I stopped lamotrigine and sertraline (Zoloft) two months ago, but still have persistent muscle and joint pain; what other conditions could be causing this?

Persistent Muscle and Joint Pain After Stopping Lamotrigine and Sertraline

Since your muscle and joint pain persists 2 months after discontinuing lamotrigine and sertraline, you need a comprehensive workup for alternative causes, as drug-related symptoms should have resolved by now.

Why the Medications Are Unlikely the Cause

The temporal relationship argues against lamotrigine or sertraline as the culprit:

• Lamotrigine is not an effective treatment for neuropathic pain or musculoskeletal pain and has no established mechanism for causing persistent myalgias after discontinuation 1, 2
• Drug-induced myopathies typically resolve within weeks to months after stopping the offending agent 3
• The 2-month timeframe without medication should have allowed resolution if the drugs were causative 4

Alternative Causes to Investigate

Rheumatologic and Inflammatory Conditions

You need evaluation for:

• Inflammatory arthritis (rheumatoid arthritis, reactive arthritis, or seronegative spondyloarthropathy) with complete rheumatologic examination of all peripheral joints for tenderness, swelling, and range of motion 4
• Autoimmune blood panel including ANA, rheumatoid factor (RF), anti-CCP antibodies, and inflammatory markers (ESR and CRP) 4
• Plain X-rays or imaging to exclude joint damage, erosions, or metastases if clinically appropriate 4

Polymyalgia Rheumatica-Like Syndrome

Consider this if you have:

• Severe proximal muscle pain in upper and lower extremities with fatigue 4
• Highly elevated inflammatory markers (ESR/CRP) but normal creatine kinase (CK) levels 4
• Pain without true weakness (distinguishing it from myositis) 4

Inflammatory Myositis

This requires urgent evaluation if you have:

• Proximal muscle weakness (difficulty standing up, lifting arms, moving around) rather than just pain 4
• Elevated creatine kinase (CK) levels 4
• Consider EMG showing muscle fibrillations or MRI showing increased muscle signal 4

Degenerative and Mechanical Causes

Don't overlook:

• Osteoarthritis or degenerative joint disease 4
• Soft tissue rheumatic disorders (rotator cuff tendinitis, bursitis) 4
• Crystal arthropathies (gout, pseudogout) - these can flare independently 4

Other Drug Exposures

Evaluate for:

• Statin use (current or recent) - the most common cause of drug-induced myopathy 3
• Glucocorticoids, immunologic drugs, or antimicrobials that can cause myopathies 3
• Drug-drug interactions if you're taking other medications metabolized by cytochrome P450 3

Recommended Diagnostic Approach

Initial laboratory workup should include:

• Complete blood count, comprehensive metabolic panel
• Creatine kinase (CK) level 4, 3
• ESR and CRP 4
• Rheumatoid factor and anti-CCP antibodies 4
• ANA panel 4
• Thyroid function tests (hypothyroidism causes myalgias)
• Vitamin D level (deficiency causes musculoskeletal pain)

Imaging considerations:

• Plain radiographs of affected joints 4
• Ultrasound or MRI if inflammatory arthritis suspected 4
• MRI of muscles if myositis suspected 4

Critical Pitfalls to Avoid

• Don't assume the medications are still causing symptoms after 2 months of discontinuation - this timeline strongly suggests an alternative diagnosis 4
• Don't miss septic arthritis if a single joint is hot, swollen, and painful 4
• Don't delay workup for inflammatory myositis as it can progress to rhabdomyolysis and require urgent treatment 4
• Don't forget to ask about all other medications, particularly statins, which are the most common cause of drug-induced myopathy 3