Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients

Background: Neuropsychiatric adverse drug reactions (NPADRs) are not commonly associated with low dose methotrexate (LDMTX) in patients with rheumatoid arthritis (RA).

Research design and methods: In this case series assessment, we described the nature and frequency of NPADRs with LDMTX in the Dutch DREAM-RA registry, including causality of NPADRs, the impact on further LDMTX treatment and the impact on patient reported Health Related Quality of Life (HRQoL).

Results: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years. Headache, dizziness and depression were most frequently reported. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected.

Conclusions: Knowledge on the nature, frequency and impact of the demonstrated NPADRs during LDMTX therapy will enhance attention toward these potential ADRs allowing better risk assessment and communication to patients.