Doxepin Uses and Applications
Doxepin is primarily used for treating depression, anxiety disorders, insomnia (particularly sleep maintenance insomnia at low doses of 3-6mg), and certain psychiatric conditions. 1
Primary Indications
Doxepin has several FDA-approved uses:
- Treatment of psychoneurotic patients with depression and/or anxiety
- Depression and/or anxiety associated with alcoholism
- Depression and/or anxiety associated with organic disease
- Psychotic depressive disorders with associated anxiety 1
Specific Uses Based on Dose
Higher Doses (25-150mg)
- Depression and anxiety disorders
- Particularly effective for depression with comorbid anxiety
- Beneficial for patients with depression who have sleep disturbances 2
Low Doses (3-6mg)
- Sleep maintenance insomnia (difficulty staying asleep)
- Recommended specifically for elderly patients with sleep maintenance difficulties 3
- Improves sleep parameters including:
- Mean Insomnia Severity Index scores
- Sleep onset latency
- Total sleep time
- Wake after sleep onset 3
Pharmacological Properties
Doxepin belongs to the tricyclic antidepressant class and has the following properties:
- Dibenzoxepin derivative with a structure similar to amitriptyline
- Combines antidepressant activity with sedative effects
- Mechanism of action likely involves preventing reuptake of norepinephrine at nerve terminals
- Has anticholinergic, antiserotonin, and antihistamine effects 1, 2
Clinical Efficacy
- For depression: Similar mood-elevating effects to amitriptyline but possibly less marked than imipramine 2
- For insomnia: Low-dose doxepin (3-6mg) significantly improves sleep maintenance with moderate-quality evidence 3
- For anxiety with depression: More effective than benzodiazepines like chlordiazepoxide or diazepam 2
- For comorbid insomnia and anxiety: Low-dose doxepin (12.5mg) significantly improves sleep latency, duration, and quality 4
Safety Considerations
- Suicidality risk: Requires monitoring for clinical worsening and suicidal ideation, especially in patients under 24 years old 1
- Not approved for use in pediatric patients under 12 years 1
- Generally well-tolerated, particularly by elderly patients and those with cardiovascular disease 2
- Common side effects include dry mouth, drowsiness, and constipation 2
- May cause angle-closure glaucoma in susceptible individuals 1
- Rebound insomnia may occur in some patients after discontinuation 5
Dosing Considerations
- For insomnia: 3-6mg is recommended, particularly for sleep maintenance issues 3
- For depression/anxiety: Typically starts at higher doses (25-150mg)
- Lower doses should be used in elderly patients
- Long-term use for chronic depression has been shown to be feasible, efficacious, and safe 6
Advantages Over Other Medications
- At therapeutic doses, causes fewer cardiovascular side effects than some other tricyclics 2
- Low-dose formulation (3-6mg) for insomnia has a safety profile comparable to placebo with no significant next-day residual effects 7
- When treating depression with anxiety, has fewer or less troublesome side effects than imipramine, amitriptyline, or amitriptyline-perphenazine 2
Doxepin's dual utility for both mood disorders and sleep disturbances makes it particularly valuable when these conditions co-occur, though the appropriate dose varies significantly depending on the primary indication.