Rituximab was associated with progressive changes in the brain’s white matter, causing symptoms such as weakness, speech impairment and personality changes. High doses of methotrexate were found to cause headaches, while newer agents that block tumor necrosis factor (TNF) were associated with cases of demyelination and an increased risk of CNS infection.

“Previous neurological diseases or a high level of disease activity may predispose patients to brain complications [with treatment]. However, more studies have to be done to prove [the connection],” Dr. Joaquim said.

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Immunosuppressive drugs, disease-modifying anti-rheumatic drugs, and TNF inhibitors also make RA patients more susceptible to CNS infections, which can lead to cognitive dysfunction.

“The clinician must be aware that patients with RA can have neurological symptoms secondary to a multitude of causes,” Dr. Joaquim emphasized.

Routine Evaluations Needed

As with most chronic diseases, early detection and treatment of RA can lead to better outcomes. In RA patients, symptom control may reduce the risk for psychiatric manifestations.

“In general, better disease control is associated with better psychosocial functioning. Pain, in particular, is very predictive of mood disturbance. How patients cope with their pain and medical condition can also affect mood,” Dr. Nicassio said.

Rheumatologists, however, do not typically screen their patients for neuropsychiatric symptoms.

“Although they may ask some general questions about patients’ psychological functioning, there is not much evidence that they do formal psychological screening,” Dr. Nicassio said, citing factors such as lack of training, inadequate staffing, and time constraints.

According to Dr. Nicassio, routine evaluations do not need to be cumbersome or time-consuming.

“There are screening measures for depression and anxiety, for example, that take only 5 minutes to administer,”Dr. Nicassio said. “If [clinicians] are not inclined to do the screening themselves, they should not hesitate to refer patients to a behavioral medicine psychologist for future evaluation.”

Clinicians treating RA patients should also be aware that many symptoms, such as pain, are not only caused by a joint deformity but can also have a neurological cause, such as compressive neuropathy.

Potential medication side effects and the differential diagnosis for neuropsychiatric symptoms should also be taken into account, Dr. Joaquim added, recommending that patients should be encouraged to self-monitor for changes in mood and other aspects.