Psychiatric drugs perturb neurotransmitter pathways in the brain, and in response to that perturbation, the brain undergoes a series of compensatory adaptations in an effort to maintain normal functioning of those systems. In scientific terms, the brain is trying restore its “homeostatic equilibrium.” Fava has dubbed this compensatory response to a psychiatric drug “oppositional tolerance.”
For instance, a selective serotonin reuptake inhibitor (SSRI) blocks the normal reuptake of serotonin from the synaptic cleft, which is the tiny gap between neurons. Serotonin now stays in the cleft longer than normal, and feedback mechanisms immediately kick into gear. The presynaptic neurons begin putting out less serotonin than usual, while the postsynaptic neurons—the neurons receiving the message—decrease the density of their receptors for serotonin. The drug is acting as an accelerator of serotonergic activity; the brain responds by putting down the brake.
More from Psychology Today. Bottom line: with antidepressant medications, the cure may be worse than the disease.