- Ambien and Ambien CR (already carry the warning!)
- Butisol sodium (Does anyone still prescribe this dinosaur?!)
- Carbrital (pentobarbital and carbromal) (Do they really still manufacture this stuff?!)
- Dalmane (a benzodiazepine)
- Doral (a benzodiazepine)
- Halcion (a benzodiazepine)
- Placidyl (Does anyone still prescribe this dinosaur?!)
- Prosom (a benzodiazepine)
- Restoril (a benzodiazepine)
- Rozerem (probably acts like melatonin, a hormone)
- Seconal (Does anyone still prescribe this dinosaur?!)
Even more confusing and potentially dangerous than the inclusion of Rozerem is the exclusion of a number of other central nervous system depressants and other sedating drugs which are often used to aid sleep. Of greatest concern is the omission of all the other benzodiazepines, sedative hypnotics, including even barbiturates, that are not explicitly approved for treating insomnia, despite the fact that these might be the drugs one would most likely expect to be associated with this phenomenon. Drugs frequently prescribed for insomnia such as quetiapine, mirtazapine, trazodone, and sedating antihistamines, such as diphenhydramine are conspicuously absent. Of course melatonin is omitted even though ramelteon is included, despite the fact that they probably share the same mechanism of action, presumably because melatonin, a hormone, is regulated by the FDA as a dietary supplement while Rozerem is regulated as a prescription pharmaceutical. The omission of sodium oxybate might be related to the tight control over its use.
The FDA overvalues its approval designations to the extent that they appear to consider approved indication to determine clinical class. This approach risks creation of increased confusion and potential for ill advised switching to drugs that might be even less safe. For example, a physician might switch a patient from Ambien to diazepam despite the drug's similarity to Halcion, eschewing Rozerem, which might not be associated with this effect, simply because Rozerem is included in the warning.
The FDA should adopt a more rational application of categories that does not depend solely on approved indication. Drug categories frequently overlap and may be based on different properties. The class of "benzodiazepines" is based on the similarities in chemical structure among the drugs in the class. The class of "hypnotics" is based on the drugs' effectiveness in induction of sleep. The class of serotonin reuptake inhibitors is based on the drugs' common mechanism of action. Approval is driven by the marketing choices of the company that holds the patent on the drug. Obtaining approval for a spcific indication requires evidence of safety and effectiveness, and the process costs the company millions of dollars with no guarantee of ultimate approval. The FDA should develop a more uniform and rational approach to approval as well as categorization. All drugs effective for treating insomnia should be approved for that indication and classified as hypnotics regardless of the business goals of the company that markets the entity, but only the drugs for which there is compelling evidence of a given adverse effect should carry the appropriate warning.