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Psychopharmacology book



Doxepin (Sinequan) was released in 1969 as a tricyclic antidepressant (TCA). It  is an incredibly strong antihistamine. It is available as a topical cream for pruritus. 

Doxepin Silenol Sinequan by Dr Jason Cafer MD

Doxepin is rarely prescribed at antidepressant strength (150–300 mg capsules) but is commonly used at 10 mg for insomnia. The advantage of doxepin over other antihistamines for sleep is doxepin has minimal anticholinergic activity at a low dose. Traditional antihistamines such as diphenhydramine (Benadryl) and doxylamine (Unisom) are highly anticholinergic, as are the other sedating TCAs such as amitriptyline (Elavil) and clomipramine (Anafranil). In most circumstances, anticholinergic effects are undesirable. Anticholinergics constipate, cause xerostomia, impair cognition (“mad as a hatter”) and increase risk of dementia with long-term use. Doxepin’s advantage is lost at a high dose where it becomes highly anticholinergic. 

Doxein Silenor Sinequan interactions and indications by Dr Jason Cafer MD

Overdosing on a bottle of any full-strength TCA can be fatal, However, low dose Doxepin is safe to prescribe, even for patients at risk for suicidal overdose for whom you would never prescribe most TCAs. A 30-day supply of Doxepin 10 mg is only 300 mg, which would not kill a patient downing the full bottle (although 300 mg could theoretically be contributory to a fatal multidrug overdose). 


The original trade name of the (now generic) doxepin capsule is Sinequan. A tiny dose doxepin tablet was released in 2017, branded as Silenor, available in 3 mg and 6 mg strengths. Generic 3 mg or 6 mg pills do not exist. Branded Silenor costs about $15 per tablet, which is about $450 monthly. Compare this to 10 mg generic doxepin capsules, which are only $0.33 per capsule (about $10 monthly). 


Generic doxepin (Sinequan) carries the same black box warning as all other antidepressants regarding suicidal thoughts and behaviors in children and young adults. Silenor (3 mg, 6 mg) does not have the boxed warning.


Doxepin 5% cream is approved as a topical antihistamine for pruritus, branded as Zonalon, priced at $300–$660 per tube. The cream may cause systemic symptoms including sedation and anticholinergic effects, especially if applied to > 10% of body surface. The cream is intended for no longer than 8 days of treatment. 

Doxepin cream visual mnemonic by Dr Jason Cafer MD antihistamine snake

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