Story at a Glance
- The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, published in 2006, was the largest and longest-running antidepressant effectiveness trial ever conducted, and, importantly, it used real-world patients.
- The authors claimed an overall cumulative remission rate of 67 percent; this study has since been used to prop up the idea that antidepressants work in the real world.
- However, the widely made claim that antidepressants work for nearly 7 in 10 patients in real-world clinical settings is based on scientific misconduct and fraud.
- In his reanalysis of the STAR*D study, psychologist Ed Pigott and colleagues showed that, had the study protocol been followed, the cumulative remission rate would have been only 35 percent. Moreover, the STAR*D report omitted the stay-well rate. Only 3 percent of the 4,041 patients who entered the trial and went into remission were still in remission at the end of their one-year follow-up.
- Most clinical drug trials have found the effectiveness of antidepressants is on par with placebo, and many studies have debunked the serotonin theory that underpins the use of antidepressants. Meanwhile, large-scale meta-analyses show that physical exercise is the most effective remedy—about 1.5 times more effective than antidepressants—for depression.
The STAR*D Study
The study in question, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study,2 was published in 2006. This was the largest and longest-running antidepressant effectiveness trial ever conducted and, importantly, it used real-world patients, who often cannot participate in industry trials due to exclusionary criteria.“The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”
Research Misconduct Revealed
However, a reanalysis5 of the STAR*D data in 2010 by psychologist Ed Pigott and colleagues revealed serious problems. As explained by Mr. Whitaker in early September 2023,6 Mr. Pigott filed a Freedom of Information Act request to obtain the complete STAR*D protocol and previously undisclosed data, and with that, he was able to identify the ways in which the STAR*D investigators had inflated the remission rate.While complex, Mr. Whitaker does a fine job explaining how the fraud was carried out, step by step, by violating the study protocol. In just one example, patients who didn’t qualify as depressed enough to even be included in the study in the first place were counted as remitted, as were patients who dropped out, mostly due to intolerance to the drugs. They also switched outcome measures and introduced theoretical elements in clear violation of the study protocol.
In summary, Mr. Pigott’s team was able to show that, had the study protocol been followed, the cumulative remission rate would only have been 35 percent, not 67 percent. Moreover, the STAR*D report omitted the stay-well rate, probably because only 3 percent of the 4,041 patients who entered the trial and went into remission were still in remission at the end of their one-year follow-up.
As noted by Mr. Whitaker, Dr. Insel was telling the public and working psychiatrists that 70 percent of the patients in the study got well and stayed well, “a statement that exemplifies the grand scale of the STAR*D fraud.”
Scientific Misconduct Rising to the Level of Fraud
Mr. Whitaker continues:10“Seventy percent versus a reality of 3%—those are the bottom-line numbers for the public to remember when it judges whether, in the reporting of outcomes in the STAR*D study, there is evidence of an ‘intent to deceive’ ...
“The protocol violations and publication of a fabricated ‘principal outcome’—the 67% cumulative remission rate—are evidence of scientific misconduct that rises to the level of fraud.
“Yet, as Pigott and colleagues have published their papers deconstructing the study, the NIMH investigators have never uttered a peep in protest.
“They have remained silent, and this was the case when Pigott and colleagues, in August of this year, published their latest paper11 in BMJ Open. In it, they analyzed patient-level data from the trial and detailed, once again, the protocol violations used to inflate the results ...
“The one time a STAR*D investigator was prompted to respond, he confirmed that the 3% stay-well rate that Pigott and colleagues had published was accurate ... That was 13 years ago.
“The protocol violations, which are understood to be a form of scientific misconduct, had been revealed. The inflation of remission rates and the hiding of the astoundingly low stay-well rate had been revealed.
“In 2011, Mad in America published two blogs12,13 by Ed Pigott detailing the scientific misconduct and put documents14 online that provided proof of that misconduct. In 2015, Lisa Cosgrove and I ... published a detailed account of the scientific misconduct in our book ‘Psychiatry Under the Influence.’ The fraud was out there for all to see ...
“Yet, there has been no public acknowledgement by the American Psychiatric Association (APA) of this scientific misconduct. There has been no call by the APA—or academic psychiatrists in the United States—to retract the studies that reported the inflated remission rates. There has been no censure of the STAR*D investigators for their scientific misconduct ...
“Thus, given the documented record of scientific misconduct, in the largest and most important trial of antidepressants ever conducted, there is only one conclusion to draw: In American psychiatry, scientific misconduct is an accepted practice.”
Action Item: Demand the Withdrawal of the STAR*D Report
Since the APA is refusing to take action and has allowed the deception to stand for 17 years, Mr. Whitaker is now calling on the public to make the fraud known and demand that the 2006 STAR*D report15 be withdrawn.Corruption Puts Real People in Lethal Jeopardy
Considering the severity of the misconduct, it comes as no surprise to find that eight of the 12 STAR*D investigators had ties to the manufacturer of citalopram, the first-line antidepressant used in this study. In all, the 12 investigators had 151 different ties to drug companies.As noted by Mr. Whitaker, this scientific misconduct “has done extraordinary harm” to the public because the study was expressly designed to assess outcomes in real-world patients and guide future clinical care. As it stands, the study has lured patients into one of the least effective and most hazardous treatment options there is.
