Rheumatology Advance Access originally published online on May 31, 2008
Rheumatology 2008 47(8):1254-1255; doi:10.1093/rheumatology/ken212
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Acute psychosis in three patients receiving anti-tumour necrosis factor-
therapy
1Wishaw General Hospital, Wishaw and 2Gartnavel General Hospital, Glasgow, Scotland, UK
Correspondence to: L. McGregor, Wishaw General Hospital, Wishaw, Scotland, UK. E-mail: loramcg{at}hotmail.com
SIR, With any new therapy uncommon or long-term adverse events will not be identified by randomized controlled trials. Post-marketing reporting of suspected adverse events is therefore essential. We report two cases, where a new diagnosis of acute psychosis was made in patients receiving anti-TNF therapy.
A 53-year-old gentleman with a 17-year history of psoriatic arthritis, secondary AA amyloidosis and chronic renal failure requiring peritoneal dialysis was established on etanercept in 2003. During a recent admission due to dialysis complications, his primary problem was noted to be the development of an acute paranoid psychosis. Prior to this event, there was no history of psychiatric illness. An MRI scan revealed changes consistent with small vessel ischaemia, with no evidence of cerebral amyloid deposition. Etanercept was discontinued for a short period of time, but re-introduced when intercurrent infection was excluded. Olanzapine was commenced. Following a further decline in mental health, etanercept has been withdrawn indefinitely.
A 52-yr-old female with a past medical history of chronic obstructive pulmonary disease (COPD) and migraine was diagnosed with RA at the age of 46 yrs. Conventional treatment with six different DMARDs failed and she was commenced on etanercept in 2003. This led to a marked improvement in symptoms. The medication was well tolerated, except for one episode of sepsis, until July 2006. At this time she developed an acute psychosis associated with visual and auditory hallucinations, with strong religious overtones. There is no personal or family history of psychiatric illness. A CT of brain revealed no abnormality. While no organic cause has been found to explain her psychosis, no formal psychiatric diagnosis has been made to date. Etanercept was discontinued and risperidone commenced. Her psychiatric symptoms have improved but her RA has flared. Etancercept was recently restarted with no immediate complications. She remains under psychiatric review.
Psychosis is a disorder resulting in personality distortion, construction of false environments, delusions and hallucinations, in which the patient lacks insight.
Predisposing factors to developing a psychotic illness include genetics, prenatal and perinatal factors, abnormal pre-morbid personalities and drug use (e.g. amphetamines, morphine, steroids, etc.). However, previous observational studies have shown that patients with RA are at a decreased risk of developing illnesses such as schizophrenia [1, 2].
A variety of studies have shown that TNF-
is a mediator of neonatal [3, 4] and post-traumatic brain injury [5, 6]. It could therefore be hypothesized that inhibition of TNF- would reduce excitotoxic brain injury. However, study results are mixed with some showing benefit with attenuation of damage [4, 7], while others have shown increased hippocampal damage [3].
Anti-TNF therapy has numerous well-recognized adverse events, such as infection and malignancy. Toxicity to the central nervous system in the form of demyelination is also documented; however, there is very little in the literature pertaining to psychiatric side-effects. To date there is one reported case of infliximab-associated panic attacks, which ultimately resulted in a suicide attempt [8]. The patients’ past psychiatric history was not documented.
A third patient also developed symptoms but declined consent to publish. No pre-existing risk factors were identified in Cases One and Two. The emergence of an acute psychosis in all cases could have been coincidental. However no organic pathology was identified and in particular, toxic confusional state was excluded in all cases. This therefore raises the possibility that anti-TNF therapy may be implicated as an aetiological factor.
Disclosure statement: All authors have declared no conflicts of interest.
 |
References |
|---|
 Top References |
|---|
- Allebeck P, Rodvall Y, Wistedt B. Incidence of RA among patients with schizophrenia, affective psychosis and neurosis. Acta Psychiatr Scand (1985) 71:615–9.[Web of Science][Medline]
- Gorwood P, Pouchot J, Vinceneux P, et al. Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level. Schizophrenia Res (2004) 66:21–9.[CrossRef][Web of Science][Medline]
- Galasso JM, Wang P, Martin D, Silverstein FS. Inhibition of TNF-alpha can attenuate or exacerbate excitotoxic injury in neonatal rat brain. Neuroreport (2000) 11:231–5.[Web of Science][Medline]
- Liu XH, Xu H, Banks JD. Tumour necrosis factor-alpha attenuated N-methyl D-aspartate mediated neurotoxicity in neonatal rat hippocampus. Brain Res (1999) 851:94–104.[CrossRef][Web of Science][Medline]
- Tchelingerian JL, Quinonero J, Booss J, Jacque C. Localisation of TNF alpha and IL-1 alpha immunoreactivites in striatal neurons after surgical injury to the hippocampus. Neuron (1993) 10:213–24.[CrossRef][Web of Science][Medline]
- Tchelingerian JL, Le Saux F, Jacque C. Identification and topography of neuronal cell populations expressing TNF alpha and IL-1 alpha in response to hippocampal lesion. J Neurosci Res (1996) 43:99–106.[CrossRef][Web of Science][Medline]
- Barone FC, Arvin B, White RF, et al. Tumour necrosis factor-alpha. A mediator of focal ischaemic brain injury. Stroke (1997) 28:1233–44.
[Abstract/Free Full Text] - Roblin X, Oltean P, Heluwaert F, Bonaz B. Panic attack with suicide: an exceptional adverse effect on infliximab. Dig Dis Sci (2006) 51:1056.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||