Can Doxepin Cause Hypotension?
Yes, doxepin can cause orthostatic hypotension, though it appears to cause this less frequently than some other tricyclic antidepressants like imipramine. 1, 2
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for doxepin explicitly lists severe hypotension as a critical manifestation of overdose, and notes that cardiovascular effects are among the documented adverse reactions. 1
Comparative Risk Profile
Doxepin causes significantly less orthostatic hypotension than imipramine in elderly depressed patients, with mean systolic postural drops of 10.5 mm Hg for doxepin versus 25.9 mm Hg for imipramine (compared to 12.4 mm Hg for placebo). 2
Historical literature from the 1970s-1980s suggested that postural hypotension is uncommon with doxepin compared to other tricyclics. 3
However, more rigorous prospective evaluation in patients with preexisting cardiac disease found that doxepin caused a significant increase in orthostatic hypotension, with 16% of patients dropping out due to cardiovascular side effects. 4
Clinical Context and Risk Factors
The risk of orthostatic hypotension with doxepin increases substantially in patients with:
- Severe heart disease, where the incidence rises dramatically 5
- Concurrent cardiac medications, which show significant association with symptomatic orthostatic hypotension (p < 0.01) 5
- Reduced ejection fraction and altered baseline vascular resistance 5
Comparative Safety Among Tricyclics
In elderly patients without severe cardiac disease, doxepin shows no significant differences in orthostatic blood pressure changes compared to maprotiline during treatment phases. 6
The cardiovascular effects of doxepin in depressed patients with heart disease are comparable to those documented for imipramine and nortriptyline, affording no greater margin of cardiovascular safety. 4
Clinical Implications
Monitor orthostatic blood pressure in all patients starting doxepin, particularly:
- Elderly patients (age >55 years) 2
- Those with preexisting cardiovascular disease 4, 5
- Patients taking concurrent antihypertensive or cardiac medications 5
The orthostatic effect occurs early in treatment and at low doses, so vigilance is required from treatment initiation rather than only at higher doses. 2