Evidence-Based Reviews

Hypnotics and driving: FDA action, clinical trials show need for precautions

Current Psychiatry. 2007 April;6(4):39-53

References

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Clinical Point

When prescribing hypnotics, adopt a risk management approach as you would with other medications that can have serious side effects

Driving impairment. Bocca et al²⁴ compared degree of driving impairment by zolpidem, zopiclone, flunitrazepam (not approved in the United States), and placebo. The 16 subjects received each medication at 11 pm, with a 2-week washout between medications. One group of 8 was tested at 9 am and the other 8 subjects at 11 am. Those taking zolpidem showed no residual performance impairment, as measured by simulated driving, a test drive, and saccadic eye movements.

Staner et al²⁵ reported similar results when comparing zolpidem, zopiclone, lormetazepam (not approved in the United States), and placebo. Using a driving simulator and electroencephalography (EEG), they evaluated 23 subjects diagnosed with insomnia at 9 and 11 hours post-dose. Zolpidem did not significantly impair driving ability and did not differ from placebo on EEG analysis (resting or driving). The study showed driving impairment with zopiclone and lormetazepam, along with characteristic benzodiazepine EEG changes. This study further supports evidence of limited impairment on driving after appropriate use of zolpidem.

Informed consent

In the informed consent process, failing to warn a patient about medication side effects can lead to legal claims against both manufacturers and prescribers. With any medication, patients have the right to know about a drug’s risks, benefits, and alternate therapies—including no therapy.

Two standards are associated with informed consent and negligence:

The “reasonable practitioner” standard outlined in Natanson v. Kline (1960)²⁶ mandates that the prescribing physician has revealed all that an “average, reasonable practitioner” would disclose in similar circumstances.
The “reasonable patient” standard set in Canterbury v. Spence (1972)²⁷ mandates that the prescribing physician has informed the patient about the proposed treatment, its side effects, and alternatives to the proposed treatment that a reasonable patient would consider material to the decision of whether or not to undergo treatment.

Failure to warn. Plaintiffs may allege a failure to warn if a drug manufacturer withheld information, thus not adequately warning the dispensing provider. In Reyes v. Wyeth Laboratories, for example, the U.S. Fifth Circuit Court of Appeals ruled that the polio vaccine’s manufacturer failed to warn the parents of a child who contracted polio from the vaccine about the 1-in-a-million chance of this adverse effect.²⁸

The vaccine was licensed as a prescription drug but administered through county health departments. In 1970, a nurse in a Texas Department of Health clinic administered the vaccine to 8-month-old Anita Reyes without telling the girl’s parents of warnings in the package circular. Holding Wyeth Laboratories to a reasonableness standard, the court found that the company knew or should have known how the vaccine would be distributed.

The package insert was not shown to have given inadequate warning, and the vaccine was not shown to be defective (it was a trivalent live-virus Sabin oral polio vaccine, as intended).

Vioxx cases. Similarly, some plaintiffs have been awarded millions of dollars (as in Ernst v. Merck & Co., Inc.²⁹) in rulings that Merck & Co. failed to disclose the risk of cardiotoxicity with the arthritis drug rofecoxib (Vioxx) and thus failed to provide physicians with information needed when prescribing the drug. In Humeston v. Merck & Co.,³⁰ a Texas court in 2005 held that Vioxx’s warning labels were adequate. In a retrial, however, the New Jersey Superior Court awarded the plaintiff $47.5 million.³¹

As with the polio vaccine and Vioxx litigations, courts are being asked to decide if patients were adequately informed about sleep-driving and other risks associated with the use of sedative-hypnotics.

Clinical recommendations

Zolpidem—like many other medications—carries a substantial risk of side effects, even when used appropriately. However, given the medical and mental health risks of untreated insomnia, the benefits of a medication such as zolpidem will likely outweigh its risks.

Numerous studies have shown that zolpidem is effective for improving sleep latency and that there are mild, if any, residual side effects beyond what would normally be a restful night’s sleep. Impairments are evident, however, during the hours following the drug’s administration, with some effects lasting >5 hours depending on the dose.

Risk management. When prescribing nonbenzodiazepine hypnotics such as zolpidem, you may want to adopt a risk management approach as you would with other medications that can have serious side effects. An approach to benzodiazepine prescribing proposed by Bursztajn et al³¹ advocates:

using the informed-consent process to build an alliance with patients
not prescribing the medication in isolation of other beneficial therapies
being aware of and always documenting your decision-making process.