Novel Aerosol Spray May Provide On-Demand Relief for Social Anxiety

Laird Harrison

April 11, 2014

An experimental nasal drug, 3b-androsta-4,16-dien-3-ol (PH94B), works through pheromone pathways to calm symptoms of social anxiety, a new study shows.

"The treatment represents a novel medical treatment for social anxiety and a novel pathway for medications affecting the central nervous system," first author Michael Liebowitz, MD, a professor of clinical psychiatry at Columbia University in New York City, told Medscape Medical News.

Dr. Liebowitz and his colleagues reported the finding online April 4 in the American Journal of Psychiatry.

Many animals use pheromones to communicate sexual readiness, alarm, and other messages. Researchers have known of pheromone receptors at the base of the human nasal septum and speculated whether pheromones might affect human beings.

For example, some experiments have suggested that pheromones in women's perspiration can affect other women's menstrual cycles. But until now, no one has created a drug that can influence human behavior through this pathway, Dr. Liebowitz said.

In addition to its novel route of administration, PH94B is the first synthetic neuroactive steroid to have shown efficacy for social anxiety.

Social anxiety interferes with normal social interaction, such as giving speeches and attending parties.

Clinicians treat the disorder with cognitive-behavioral therapy and with drugs, including serotonin reuptake inhibitors, monoamine oxidase inhibitors, benzodiazepines, and beta blockers.

But these treatments are not completely effective for everyone who tries them, and they may cause adverse reactions. Some must be taken for many days to be effective.

On-Demand Relief?

PH94B looks promising because patients could use it just before a stressful social situation, said Dr. Liebowitz.

To test its benefits, the researchers randomly divided 91 women diagnosed with social anxiety into 2 groups.

They tested both groups by giving them an intranasal placebo. Fifteen minutes later, the women had to pick a topic for a 5-minute speech, take 2 minutes to prepare, then deliver the speech to an audience of strangers.

The women rated their anxiety at intervals throughout this process on the Subjective Units of Distress Scale, in which 0 = no anxiety, 30 = mild anxiety, 60 = moderate anxiety, and 90 = severe anxiety.

The anxiety scores of both groups rose from about 55 before the challenge to about 80 when they were delivering the speech.

Half an hour later, the women took another dose of their placebos. Then they participated in a mock party with role players, and once again rated their anxiety at intervals. Once again, the scores of the 2 groups rose more or less in tandem, though the women did not express as much anxiety this time.

At their next visit, one group took the placebo again, but the other group took PH94B. Each spray of the active drug contained 50 microliters of fluid and delivered 0.4 microliters of PH94B.

The women gave another speech, participated in another party, and once again rated their anxiety throughout. This time, the women taking the PH94B rated their anxiety lower than the placebo group did at all phases of the 2 social challenges.

Table. Speech Challenge Distress Scores

  Resting Anticipation Performance
Placebo group 50.22 60.87 66.68
PH94B group 46.22 47.72 52.55


The same held true of the party simulation, though both groups had less anxiety at each stage, and there was less difference between the 2 groups.

Both groups had less anxiety overall during the second visit than during the first, but the decrease in anxiety was greater for the PH94B group. The difference in change between the 2 groups was 12.68 units for the performance phase of the speech challenge. This difference was statistically significant (P = .002).

The decrease in anxiety during the performance phase of the mock party was also significantly greater for the PH94B group than for the placebo group.

Physicians also evaluated the women on the Clinical Global Impressions Scale (CGI) between the 2 visits. Participants with CGI improvement scores of 1 (very much improved) or 2 (much improved) at the second visit were considered responders. In the PH94B group, 75.6% were considered responders, compared with 37.0% in the placebo group.

Both groups reported some mild adverse reactions, such as nasal soreness and headache, but the rate of these adverse reactions did not differ significantly between the 2 groups.

Dr. Liebowitz said he anticipated very little potential for abuse of the drug. "I don't think we're going to obliterate anxiety," he said. "I don't think people are going to take this and step in front of cars."

It will be easy to limit the amount that people can take because if they squirt too much into their noses, it will just dribble out, he said.

In the next study, participants will carry the drug around with them and try it in real-life events in which they anticipate social anxiety.

Worth Further Study

Commenting on the findings for Medscape Medical News, Carol Bernstein, MD, an associate professor of psychology at New York University in New York City and past president of the American Psychiatric Association, called the finding "intriguing."

"I think it's worth further study," she said. But she wondered how different the effects of PH94B are from drugs already prescribed for social anxiety. And she emphasized that the drug needed to be tested in a larger group of people during a longer period.

"If you use it over time, will its effects wear off?" she asked. "Are you going to be squirting this up your nose all the time?"

Neither Dr. Liebowitz nor Dr. Bernstein has disclosed any relevant financial relationships.

Am J Psychiatry. Published online April 4, 2014. Abstract


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