Clinicians should understand the distinctions among the various types of pharmacotherapy for insomnia. Sedative-hypnotics include medications with varying half-lives and metabolic pathways. Short-acting benzodiazepines such as triazolam or alprazolam and the “z-drugs” zolpidem or zaleplon may help initiate sleep in patients with sleep-onset insomnia. Longer-acting benzodiazepines such as diazepam, clonazepam, or temazepam and the z-drug eszopiclone may also help with sleep maintenance.23 Based on my clinical experience, individual patients may respond better to 1 type of medication over another, or even to different agents within the same class of sedative-hypnotics.
Some clinicians prescribe nonbenzodiazepine medications for sleep, such as doxepin (which is FDA-approved for treating insomnia) or off-label trazodone, mirtazapine, or quetiapine. Their antihistaminic properties confer sedating effects. Virtually all over-the-counter (OTC) medications for insomnia are antihistaminic. These OTC medications are not designed to treat insomnia, and the optimal dosage to maintain sleep without daytime sedation must be determined by trial and error. Sedating nonbenzodiazepine medications may be slowly absorbed if taken at bedtime (depending on whether they are taken with or without food) and cause daytime sedation and cognitive slowness in patients with sleep-onset and maintenance insomnia who must wake up early. Starting trazodone at 50 to 75 mg may cause slow metabolizers to wake up with considerable sedation, while fast metabolizers might never feel soundly asleep.24
Patients with mood and anxiety disorders that complicate insomnia are often prescribed second-generation antipsychotics such as quetiapine, lurasidone, or olanzapine, which are sedating as well as mood-stabilizing. These approaches require careful attention to titrating doses and timing their use.
Problems with pharmacotherapy
When either benzodiazepines or nonbenzodiazepine medications are used on a long-standing, nightly basis, they often stop working well. It is not unusual that after days to weeks of taking a benzodiazepine, patients find they no longer stay asleep but can’t fall asleep if they don’t take them. Once tolerance develops, the individual experiences pharmacologic withdrawal with an inability to fall asleep or stay asleep. The medication becomes necessary but ineffective, and many patients increase their use to higher doses to fall asleep, and sometimes in early morning to maintain sleep. This leads to negative effects on cognition, coordination/balance, and mood during the day, especially in older patients.
Nonbenzodiazepine sedating medications do not lead to pharmacologic tolerance but do lead to tachyphylaxis as the CNS attempts to downregulate sedation to keep the organism safe. For some patients, this happens quickly, within a matter of days.25 Others increase doses to stay asleep. For example, a patient with a starting dose of trazodone 75 mg/d might increase the dosage to 300 mg/d. While trazodone is approved in doses of 300 to 600 mg as an antidepressant, it is preferable to keep doses lower when used only for sedation.
Continue to: An alternating medication strategy