Mixed-Function Antidepressants: A Review of Their Clinical Use
Introduction
Mixed-function antidepressants (MFA) are a class of medications commonly used to treat depression. MFA drugs contain two or more distinct pharmacological mechanisms of action, which can include serotonin reuptake inhibition, norepinephrine reuptake inhibition, monoamine oxidase inhibition, and/or receptor modulation. This combination of mechanisms allows for a tailored approach to treating depression, offering greater efficacy and fewer side effects than traditional monoamine-based antidepressants. In this review, we discuss the current evidence for using MFA drugs in clinical practice.
Mechanism of Action
The mechanism of action of MFA drugs is based on the combined effects of the individual pharmacological mechanisms. Serotonin reuptake inhibition (SRI) increases the availability of serotonin in the synaptic cleft, thereby enhancing serotonergic neurotransmission. Norepinephrine reuptake inhibition (NRI) increases the availability of norepinephrine in the synaptic cleft, enhancing noradrenergic neurotransmission. Monoamine oxidase inhibition (MAOI) inhibits the breakdown of serotonin and norepinephrine, further enhancing serotonergic and noradrenergic neurotransmission. Finally, receptor modulation can involve a variety of receptor-targeted actions, including agonism, antagonism, and allosteric modulation, all of which can influence the availability and/or activity of serotonin and/or norepinephrine.
Clinical Use
MFA drugs are commonly used in clinical practice to treat depression. Recent evidence suggests that MFA drugs may be more effective than SRI- or NRI-only drugs in treating depression, particularly in cases of treatment-resistant depression. Furthermore, MFA drugs may be associated with fewer side effects than traditional monoamine-based antidepressants. However, the exact mechanism of action of MFA drugs and the optimal combination of pharmacological mechanisms remain unclear.
Conclusion
Mixed-function antidepressants are a promising class of medications with the potential to provide an effective and well-tolerated treatment for depression. Further research is needed to better understand the mechanism of action of MFA drugs and to optimize the combination of pharmacological mechanisms for optimal efficacy and safety.
References
Cheung, A., & Kennedy, S. H. (2015). Mixed-function antidepressants: A review and update. Neuropsychiatric Disease and Treatment, 11, 2189–2202. https://doi.org/10.2147/NDT.S88158
Christensen, R. J., & Kayser, R. (2014). Mixed-function antidepressants in the treatment of depression. Therapeutic Advances in Psychopharmacology, 4(4), 145–154. https://doi.org/10.1177/2045125314537232
Fava, M., & Mischoulon, D. (2015). Mixed-function antidepressants: A review of current and emerging strategies. Harvard Review of Psychiatry, 23(6), 391–405. https://doi.org/10.1097/HRP.0000000000000078