Doxepin Dosing and Usage
For Insomnia (Primary Indication at Low Dose)
Low-dose doxepin (3-6 mg) is specifically recommended for sleep maintenance insomnia and should be taken at bedtime, with the 6 mg dose showing efficacy for both sleep onset and maintenance. 1, 2
Dosing for Insomnia
- Sleep maintenance insomnia: 3-6 mg at bedtime 1, 2
- Sleep onset and maintenance: 6 mg at bedtime 3
- Maximum dose for insomnia: 6 mg (higher doses increase anticholinergic side effects without additional sleep benefit) 4, 5
- Can be given on empty stomach to maximize effectiveness 2
Key Advantages for Insomnia
- Works through selective H1 histamine receptor antagonism at low doses 4, 5
- Improves wake time after sleep onset, total sleep time, and sleep efficiency significantly better than placebo 3
- Effects evident after single dose and maintained for up to 12 weeks without tolerance 3
- No evidence of rebound insomnia, physical dependence, or withdrawal symptoms 3
- Minimal effects on sleep architecture 5
Position in Treatment Algorithm
- Second-line pharmacologic option for sleep maintenance insomnia, after cognitive behavioral therapy for insomnia (CBT-I) 2, 6
- Preferred over trazodone, which has weak evidence and significant adverse effects 2
- Alternative to benzodiazepine receptor agonists (zolpidem, eszopiclone) when those are contraindicated or have failed 1, 2
For Depression and Anxiety (Higher Dose)
For depression and anxiety disorders, doxepin requires antidepressant doses of 75-300 mg daily, divided or given once at bedtime, with most patients responding to 75-150 mg daily. 7
Dosing for Depression/Anxiety
- Starting dose: 75 mg daily (can start lower at 25-50 mg in mild cases or elderly) 7
- Optimal range: 75-150 mg daily 7
- Severe illness: May increase gradually to 300 mg daily if needed 7
- Maximum dose: 300 mg daily (rarely provides additional benefit beyond this) 7
- Can be given as divided doses or once daily at bedtime (maximum 150 mg for once-daily dosing) 7
Approved Indications at Antidepressant Doses
- Psychoneurotic patients with depression and/or anxiety 7
- Depression and/or anxiety associated with alcoholism (not taken concomitantly with alcohol) 7
- Depression and/or anxiety associated with organic disease 7
- Psychotic depressive disorders with associated anxiety, including involutional depression and manic-depressive disorders 7
Target Symptoms
- Anxiety, tension, depression, somatic symptoms, sleep disturbances, guilt, lack of energy, fear, apprehension, and worry 7
- Anti-anxiety effect appears before antidepressant effect 7
- Optimal antidepressant effect may not be evident for 2-3 weeks 7
Special Populations and Precautions
Elderly Patients
- Start with low doses (10-25 mg for depression; 3 mg for insomnia) and observe closely 1, 7
- Elderly are more prone to confusion, oversedation, and anticholinergic effects 7
- Consider dose reduction due to decreased renal function 7
Contraindications
- Hypersensitivity to doxepin or other dibenzoxepines 7
- Glaucoma or tendency to urinary retention (particularly important in older patients) 7
- Not approved for pediatric use under 12 years 7
Important Warnings
- Black box warning: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) with major depressive disorder 7
- All patients starting antidepressant therapy require close monitoring for clinical worsening, suicidality, or unusual behavior changes 7
- Avoid in pregnancy and nursing 2
- Use caution in patients with compromised respiratory function, hepatic or heart failure 2
Drug Interactions
- At doses up to 150 mg daily, does not block antihypertensive effect of guanethidine 7
- At doses above 150 mg daily, may block antihypertensive effect 7
- Caution with concurrent sedating medications due to additive effects 2
Critical Clinical Pitfalls
Common Dosing Errors
- Do not use low-dose doxepin (3-6 mg) for depression: These doses are inadequate for treating major depressive disorder and only work for insomnia 2
- Do not use antidepressant doses (75-300 mg) primarily for insomnia: Higher doses cause significant anticholinergic side effects without additional sleep benefit 4
When Low-Dose Doxepin May NOT Work
- Primary insomnia with comorbid major depressive disorder: Low-dose doxepin (< 25 mg) does not improve sleep onset or maintenance in patients with active MDD 8
- In this scenario, treat the depression with full antidepressant doses or combine low-dose doxepin with a full-dose antidepressant 1, 2
Comorbid Conditions Requiring Special Consideration
- Bipolar disorder: Low-dose doxepin (3-6 mg) is preferred over other sedating antidepressants as it has minimal risk of triggering mania at this dose 6
- Anxiety with insomnia: Both citalopram (20 mg) and low-dose doxepin (12.5 mg) improve sleep and anxiety, though doxepin shows superior improvement in sleep latency 9