Case Presentation: A 39 year old Indian female with a medical history of rheumatoid arthritis, maintained on bi-weekly Adalimumab for the past year, presented with anxiety and forgetfulness, which had progressed to extreme paranoia and delusions over the past month. In the 3 days leading to admission, she had exhibited intermittent catatonic episodes, prompting her husband to bring her to the emergency room. Her last dose of adalimumab was given the week prior to her visit. History was obtained from her husband who denied any recent fevers, additional medications or psycho-social stressors, and no family history of seizures of psychiatric disorders. Upon admission, her vitals were stable. Physical exam revealed severe psychomotor retardation concerning for an affective disorder. Basic lab work including electrolytes along with a toxicology screen were normal, and negative for any signs of meningeal irritation. Computed tomography (CT), followed by magnetic resonance imaging (MRI) of her brain were unremarkable. Neurology was consulted and ruled out any organic etiology. She was admitted to the psychiatric ward and her medications were held. After 7 days of profound psychosis, she started to improve, and after 10 days she began moving and conversing appropriately. She was diagnosed with TNF inhibitor induced psychosis, and discharged on hydroxychloroquine, risperidone, and sertraline. Upon follow up visit 4 weeks later, patient had stopped all medications except hydroxychloroquine, and reported complete resolution of her symptoms, which was also confirmed by her husband.

Discussion: The half-life of adalimumab ranges between 10-20 days, with a systemic clearance of 12mL per hour. After holding all her medications, she began to improve 14 days following her last dose, allowing for sufficient clearance of serum drug levels. Neuroimaging and lab work were unremarkable, and ruled out alternative etiologies. The only management was the withholding of her adalimumab. TNF inhibitor psychosis is estimated to occur in less than 1% of cases, and is likely under-diagnosed. The pathophysiology of this phenomenon is not well understood, but interactions between TNF cytokines and neuronal pathways have been identified. A variety of studies have shown that TNF-α is a mediator of neonatal and post-traumatic brain injury. It could therefore be hypothesized that inhibition of TNF-α would reduce excitotoxic brain injury. However, results are mixed with some showing benefit with attenuation of damage, while others have shown increased hippocampal damage.

Conclusions: Adalimumab is a TNF inhibitor used in a variety of rheumatological diseases. It has revolutionized treatments for many conditions including rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis. Anti-TNF therapy has numerous well described adverse events, such as opportunistic infection, systemic lupus erythematosus and hematologic malignancy. Toxicity to the central nervous system in the form of demyelination is also reported; however, there is not much in the literature pertaining to psychiatric disorders. We believe that this rare side effect should be further investigated, and alternative etiologies postulated prior to considering a psychiatric diagnosis for acute psychosis.