Indeed, melatonin has previously been studied for its mood-stabilizing (antidepressive) effects and the first melatonergic drug for the treatment of depression has been approved for human use.34 This suggests that the combination of typical antipsychotics with melatonergic agonists may capture some of the beneficial, antidepressive, atypical antipsychotic effects of clozapine, whereas avoiding its limiting side effects.8 Finally, the signature for the atypia of clozapine includes CHRM1 and CHRM3 in PFC. Here, CHRM1 is linked to major depressive disorder.