General Information

Silenor (doxepin) binds with high affinity to the histamine H1 receptor where it functions as an antagonist. The exact mechanism by which doxepin exerts its sleep maintenance effect is unknown, but is believed due to its antagonism of the H1 receptor.

Silenor is specifically indicated for the treatment of insomnia characterized by difficulty with sleep maintenance.

Mechanism of Action

Silenor (doxepin) binds with high affinity to the histamine H1 receptor where it functions as an antagonist. The exact mechanism by which doxepin exerts its sleep maintenance effect is unknown, but is believed due to its antagonism of the H1 receptor.

Side Effects

Adverse events associated with the use of Silenor may include, but are not limited to, the following:

• somnolence
• sedation
• nausea
• upper respiratory tract infection

Dosing/Administration

Silenor is supplied as an immediate-release tablet for oral administration. The recommended dose of Silenor for adults is 6 mg once daily. The recommended starting dose of Silenor in elderly patients (>65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg if clinically indicated. Silenor should be taken within 30 minutes of bedtime. The total Silenor dose should not exceed 6 mg per day.

Clinical Trial Results

The efficacy of Silenor for improving sleep maintenance was supported by six randomized, double-blind studies in a total of 1,423 subjects, 18 to 93 years of age, with chronic or transient insomnia. Silenor was evaluated at doses of 1 mg, 3 mg and 6 mg relative to placebo. The primary efficacy measures for assessment of sleep maintenance were the objective and subjective time spent awake after sleep onset (respectively, objective wake after sleep onset [WASO] and subjective WASO).
Chronic insomnia: adults
A randomized, double-blind, parallel-group study was conducted in 221 adults with chronic insomnia. Silenor 3 mg and 6 mg were compared to placebo out to 30 days. Silenor 3 mg and 6 mg were superior to placebo on objective WASO. Silenor 3 mg was superior to placebo on subjective WASO at night 1 only. Silenor 6 mg was superior to placebo on subjective WASO at night 1, and nominally superior at some later time points out to day 30.
Chronic insomnia: elderly
Elderly subjects with chronic insomnia were assessed in two parallel-group studies. The first randomized, double-blind study assessed Silenor 1 mg and 3 mg relative to placebo for three months in inpatient and outpatient settings in elderly subjects (N=240) with chronic insomnia. Silenor 3 mg was superior to placebo on objective WASO. The second randomized, double-blind study assessed Silenor 6 mg relative to placebo for four weeks in an outpatient setting in elderly subjects (N=254) with chronic insomnia. On subjective WASO, Silenor 6 mg was superior to placebo.
Transient insomnia
A randomized, double-blind, parallel-group, single-dose study enrolled 565 healthy adults who were experiencing transient insomnia during the first night in a sleep laboratory. Silenor 6 mg was superior to placebo on objective WASO and subjective WASO.
Withdrawal effects
Potential withdrawal effects were assessed in a 35-day, double-blind study of adults with chronic insomnia who were randomized to placebo, Silenor 3 mg or Silenor 6 mg. There was no indication of a withdrawal syndrome after discontinuation of Silenor treatment (3 mg or 6 mg) as measured by the Tyrer symptom checklist. Discontinuation-period-emergent nausea and vomiting occurred in 5 percent of subjects treated with 6 mg Silenor versus 0 percent in 3 mg and placebo subjects.
Rebound insomnia effects
Rebound insomnia, defined as a worsening in WASO compared with baseline following discontinuation of treatment, was assessed in a double-blind, 35-day study in adults with chronic insomnia. Silenor 3 mg and 6 mg showed no evidence of rebound insomnia.