Effect of as-needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder

Depress Anxiety. 2016 Dec;33(12):1081-1089. doi: 10.1002/da.22546. Epub 2016 Aug 25.


Background: There are no medications approved for as-needed use for feared situations for individuals with social anxiety disorder (SAD). In the present study, intranasal PH94B was provided for use as needed during stressful events.

Methods: Twenty-two subjects were randomized (double-blind) to 2 weeks of treatment with intranasal PH94B or placebo. Following self-administration of medication prior to a feared event, peak levels of anxiety were recorded using the Subjective Units of Distress Scale (SUDS). After 2 weeks, subjects were crossed over to the opposite treatment for 2 weeks. Average peak SUDS during treatment with PH94B and placebo were compared using a paired t-test.

Results: Significant differences in favor of PH94B were found on the primary outcome measure: mean peak SUDS change from baseline for all subjects receiving PH94B was 15.6 points versus 8.3 points for placebo (paired t = 3.09, P = .006, effect size of .658). PH94B showed less superiority over placebo when placebo was given second rather than first, likely due to a carryover effect. Looking between groups at just the first 2 weeks of treatment, PH94B also showed trend superiority to placebo on the Liebowitz Social Anxiety Scale (LSAS) (P = .07) and a significant difference on the Patient Global Impression of Change (P = .024) and the LSAS Avoidance subtotal (P = .02).

Conclusions: While further study is needed, these results, combined with earlier findings, suggest that PH94B could represent a useful as-needed treatment for SAD, and continue to validate the nasal chemosensory system as a novel mechanism for medication delivery.

Trial registration: ClinicalTrials.gov NCT02622958.

Keywords: SAD/social anxiety disorder/social phobia; anxiety/anxiety disorders; pharmacotherapy; phobia/phobic disorders; treatment.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Aged
  • Androstenols / administration & dosage
  • Androstenols / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Performance Anxiety / drug therapy*
  • Phobia, Social / drug therapy*
  • Pilot Projects
  • Self Administration
  • Treatment Outcome
  • Young Adult


  • 3-androsta-4,16-dien-3-ol
  • Androstenols

Associated data

  • ClinicalTrials.gov/NCT02622958