![]() In addition, depressive illnesses are too-often fatal. An estimated 30% of persons with depressive illnesses fail to respond to multiple, evidence-based interventions ( 4), and the depression is then categorized as “treatment resistant.” Depressive illnesses tend to start young, with onsets peaking between ages 15 and 24 ( 3). High prevalence, heterogeneous causes of depressions, young ages of onset, and variable treatment responses are well understood as leading reasons for disability.WHO data estimate that more than 300 million people worldwide struggle with depressive illnesses. Its litany of devastation is frightening. ![]() Major depressive disorder is a pervasive, toxic, highly prevalent, early-onset illness, ignominiously holding the World Health Organization’s (WHO’s) ranking as the leading cause of disability ( 1, 2). ![]() The authors provide guidance in determining how to discontinue antidepressants if that decision is made despite risks. Measurement-based care and precision medicine would be the foundation for informing clinical decisions. Clinical trials would need to be greatly lengthened. Risk factors would need to be assessed and used to formulate clinical treatment guidelines for risk of recurrence. Current approaches would need to be transformed from attainment of clinical remission to attainment and maintenance of lifetime wellness, with the knowledge that some individuals may need continuous treatment. The authors describe actions required to achieve a “lifetime wellness” focus for treatment. Reasonably well-established clues and guidelines are presented about the high risk and profound consequences of recurrence of major depressive disorder if successful antidepressant treatments are discontinued. If clinical remission is not attained and sustained, episodes tend to recur with greater severity and with lessening responsivity to conventional treatments. According to the World Health Organization, major depressive disorder is the world’s leading cause of disability.
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