Current Therapies for Insomnia

By | March 23, 2015

Most individuals who suffer from insomnia either self-treat with nonprescription sleep aids (e.g., antihistamines, herbal remedies), use alcohol as a sedative, or take no drug therapy at all. For those who do seek professional help (approximately one-third of insomniacs), the majority receive physician-prescribed benzodiazepine or non-benzodiazepine sedative hypnotics to treat their insomnia. Such hypnotic agents produce drowsiness and facilitate the onset and maintenance of sleep from which the individual may be easily aroused.

Historically, prior to the advent of the benzodiazepines, low-dose barbiturates and alcohols (e.g., chloral hydrate) were widely used to treat insomnia. Today, however, these agents are rarely used because they are associated with several adverse reactions (e.g., addiction, respiratory suppression, hepatic disease, unexpected deaths) and because newer, safer hypnotics such as the benzodiazepines and non-benzodiazepine hypnotics are available.

TABLE Prescription Drugs Used for Insomnia

Agent Company / Brand Daily Dose(a) Availability
Benzodiazepine hypnotics c
Triazolam Pfizer’s Halcion, generics 0.25-0.5 mg US, France, Germany, Italy,Spain, Japan
Temazepam Mallinckrodt’s Restoril, generics 30 mg US, France, Germany, Italy, UK
Flurazepam Valeant’s Dalmane, generics 15-30mg US, Germany, Italy, Spain, UK, Japan
Sedating antidepressants d
Trazodone Aventis’s Molipaxin, Bristol-Myers Squibb’s Desyrel, generics 50-100 mg US, Germany, Italy, Spain, UK, Japan
Mirtazapine Organon’s, Remeron / Remergil / Zispan, generics 15-30mg US, France, Germany, Italy,Spain, UK

a Medication is generally taken shortly before bedtime; elderly patients frequently take lower doses (i.e., one-half the strength) than those cited here for the benzodiazepine (benzodiazepine) and non-benzodiazepine hypnotics.

b As a result of the Sanofi-Aventis merger (approved by the European Commission in April 2004), Aventis will divest itself of all marketing rights for Imovane (zopiclone) in European countries.

c Numerous benzodiazepines are used to treat insomnia (see text discussion of benzodiazepine hypnotics); the three presented in this table are among the most widely prescribed.

d Other antidepressants with sedating properties, such as the tricyclic antidepressants amitriptyline (Roche’s Laroxyl, AstraZeneca’s Elavil, generics), doxepin (Roerig’s Sinequan, generics), and trimipramine (Aventis’s Surmontil, generics) are also used to treat insomnia. Doses used for insomnia are lower than those used for depression.

Benzodiazepines, introduced in the early 1960s, were the first class of relatively selective hypnotics available. By the late 1980s, even more-selective non-benzodiazepine hypnotics such as zopiclone (Aventis’s Imovane / Amoban, Chugai’s Amban, generics) and zolpidem (Sanofi-Synfhelabo’s Ambien / Stilnox, Fujisawa’s Myslee, generics) became available. Today, these traditional benzodiazepines and non-benzodiazepine hypnotics constitute the bulk of physician prescriptions for the short-term treatment of insomnia. (Traditional benzodiazepine and non-benzodiazepine hypnotics are not indicated for long-term treatment of insomnia.)

Less frequently prescribed for insomnia are the sedating antidepressants such as trazodone (Bristol-Myers Squibb’s Desyrel, Aventis’s Molopaxin, generics), mirtazapine (Organon’s Remeron / Remergil), and amitriptyline (Roche’s Laroxyl, AstraZeneca’s Elavil, generics), among others. Physicians sometimes prescribe these agents in place of the sedative hypnotics for patients who suffer from comor-bid depression and insomnia or for patients who require long-term treatment for insomnia.

Finally, physicians sometimes recommend natural remedies such as herbal drugs and, in certain markets (primarily the United States), melatonin, to individuals suffering from insomnia who prefer not to take a chemical drug. This practice is particularly common in France and Germany, where physicians use herbal remedies such as valerian and crataegus oxaycantha nearly as frequently as they use prescription hypnotics. However, these remedies can be purchased without a prescription in most countries; these products are not discussed further here because the focus is on prescription drugs for insomnia.

Table Prescription Drugs Used for Insomnia summarizes the leading prescription drug therapies available to treat insomnia. Table Comparison of Current Therapies for Insomnia compares the relative efÞcacy of these therapies and summarizes their advantages and disadvantages.

TABLE Comparison of Current Therapies for Insomnia

Compound / Class Advantages Disadvantages
Zolpidem • Effective in shortening sleep latency • Provides only six-hour duration of effect in some patients
• Effective in improving sleep duration • Cannot be taken for middle-of-the-night waking
• Effective in reducing early morning awakening • Only indicated for short-term use
• Low propensity for tolerance and dependence • Not recommended for those with addictive personalities
• No memory impairment or loss of coordination
• Can be used on an “as needed” basis
• No negative effect on sleep architecture
Zopiclone • Effective in shortening sleep latency • Can cause residual effects reminiscent of benzodiazepines in some patients
• Effective in improving sleep duration • Cannot be taken for middle-of-the-night waking
• Effective in reducing early morning awakening • Only indicated for short-term use
• Low propensity for tolerance and dependence • Not recommended for those with addictive personalities
• No memory impairment or loss of coordination
• Can be used on an “as needed” basis
• No negative effect on sleep architecture
Zaleplon • Effective in shortening sleep latency • Too short-acting to provide full-night duration of effect
• Can be used for middle-of-the-night waking • Propensity to induce rebound insomnia
• Low propensity for tolerance and dependence • Only indicated for short-term use
• No memory impairment or loss • Not recommended for those with

addictive personalities

of coordination
• Can be used on an “as needed” basis
• No negative effect on sleep architecture
Traditional benzodiazepine hypnotics • Effective in shortening sleep latency • Can induce tolerance and dependence
• Effective in improving sleep duration • Can cause memory impairment and loss of coordination
• Effective in reducing early morning awakening • Negative effect on sleep architecture
• Can be used on an “as needed” basis • Only indicated for short-term use

• Not recommended for those with addictive personalities

• Not recommended for those with respiratory conditions (e.g., sleep apnea)
Sedating antidepressants • Effective in improving sleep duration • Slow to elicit hypnotic effect
• Effective in reducing early morning awakening • Not an option for “as needed” use
• Antidepressant as well as sleep-enhancing properties • Numerous side effects (e.g., daytime sedation, weight gain)
• No tolerance or dependence
• No memory impairment or loss of coordination
• Ideal for long-term treatment
• No negative effect on sleep architecture

Nonbenzodiazepine Hypnotics

Benzodiazepine Hypnotics

Sedating Antidepressants

Nonpharmacological Approaches

Behavioral therapies are occasionally used to manage patients with insomnia. Such therapies are designed to change bad sleep habits and alter dysfunctional beliefs and attitudes that contribute to insomnia. Behavioral therapies used to manage insomnia include sleep hygiene, relaxation therapy, sleep restriction therapy, stimulus control therapy, and cognitive therapy. Bright light therapy is another nonpharmacological approach that is occasionally recommended for insomnia related to altered circadian rhythms, as well as certain depressive states (e.g., seasonal affective disorder).