Relationship between polydipsia and antipsychotics: A systematic review of clinical studies and case reports

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jan 10;96:109756. doi: 10.1016/j.pnpbp.2019.109756. Epub 2019 Aug 28.


Objective: This systematic review aimed to elucidate the relationship between polydipsia and antipsychotics.

Methods: We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsia induced or improved by antipsychotics.

Results: We identified 61 articles: 1 double-blind randomized controlled trial (RCT), 4 single-arm trials, 1 cross-sectional study, 3 case series, and 52 case reports. The double-blind RCT demonstrated no significant difference in improvement in polydipsia between olanzapine and haloperidol. Two single-arm trials showed that polydipsia improved during clozapine treatment, whereas the other 2 showed that risperidone did not improve polydipsia. The cross-sectional study showed the prevalence of hyponatremia with first-generation antipsychotics (FGAs: 26.1%) and second-generation antipsychotics (SGAs: 4.9%). Two case series reported that clozapine improved polydipsia; the other one indicated that patients with polydipsia who were treated with FGAs had schizophrenia (70.4%) and mental retardation (25.9%). Of 90 cases in the case reports, 67 (75.3%) were diagnosed with schizophrenia. Of 83 cases in which antipsychotic treatment started before the onset of polydipsia, 75 (90.3%) received FGAs, particularly haloperidol (n = 24, 28.9%), and 11 (13.3%) received risperidone. Among 40 cases in which polydipsia was improved following antipsychotic treatment, 36 (90.0%) received SGAs, primarily clozapine (n = 14, 35.0%).

Conclusions: Although the causal relationship between polydipsia and antipsychotics remains unclear because of the paucity of high-quality studies, antipsychotics with high affinity to dopamine D2 receptors may be associated with an increased risk of polydipsia while clozapine may be effective for treating polydipsia.

Keywords: Antipsychotics; Clozapine; Polydipsia; Water intoxication.

Publication types

  • Case Reports
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / metabolism*
  • Clozapine / therapeutic use
  • Humans
  • Polydipsia / chemically induced*
  • Polydipsia / drug therapy
  • Polydipsia / metabolism*
  • Randomized Controlled Trials as Topic / methods
  • Receptors, Dopamine D2 / metabolism


  • Antipsychotic Agents
  • Receptors, Dopamine D2
  • Clozapine