There are three main classification of drugs used to treat major depressive disorder: selective serotonin reuptake inhibitors (SSRIs) as well as serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclics, and monoamine oxidase inhibitors (MAOIs) (NIMH).
In regards to the first class of drug, SSRIs and SNRIs such as Prozac, Zoloft, Lexapro and Effexor work by not allowing a neuron to reabsorb neuro-transmitter from the synaptic cleft. A specific SSRI investigated by Hvenegaard et al. (2012) (Lu AA21004) was shown to be a partial agonist and inhibitor of the 5-HT transporter; the 5-HT transporter is what is responsible for serotonin reentering the neuron after being released. These drugs work by binding to these transport proteins and not allowing serotonin, (or in the case of SNRIs serotonin and norepinephrine) to renter the presynaptic neuron, resulting in a prolonged activity of these molecules (see Figure 8). It is logical to administer this drug to a patient with MDD, because the increased amount of MAO-A is destroying the serotonin in their neurons. By increasing the amount of time the remaining serotonin has to react in the synaptic cleft, the problem of degradation is somewhat alleviated. It no longer matters that most of the serotonin and norepinephrine is destroyed because the remaining amount will be allowed to work longer, resulting in a greater net effect of activation. This is one of the most common treatments administered today. The next class of drug, tricyclics, is composed of drugs that work in a similar fashion to SSRIs and SNRIs; these drugs also block the reuptake of serotonin and norepinephrine into the presynaptic neuron, allowing for these molecules to remain in the synaptic cleft longer and react longer with the postsynaptic cell. These drugs have been less popular, as treatment with SSRIs and SNRIs usually have less negative side effects (MAYO Clinic 2014).
The last class of drugs, MAOIs, is the drug class that is the most relevant to the literature today. These drugs are some of the first drugs to be administered for MDD, and have also been phased out due to negative side effects associated with them; one such side effect includes cardiovascular reactions (Finberg 2014). The mechanism of action of these drugs is covalent bonding to the MAO, resulting in an irreversible bond to the enzyme. MAOIs are often referred to as suicide inhibitors because of their irreversible reaction. These drugs would seem to be outclassed by many of the SSRIs and SNRIs available today with fewer side effects (see Figure 9), but the research of Goldberg et al. (2014) illuminates issues seen with using just SSRIs or SNRIs; even though serotonin and norepinephrine reuptake are stopped, GABA degradation is still going on in excess from the abundance of MAO-A. The high resurgence rate of MDD might be associated with the GABA breakdown, as SSRIs and SNRIs will not be able to help stop this process. To stop MDD, one might need to find a way to make sure problems associated with dopamine, serotonin, norepinephrine and dopamine.
Other Management Techniques
MDD can be managed through a variety of different methods: talk therapy sessions in which one is able to develop mental strategies to combat negative thoughts, hypnotherapy in which one is hypnotized and the psychologists will have a talk therapy session, regiments of serotonin and GABA boosting vitamins, and in extreme cases electroshock therapy in which a current of electricity is sent through the brain (NIMH). Combined with antidepressants, the resurgence rate of MDD is still 50%, so a patient might experience symptoms of depression and have to utilize management techniques for a long time.