Can hydroxychloroquine (HCQ) cause hallucinations in patients with systemic lupus erythematosus (SLE)?

Hydroxychloroquine and Hallucinations in Lupus

Yes, hydroxychloroquine can cause hallucinations in patients with lupus, though this is a rare psychiatric complication that should be recognized and managed promptly by discontinuing the medication.

Evidence for Psychiatric Side Effects

Hydroxychloroquine-induced hallucinations, while uncommon, are a documented adverse effect that requires clinical awareness:

• A case report documented auditory and visual hallucinations, nightmares, and decreased consciousness in a 37-year-old woman with discoid lupus erythematosus after one week of hydroxychloroquine 200 mg daily 1
• The hallucinations resolved completely after hydroxychloroquine discontinuation, with no recurrence when alternative treatment was used 1
• This psychiatric complication has been reported specifically in cases of connective tissue diseases, suggesting a potential disease-specific vulnerability 1

Clinical Context and Risk-Benefit Assessment

Despite this rare complication, hydroxychloroquine remains the backbone therapy for all SLE patients due to overwhelming benefits:

• Hydroxychloroquine is recommended for all patients with SLE due to multiple beneficial effects including reduction of disease flares, prevention of organ damage, and improved survival 2
• The drug reduces mortality risk significantly (OR 0.128,95% CI 0.054 to 0.301) even after adjusting for confounding factors 3
• Hydroxychloroquine prevents disease flares (2.5 times higher flare risk when discontinued), reduces thrombotic events, and allows glucocorticoid dose reduction 4, 5

Management Algorithm When Hallucinations Occur

If hallucinations develop on hydroxychloroquine:

1. Immediately discontinue hydroxychloroquine and obtain neurology/psychiatric consultation to exclude other causes 1
2. Rule out SLE neuropsychiatric manifestations (lupus cerebritis can cause psychosis independent of medication) 6
3. Consider alternative antimalarials such as quinacrine for cutaneous manifestations if hydroxychloroquine cannot be reintroduced 2
4. Intensify immunosuppressive therapy to maintain disease control without hydroxychloroquine, using agents like azathioprine or methotrexate 2

Common Pitfalls to Avoid

• Do not attribute all psychiatric symptoms to lupus itself without considering medication effects, as hydroxychloroquine-induced hallucinations can occur even with normal neurological workup 1
• Do not restart hydroxychloroquine after documented hallucinations, as the mechanism is not fully elucidated and recurrence risk is unknown 1
• The mechanism of hydroxychloroquine-induced psychiatric effects remains unclear, but the temporal relationship and resolution upon discontinuation strongly support causality 1

Monitoring Recommendations

While psychiatric complications are rare, standard hydroxychloroquine monitoring focuses primarily on retinal toxicity:

• Annual ophthalmologic examination should begin after 5 years of therapy, or after 1 year if additional risk factors are present 6
• Daily dose should not exceed 5 mg/kg real body weight to minimize toxicity risk 2, 4
• Retinal toxicity is the most common serious adverse effect, occurring in 0.5% after 6 years and potentially exceeding 20% after 20 years of use 4