Doxepin (Silenor) for Insomnia

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August 15, 2011
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Volume 84, Number 4 www.aafp.org/afp American Family Physician 453
SAFET Y
Doxepin is safe when used at low dosages.
Antidepressants are required to have label-
ing that warns of an increased risk of sui-
cide; however, there have been no reports
of suicide among patients taking low-dose
doxepin. Unlike higher-dose formulations
of doxepin, Silenor does not have a boxed
warning for suicide risk.1 No dosage adjust-
ments are necessary in patients with renal
impairment. Doxepin should not be used
in patients with severe urinary retention or
in those who also take or who have recently
stopped taking monoamine oxidase inhibi-
tors. Abrupt discontinuation is not asso-
ciated with a withdrawal syndrome.1 The
metabolism of doxepin is affected by cimeti-
dine (Tagamet); patients who take both
drugs should not take more than 3 mg of
doxepin per day. Low-dose doxepin does not
seem to be affected by other drugs that affect
the cytochrome P450 system. Silenor is a U.S.
Food and Drug Administration pregnancy
category C drug.1
TOLERABILITY
Silenor has an adverse effect profile com-
parable to that of placebo. In clinical trials
of 1,017 patients, approximately 1 percent
withdrew because of adverse effects.1 Rebound
insomnia and withdrawal symptoms have not
been reported. Next-day sedation, anticholin-
ergic effects, and memory impairment do not
occur at low dosages.2,3 The use of central ner-
vous system depressants, alcohol, and sedating
antihistamines may increase the sedative effect
of doxepin and should be avoided.1
EFFECTIVENESS
Silenor has been studied mainly in older
patients with primary insomnia and dif-
ficulty falling asleep, frequent waking, or
sleep duration of less than 6.5 hours. In
sleep studies comparing 3-mg and 6-mg
doses for two nights, total sleep dura-
tion increased 25 to 38 minutes compared
with placebo.2,3 Time to sleep onset (sleep
latency) did not decrease significantly. The
benefit in younger adults does not seem to
be as pronounced.1 When given nightly for
up to three months, the 3-mg dose produces
consistent results without causing next-day
residual effects on cognitive performance;
the long-term effects of the 6-mg dose have
not been studied.4 No research has com-
pared Silenor with other hypnotics.
Silenor is a new low-dose formulation of the tricyclic antidepressant doxepin (which is typi-
cally taken as a 25- to 150-mg dose at bedtime). Low-dose doxepin is labeled for the treatment
of insomnia characterized by difficulty maintaining sleep. The exact mechanism by which the
medication exerts its sleep maintenance effect is unknown, but is thought to be antagonism
of histamine H1 receptors.1
Doxepin (Silenor) for Insomnia
DHIREN PATEL, PharmD, and JENNIFER D. GOLDMAN-LEVINE, PharmD
Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts
STEPS new drug reviews
cover Safety, Tolerability,
Effectiveness, Price, and
Simplicity. Each indepen-
dent review is provided
by authors who have no
financial association with
the drug manufacturer.
The series coordinator for
AFP
is Allen F. Shaugh-
nessy, PharmD, Tufts
Universit y Family Medicine
Residency Program at
Cambridge Health Alli-
ance, Malden, Mass.
A collection of STEPS pub-
lished in
AFP
is available
at http://www.aafp.org/
afp/steps.
STEPS
New Drug Reviews
Drug Dosage Dose form Monthly cost*
Doxepin (Silenor) 3 to 6 mg daily 3-mg and 6-mg tablets $208
*—Price for 30 3-mg or 6-mg tablets at CVS Pharmacy on May 18, 2011.
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STEPS
PRICE
Silenor costs approximately $208 for 30 3-mg
or 6-mg tablets. Less expensive formulations
of doxepin are available, such as a generic
oral solution (10 mg per mL; approximately
$24 per 120-mL bottle) and a generic 10-mg
capsule (approximately $20 for 90 capsules).
Pharmacists cannot substitute these products
for Silenor; the generic name must be used
on the prescription.
SIMPLICIT Y
Patients older than 65 years should begin
with a 3-mg dose, and increase to 6 mg if nec-
essary. In younger adults, the recommended
starting dose is 6 mg. Patients with hepatic
impairment or with a tendency for urinary
retention should start with the lower dose.
Doxepin should be taken within 30 minutes
before bedtime, but not within three hours of
a meal. Dependence has not been shown in
studies, and there are no limitations on the
duration or frequency of use.
Bottom Line
In older patients with primary insomnia,
Silenor can increase duration of sleep with-
out next-day effects. However, it does not
significantly decrease the time to sleep onset,
and it is less effective in younger adults. Less
expensive options for insomnia treatment are
available, including a generic oral solution of
doxepin and a generic 10-mg capsule.
Address correspondence to Dhiren Patel, PharmD, at
dhiren.patel1@mcphs.edu. Reprints are not available
from the author s.
Author disclosure : No relevant financial affiliations to
disclose.
REFERENCES
1. Silenor (doxepin) [prescribing information]. San Diego, Calif.:
Somaxon Pharmaceuticals, Inc.; 2010. http://www.silenor.
com /pub /d ownlo ada shx?key= %2f wE CFQ %3d%3d.
Accessed November 1, 2010.
2. Roth T, Rogowski R, Hull S, et al. Efficacy and safety of
doxepin 1 mg, 3 mg, and 6 mg in adults with primary
insomnia. Sleep. 2007;30(11):1555-1561.
3. Schar f M, Rogowski R, Hull S, et al. Efficacy and safety
of doxepin 1 mg, 3 mg, and 6 mg in elderly patients
with primar y insomnia: a randomized, double-blind,
placebo-controlled crossover study. J Clin Psychiatry.
2008;69 (10):1557-1564.
4. Krystal AD, Durrence HH, Scharf M, et al. Efficacy and
safety of doxepin 1 mg and 3 mg in a 12-week sleep labo-
ratory and outpatient trial of elderly subjects with chronic
primary insomnia. Sleep. 2010;33(11):1553-1561. ■