429 - Seasonal Affective Disorder, Research “Spin”, Rising Together

From the Literature and Timely Topic Review 

1) Seasonal Affective Disorder (SAD): Winter Depression Variation

Seasonal affective disorder (SAD) is a seasonal pattern of major depressive episodes associated with either bipolar or recurrent major depressive disorder.  The most prevalent form of SAD is winter depression, which is characterized by recurrent episodes of unipolar depression that begin in the fall or winter with a peak in January and February and which will generally resolve by spring or summer if left untreated.  It occurs more often in women than men and appears to be caused by seasonal changes in daylight.

 The best metaphor cyclical winter depression is hibernation.  Unlike people with classical depression, who typically eat less and sleep less, people with SAD eat more and sleep more, much like animals hibernating for the winter. People with SAD are not actually sad; mainly, they just feel tired and less interested in things (ie, anhedonic) and because of this often don’t realize they have depression.

 In DSM-5, the winter depression form of SAD is now known as depressive disorder with seasonal pattern, for which the diagnostic criteria are as follows:

·        A regular temporal relation between the onset of major depressive episodes and a particular time of year

·        Full remissions that also occur at a characteristic time of year

·        No episodes of depression during the time of year when the individual experiences a normal mood

·        Seasonal major depressive episodes substantially outnumber the nonseasonal major depressive episodes that may have occurred over the individual's lifetime

 It is important to note there can be an association with bipolar disorder, and for those who experience spring/summer mania as part of their pattern, treating this is important as part of the care plan.

 No large studies have found any one treatment to be superior. Daily light therapy within an hour of awakening at 10,000 lux for 20-30 minutes has been shown to be helpful as has dawn light simulation (timing lights in the bedroom to come on gradually, over a period of 30 minutes to 2 hours before awakening to simulate dawn). The time should be adjusted based on response. The bright light therapy has been found in some studies to be more effective for severe depression. 

 It is important to ensure the light box blocks UV light and can be used at least 16-24 inches from the face.  They can be purchased without a prescription and it should be noted that they not approved or regulated by the FDA for SAD treatment and not usually covered by insurance.  The cost of some well-made devices is now as low under $100. Response can be within 1-2 weeks.

 Antidepressants such as bupropion, fluoxetine, sertraline may improve symptoms of SAD.  There is weak evidence for the benefits of melatonin, tryptophan, and vitamin D supplementation.  Often the combination of medications and light therapy is necessary. A randomized trial showed that cognitive behavioral therapy (CBT-SAD) and light therapy are comparably effective for SAD during an acute episode, and both may be considered as treatment options. A Cochrane review found that the evidence was limited regarding using light therapy or CBT as a preventive measure.  

 Other recommended interventions to help with both treatment and prevention include sleep hygiene, daily walks outside, even on cloudy days, aerobic exercise, and enhanced indoor lighting with regular lamps and fixtures.   

 Mark’s Comments:

It is exciting to see greater understanding about circadian rhythms and the impact of light on our mental health. Be on the lookout for these symptoms in your patients over the next 3 months and be sure to get some regular outdoor “light therapy” of your own!

 Note that many people experience fall/winter symptoms that are below the full syndrome threshold for a clinical depressive episode. These are the individuals for whom the term winter blues was coined.  The light therapy interventions above should be considered for this as well.

 eferences:

·       Rohan KJ, et al. Randomized Trial of Cognitive-Behavioral Therapy Versus Light Therapy for Seasonal Affective Disorder: Acute Outcomes. Am J Psychiatry. September 2015; 172(9):862-9.  Link

·       Cochrane Reviews – Light therapy and psychological therapies for prevention of winter depression.  March 18, 2019 (Link) and May 24, 2019 (Link)

From the Literature

 2)  “Spin” in Non-inferiority Studies

A central tenet of the critical appraisal of randomized controlled trials is to make sure you know what the researchers designate as the primary outcome for their study, and then make sure they report that. Too often, the authors of a study that fails to show a significant difference in the primary outcome will report significant secondary outcomes instead or talk about a “trend” toward significance. This would be fine if they treated these findings as testable hypotheses for future research. “Spin” is defined as the use of the results of these non-primary outcomes as actionable conclusions instead. We think of this spin as more common in research funded by industry, but in this age of intense competition for publication and grants, it can happen in any setting.

 A systematic review of oncology studies looked for spin in “non-inferiority studies” of cancer treatments. Non-inferiority (NI) studies are difficult to critically appraise, so this spin is more difficult to detect. NI studies are done when a new therapy that might be less costly or has fewer safety or tolerability issues is compared to a standard therapy. The purpose is to ensure that the novel therapy is at least as effective as the standard therapy. For that, the researchers hope to show that the confidence interval for the comparison does not cross a certain minimal threshold of effectiveness.  How that threshold is set depends on prior studies and some amount of judgment. (See 2^nd reference below for more details).

