title: Acquired lithium resistance revisited: discontinuation-induced refractoriness versus tolerance.
abstract: BACKGROUND
  While some patients fail to respond to lithium from the outset, others are initially responsive and then develop treatment resistance. These acquired forms of lithium resistance have received relatively little clinical attention.
  
  
  METHODS
  We review the literature on the two different forms of acquired treatment resistance lithium that occur following an initial good response to lithium-discontinuation-induced refractoriness and tolerance- and discuss the possible neurobiological mechanisms involved.
  
  
  RESULTS
  Multiple investigators have reported cases of discontinuation-induced refractoriness, where following a good long-term response, patients discontinue lithium, suffer a major recurrence, and then do not again respond as well or at all to lithium once it is reinstituted at previously effective doses. The development of tolerance has similarly been multiply documented where lithium doses are consistently maintained, but after an extended period of excellent responsiveness, affective episodes of increasing severity, frequency, or duration begin to break through. These two forms of acquired treatment resistance appear to have different underlying neurobiological mechanisms and require differential treatment strategies.
  
  
  CONCLUSIONS
  Recognition of acquired forms of lithium resistance depends on careful case descriptions and longitudinal monitoring of patients who are usually treated naturalistically and not in controlled clinical trials.
  
  
  CONCLUSIONS
  To the extent that these forms of acquired lithium resistance can be better recognized and their development slowed, prevented, or ameliorated, it could yield substantial clinical and public health benefits in avoiding the morbidity and mortality that can accompany lithium non-responsive bipolar disorder.
authors.affiliation: Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201B, Bethesda, MD 20814, United States. robert.post@speakeasy.net
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000368:Aged; D018692:Antimanic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004351:Drug Resistance / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D012008:Recurrence; D017211:Treatment Failure
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds