What is the role of dosulepin (tricyclic antidepressant) in managing osteoarthritis, particularly in older adults with potential comorbid conditions and a history of depression or chronic pain?

Dosulepin in Osteoarthritis

Dosulepin (dothiepin), a tricyclic antidepressant, is NOT recommended for osteoarthritis management and should be avoided, particularly in older adults, due to significant safety concerns including risks of confusion, falls, and lack of evidence supporting its efficacy for osteoarthritis pain.

Why Dosulepin Should Not Be Used

Tricyclic antidepressants like dosulepin carry substantial risks in older adults with osteoarthritis. The CDC explicitly states that "in older adults, decisions to use tricyclic antidepressants should be made judiciously on a case-by-case basis because of risks for confusion and falls" 1. This warning applies to neuropathic pain and fibromyalgia contexts—conditions where tricyclics have some evidence base—yet dosulepin has no established role in osteoarthritis treatment 1.

There is no guideline support or high-quality evidence for using dosulepin specifically in osteoarthritis. Current guidelines do not mention dosulepin as a treatment option for osteoarthritis pain 1, 2, 3.

The Preferred Antidepressant for Osteoarthritis: Duloxetine

If an antidepressant is indicated for osteoarthritis (particularly with comorbid depression or when first-line treatments fail), duloxetine is the evidence-based choice, not dosulepin. The CDC guidelines specifically recommend that "for patients with osteoarthritis pain in multiple joints or incompletely controlled with topical NSAIDs, duloxetine or systemic NSAIDs can be considered" 1.

Evidence Supporting Duloxetine Over Dosulepin

• Duloxetine has FDA approval and guideline support for osteoarthritis pain management 1
• High-certainty evidence demonstrates duloxetine provides clinically meaningful pain relief in a subset of osteoarthritis patients, with 45% achieving ≥50% pain reduction compared to 28.6% with placebo (NNTB = 6) 4
• Duloxetine is particularly beneficial for patients with comorbid depression and osteoarthritis, addressing both conditions simultaneously 5, 6
• Moderate functional improvements occur with duloxetine (5.65-point improvement on WOMAC function scale) 4

Recommended Treatment Algorithm for Osteoarthritis

Step 1: Non-Pharmacologic Foundation (Mandatory First-Line)

• Structured exercise program including quadriceps strengthening and aerobic fitness 2
• Weight reduction if overweight 1, 2
• Patient education and self-management 2

Step 2: First-Line Pharmacologic Treatment

• Acetaminophen up to 4000 mg daily (consider ≤3000 mg daily in elderly for enhanced safety) 2
• Topical NSAIDs (diclofenac 1-1.5% gel) for localized joint pain: 40 drops or 4 grams four times daily to affected joint 3

Step 3: Second-Line Pharmacologic Treatment (If Steps 1-2 Insufficient)

• Duloxetine 30-60 mg daily for multiple joint involvement or inadequate response to topical agents 1, 7
• Oral NSAIDs at lowest effective dose with proton pump inhibitor for gastroprotection, used cautiously in elderly 1, 2

Step 4: Assess for Comorbid Depression

• Screen for depression using PHQ-9 in all osteoarthritis patients, as 21% have comorbid depression 5, 6
• If depression is present, duloxetine becomes the preferred pharmacologic option as it addresses both pain and mood 5, 7

Critical Safety Considerations in Older Adults

Dosulepin poses unacceptable risks in the osteoarthritis population:

• Anticholinergic effects causing confusion, urinary retention, and constipation 1
• Increased fall risk in a population already at high risk due to joint instability 1
• Cardiac conduction abnormalities and orthostatic hypotension 1
• No evidence of efficacy for osteoarthritis pain specifically 1, 4

In contrast, duloxetine has a more favorable safety profile with primarily gastrointestinal adverse events (nausea, constipation) that are manageable and typically transient 7, 4.

Common Pitfalls to Avoid

• Do not use tricyclic antidepressants like dosulepin as a substitute for duloxetine in osteoarthritis management 1, 4
• Do not prescribe oral NSAIDs before trying topical NSAIDs, as systemic exposure and adverse events are significantly higher 2, 3
• Do not initiate pharmacologic therapy without establishing core non-pharmacologic treatments first (exercise, weight loss, education) 2
• Do not overlook screening for depression in osteoarthritis patients, as this changes the treatment approach toward duloxetine 5, 6
• Avoid high-dose or long-term NSAID use in elderly patients due to elevated risks of GI bleeding, renal insufficiency, and cardiovascular complications 1, 2

Special Considerations for Patients with Comorbidities

For patients with cardiovascular disease, renal impairment, or gastrointestinal risk factors:

• Acetaminophen remains the safest first-line option 2
• Topical NSAIDs provide localized relief with minimal systemic absorption 3
• Duloxetine can be used when acetaminophen and topical agents fail, as it lacks the cardiovascular and renal risks of NSAIDs 1, 7
• Dosulepin should be avoided entirely due to cardiac conduction risks and lack of efficacy data 1