Hyponatremia during treatment with the clozapine-amisulpride combination: a suspected association and improvement with dose reduction

Clozapine is the only antipsychotic that is effective in treatment-resistant schizophrenia, but in certain cases its effectiveness is limited. To improve efficacy, clinicians commonly augment clozapine with another antipsychotic. Clozapine has serious side effects due to its receptor profile. The second antipsychotic to be added to clozapine should be less likely to cause these side effects. Amisulpride may be a suitable medication for clozapine-augmentation therapy. However, side effects may also occur in this combination. Here we report for the first time in a 31-year-old male patient diagnosed with schizophrenia who presented with hyponatremia following the addition of amisulpride to clozapine and the improvement of this condition with dose reduction. When adverse effects are non-fatal or can be controlled by supportive treatments, dose reduction may be more useful than discontinuing the drug. In conclusion, we should not prematurely change the combination of clozapine and amisulpride in treatment-resistant schizophrenia.