Sulpiride is a commonly used treatment for depression in Europe and Japan. Here we describe its use in combination with a complex homeopathic preparation based on the Krebs cycle elements for the treatment of depression. Sixty-seven women with depressive symptoms selfselected treatment with low-dose sulpiride (20mg) and homeopathy (n=35), sulpiride alone (n=32), or homeopathy alone (n=15), administered parenterally as once-daily subcutaneous injections for three months. Depressive symptoms were assessed semi-quantitatively before and after treatment using the Hamilton rating scale for depression (HAMD). The HAMD score significantly decreased in the group treated with combined sulpiride and homeopathy (from 21.3 ± 5.0 before treatment to 8.8 ± 4.1 after treatment; p<0.0001), but not in the other treatment groups. This observation suggests that a low parenteral dose (20 mg) of sulpiride, when administered subcutaneously with a complex homeopathic remedy, may have a synergistic effect when used for the treatment of mild to moderate depression. Further clinical testing in randomized controlled trials is warranted.