinephrine reuptake inhibitor may be considered.

  • Disclosures for Joel Yager, MD at time of publication Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Research; Eating Disorders Review (Editor-in-Chief); Harvard Review of Psychiatry; International Journal of Eating Disorders; UpToDate Leadership positions in professional societies American Psychiatric Association (Chair, Steering Committee and Executive Committee on Practice Guidelines; Co-Chair, DSM5 Clinical and Public Health Committee; Chair, Council on Research and Quality Care)


Reader Comments (4)

Michel Philippart, M.D. Physician, Orthopaedic Institute for Children

Clonazepam which is the most popular benzodiazepine ias indeed addictive and lose efficay with time. Lorazepam contrary to a prevalent misconception is not addictive and does not lose efficacy even at high dose (24 mg daily for 15 years in a case of psychotropic-induced severe dyskinesia).

Joel Yager, MD Physician, Psychiatry, Professor, Department of Psychiatry, School of Medicine, University of Colorado
Competing Interests: Summary author

In practice many psychiatrists might find buspirone or hydroxyzine to be worth trying for various anxiety conditions. Be that as it may, those agents weren't included in this study. It’s also true that some patients develop tolerance to benzodiazepines and that in practice, many other combinations of therapy and various medications can be helpful. Our field would benefit from much more systematic study examining the comparative effectiveness of all these approaches.

Joy St. John, MA Other Healthcare Professional, Psychiatry, Private Practice

what about good old Buspar or Atarax? Why have they fallen by the wayside? Neither are addictive and while they have some mild side effects, they seem to work for a lot of people in my practice who were being given tons of other heavier drugs for years without ever having been tried on these oldies.

Diana Havill MD Physician, Psychiatry

Benzodiazepines will certainly help in early treatment--but tolerance ultimately develops, and there is the strong risk of abuse too. Therapy should be recommended early on, and I have found many different combinations of safe medications that prove effective in the long-run.

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