Does Plaquenil (hydroxychloroquine) cause short‑term memory impairment?

Does Plaquenil Cause Short-Term Memory Issues?

Plaquenil (hydroxychloroquine) can cause short-term memory impairment and other cognitive disturbances, though this is not among its most commonly recognized adverse effects. The FDA label specifically warns about "neuropsychiatric events" as a recognized toxicity 1.

Evidence for Cognitive and Memory Effects

Direct Evidence from Recent Research

The most compelling evidence comes from a 2026 animal study demonstrating that hydroxychloroquine "interfered with both short-term and long-term memory retrieval pathways" in a controlled experimental setting 2. This study specifically documented impaired short-term memory performance in the Y-maze test, alongside long-term memory deficits in passive avoidance testing.

A 2025 systematic review of psychiatric adverse effects found that HCQ triggers cognitive impairments among its neuropsychiatric side effects, which also include psychosis, depression, anxiety, and sleep disturbances 3. The onset of these effects varies considerably—appearing anywhere from shortly after starting the medication to after prolonged use.

A 2023 systematic review corroborated these findings, noting evidence for "short-term psychiatric adverse effects" including cognitive disturbances from both chloroquine and hydroxychloroquine 4. Importantly, this review found that most patients developing psychiatric adverse effects had no family history of psychiatric disease, suggesting the drug itself as the causative agent.

FDA Recognition

The FDA label for Plaquenil explicitly warns about "neuropsychiatric events" under its WARNINGS section 1. While the label doesn't specifically enumerate "memory problems" as a distinct category, it acknowledges the broader spectrum of neuropsychiatric toxicity.

Clinical Context and Mechanism

The cognitive effects appear related to:

• Neurochemical alterations: The animal study documented changes in neurotransmitter levels in the prefrontal cortex, hippocampus, and striatum—brain regions critical for memory function 2
• Neuroinflammatory changes: Alterations in TNF-α levels in memory-related brain structures 2
• Dose-independent effects: Interestingly, the frequency of psychiatric adverse effects does not appear strictly dose-dependent, though it may vary by patient sex, age, and body mass index 4

Important Caveats

Distinguishing from Primary Disease Effects

Rheumatoid arthritis and systemic lupus erythematosus themselves can cause cognitive dysfunction and "brain fog." The challenge lies in differentiating drug-induced cognitive effects from disease-related symptoms. A psychiatric consultation for thorough clinical evaluation is recommended to distinguish primary psychiatric/cognitive disorders from drug-induced adverse effects 3.

Contrast with Long-Term Dementia

One 2001 study examined whether HCQ could slow Alzheimer's disease progression (based on anti-inflammatory properties) and found no effect—neither beneficial nor harmful—on cognitive decline over 18 months 5. This suggests HCQ doesn't cause progressive dementia-type cognitive decline, but doesn't address acute/subacute memory complaints.

Not the Primary Toxicity Concern

The major established toxicities of HCQ remain:

1. Retinopathy (the most serious long-term concern, affecting 8.6-11.5% after 15 years) 6, 7
2. Cardiac effects including cardiomyopathy and QT prolongation 1
3. Hypoglycemia 1

Clinical Recommendations

If a patient on Plaquenil reports new short-term memory problems:

1. Take the complaint seriously—this is a recognized adverse effect, not merely anxiety or disease-related symptoms
2. Evaluate for other neuropsychiatric symptoms: depression, anxiety, sleep disturbances, psychotic symptoms 3
3. Consider psychiatric consultation to differentiate drug-induced from primary psychiatric/neurological conditions 3
4. Review the risk-benefit ratio with the prescribing rheumatologist/dermatologist
5. Management options if HCQ is determined to be causative 3:
   • Dosage adjustment
   • Discontinuation if feasible (though this increases disease flare risk)
   • Symptomatic treatment with psychotropic medications if needed

The decision to continue or discontinue HCQ must weigh the cognitive symptoms against the substantial benefits of HCQ in controlling autoimmune disease and preventing flares, cardiovascular events, and other complications.