Insomniacs: Beware Newly Approved Recycled Drug With Suicide Risk

by Heidi Stevenson

27 March 2010

After refusing to approve it twice, the FDA has just allowed Silenor, an old antidepressant drug, to be recycled as a treatment for insomnia. The FDA's first rejection was based on depressing heart rate, and the second was for Silenor's lack of efficacy. Doxepin hydrochloride, the generic name, carries an FDA warning of increased suicide risk when marketed as an antidepressant.

Somaxon Pharmaceuticals, the company that's marketing Silenor, claims that its trials show that it's safe. Their first attempt at FDA approval was for use at 50 milligram doses. They dropped the dosage to 3 and 6 milligrams for their second attempt, but were turned down for lack of efficacy. The approval on the third try was for 3 and 6 milligram doses.

According to Somaxon's CEO, a meeting took place towards the end of January. It must have had a beneficial effect for the company, because the FDA sent them a letter saying that they could reapply by using a subset of the existing data.

Shades of Prozac! That's how Prozac was approved—by shaving down the data set until there was just a small fraction left, and gaining approval on that basis. It's inconceivable that this can ever be considered an acceptable means of gaining approval for any drug. It certainly leads one to suspect nefarious things going on in the background.

In the case of Silenor, it's even more questionable. The entire process of testing and examining results has been carried out in the dark. Somaxon is a one-product company, obviously created to market Silenor. The only published studies I could find about treating insomnia with doxepin were published two or more years before the company was founded. All other references and claims are from company marketing and presentations.

How can a member of the public or a doctor know if Somaxon's claims for Silenor are legitimate, when the entire approval process has been done behind closed doors and the studies used for approval haven't been made public?

The information available to the public is based on Silenor's use in its previous incarnation as an antidepressant. Here's a list of adverse effects from Medscape:

• Most Frequent: Dizziness, Drowsiness, Dysgeusia, Headache Disorder, Increased Appetite, Weight Gain, Xerostomia
• Less Frequent: Abnormal Sexual Function, Blurred Vision, Bradycardia, Conduction Disorder of the Heart, Constipation, Diarrhea, Dysuria, Erectile Dysfunction, Hallucinations, Heartburn, Hyperhidrosis, Hypotension, Impaired Cognition, Insomnia, Nervousness, Parkinsonism, Tremors, Vomiting
• Rare: Agranulocytosis, Allergic Dermatitis, Allergic Reactions, Alopecia, Angioedema, Anxiety, Blood Dyscrasias, Galactorrhea not associated with Childbirth, Gynecomastia, Hyperbilirubinemia, Prolonged QT Interval, Pruritus of Skin, Seizure Disorder, SIADH, Skin Photosensitivity, Skin Rash, Suicidal Ideation, Testicular Swelling, Tinnitus

Perhaps Silenor doesn't have these adverse effects when taken at the lower dosage. But how can we know? We don't get to see the trials themselves. As bad as trials for drug approval have been in the past, at least they were generally published in journals. All we know for sure is that all of the adverse effects listed above have definitely been associated with the drug—plus one more: increased risk of suicide, as documented by the FDA itself.

Do you want to ease insomnia with risks like these? Clearly, this drug affects the heart and has the potential of stopping it. It affects the ability to fight infections. It can cause hallucinations. Even the common adverse events are nothing to take lightly. Dizziness. Headaches. Weight gain, often a precursor to diabetes. Dry mouth, which can result in tooth loss and increased susceptibility to infections. Distortion of taste.

As ever, the bottom line is the bottom line. Doxepin hydrochloride, whose patent as an antidepressant has run its course, is now being recycled as Silenor, a drug to help you sleep. This time, there were no development costs, only the costs of a few studies. Even the usual trouble of publishing the results seems to have been dispensed with. The approval process was handled behind closed doors. There is no documentation available on the FDA's website.

Who does the FDA work for? It certainly doesn't seem to be the people.

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