Voltage-gated calcium channels have been implicated in schizophrenia aetiology; however, little is known about their involvement in antipsychotic treatment response. This study investigated variants within the calcium channel subunit genes for association with antipsychotic treatment response in a first episode schizophrenia cohort. Twelve regulatory variants within seven genes were shown to be significantly associated with treatment outcome. Most notably, the CACNA1B rs2229949 CC genotype was associated with improved negative symptomology, where the C allele was predicted to abolish a miRNA-binding site (has-mir-5002-3p), suggesting a possible mechanism of action through which this variant may have an effect. These results implicate the calcium channel subunits in antipsychotic treatment response and suggest that increased activation of these channels may be explored to enhance or predict antipsychotic treatment outcome.