Medications for Insomnia
Pharmaceutical Hypnotics: Benzodiazepines & Z-Drugs
Hypnotic drugs within the benzodiazepine class (also known as depressants) act on GABA receptors in the brain, which modulate activity in major areas associated with the sleep-wake cycle. GABA is an inhibitory neurotransmitter, meaning its role is to suppress brain activity.
Benzodiazepine hypnotics are classified according to their length of action — long, moderate, or short. A shorter half life means the drug will take effect quickly but also leave the system faster. Some examples include Xanax, Ativan, Valium, and Klonopin. Given their sedating effects, these drugs are also used (generally in smaller doses) to treat anxiety.
The Z-drugs, or non-benzodiazepine hypnotics, similarly act on the GABA receptors with some differences as to how, where, and for how long. Some examples include Imovane/Zimovane, Sonata, Lunesta, and Ambien. Individuals with more severe insomnia and greater functional impairment due to sleep problems often prefer these prescription drugs over options that take longer to work (e.g., melatonin, psychotherapy).
There is some concern over prescribing hypnotic sleep medications (both of the benzodiazepine and non-benzodiazepine Z-drug form) given their abuse or addiction potential, as well as their effect on next-day functioning. The day after taking the medication, one might experience a “hangover-like” effect marked by grogginess and/or memory impairments. Suppressed respiration and interactions with other drugs also raise safety concerns. Complex tasks, such as driving, can also be impaired while an individual is under their influence. This is especially a concern in the elderly.
The non-benzodiazepine hypnotics (Z-drugs) have become increasingly prescribed in the past decade, while prescription rates of benzodiazepines have decreased. While Z-drugs have similar but less potent effects, it is unclear where they pose less of a safety risk than benzodiazepines. Patients should have a collaborative discussion to decide which treatment may be best.
A recent study (2012) reviewed FDA data on Z-drugs for reducing sleep latency (time to fall asleep). They found that in 13 studies there were only small effects on sleep latency within persons who were given both Z-drug and placebo. Importantly, their overall conclusions suggested that up to half of the effects of Z-drugs could be attributed to placebo. Because the placebo effect is a psychological phenomenon, the authors of this study suggested looking further toward psychological treatments for insomnia, which may accrue benefits without drug-related side effects.
Melatonin is one of the most commonly-recommended and doctor-prescribed medication agents for treating sleep problems. The effects of melatonin have been evaluated in several research studies among adults and children. The results show that, compared to placebo, melatonin is effective at improving people’s quality of sleep, increasing total sleep time, and reducing the time it takes individuals with insomnia to fall asleep (termed sleep latency). Additionally, melatonin is absent of the adverse side effects and risks associated with hypnotic sleep drugs and, therefore, has become increasingly prescribed in recent years.
Generally, taking melatonin for long durations and in higher potency appears to be more effective at improving total sleep time than taking melatonin for a shorter duration/lower dosage. Dose and duration do not seem as important for aiding sleep quality, as various doses and durations of melatonin use seem to help equally.
Melatonin can be bought over-the-counter or prescribed by a physician, and the health risks appear to be minimal.
Originally considered a “side-effect” of allergy drugs, the sedating effects of antihistamines have now become utilized as a direct sleep-aid. Both their anti-allergy and sedating effects are caused by inhibiting activity of histamine (H1) receptors in the brain.
They are most effective at treating insomnia in those with a brief history of sleep problems who seek short-term relief.
Conveniently, antihistamines can be bought over-the-counter (e.g., Benadryl, doxylamine).
Sedating antidepressants with hypnotic effects have also proven effective as a sleep aid. They are most commonly prescribed among individuals with insomnia related to depression and in individuals with short-term primary insomnia who have a history of depression. Guidelines proposed by the medical community suggest choosing a sedating antidepressant that acts on the serotonin system (serotonin reuptake inhibitors — or SSRIs) and to start at initially small doses (e.g., mirtazapine 15mg, trazodone 50mg, trimipramine 25mg, doxepin 25mg; Wiegand, 2008).
Fortunately, antidepressants are considered safer when taken long term. There is a lesser risk of dependence and tolerance associated with frontline hypnotic sleep drugs. Thus antidepressants may be ideal for treating insomnia in depressed/anxious patients.
In most cases of primary insomnia, off-label use of antidepressants is not considered the most appropriate medication choice given the lack of research supporting their effectiveness in non-depressed insomniacs. Thus, in uncomplicated insomnia, benzodiazepines or Z-drugs are generally recommended over antidepressants due to their fast-acting, reliable effects.