How do tricyclic/tetracyclic antidepressants primarily ease depression?

Tricyclic and tetracyclic antidepressants primarily ease depression by blocking the reuptake of neurotransmitters such as serotonin and norepinephrine. This mechanism involves inhibiting the proteins in the presynaptic neuron that are responsible for reabsorbing these neurotransmitters back into the cell after they have been released into the synaptic cleft. By preventing this reuptake, these medications increase the availability of these neurotransmitters in the synaptic cleft, leading to enhanced neurotransmission and improved mood.

This increased concentration of serotonin and norepinephrine in the synaptic space is believed to contribute to the alleviation of depressive symptoms, making this mechanism a central aspect of their therapeutic effect. The importance of neurotransmitter levels in mood regulation is well-established, and the ability of tricyclic and tetracyclic antidepressants to maintain higher levels of these neurotransmitters plays a significant role in their efficacy in treating depression.