As a standing member of the Editorial Board of Psychiatric Times, I read with particular interest the front-page story in the March issue, “Pharmonitor: Reality-Checking and Journalistic Integrity” by Editor in Chief Ronald Pies, MD. In it, Dr Pies pointed out that “disclosures do not guarantee scientific or journalistic objectivity and accuracy.” He set out the critical scientific questions that ought to be asked, and he promised that “Pharmonitor” would be “a reader-driven commentary . . . focusing on articles and reports in Psychiatric Times that the reader considers biased.”
With Dr Pies’ words fresh in my mind, I turned to the CME supplement on insomnia that accompanied the March issue—“Expanding the Armamentarium in the Treatment of Insomnia: Understanding the Pharmacology of Current and Emerging Treatments.” This subject is of great interest to all physicians.
The first of the 2 articles was a straightforward discussion by Gary K. Zammit, PhD, of the impact and current diagnostic conception of insomnia. The second article, by Thomas Roth, PhD, “Current and Emerging Pharmacotherapies for the Treatment of Insomnia: Efficacy and Safety” promised more. Dr Roth began with a helpful account of the receptors targeted by various medications. He advised readers that “histamine in general, and low-dose doxepin (Sinequan) specifically, will be discussed in terms of insomnia therapeutics.”
Most over-the-counter sleep aids (eg, diphenhydramine) are antihistamines that affect H1 receptor activity; they also have some effects on other receptors. Psychiatrists have long known that the tricyclic antidepressant, amitriptyline, also helps patients sleep. It, of course, affects multiple receptors in its antidepressant activity, not just H1.
Dr Roth then discussed something relatively new in the treatment armamentarium. “Low-dose doxepin hydrochloride (1 mg, 3 mg, and 6 mg) is currently being investigated for the treatment of primary insomnia in adult and geriatric patients.” Roth cited a 2007 article by Singh and Becker1 suggesting that at these low dosages “doxepin is a very highly specific H1 antagonist without any effects on those other receptor systems.” He goes on to discuss the efficacy of doxepin at these low doses, citing one study in which he is the principal investigator and another by Scharf and colleagues.2,3 Briefly, his claim was that even the 1-mg dose improved sleep efficacy in both young and elderly participants in double-blind placebo-controlled studies. The improvement in sleep
efficacy was based on better sleep maintenance. Roth, though admitting the evidence was less robust, suggests that at 6-mg doses there was an improvement in sleep initiation. Other claims were made for doxepin, but Roth conceded that relative efficacy with other H1 antagonists needed to be studied.
I came away from reading this CME supplement with a very positive take on low-dose doxepin for insomnia, but I wondered whether the information provided was biased. I obtained copies of the cited articles from which Roth made the case. Other more expert methodologists can opine whether what I found was dispositive of the bias question. Both Zammit and Roth include Somaxon in their long list of disclosures. The supplement was “supported by an educational grant from Somaxon Pharmaceuticals, Inc.” and was based on presentations made at a meeting in October 2008. At that time, Somaxon was seeking approval from the FDA for its low-dose (1 mg, 3 mg, and 6 mg) doxepin (Silenar) formulations.
When I pursued my inquiry on the Web, I discovered that Silenar was Somaxon’s leading product. Weeks before the CME supplement was published, the value of the company’s stock had dropped precipitously on news that the FDA was withholding approval. Somaxon’s own response to the FDA letter was that they would no longer claim efficacy of the 1-mg dose, which contrasts with Dr Roth’s article. Furthermore, the company would no longer claim that Silenar was effective in sleep initiation, which is also in contrast with Dr Roth’s suggestion.
My personal opinion is that the information in the supplement about this drug was, in fact, biased. Readers were given an account of efficacy that was rejected by the FDA and that has been amended significantly by Somaxon. This supposed CME activity was much like the format of television programs. Along with the entertainment (medical education) come the commercials that praise the sponsors.
