Doxepin Side Effects
Doxepin causes anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention), drowsiness, and cardiovascular effects (hypotension, hypertension, tachycardia) as its most common side effects, with dry mouth and drowsiness being the most frequently reported. 1
Most Common Side Effects
Anticholinergic Effects
- Dry mouth is the most commonly reported side effect at therapeutic doses 1, 2
- Blurred vision, constipation, and urinary retention occur frequently 1
- These effects may subside with continued therapy, but if they become severe, dosage reduction may be necessary 1
Central Nervous System Effects
- Drowsiness is the most commonly noticed side effect and tends to disappear as therapy continues 1
- Confusion, disorientation, hallucinations, numbness, and paresthesias occur infrequently 1
- Ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor have been reported 1
Cardiovascular Effects
- Hypotension, hypertension, and tachycardia have been reported occasionally 1
- Doxepin causes fewer cardiovascular side effects at usual therapeutic doses compared to other tricyclics 3
- However, it has similar intrinsic cardiotoxicity on overdosage as other tricyclic antidepressants 3
Gastrointestinal Effects
- Nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis have been reported 1
Other Notable Side Effects
Allergic Reactions
- Skin rash, edema, photosensitization, and pruritus occur occasionally 1
Hematologic Effects
- Eosinophilia has been reported in a few patients 1
- Occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura 1
Endocrine Effects
- Raised or lowered libido, testicular swelling, gynecomastia in males 1
- Enlargement of breasts and galactorrhea in females 1
- Raising or lowering of blood sugar levels 1
- Syndrome of inappropriate antidiuretic hormone secretion 1
Additional Effects
- Dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing 1
- Jaundice, alopecia, headache 1
- Exacerbation of asthma, angle closure glaucoma, mydriasis 1
- Hyperpyrexia (in association with chlorpromazine) 1
Comparative Tolerability
Doxepin tends to cause fewer or less troublesome side-effects than imipramine, amitriptyline, or amitriptyline-perphenazine at dosages achieving similar overall response rates. 3
- Doxepin is usually well tolerated, particularly by the elderly and those with cardiovascular disease 3
- Postural hypotension is uncommon with doxepin 3
- In comparative studies, doxepin caused more daytime drowsiness than amoxapine but less constipation 4
- At low doses (1-6 mg) for insomnia, doxepin was well tolerated with sedation/sleepiness and headache being the most common adverse events, mainly at placebo level or less 5
Special Populations
Elderly Patients
- Sedating drugs like doxepin may cause confusion and oversedation in the elderly 1
- Elderly patients should be started on low doses and observed closely 1
Drug Interactions
- Alcohol ingestion may increase the danger of intentional or unintentional doxepin overdosage 1
- Cimetidine can produce clinically significant fluctuations in steady-state serum concentrations, causing serious anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) 1
Withdrawal Symptoms
- Withdrawal symptoms may develop upon abrupt cessation of treatment after prolonged doxepin administration 1
- These symptoms are not indicative of addiction, and gradual withdrawal should prevent them 1
Critical Safety Considerations
- Patients should be warned about drowsiness and cautioned against driving or operating dangerous machinery 1
- Response to alcohol may be potentiated 1
- Deaths may occur from overdosage with this class of drugs 1
- Suicide is an inherent risk in depressed patients; close supervision during early therapy is essential 1