Clinical Guide > Neuropsychiatric Disorders > Insomnia

Insomnia

January 2011

Chapter Contents

Background

Insomnia is a common accompaniment to HIV infection, especially as the disease progresses and complications worsen. Once present, insomnia tends to be chronic, unlike the transient disturbances of sleep that are a normal part of life. Most insomnia related to HIV can be characterized by the amount, quality, or timing of sleep. Insomnia may cause progressive fatigue and diminished functioning.

S: Subjective

The patient may complain of the following:

Ask about the symptoms above, and about the following:

Ask about the following:

O: Objective

Perform a general symptom-directed physical examination, including evaluation of body habitus, neurologic status, and mental status.

A: Assessment

A partial differential diagnosis includes the following:

Pain

Underlying systemic medical conditions that can interfere with sleep, such as delirium, lung disease, congestive heart failure, renal failure, diarrhea, and incontinence

P: Plan

Evaluation

The diagnosis usually is based on history. A sleep evaluation (including polysomnography) may be indicated when a physiologic cause (e.g., obstructive sleep apnea) is suspected or insomnia is severe.

Treatment

Treat underlying illnesses that may be causing or contributing to insomnia.

The following options are available for treatment:

Behavioral strategies

Pharmacotherapy

Choosing a pharmacologic agent for insomnia

A number of medications may be effective in treating insomnia. In selecting a medication for an individual patient, consider the following about a specific medication:

Treatment considerations

There are limited data to guide the frequency (nightly, intermittently, as needed) and duration (brief, intermediate, long-term) of hypnotic medications. Hypnotics generally should be prescribed at the lowest effective dosage for the shortest possible period. The greater the degree of physical illness, the more likely the patient will need a low dosage of a hypnotic agent. When long-term treatment is necessary, benzodiazepines pose the greatest risk of tolerance, abuse, and dependence.

Possible adverse effects of all hypnotics include excess sedation, daytime grogginess, and disruption of the sleep architecture (e.g., causing sleepwalking).

Interactions may occur between certain antiretrovirals (ARVs) and agents used to treat insomnia. Some combinations may be contraindicated and others may require dosage adjustment. Refer to medication interaction resources or consult with an HIV expert, psychiatrist, or pharmacist before prescribing.

Agents with FDA-Approved Indications for Insomnia

Antihistamines

  • The antihistamines diphenhydramine, doxylamine, and hydroxyzine, given at doses of 25-50 mg QHS, can be used for sleep. Adverse anticholinergic effects often interfere with long-term use.

Antidepressants

  • Trazodone, 25-50 mg; maximum dose: 200 mg QHS.
    • Trazodone, a triazolopyridine derivative antidepressant and sedative, is the only antidepressant with a U.S. Food and Drug Administration (FDA) indication for insomnia, and it is widely used for this purpose. However, levels are increased by ritonavir-boosted PIs. Do not use with saquinavir/ritonavir; use lower dosages for patients receiving other PIs. Trazodone may (rarely) cause priapism. Trazodone can be used for an indefinite period of time as it is not associated with tolerance or addiction.

Non-benzodiazepine hypnotics (agonists of the benzodiazepine receptor)

  • Zolpidem (Ambien) 5-10 mg, zolpidem-CR (Ambien-CR) 6.25-12.5 mg, zaleplon (Sonata) 5-10 mg, and eszopiclone (Lunesta) 2-3 mg QHS.
    • These newer hypnotic agents are benzodiazepine receptor agonists with shorter half-lives than benzodiazepines and are not likely to result in day-after drowsiness. They may have decreased addiction potential compared with benzodiazepine hypnotics. Patients should be advised to use these hypnotics on an as-needed basis rather than nightly; it is easier for patients to discontinue a drug that they are not taking every day. The inhibition of CYP 3A4 enzyme activity by PIs may increase levels of these benzodiazepine receptor agonists, particularly eszopiclone; this may cause excessive sedation or respiratory depression.

Melatonin agonists

  • Ramelteon (Rozerem), 8 mg QHS.
    • The first of a new class of melatonin agonists to receive FDA approval, ramelteon may have some advantages over sedative/hypnotic agents, such as reduced dependence and overuse. However, it may have severe adverse reactions, including hypersensitivity reactions such as anaphylaxis and angioedema. Long-term interactions with ARV agents are unknown.

Benzodiazepine hypnotics

  • A number of benzodiazepines have FDA-approved indications for the short-term treatment of insomnia. They carry a risk of addiction and residual drowsiness the following day.
  • Metabolized by glucuronidation; predicted to have few drug interactions with ARVs:
    • Temazepam (Restoril) 7.5-30 mg; intermediate half-life
    • Lorazepam (Ativan), 2-4 mg; intermediate half-life
  • Metabolized by CYP 34A; PIs may prolong their duration, resulting in excessive daytime somnolence. These may be most beneficial for use with patients whose insomnia is associated with anxiety:
    • Flurazepam (Dalmane) 15-30 mg
    • Quazepam (Doral) 7.5-15 mg
    • Estazolam (ProSom) 1-2 mg
  • Clonazepam (Klonopin) at a dose of 0.5-2 mg has been approved for treatment of periodic leg movements. PIs may prolong its duration and increase risk of adverse effects; start at low dosage and titrate slowly.
  • Triazolam (Halcion), another approved agent for insomnia, is contraindicated for use with all PIs and some nonnucleoside reverse transcriptase inhibitors (NNRTIs) (delavirdine, efavirenz) because of potentially life-threatening reactions (e.g., respiratory depression)

Agents Used for Sedating Side Effects (no FDA indication for insomnia)

Antidepressants

  • Tricyclic antidepressants at doses of 10-50 mg can be beneficial for sleep, but they have longer half-lives than short-acting hypnotic agents, and potential adverse effects include cardiac dysrhythmias and pulmonary complications. Also, levels of tricyclics are elevated by ritonavir and lower dosages may be needed for patients taking ritonavir or ritonavir-boosted PIs. Routine testing of tricyclic blood levels should be performed on patients receiving higher doses (eg, 100 mg per day; 50 mg for nortriptyline), those on concurrently on ritonavir, and those with risk factors for cardiac conduction abnormalities. A routine electrocardiogram should be performed before prescribing tricyclics, and this class of drugs should not be prescribed to patients with cardiac conduction problems. However, tricyclic antidepressants also have characteristics that may benefit some patients, including treatment of chronic pain, promotion of weight gain, and reduction of diarrhea. Amitriptyline (Elavil) and doxepin (Sinequan) are the most sedating of the tricyclic antidepressants and therefore are the drugs in this class most often used for sleep.
  • The tetracyclic antidepressant mirtazapine (Remeron) is sedating and has been effective in treating insomnia at low dosages (7.5-15 mg). Higher dosages may result in increased activation owing to increased NE receptor antagonism.
  • The selective serotonin reuptake inhibitor (SSRI) antidepressants are not sufficiently sedating to be used as sleeping agents, but when insomnia is caused by depression, sleep will improve as the depression lifts.

Anticonvulsants

  • Gabapentin (Neurontin) can be useful for patients with insomnia and has been demonstrated to be particularly beneficial for patients with alcohol and other substance-use disorders; it is widely prescribed for neuropathic pain. Tiagabine (Gabitril) has demonstrated efficacy in adults with insomnia.

Patient Education

References

HRSA HAB Core Clinical Performance Measures