Abstract
To the Editor
Infliximab is described (Janssen-Cilag Pty Ltd, 2011) as a chimeric monoclonal antibody that binds to human tumour necrosis factor alpha (TNFα), thus inhibiting binding of TNFα to its receptors and preventing its pro-inflammatory actions. TNFα is implicated in mediating chronic inflammation in diseases such as Crohn’s disease and rheumatoid arthritis. Socynska et al. (2009) describe a growing interest in the role of TNFα in the pathophysiology of bipolar affective disorder and in the potential antidepressant actions of TNFα antagonists. We are aware of two previous cases of TNF antagonist-associated mania. The first is described by Kaufman (2005), a young woman with a past history of episodes of depression and one episode of manic switch with an antidepressant, who then later developed mania when treated with etanercept (a TNF blocker) for psoriatic arthritis. The second case reported (Elisa and Beny, 2010) is a 43-year-old woman who had a history of major depression successfully treated with, and continued on, citalopram who developed mania after starting infliximab for ulcerative colitis. We report a third case of mania starting after an infusion of infliximab for Crohn’s disease. This is the first case described, to our knowledge, of mania developing in a patient after treatment with a TNFα antagonist with no prior history of mental illness and with no other cause identified.
A 62-year-old man living with his family in a rural location presented to Launceston General Hospital, Launceston, Tasmania, Australia with mental state disturbance after being given his first intravenous infusion of infliximab. He had a 12-year history of Crohn’s disease requiring bowel resection surgeries and maintenance immunomodulators. He had developed worsening bowel symptoms over a few months with diarrhoea, raised inflammatory markers, and elevated faecal calprotecin indicative of inflammation in his bowels. Infliximab infusion was commenced for his inadequately controlled Crohn’s disease. He then presented to his general practitioner a week after the infusion with pressure of speech, marked circumstantiality of thought form, irritability and euphoria, sleeplessness, and increased activity levels. His family reported that the symptoms had begun only 5 hours after the infliximab infusion, and then peaked over the next few days. He had made impulsive new plans and had been very active. These symptoms persisted and he was admitted to a general hospital for further investigation.
Blood tests showed a mild normocytic anaemia, a low lymphocyte count of 0.9×109/l, and elevated inflammatory markers, thought to be consistent with having a chronic inflammatory illness and long term azathioprine treatment. Electrolytes, urea, and creatinine were within normal limits, as were liver function tests, calcium, magnesium, and phosphate. Microscopy and cultures of blood, sputum, urine, and cerebrospinal fluid did not show any signs of infection. Likewise, analysis of the cerebrospinal fluid did not reveal any abnormalities. Magnetic resonance imaging of the brain and spinal cord was unremarkable.
This man had a background of no previous episodes or treatment of mental illness. He was described as normally being polite and reserved but socially active. There was no family history of mental illness. His family reported that over the last 6 months he had been under considerable stress with his poor physical health making it difficult to keep up with his significant social commitments and there had been several deaths in his extended family. In the months leading up to his presentation, he had seemed a little dysphoric and withdrawn, but not enough to impair his functioning and without any other symptoms indicative of depression. His medications included azathioprine, aspirin, iron, folic acid, and Vitamin B12 injections. He had received an infusion of a bisphosphonate for corticosteroid induced osteoporosis two months earlier. There had been no other recent changes to his medications apart from starting infliximab. There was no illicit substance abuse and minimal alcohol consumption.
In hospital, he had persistent thought disorder, pressure of speech, and irritability. He was commenced on 5 mg nocte of olanzapine and settled over the next few days. He was discharged back to the care of his general practitioner with instructions to continue the olanzapine for several weeks. He made a rapid and full recovery. A subsequent re-challenge with infliximab on a further two occasions did not result in a relapse of the symptoms.