Neuropharmacological basis of combining antidepressants

To review the neuropharmacological basis of antidepressant combination therapy.

Literature searches and other relevant material were obtained and reviewed.

The overall clinical aim of combining antidepressants is to increase the efficacy whilst minimizing the side effects. Although such prescriptions are frequently based on the previous experience and knowledge, a sound neuropharmacological basis to support these combinations is desirable. When combining antidepressants, it is important to combine mechanisms of action, rather than simply one drug with another, and to aim for synergistic effects. The possibilities of combining mechanisms of action should also be exploited to the full if necessary, and the potential exists for combining two independent actions that have synergistic effects on the serotonergic, noradrenergic and even the dopaminergic systems.

Unfortunately, there are still, as yet, insufficient data to categorically justify choosing one or other combination based only on the neuropharmacological evidence.