Abstract
Suicidality induced by steroid treatment
Steroid-induced mental disturbance is a common phenomenon. The specific types of neuropsychiatric impairments consist of a range of symptoms from anxiety and irritability [1] to affective and psychotic symptoms [1]. Suicidal ideation secondary to steroids has previously been reported only in association with psychotic, manic or depressive symptoms. This is a report of an emotionally stable adult who experienced acute-onset suicidal ideation while being treated with prednisone for tuberculosis meningitis.
A 20-year-old Bangladesh student presented to the Emergency Department of Royal Prince Alfred Hospital with headache, neck pain, intermittent fever and confusion on a background of feeling unwell for 6 weeks and not responding to three courses of antibiotics. Investigations including positive polymerase chain reaction in cerebrospinal fluid confirmed a diagnosis of tuberculosis (TB) meningitis. HIV serology was negative, he was otherwise medically well. He was admitted to a medical ward under a physician, and started on the anti-TB medications isoniazid, ethambutol, pyrazinamide and rifampicin. Prednisone 40 mg daily was begun on day 2, and increased to 50 mg daily on day 8. He was discharged on day 15, following three normal induced sputum tests. He was advised to continue with the anti-TB medications for 1 year, and a weaning dose of prednisone, from 50 mg, for 3 weeks.
The patient returned to the hospital 3 days following discharge, presenting with suicidality particularly thoughts of wanting to kill himself by jumping from a tall building, and agitation and irritability. These symptoms had been present, and worsening, for 10 days. He did not have any psychotic, manic or depressive symptoms. There was no history of illicit drug or alcohol use; he had no past or family psychiatric history. The physical examination and basic blood tests were unremarkable.
Steroid treatment in the form of oral prednisone 50 mg daily was deemed the most likely cause of his acute suicidality. The patient was admitted to the psychiatric unit as a voluntary patient. Olanzapine 5 mg nightly was added to relieve his irritability and anxiety. After consultation with the neurology team, the prednisone dose was halved the following day. His prednisone continued to be weaned over 5 days. His suicidal ideation had resolved completely by day 2 of the psychiatric admission. There was no sign of meningism or encephalopathy following the prednisone eduction. Isoniazid has, rarely, been associated with psychosis and suicidality [2], but his rapid improvement upon cessation of prednisone suggests that prednisone was the causative agent in this case.
To our knowledge, this is the first report of steroid-induced suicidality presenting in an isolated way, with no associated affective or psychotic symptoms. The mechanism of the suicidality is unclear. Braunig suggested that the disturbance of the hypothalamus–pituitary–adrenal axis and its interplay with reduced serotonin turnover may play a role in the formation of suicidal ideation [3].
Psychiatric reactions in patients receiving prednisone are common, occurring in up to 18.4% of patients receiving >80 mg daily [1]. Patients usually develop mental state changes within 3–14 days of initiation of treatment [4]. Given its common occurrence, its potential severity and the lack of reliable predicting factors [5], it is essential that these neuropsychiatric complications are actively screened for in every patient who is on a high dose of steroids.
Valproate-induced reversible pseudoatrophy of the brain and hyperammonemic encephalopathy in a bipolar patient
In spite of the safety profile of valproate, it can lead to rare severe neurological side-effects such as encephalopathy with or without hyperammonemia, extrapyramidal disorders, reversible dementia and pseudoatrophy of the brain [1, 2]. We describe the case of a bipolar patient who was treated with valproate and who developed reversible pseudoatrophy of the brain and hyperammonemic encephalopathy.
The patient was a 47-year-old woman who had been treated for bipolar disorder type I (DSM-IV) for 10 years. She had been using valproate at a dose of 2000 mg day−1 for 5 years without any symptoms of intoxication or other neurological complications. After an episode of psychotic mania, valproate was increased to 2500 mg day−1, with blood levels of 83.5 µg dL−1. After 7 months the patient developed confusion, memory loss, apathy and parkinsonism. The symptoms worsened in the next 2 weeks and the patient developed severe parkinsonism, lack of orientation, incoherent speech and lethargy. After 1 week the patient became catatonic. After admission to a psychiatric unit, blood level of ammonia was measured at 48 µmol L−1 (normal level = 11–32 µmol L−1). Computed tomography showed marked sulci atrophy and ventricles enlargement.
Valproate was ceased and electroconvulsive therapy was started, and in 1 week the parkinsonism, memory loss, apathy and lethargy improved consistently. Three months after discharge, magnetic resonance imaging was performed and the sulci atrophy and ventricles enlargement had diminished.
The mental deterioration observed in the present patient was observed previously in neurological patients who were chronic users of valproate. There is a clinical relationship between the development of encephalopathy and blood ammonia levels, as seen in the present case, although the pathogenesis is not completely understood, and multiple studies obtained mixed results on the search for an association between dose and plasma concentrations of valproate with serum ammonia levels [3, 4] and the appearance of clinical symptoms [4]. The prevalence of symptomatic hyperammonemia leading to encephalopathy from valproate is unknown but thought to be rare in adults [4]. The aetiology of pseudoatrophy remains unclear also, and only a few cases have been described in the literature [1, 3]. In all of them there was some improvement after discontinuation of valproate. Therefore, even in therapeutic blood levels, valproate can cause severe neurological symptoms. Clinicians should be aware of this rare but severe side-effect when treating bipolar patients. The recommendation should always be to discontinue valproate because hyperammonemia leading to encephalopathy could be a completely reversible side-effect.