Table 3.
Studies on the Risk or Incidence of Hyponatremia With the Use of Antipsychotics
| Study design | Patient characteristics | Outcome | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author, y | Duration (y) | Sample size (n) | SNa+ active monitoring | Cutoff SNa+ (mEq/L) | In/Out | Disease | Age (mean± SD) | F (%) | Exposed to AP (n) | Cases of hyponatremia / no. exposed or no. of controls | Type of AP used | Type of measure | Overall | TAs | ATy APs |
| Case-control studies (hyponatremia vs normonatraemia) | |||||||||||||||
| a Jun et al., 2020 | 5 (with ≥30 d follow- up for recurrent hyponatremia) | 19 173 | No | <135 | Out | Recurrent hyponatremia | >65 (range: 65–75) | 52.1 | 1535 | 79/1,456b | Any | OR [95% CI] |
0.83 [0.64–1.09] | — | — |
| Falhammar et al., 2019 | 9 | 71 741 | No | <135 | In | Ad | Median 76 (range: 18–103) | 72 | 317 (newly initiated) |
148/169b | Any | OR [95% CI] |
1.80 [1.38–2.34] | 2.94 [2.09–4.13] | 1.05 [0.75–1.47] |
| Yamamoto et al., 2019 | 12 | 7442 | Yes | <130 | In/ out |
Epilepsy | 36.2 ± 14.4 | 46.7 | 504 | 17/487b | Any + anticonvulsant (except CBZ) | Incidence (%) |
3.40 | — | — |
| OR [95% CI] |
3.47 [2.03–5.95] | — | — | ||||||||||||
| Yang and Cheng, 2017 | 15 | 2051 | No | <135 | In/ out |
Psychiatric illness | 54.7± 13.9 | 43.8 | 1069 | 92/977b | Any | Incidence (%) |
8.61 | 10.66 | 10.05 |
| HR [95% CI] |
— | 3.13 [1.83–5.34] | 2.09 [1.36–3.23] | ||||||||||||
| Manu et al., 2012 | 1 | 924 | No | <136 | In | Ad | 45.15 ± 19.6 |
46.8 | 642 | 37/605b | Any | Incidence (%) |
6.11 | 11.84 | 5.29 |
| Bun et al., 2011 | 1 | 248 | Yes | <130 | In | Psychiatric illness | 46.45 ± 17.0 | 38.3 | 248 | 91/157b | Any | OR [95% CI] |
1.79 [1.04–3.10] | — | — |
| Cohort Studies (antipsychotic users vs nonantipsychotic users) | |||||||||||||||
| Gandhi et al., 2016 | 9 | 116 016 | No | ≤132 | Out | Ad | 81 ± 7.7 | 66.8 | 58 008 | 86/58 008 | ATyAPs | Incidence (%) |
— | — | 0.15 |
| RR [95% CI] |
— | — | 1.62 [1.15–2.29] | ||||||||||||
| Lange- Asschenfeldt et al., 2013 | 3 | 7113 | Yes | <135 | In | Psychiatric illness | Median 67 (range: 21–101)c | NR | 4976 | 199/4976 | Any | Incidence (%) |
3.99 | 6.00 | 3.40 |
| Cross-sectional | |||||||||||||||
| Shepshelovich et al., 2017 | 6 | 198 | No | <135 | In | SIADH | 66.6 ± 17.3 | 55.5 | 22 | 19/22 | Any | Incidence (%) |
86 | — | — |
| Serrano et al., 2014 | 4 | 219 | No | <135 | In/Out | Psychiatric illness | 44.2 ± 15.7 | 52.5 | 183 | 13/183 | Any | Incidence (%) | 7 | 26 | Clozapine = 3; others = 5 |
| Clozapine vs any other AP | OR [95% CI] |
— | 31.3 [3.9–247.0] | 2.9 [0.5–18.2] | |||||||||||
| Observational multidrug surveillance program/adverse drug reaction monitoring | |||||||||||||||
| Letmaier et al., 2012 | 14 | 263 864 | No | <130 | In | Psychiatric illness | 60.7 ± 15.9 | 55.7 | 189 462 | 5/189 462 | Any | Incidence (%) | 0.003 | Perazine = 0.015; haloperidol = 0.007 | Risperidone = 0.004 |
Abbreviations (patient characteristics and outcome): Ad, hospital admission for hyponatremia; AP, antipsychotic; AtyAPs, atypical antipsychotics; CBZ, carbamazepine; F, females; HR, hazard ratio; In, inpatient; NR, not reported; OR, odds ratio (where provided we report only adjusted ratio); Out, outpatient; RR, relative risk ratio; SIADH, syndrome of inappropriate antidiuretic hormone secretion; TAs, typical antipsychotics.
a Cases and control were drawn from the population in a fully enumerated cohort
b Number of patients without hyponatremia (controls)
c Values related only to patients who experienced hyponatremia .