(The article in question is the Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and Long-Term Outcomes of a Single-Blind Randomized Study in the July 2011 American Journal of Psychiatry, in case you want to follow-along while I read aloud)
Well, don’t exactly blame the patients. Blame the study authors for possibly not diagnosing their subjects correctly during subject recruitment. I want to spend this article talking about the patients in the trial and may leave discussion of the article’s results (simply, that no treatment combo outperformed any other) to another post, because this subject-selection problem is a big deal.
Now, this issue of subject selection is important, too, because it directly impacts our assessment of the results of this trial. Ordinarily, we might accept the results and start second-guessing the quality of our psychopharmacology (which is all the rage in the New York Times these days). But if the subjects in the trial don’t have the illness the trial purportedly studies, then we can not accept the results; we can’t draw any conclusions whatsoever.
Before even reading the article, I predicted that the subject population would primarily include 40 year old women and, lo, that is indeed the subject average (68% of subjects were women about 42 years-old). See my previous posts for other recent examples. We are given a bunch of good demographic data, but not much about their overall health; their BMIs would have been helpful, too. Most curiously, we are not even told if these subjects are married or not. So, in toto, these subjects tended to be white 42-year old women who attended just under two years of college, and make about $33000 a year.
The average age of the first depressive episode was 24 but just under half (44.6%) of the subjects reported that their first episode began before age 18. This is red flag number one. This is not typical for major depressive disorder; it tends to have a later onset. This may only indicate that the age-of-onset data was wildly skewed, but nevertheless, almost half of the subjects had very early onset of depressive symptoms which is more typical of bipolar illness, personality disorders, substance-induced mood disorders, etc.
Further, a substantial portion were abused. Fully 21% had been sexually abused, almost 20% had been physically abused, and almost 40% had been emotionally abused. This is red flag number two. Based on National Comorbidity Survey data (as reported in the NCS Kessler data), we might expect that these numbers should be closer to: 4.4% experiencing physical abuse (0.32 * 3% [percent of men in this study times rate of physical abuse reported by men in NCS] + 0.68 * 5% [percent of women in this study times rate of physical abuse reported by women in NCS] = 4.4%) and almost 16% experiencing sexual abuse (0.32 * 4% [percentage of men times rate of rape plus molestation in NCS] + 0.68 * 21% [percentage of women in study times rate of rape plus molestation in NCS] = 15.56%). So, as compared with traditional averages, 15% more patients in this study were exposed to physical abuse and 5% more patients were exposed to sexual abuse.
Also questionable (and this is alluded to in the accompanying editorial) is that the average index episode of depression lasted almost five years! This is red flag number three. How many patients have you ever seen who had index episodes (or any episode) lasting so long? The typical median duration of an untreated major depressive episode is about 8 months. You are probably scratching your head, for good reason. Who in the world are these subjects, who have depressive episodes that last abnormally long? They might just be patients who over-endorse the nature of their depressive symptoms… …and the study authors should spot this and call bullshit, immediately.
And I can keep going, there are so many problems…and I’m going to stop calling them red flags, because there are just too many. 75% of subjects had co-morbid medical diagnoses and we are not told what they were or if (importantly) they were treated (because we sure as heck know they aren’t getting their 5-year long depressive episodes treated). It is of the utmost importance to determine if these depressive episodes are due to medical illness, which to be fair, is a tragedy of almost every other depression study– we need to know if these (or any) subjects have hypothyroidism, sleep apnea, anemia, autoimmune disease, and on and on and on.
And almost inexcusably, there is no indication as to whether these subjects were actively addicted to or abusing drugs or alcohol. There is no indication in the article that they were even asked about their drug histories or asked to submit to urine drug screens. I tell you, chronic alcoholism sure can produce 5-year-long depressive episodes. So can crashing from coke every day for five years. So can smoking 5 bowls of marijuana a day for 5 years.
In the discussion, the authors admit that they did not use a structured interview to diagnose depression. Reading this, I initially assumed that they meant they didn’t SCID the subjects upon enrollment, but then I realized that I was probably assuming too much. Maybe they didn’t interview the subjects beyond screening for depression and for the few exclusion criteria. We know they didn’t ask about drugs. I bet they didn’t screen for personality disorders. And it’s not clear they even asked about particular medical illnesses. We know these things because they didn’t report them and that none of these things were factored into the exclusion criteria. “But the study approximates real world psychiatry” you say…. No, it doesn’t. I don’t give my chronic alcoholics venlafaxine plus mirtazepine for their depressive symptoms when it is not clear that alcohol isn’t causing the whole problem. I don’t give escitalopram plus bupropion to my patients who have untreated hypothyroidism.
Word of advice– don’t draw any clinical conclusions from this study. Use it to better inform your research methods, so you don’t make the same mistakes these folks did.