11 The neuropsychiatry of nitrous oxide

Objectives/AimsThe abuse of nitrous oxide (N2O) may be increasing globally and users and clinicians may not be aware of harms. We highlight these potential harms through the case of a woman treated for psychotic disorder for 11 months before developing severe N2O induced myeloneuropathy which should have been preventable. We review the clinical literature regarding N2O abuse to raise the profile of this emerging neuropsychiatric disorder.MethodsA case study was undertaken and a literature review performed of relevant databases for cases of N2O abuse presenting with psychiatric symptoms.ResultsIn our case a 37 year old woman presented with florid polymorphic psychosis and subtle cognitive impairment two weeks after inhaling large amounts of N2O. This was treated with antipsychotics and her symptoms waxed and waned over eleven months by which time she had developed a severe myeloneuropathy, confirmed on MRI cervical spine, and a functional B12 deficiency confirmed by high homocysteine and methylmalonic acid (MMA) which was then treated with intramuscular B12. N2O has a variety of effects including the stimulation of endogenous opioids; GABAA receptor stimulation; NMDA receptor antagonism; BDNF receptor activation; cortical excitation and depression on the encephalogram; activation of the anterior cingulate and deactivation of the hippocampal and parahippocampal cortices; and importantly, the deactivation of Vitamin B12 leading to build up of toxic homocysteine and MMA. There are 13 cases excluding this described in the literature of N2O abuse presenting primarily with psychiatric symptoms. They range from 23–64 years old and 12 were male. The most common presenting psychiatric symptoms in the 13 cases were delusions (reported by 8 individuals); cognitive impairment (6); visual hallucinations (4); bizarre or inappropriate behaviour (4); affective lability (3); anxiety (3); and depression, mania or auditory hallucinations in two respectively. Investigations were inconsistently reported but where tested, B12 was mostly low or low normal, and homocysteine and MMA were raised. In nine out of ten cases reported, the outcome was favourable, following cessation of N2O, administration of intramuscular B12, and antipsychotics.ConclusionsN2O abuse is widespread in the UK and may be increasing. Heavy users are at risk of psychosis, cognitive impairment and myeloneuropathy, which may be irreversible. Importantly, some patients initially present with psychiatric symptoms before myeloneuropathy, and N2O abuse should always be considered in cases of new onset psychosis or cognitive impairment. Testing of homocysteine, MMA and B12 should be considered in these cases, and intramuscular B12 given without delay.