Propranolol a Promising Treatment for PTSD

Several Studies Suggest Benefits of 1 or 2 Doses, but "Placebo Effect Is Alive and Well," Reports 1 Investigator

Kate Johnson

October 05, 2010

October 5, 2010 — Correction: The original text regarding the second study described an initial propranolol dose of 40 mg/kg immediately followed by 80 mg/kg 90 minutes later. This is incorrect. The doses should be 40 mg total followed by 80 mg total.

September 27, 2010 (Toronto, Ontario) — The β-blocker propranolol may interrupt reconsolidation of traumatic memories through protein synthesis inhibition, presenting a promising treatment option for posttraumatic stress disorder (PTSD), 2 new studies suggests.

Presented here at the Canadian Psychiatric Association 60th Annual Conference, 1 study shows a single, 40-mg, fast-acting dose administered immediately after memory recall, with an additional 60-mg, extended-release dose administered about 2 hours, later seems to "fragment" the memory and induce a partial amnesia, reported Robin Menzies, MD, a psychiatrist in private practice in Saskatoon, Saskatchewan.

"Our findings suggest that it is not amnesia," said Daniel Saumier, PhD, who also reported promising results with the drug. Dr. Saumier is a psychologist and assistant professor in the Department of Neurology and Neurosurgery from McGill University in Montreal, Quebec. He works with Alain Brunet, PhD, who was one of the first to report results of this kind. "We are attenuating the emotional aspect of the memory without affecting the memory itself. We are making it less emotionally stressful."

Both investigators reported their different approaches to evaluating the efficacy of the treatment, which is based on the theory that memory consolidation involves adrenergic activation. Propranolol blocks β-adrenergic receptors and, if administered after subjects have actively recalled their memory, may have a 6-hour window to interrupt memory reconsolidation.

Dr. Saumier reported results from a randomized controlled trial that included 19 chronic PTSD patients with an average symptom duration 10 years (J Psychiatr Res. 2008;42:503-506). The patients were asked to recall their memory by writing a trauma script, outlining the details of their traumatic experience and the emotions they felt.

Nine patients were then given a 2-dose regimen of fast-acting and then extended-release propranolol (as described above), and the other 10 patients received placebo. One week later, after review of the trauma script, patients' physiologic responses to the memories were compared, using heart rate, skin conductivity, and corrugator electromyography (EMG) measurements.

"There were significant differences between the placebo and treatment groups on heart rate and skin conductivity tests but not on EMG," he said. And there was a trend toward decreased symptoms, measured on the self-report Impact of Event Scale–Revised.

The researchers have since completed 2 open-label studies (under review for publication) using 6 weekly doses of propranolol in PTSD patients with a wide range of traumatic experiences.

One study with 35 subjects involved an initial dose of 0.67 mg/kg after memory recall, followed by a dose of 1.0 mg/kg 90 minutes later. Five subsequent weekly sessions involved both doses given concomitantly.

The second study, with 7 subjects and 25 controls, used an initial dose of 40 mg immediately after memory recall followed by 80 mg 90 minutes later. Five subsequent weekly sessions involved both doses concomitantly.

Remission rates at the end of the sixth weekly session were 86% for the first study and 71% for the second study, compared with 8% in controls.

The group is currently conducting a Canadian government–funded trial to see whether there is a difference between treated subjects who are and are not asked to actively recall their memory after treatment.

Dr. Menzies has focused only on the clinical symptoms of PTSD. "I don't get patients coming in and complaining of increased skin conductivity," he explained.

He instructs patients to write down their traumatic memories and then discuss them with him before treatment. However, on follow-up he does not induce active recall — he simply asks them if there has been any improvement in their symptoms.

Dosing is normally 40 mg of fast-acting propranolol immediately following memory recall, followed by 60 mg of extended-release propranolol 2 hours later, he said.

However, in some patients who have asthma he prefers a lower dose (20 mg followed by 40 mg) because of the drug's potential to cause respiratory adverse effects.

In 31 patients (21 men) treated during a 2-year period, he reported a 90% response rate, with duration of effect continuing up to 2 years.

The patients' duration of traumatic memories ranged from 3 months to 38 years. Some subjects were dealing with a single memory, whereas others were dealing with a traumatic history.

A total of 25 subjects came for a single session, whereas others came for multiple sessions.

A total of 28 of 31 patients responded, with an average improvement score of 8.8 of 10, he reported.

Of the 3 patients who did not respond, 2 had amputations associated with their trauma and 1 had been receiving long-term β-blocker medication for a cardiac indication.

"She probably had all the improvement she was going to get on the medication, and for the amputees, if there is pain associated with the memory this will always be a trigger," said Dr. Menzies.

Patients who benefited from propranolol reported fragmented memories, emotional distance, or amnesia associated with the trauma, he said.

He has just started a placebo-controlled trial and "let me tell you, the placebo effect is alive and well," he said.

The evidence is favorable for propranolol as a viable treatment for PTSD, with "potential indications for alcohol and drug addiction, depression, anxiety disorder, and phobias," said Dr. Saumier.

It is possible that the drug may reduce the emotion associated with a memory, whether it is a good or bad memory, he explained.

Therefore, in addictions, where a positive memory is associated with a substance, the drug could potentially detach the memory from the positive emotion.

"I'm going to try it in my practice," said Donald Richardson, MD, a psychiatrist with a focus on PTSD at the Parkwood Hospital Veteran's Care Program in London, Ontario, who was not involved in the research, told Medscape Medical News.

"It's certainly an option in treatment-resistant patients. Combat veterans and any military veterans are exposed to long-term trauma, so maybe you could choose some specific, more upsetting events and see if the treatment is helpful. Dr. Menzie's comment that the placebo effect is high would be of concern. But if we could have a medication that is taken only twice to treat a chronic condition, that would be very, very good."

Dr. Menzies reports receiving honoraria or other fees from Wyeth Pharmaceuticals. Dr. Saumier is a former employee of Pfizer Canada Inc.

Canadian Psychiatric Association (CPA) 60th Annual Conference: Abstracts PS2a and PS2c. Presented September 23, 2010.


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