title: Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study.
abstract: BACKGROUND
  It has been estimated that, at any point in time, about 1% of the general adult population of the United Kingdom is receiving long-term (ie, ≥ 3 months) oral glucocorticoid therapy. These patients may develop neuropsychiatric disorders when the drug is discontinued.
  
  
  METHODS
  Data were obtained for all adult patients registered from January 1, 1990, through December 31, 2008, at UK general practices that were contributors to The Health Improvement Network database. Data from 21,995 adult patients who had been exposed to long-term oral glucocorticoids and who had discontinued the drugs after an exposure ranging from 1 to 3 years were analyzed. The within-person incidence rate ratios (IRRs) for Read codes and/or prescriptions for depression, delirium/confusion, mania, panic disorders, and suicide or suicide attempt during the withdrawal period were estimated using a self-controlled case series methodology. The predictors of the outcomes were ascertained using Cox proportional hazards models.
  
  
  RESULTS
  The risk of depression (IRR = 1.13; 95% CI, 1.00-1.28; P = .04) and of delirium/confusion (IRR = 2.67; 95% CI, 1.96-3.63; P < .001) was significantly higher during the discontinuation period compared to a reference period defined as ranging from 5 to 3 months before the drug cessation. Older people were at higher risk of delirium/confusion. The use of long-acting glucocorticoids was associated with a higher risk of both depression (adjusted hazard ratio [HR] = 1.92; 95% CI, 1.07-3.46) and delirium/confusion (adjusted HR = 4.96; 95% CI, 2.60-9.49) during the withdrawal period.
  
  
  CONCLUSIONS
  Discontinuation of long-term glucocorticoid therapy is associated with an increased risk of both depression and delirium/confusion. People treated with long-acting glucocorticoids are particularly at risk.
authors: Research Department of Primary Care and Population Health, University College London Medical School, London, United Kingdom. laurence.fardet@sat.aphp.fr
authors: Laurence
authors: L
authors: Fardet
authors: Irwin
authors: I
authors: Nazareth
authors: Heather J
authors: HJ
authors: Whitaker
authors: Irene
authors: I
authors: Petersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000377:Agnosia / Q000150:complications; D015331:Cohort Studies; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000209:etiology; D008875:Middle Aged; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000209:etiology; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005938:Glucocorticoids