It Is Time to Rethink Treatment-Resistant Depression & More Trending News – UP Jobs News

An uncomfortable truth exists about depression: Many people, perhaps most, respond poorly to treatment. This disappointing pattern persists despite decades of evolving psychotropics—MAO inhibitors, tricyclic antidepressants, and SSRIs—as well as validated psychotherapies such as cognitive behavior therapy (1). Clinical trials that best simulated real-world treatment conditions by using broad inclusion criteria, in fact, indicate that nearly 50% of patients experience poor outcomes or relapse of symptoms after two psychotropic interventions, with even lower rates of success observed with further treatments (2). Perhaps most discouraging of all is that rates of treatment-resistant depression do not appear to be improving over time; a person experiencing depression in 2022 enters treatment with roughly the same coin-flip probability of enjoying a sustained remission of their symptoms as in 1992.

Traditionally, the treatment of depression has been guided by the theory that depression symptoms result from deficits and dysfunction in key neurotransmitters such as dopamine, norepinephrine, and serotonin. Based on this model, for example, medication and psychotherapy treatments theoretically upregulating the availability of brain serotonin have become first-line treatments for depression. Although many people with depression do respond favorably to treatments targeting serotonin function, the neurotransmitter theory of depression has long suffered from a lack of empirical support as a comprehensive model. Although a new review casting doubt on the role of serotonin and other neurotransmitters in depression received wide press coverage in this month (3), for example, these scientific shortcomings have been well known to researchers for decades (e.g., 4).

In short, the field of depression treatment has long been practiced under a model of depression homogeneity. This is the theory that depression uniformly results from the same underlying neurobiological causes. The depression homogeneity model contrasts with the model of depression heterogeneity—the latter suggesting that depression results from different causes, potentially requiring different treatments. The fact that the homogeneity model of depression endures despite limited empirical evidence and high rates of treatment resistance is no coincidence: this model is enormously profitable for the mental health treatment industry.

Acknowledging the suboptimal modern state of depression theory and treatment, it may finally be time to rethink treatment-resistant depression. Instead of a failure to respond to one or more conventional psychotropics or psychotherapies, for instance, treatment-resistant depression may be more accurately considered a failure of diagnosis—a case of heterogeneous depression mischaracterized as homogeneous depression. Importantly, conceptualizing treatment-resistant depression through the lens of a heterogeneous depression model isn’t an abstraction. As shown in the figure below, the shift is highly practical.

From a homogeneous model of depression, every person experiencing depression symptoms is evaluated using standardized clinical assessment tools (such as depression questionnaires or a diagnostic interview) and their provider makes recommendations following a narrow treatment algorithm of antidepressants and psychotherapies. In contrast, the heterogeneous model encourages a broader approach to both assessment and treatment. Combined with a depression questionnaire or interview, for example, the provider may also perform a comprehensive medical evaluation, conduct laboratory tests to assess hormone function, inflammation levels, and vitamin panels, and collect detailed information about the person’s sleep, physical activity, dietary patterns, and psychosocial circumstances. The results would then be used to support one or more treatment approaches customized to the person. Notably, this treatment result would in many cases still include conventional antidepressants and psychotherapies. In other cases, however, the result might instead favor nutritional interventions, exercise, hormone treatments, and sleep therapies, among other approaches.

Summary

Even in an era of evidence-based interventions, treatment-resistant depression remains a stubbornly frequent outcome. The cost of treatment-resistant depression in our society—in metrics such as impaired quality of life and lost economic productivity—is enormous. Accumulating evidence suggests that these high rates of treatment resistance may be the result of incorrectly conceptualizing depression as a homogeneous rather than heterogeneous condition. Reconceptualizing depression as a condition with multiple etiologies could be the vanguard of a new era of individually-tailored depression treatments, as well as a much-needed means of expanding treatment options for the millions failing to respond to conventional therapies.

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