Inflammation and Depression
If low serotonin in the brain is not the cause behind depression, what is? One highly probable culprit is inflammation. Certain biomarkers, such as cytokines in your blood and inflammatory messengers like CRP, IL-1, IL-6, and TNF-alpha, show promise as potential new diagnostic tools, as they’ve been found to be “predictive18 and linearly19 correlative” with depression.“The fully adjusted odds ratios (ORs) with 95% confidence intervals of depressive symptoms were 1.994 (1.298–3.063) and 1.592 (1.047–2.421) for the highest versus lowest quartile of intake of oleic acid (OA) and linoleic acid (LA), respectively. Intake of OA and LA may be positively associated with depressive symptoms in perimenopausal women.”Another 2022 paper24 found that middle-aged adults with the highest LA intakes (top quartile) were 41 percent more likely to be depressed compared to those with the lowest intakes (bottom quartile). An earlier study, published in 2009, which followed patients for an average of 10.6 years, also reported a link between higher LA intake and severe depression among men.25
The Links Between Gut and Mental Health
Many studies have also confirmed that gastrointestinal inflammation specifically can play a critical role in the development of depression, suggesting that beneficial bacteria (probiotics) may be an important part of treatment. For example, a Hungarian scientific review26 published in 2011 made the following observations:- Depression is often found alongside gastrointestinal inflammations and autoimmune diseases as well as with cardiovascular diseases, neurodegenerative diseases, Type 2 diabetes, and also cancer, in which chronic low-grade inflammation is a significant contributing factor. Thus the researchers suggested that “depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome.”
- An increasing number of clinical studies have shown that treating gastrointestinal inflammation with probiotics, vitamin B, vitamin D, and omega-3 fats may improve depression symptoms and quality of life by attenuating proinflammatory stimuli to your brain.
- Research suggests the primary cause of inflammation may be dysfunction of the “gut-brain axis.” Your gut is literally your second brain, created from the identical tissue as your brain during gestation, so optimizing your gut flora may be a key part of the equation.
Vitamin D Deficiency Predisposes You to Depression
Vitamin D deficiency is another important biological factor that can play a significant role in mental health. In one 2006 study,27 seniors with vitamin D levels below 20 ng/mL were found to be 11 times more prone to be depressed than those with higher levels.“Effective detection and treatment of inadequate vitamin D levels in persons with depression and other mental disorders may be an easy and cost-effective therapy which could improve patients’ long-term health outcomes as well as their quality of life.”Based on large-scale studies, the optimal range for general physical and mental health appears to be somewhere between 40 ng/mL and 60 ng/mL. So if you’re depressed, you’d be well-advised to get your vitamin D level checked and to address any insufficiency or deficiency.
Exercise Is the Best Medicine
As detailed in Mr. Whitaker’s books “Mad in America” and “Anatomy of an Epidemic,” physical exercise comes out on top in most studies, including when compared to antidepressant drugs. There are several likely reasons for this. For starters, exercise helps to normalize your insulin levels and boosts “feel good” hormones in your brain, including endogenous endocannabinoids like anandamide.Exercise Is 1.5x More Effective Than Antidepressants
A 2023 overview of systematic reviews34 further confirms the superior benefit of exercise for the treatment of depression. In all, 97 systematic reviews with meta-analyses of controlled trials assessing the effects of exercise on adult depression, anxiety, and psychological distress were included (amounting to a total of 1,039 trials involving 128,119 participants).“University of South Australia researchers are calling for exercise to be a mainstay approach for managing depression as a new study shows that physical activity is 1.5 times more effective than counselling or the leading medications ...
“[The study] shows that physical activity is extremely beneficial for improving symptoms of depression, anxiety, and distress. Specifically, the review showed that exercise interventions that were 12 weeks or shorter were the most effective at reducing mental health symptoms, highlighting the speed at which physical activity can make a change ...
“Lead UniSA researcher, Dr. Ben Singh, says physical activity must be prioritized to better manage the growing cases of mental health conditions ... Higher intensity exercise had greater improvements for depression and anxiety, while longer durations had smaller effects when compared to short and mid-duration bursts.
“All types of physical activity and exercise were beneficial, including aerobic exercise such as walking, resistance training, Pilates, and yoga. ‘Importantly, the research shows that it doesn’t take much for exercise to make a positive change to your mental health.’”
Dose-Response Association Between Exercise and Depression
Another systematic review,36 published in April 2022, which analyzed the association between physical activity and the risk of depression, found there’s a dose-dependent response. This review included studies from around the world published up until December 2020. In all, 15 studies were included, with a total of 191,130 participants.“... if less [sic] active adults had achieved the current physical activity recommendations, 11.5% of depression cases could have been prevented ... Health practitioners should therefore encourage any increase in physical activity to improve mental health.”Originally published Jan. 30, 2024, on Mercola.com
◇ References:
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- 2, 15 American Journal of Psychiatry November 2006; 163:11
- 3 Counterpunch January 17, 2024
- 4 Molecular Psychiatry 2023; 28: 3243-3256
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- 29 The Journal of Nutrition, Health & Aging 1999, 3(1):5-7
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- 32 Issues Ment Health Nurs. Author manuscript; available in PMC June 1, 2011
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- 34 British Journal of Sports Medicine Epub February 16, 2023
- 35 University of South Australia February 24, 2023
- 36 JAMA Psychiatry April 13, 2022; 79(6):550-559