Antidepressants: 70 Years

Dear Colleagues,

The 1950s were the most prolific in the last century in terms of novel psychotropic class agents. These same years that witnessed the introduction of neuroleptics in clinics also registered the serendipitous discovery of the first two classes of antidepressants: monoamine oxidase A (MAO-A) inhibitors (MAOIs) and tricyclic antidepressants (TCAs).

Current antidepressants are effective in about two-thirds of patients suffering from affective disorders. However, while newer-generation antidepressants present fewer adverse effects than seen with TCAs and MAOIs, bothersome side effects remain prevalent. While the short-term treatment of depressive disorders may be considered satisfactory, the prevention of relapse and recurrence, both in cases of unipolar depression and bipolar illness, is still challenging. More tolerable and efficacious treatments need to be developed to improve medication adherence and management of antidepressant adverse effects. On the other hand, antidepressants are effective in a vast range of psychic disorders and may act as antimigraine and adjuvant analgesics. Finally, antidepressants display pleiotropic activities that may be exploited in therapeutic areas besides psychiatric and neurological diseases (e.g., chemotherapy), thus indicating possible repurposing strategies.

While the monoaminergic hypothesis may serve as a starting point for interpreting most of the major psychiatric signs in affective disorders, we are now aware that severe mental diseases, including affective disorders, are the expression of complex pathological mechanisms. While we lack a thorough understanding of the neurobiology of most mental disorders, we can confirm that numerous neurotransmitters and hormones are involved. Thus, polypharmacology is generally adopted to treat the most severe forms of affective disorders, meaning the multi-target approach for drug discovery should be fruitfully pursued, and emerging therapeutic targets should be further investigated.

This commemorative Special Issue on antidepressants was conceived as an opportunity to take stock of the situation, obtain an up-to-date landscape on the most recent developments, and promote advances and collaborative endeavors in the challenging area of some of the most prevalent and life-threatening forms of mental illnesses and the major causes of morbidity worldwide.

Dr. Giovanni Lentini
Prof. Dr. Serge Mignani
Guest Editors

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• polypharmacology
• multi-target drugs
• emerging therapeutic targets
• repurposing
• unipolar depression
• bipolar disorder