Out of the Box

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January 2018. As you are well aware, mood disorders (particularly major depressive disorder) are among the most prevalent and disabling illnesses in all of medicine. One sample of statistics from the valuable “burden of disease” database of the World Health Organization is the report by Collins et al1 published in Nature in 2011, which ranked neuropsychiatric illnesses, worldwide, in terms of level of severity, using the DALY (disability-adjusted life years) metric. Unipolar depressive disorders top the Global Burden list, way above other conditions such as substance use disorders, Alzheimer’s, Parkinson’s, and many others.
No news here, you say, and you’re (mostly) right. “Mostly” because it’s surprising how many people do not know these facts. But many of us do, and the hunt is on to find better methods of prevention, early identification, early intervention, and treatment of depression. It was only in January 2016, that the US Preventive Services Task Force issued a recommendation to screen for depression in the general adult population,2 a mandate that should be a wake-up call not just in clinical treatment centers, but in wellness-focused community groups and in the social media.
Once we identify those suffering from depression and once we encourage them to accept the need for help, how effective are our treatments? Before addressing that question, it’s important to point out that not all forms of depression are of equal severity, just as “malignant” hypertension, “brittle” diabetes, and “end stage” illnesses are more challenging to treat than the garden varieties of these conditions. In the world of depression care, we see an increasing focus on “treatment-resistant” depression, or TRD. Once nonresponse or insufficient response to legitimate trials of known effective treatments such as selective serotonin reuptake inhibitors or other antidepressants, or cognitive behavioral therapy, has been determined, where do we go from there? The landmark STAR*D trial3 found that only about one-third of patients with depression achieved remission from the first stage of antidepressant treatment. Some of these patients subsequently responded when they were switched to a different antidepressant or when a different medication was added to the initial one. But the odds of beating depression decreased with each new treatment strategy.
So we have a long way to go, but here’s where my title, “Out of the Box” comes in. Innovative and/or “adjunctive” treatment strategies are receiving a lot of attention, rightly so. Witness the recognition that regular exercise may serve as a mood stabilizer for some people, or that it may be helpful as an augmentation to traditional treatments. In this issue of the Journal, Uebelacker and colleagues report a pilot study examining the potential value of an online Hatha yoga intervention for patients diagnosed with mood disorders, as an augmentation intervention added to their usual treatments. Although the “n” is small and the results preliminary, a significant reduction in negative affect was observed. Also in this issue, Chugh and colleagues report on the use of botulinum toxin as an adjunctive intervention in patients with TRD. Although an open pilot study, the results were promising; one interesting speculation by the authors is that these results might in part correlate with specific aspects of the Hindu culture. Finally, also in this issue, Vulser and colleagues provide a case report showing dramatic reduction in suicidal ideation in a patient in the general hospital setting, following the administration of IV ketamine. These and other approaches (eg, new brain stimulation technologies) are important new directions in our continued efforts to find the best treatment formula for each individual struggling with severe and disabling depression.
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