 The review authors looked for the following sources of spin in these oncology studies (based on a search of PubMed alone):

(1)  emphasizing trends in point estimates, despite lacking significance for the primary end point results

(2)  the results of the secondary end point

(3)  the results of subgroup analysis

(4)  the secondary analysis results of the primary end point, such as by changing the analysis population or measuring the treatment effect

(5)  the intragroup comparison results, such as those before and after treatment

(6)  no mention in the discussion of the experimental treatment’s unclear safety profile in reports that stated the rationale for conducting the study was safety of the experimental treatment (in other words, if the study is conducted because of safety concerns, report and discuss the safety outcomes)

(7)  based on safety alone, despite insignificant results of the primary end point analysis in the conclusion section

 The authors found spin in 75% of the reports they examined, and spin was most common in reports of novel therapies and LEAST prevalent in studies with “for-profit” funding and with a designated data manager on the study team.

 John’s Comments:

I know…this was a dense one. A few important takeaways:

·       We cannot just be automatically suspicious of industry funding; we must look more deeply at how the study was conducted and reported to appraise it.

·       The seven points above are common sense “detectors” of study reporting shenanigans that can be used for most studies, not just NI studies.

·       Look for the disclosure that a standard reporting framework for their study was used (CONSORT for RCTs, PRISMA for systematic reviews, etc.) and that they registered their study with a site like clinicaltrials.gov, which requires declaring the primary outcome, etc.  Most good quality journals will require these steps.

·       Find an “updating service” that can examine these issues for you.

 These will be important concepts to keep in mind as we get new COVID-19 vaccines or monoclonal antibody treatments – new products will likely be compared to established products with the goal of showing similar effect rather than efficacy vs. placebo.

 References:

·       Ito C, Hashimoto A, Uemura K, Oba K. Misleading Reporting (Spin) in Noninferiority Randomized Clinical Trials in Oncology With Statistically Not Significant Results: A Systematic Review. JAMA Network Open. 2021;4(12):e2135765. 35765 Link

·       Mulla SM, Scott IA, Jackevicius CA, You JJ, Guyatt GH. How to Use a Noninferiority Trial: Users’ Guides to the Medical Literature. JAMA. 2012;308(24):2605-2611. Link

From PeerRxMed (www.PeerRxMed.com)

3)  Rising Together in 2022

​​”One of the most effective things you can do to build better habits is to join a culture where your desired behavior is the normal behavior.”  James Clear, author

 When you look back on 2022 one year from now, what do you hope will be different for you?  One year ago when I posed this question for 2021, three things emerged for me that centered around the word “Cor”, which became my “word for the year.”

·       I wanted to live more from my “heart” (opening my cor) and have access to and appropriately express a fuller range of emotions, particularly in my significant relationships.

·       I desired to have greater present moment awareness (living from my core), spending less time in “reactive” mode and more in place of responsiveness or even “presponsiveness” (a made-up word that should be a real one).

·       I needed to physically get back to doing the things I love by actively recovering from a significant back injury (strengthening my core).

 In order to increase the chances of my succeeding in these intentions, I made 3 significant changes to my daily routine, which over the course of the year became ingrained habits:  journaling daily about at least 3 blessings and/or “moments of meaning”; meditating daily for at least 16 minutes using a meditation app;  joining a gym and going at least 4 times a week.  But what really made the difference was the 4^th change I made.  I swallowed my pride and shared my intentions widely, including with my PeerRxMed buddies, specifically asking for their support and accountability, and also invited others to join me.   

 Well, one year later, I’m glad to say that all 3 of these intentions have been achieved, and when I look back on 2021, despite the many challenges we all have faced, I personally consider this year a rousing success.   While my PeerRxMed buddies did not participate in each of these (and made some intentions of their own), the mutual support we provided was definitely the “secret sauce of success” for me. 

 The process of change can make anyone feel vulnerable.  Afterall, to a certain degree we are admitting “incompetence” in whatever we are aspiring to.   That vulnerability can give rise to fear.  Overcoming these takes courage and can be accelerated by the support that comes from connection.  Indeed, in his book “Atomic Habits”, James Clear writes, ​​”One of the most effective things you can do to build better habits is to join a culture where your desired behavior is the normal behavior.”  By doing so, “You’ll rise together.”  

 So this year, I am once again posing the question, “When I look back on 2022 one year from now, what do I hope will be different for me?” and invite you to do the same.  And as we do so, one thing I am certain of for me is that whatever I envision, I won’t have done it alone.  There will be others who will be crossing the finish line with me.  And that will have made all the difference.

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org