From the Guidelines
Doxepin is associated with a range of side effects, including sedation, drowsiness, and dry mouth, with the incidence of adverse events seeming to increase with longer treatment, as noted in a low-quality systematic review 1. The most common side effects of doxepin include:
- Sedation and drowsiness
- Dry mouth
- Dizziness
- Constipation
- Blurred vision
- Weight gain
- Increased appetite
- Urinary retention
- Confusion These side effects are likely due to doxepin's mechanism of action, which involves blocking multiple neurotransmitter receptors, including histamine, muscarinic, and alpha-adrenergic receptors. Elderly patients are particularly susceptible to anticholinergic effects, such as confusion and urinary problems, and may also be at risk for orthostatic hypotension, which can lead to falls. It is worth noting that none of the RCTs found statistically significant differences in adverse event rates between low-dose doxepin and placebo, although the risk for suicidal ideation associated with use of low-dose doxepin as a hypnotic agent is unknown and cannot be excluded, as reported in the 2020 study 1. To minimize the incidence of adverse events, it is recommended to start with a low dose of doxepin, such as 3 or 6 mg, and gradually increase as needed, while monitoring for potential side effects.
From the FDA Drug Label
Anticholinergic Effects: Dry mouth, blurred vision, constipation, and urinary retention have been reported Central Nervous System Effects: Drowsiness is the most commonly noticed side effect. This tends to disappear as therapy is continued Other infrequently reported CNS side effects are confusion, disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor. Cardiovascular: Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported occasionally Allergic: Skin rash, edema, photosensitization, and pruritus have occasionally occurred. Hematologic: Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura Gastrointestinal: Nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis have been reported. Endocrine: Raised or lowered libido, testicular swelling, gynecomastia in males, enlargement of breasts and galactorrhea in the female, raising or lowering of blood sugar levels, and syndrome of inappropriate antidiuretic hormone secretion have been reported with tricyclic administration Other: Dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia, headache, exacerbation of asthma, angle closure glaucoma, mydriasis and hyperpyrexia (in association with chlorpromazine) have been occasionally observed as adverse effects Withdrawal Symptoms: The possibility of development of withdrawal symptoms upon abrupt cessation of treatment after prolonged Doxepin administration should be borne in mind.
The side effects of Doxepin (Sinequan) include:
- Anticholinergic effects: dry mouth, blurred vision, constipation, and urinary retention
- Central Nervous System effects: drowsiness, confusion, disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor
- Cardiovascular effects: hypotension, hypertension, and tachycardia
- Allergic reactions: skin rash, edema, photosensitization, and pruritus
- Hematologic effects: eosinophilia, agranulocytosis, leukopenia, thrombocytopenia, and purpura
- Gastrointestinal effects: nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis
- Endocrine effects: raised or lowered libido, testicular swelling, gynecomastia, enlargement of breasts and galactorrhea, raising or lowering of blood sugar levels, and syndrome of inappropriate antidiuretic hormone secretion
- Other effects: dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia, headache, exacerbation of asthma, angle closure glaucoma, mydriasis, and hyperpyrexia 2
From the Research
Side Effects of Doxepin (Sinequan)
The side effects of Doxepin (Sinequan) are similar in nature to those of other tricyclic antidepressants, with the most common being:
- Dry mouth
- Drowsiness
- Constipation
- Postural hypotension is uncommon 3 At low doses, the most common adverse events are:
- Sedation/sleepiness
- Headache 4, 5, 6 In some studies, doxepin was found to cause:
- Rebound insomnia 7
- Specific side effects such as increased liver enzymes, leukopenia, and thrombopenia 7 It is worth noting that doxepin tends to cause fewer or less troublesome side-effects than other tricyclic antidepressants such as imipramine and amitriptyline 3.
Comparison of Side Effects at Different Doses
Low-dose doxepin (1-6 mg) has been found to have minimal effects on sleep architecture and no signal for tolerance, psychomotor impairment, residual sedation, or discontinuation symptoms 4, 5. In contrast, higher doses of doxepin (25-300 mg) have been associated with significant anticholinergic and antinoradrenergic properties, leading to dose-limiting side effects 6.
Special Considerations
Doxepin has an intrinsic cardiotoxicity on overdosage similar to other tricyclics 3. The elderly and those with cardiovascular disease may be more susceptible to the side effects of doxepin, but it is usually well tolerated in these populations 3.