Table 2.
Pooled incidences (event rates) and odds ratios (OR and aOR) for antidepressant classes
| Antidepressant (class) | Number of studies | Event rate or OR (95% confidence interval) | p-value | I2 (%) |
|---|---|---|---|---|
| Incidence (event rate) for any hyponatremia | ||||
| Antidepressants (overall) | 32 | 0.0465 (0.0248–0.0858) | <0.001 | 99.88 |
| SSRIs | 28 | 0.0559 (0.0289–0.1055) | <0.001 | 99.69 |
| SNRIs | 10 | 0.0744 (0.0225–0.2195) | <0.001 | 99.32 |
| TCAs | 8 | 0.0266 (0.0055–0.1184) | <0.001 | 98.49 |
| Atypical antidepressants (mirtazapine only) | 8 | 0.0102 (0.0025–0.0402) | <0.001 | 97.98 |
| Risk (OR) for any hyponatremia | ||||
| Antidepressants (overall) | 7 | 3.160 (1.911–5.225) | <0.001 | 99.52 |
| SSRIs | 6 | 3.199 (1.750–5.845) | <0.001 | 99.53 |
| SNRIs | 5 | 3.131 (1.795–5.462) | <0.001 | 97.71 |
| TCAs | 6 | 1.803 (1.252–2.598)a | 0.002 | 91.82 |
| MAOIs | 3 | 3.789 (1.602–8.966)a | 0.002 | 50.78 |
| Atypical antidepressants (mirtazapine only) | 4 | 2.818 (1.886–4.211)a | <0.001 | 95.23 |
| Adjusted risk (aOR) for any hyponatremia | ||||
| Antidepressants (overall) | 6 | 1.890 (1.573–2.270) | <0.001 | 91.15 |
| SSRIs | 4 | 2.243 (1.363–3.694) | <0.001 | 92.94 |
| SNRIs | 3 | 2.009 (1.853–2.179) | <0.001 | 29.83 |
| TCAs | 5 | 1.753 (1.272–2.416) | <0.001 | 84.05 |
| Atypical antidepressants (mirtazapine) | 3 | 1.886 (0.782–4.548) | 0.158 | 93.00 |
| Incidence (event rate) for clinically relevant hyponatremia | ||||
| Antidepressants (overall) | 16 | 0.0110 (0.0028–0.0421) | <0.001 | 99.91 |
| SSRIs | 13 | 0.0126 (0.0046–0.0341) | <0.001 | 99.70 |
| SNRIs | 7 | 0.0257 (0.0055–0.1109) | <0.001 | 99.52 |
| TCAs | 6 | 0.0093 (0.0013–0.0656) | <0.001 | 98.79 |
| Atypical antidepressants (mirtazapine only) | 5 | 0.0033 (0.0004–0.0283) | <0.001 | 98.27 |
| Risk (OR) for clinically relevant hyponatremia | ||||
| Antidepressants (overall) | 6 | 2.930 (1.715–5.008) | <0.001 | 99.60 |
| SSRIs | 5 | 3.085 (1.608–5.920) | <0.001 | 99.63 |
| SNRIs | 4 | 2.508 (1.343–4.683) | 0.003 | 98.82 |
| TCAs | 6 | 1.803 (1.252–2.598)a | 0.002 | 91.82 |
| MAOIs | 3 | 3.789 (1.602–8.966)a | 0.002 | 50.78 |
| Atypical antidepressants (mirtazapine only) | 4 | 2.818 (1.886–4.211)a | <0.001 | 95.23 |
Note: Any hyponatremia was defined as a serum sodium <135 mmol/L and clinically relevant hyponatremia as a serum sodium <130 mmol/L or a clinical diagnosis of hyponatremia. For any hyponatremia all studies with an outcome (<135 mmol/L if available, <130 mmol/L if no other outcome was available) were used. The incidences (event rate) and risks (OR) for antidepressant classes were calculated from the pooled outcome measures for the respective antidepressant classes and the outcome measures for specific antidepressants belonging to a certain class.
a
For TCAs, MAOIs, and mirtazapine, there were only OR outcomes for clinically relevant hyponatremia.