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Side-effects can differ within the drug class due to differences in metabolism and pharmacology.For example, long-acting benzodiazepines have problems of drug accumulation especially in the elderly or those with liver disease, and shorter-acting benzodiazepines have a higher risk of more severe withdrawal symptoms.In support of this claim an analysis of data of clinical trials submitted to the Food and Drug Administration (FDA) concerning the drugs zolpidem, zaleplon, and eszopiclone found that these sedative hypnotic drugs more than doubled the risks of developing depression compared to those taking placebo pills.Hypnotic drugs, therefore, may be contraindicated in patients suffering from or at risk of depression.This has led to the Z-drugs becoming widely prescribed for the treatment of insomnia particularly in elderly patients.A survey of patients using nonbenzodiazepine Z drugs and benzodiazepine hypnotic users found that there was no difference in reports of adverse effects that were reported in over 41% of users and, in fact, Z drug users were more likely to report that they had tried to quit their hypnotic drug and were more likely to want to stop taking Z drugs than benzodiazepine users.

Data is also limited into the long-term effects of nonbenzodiazepines.Nonbenzodiazepines have demonstrated efficacy in treating sleep disorders.There is some limited evidence that suggests that tolerance to nonbenzodiazepines is slower to develop than with benzodiazepines.Further research into the safety of nonbenzodiazepines and long-term effectiveness of nonbenzodiazepines has been recommended in a review of the literature.The first three nonbenzodiazepine drugs to enter the market were the "Z-drugs", zopiclone, zolpidem and zaleplon.

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