title: The effectiveness of restarted lithium treatment after discontinuation: reviewing the evidence for discontinuation-induced refractoriness.
abstract: OBJECTIVE
  We sought to determine whether the risk of relapse in patients with bipolar disorder is higher after discontinuation and restart of lithium treatment as compared to continuous lithium treatment in these same patients.
  
  
  METHODS
  We conducted literature searches in the Pubmed, Embase, Cochrane, and PsycINFO databases with cross-reference checks. Relevant data were extracted and pooled for meta-analysis.
  
  
  RESULTS
  Five relevant studies were included for review, of which three studies qualified for the meta-analysis and included a total of 212 analyzed cases. Two studies found lithium to be less effective after discontinuation and reintroduction and three studies found no decreased effectiveness. The pooled odds ratio for the occurrence of one or more relapses after interruption of lithium treatment compared to continuous treatment was 1.40 (95% confidence interval: 0.85-2.31; p = 0.19).
  
  
  CONCLUSIONS
  Although studies are scarce, review and meta-analysis of the available literature does not provide convincing evidence that lithium is less effective when treatment is discontinued and restarted, compared to uninterrupted treatment.
authors.affiliation: Altrecht Institute for Mental Health Care, Utrecht, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: de Vries
authors.forename: Annet
authors.initials: A
authors.lastname: van Bergen
authors.forename: Eline J
authors.initials: EJ
authors.lastname: Regeer
authors.forename: Elsje
authors.initials: E
authors.lastname: Benthem
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Kupka
authors.forename: Marco P M
authors.initials: MP
authors.lastname: Boks
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006801:Humans; D018021:Lithium Chloride / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D018021:Lithium Chloride
keywords: bipolar disorder; discontinuation; effectiveness; lithium; refractoriness; restarting