The monoamine hypothesis of depression revisited: could it mechanistically novel antidepressant strategies?

In the 1950s, the amine hypothesis of depression was formulated suggesting that depression was associated with a deficiency in the transmission within the monoamine systems, i.e. serotonin, noradrenaline, dopamine. From those days, drugs able to increase the brain concentration of monoamine have been investigated in patients using the model of L-dopa in Parkinson’s disease. We here look at the introduction and development of these drugs for patients, from tryptophan to antipsychotics with antiserotonin properties, passing through selective serotonin reuptake inhibitors, selective serotonin-noradrenaline reuptake inhibitors, norepinephrine reuptake inhibitors, and bupropion. We also illustrate another important chapter of this history which is related to the concept of drug-induced illness. Indeed, the monoamine hypothesis of depression must be nowadays revisited under the evidence of withdrawal since antidepressants may induce new illnesses, which include diseases for which they are approved to treat and efficacious. A description of antidepressant withdrawal syndromes and indications on how to diagnose and manage them, both with pharmacological and non-pharmacological interventions, is provided.