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

Abstract Objective This systematic review aimed to elucidate the relationship between polydipsiaand antipsychotics. Methods We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsiainduced 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 polydipsiabetween olanzapineand haloperidol. Two single-arm trials showed that polydipsiaimproved during clozapinetreatment, whereas the other two showed that risperidonedid not improve polydipsia. The cross-sectional studyshowed the prevalence of hyponatremiawith first-generation antipsychotics(FGAs: 26.1%) and second-generation antipsychotics(SGAs: 4.9%). Two case seriesreported clozapineimproved polydipsia; the other one indicated that patients with polydipsiawho 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 antipsychotictreatment 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 polydipsiawas improved following antipsychotictreatment, 36 (90.0%) received SGAs, primarily clozapine(n = 14, 35.0%). Conclusions Although the causal relationship between polydipsiaand antipsychoticsremains unclear because of the paucity of high-quality studies, antipsychoticswith high affinity to dopamine D2 receptors may be associated with increased risk of polydipsiawhile clozapinemay be effective for treating polydipsia.