An in-depth review of the “first” guideline for the recognition and management of major depression with mixed features, which recommended antipsychotics as a first-line treatment, found that it fails to meet any of the Institute of Medicine standards for guidelines. The three researchers who investigated the guideline found that its authors had close ties to industry; that they urged clinicians to use industry-friendly criteria for diagnosing the disorder; and that there was a lack of clinical evidence to support their recommendations.
The review, which was published in BMJ Evidence-Based Medicine, was conducted by Lisa Cosgrove of the University of Massachusetts Boston, Allen Shaughnessy of Tufts Medical School, and Terrence Shaneyfelt of the University of Alabama. Their deconstruction of the guideline, they wrote, provides “a case example of the economies of influence that contribute to the development and dissemination of untrustworthy guidelines.”
Financial conflicts of interest
Institute of Medicine standards state that guideline developers should be independent of industry. At a minimum, neither the chair nor the majority of members should have financial conflicts of interest.
In this case, the lead author of the guideline, Stephen Stahl, from the University of California, San Diego, is a member of the speaker’s bureau for Sunovion, the manufacturer of lurasidone (Latuda), which was one of two antipsychotics the guideline recommended as a preferred treatment. Stahl is also the editor-in-chief of CNS Spectrums, the journal that published the guideline. Finally, the guideline was published “in association with the Neuroscience Education Institute, a for-profit company, founded by Stahl, that provides continuing medical education for psychiatric disorders.
Of the 19 other guideline authors, at least 12 had ties to manufacturers of antipsychotics, and four in this group, like Stahl, were on Sunovion’s speaker’s bureau.
“Pharmaceutical companies refer to individuals who serve on speakers’ bureaus as ‘key opinion leaders’ because they are seen as essential to the marketing of new disorders as well as the drugs to treat them,” Cosgrove and colleagues wrote.
Expanding the market for industry
In their guideline, Stahl and his co-authors recommended that the criteria for recognizing “mixed depression” should be expanded beyond the criteria in DSM-5. They listed additional “non-DSM criteria” for making the diagnosis, without “providing adequate empirical support” for doing so, Cosgrove and her colleagues found.
The guideline also urges clinicians to “look for evidence of subthreshold symptoms,” recommending (and writing in bold) that they “ask every patient. Every time.” The guideline “emphasized that ‘mixed depression’ is significantly underdiagnosed in clinical practice and is ‘especially common in children and adolescents.”
This guideline, Cosgrove and colleagues wrote, “runs the risk of widening diagnostic boundaries and unnecessarily exposing people to treatment.”
No good clinical evidence
The guideline authors cited seven studies as evidence for recommending antipsychotics for mixed depression. Four of the seven were post-hoc analyses, rather than reports of the studies’ primary outcomes. Such analyses, Cosgrove and colleagues noted, “should only be used to generate hypotheses for future research” and not “as evidence of the efficacy of an intervention.”
The fifth study was a clinical trial for a different condition, not depression. That left two randomized clinical trials that the guideline authors reviewed.
One was of lurasidone. All of the investigators in that trial had commercial ties to the manufacturer, including six who were company employees. The second trial was of ziprasidone; six of the authors of that study, which was funded by Pfizer, the manufacturer of ziprasidone, had ties to industry.
Stahl and his guideline co-authors recommended lurasidone (Latuda) and asenaphine (Saphris) as the antipsychotics of choice for mixed depression. The authors did not list any RCT evidence to support their recommendation of asenaphine. Both of these medications are unavailable as generics and cost more than $1000 a month and $500 a month respectively.
An industry-friendly guideline
In conclusion, Cosgrove and her colleagues write:
“The ‘first ever’ guideline on the recognition and management of mixed depression highlights ongoing problems in guideline development, namely, that poorly developed, untrustworthy guidelines continue to be produced and conflicts of interest are still a major problem in guideline development.”
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Cosgrove L, Shaughnessy AF, Shaneyfelt, T. (2018). “When is a guideline not a guideline? The devil is in the details.” BMJ Evidence-Based Medicine 23:33-36. (Link)
Thank you for posting this! What in the world is “mixed depression” and why would one even think of taking an antipsychotic for it?
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I bet what the industry calls mixed depression is a mixture of classic depressive symptomology and perceptual distortions- a group you definitely don’t want to treat with standard antidepressants. The so-called antipsychotic treatments are an attempt to correct this by turning such patients into addicted (if risperidone is the father of this family of drugs) robots, incapable of any, much less serious, activity.
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“Really big mistakes” has to be pretty much the case. Come on. Neuroleptics as the “front-line” treatment for “treatment-resistant” depression? We’ve got some people anti-depressants don’t work on. How about if we put these people on neuroleptics? Neuroleptics aren’t anti-depressants. So what? Maybe they will be if we give them a chance? If the “treatment-resistant” are still “treatment resistant”, at least somebody made some money out of the matter. The “mental health” establishment has bought this idea of the drug companies that these drugs are interchangeable because, although it may not be good for the health of human beings, it’s good for business. Look a little closer at the matter, and you will realize that these drugs aren’t medicines, they are social control drugs, and that’s actually what is being aimed at here, social control, not health. Unless bad health makes people happy, the people taking neuroleptics are not likely to get much out of it, at least, not much more than they’d be getting from any other placebo.
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I don’t know, Frank. They may be getting 16+ hours of comatose sleep, per day.
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As I read through this all I could do was shake my head in disgust, the psychiatric establishment is incorrigible.
And it’s a really stupid idea to combine the antidepressants and antipsychotics, since it’s medically known that combining these drug classes can make people “psychotic,” via anticholinergic toxidrome.
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I would not go to any GP that “asks every patient, every time.” To me, that’s a clear sign that they are a dangerous quack. And my only response to questions of that nature is always “none of your business.”
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What on earth is “mixed depression” depression with psychotic features or depression with anxiety. These 2 drugs are so new they are not available in NZ yet (I think). If you use major tranquilizers for depression you will end up depressed pretty dam quickly — This is just criminal (oh yeah but we already know about psychiatry and organised crime.
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This “guideline” is definitely in tune with psychiatrists current thinking. Every time I went round the flowchart I ended up with adding a new medication! These statements are a bit disturbing because they are not evidence based:
“education about the illness should emphasize the long-term need for medicines”
“psychoeducation may be superior to an equivalent time spent in nonspecific talking therapy”
The bottom line is that guidelines can never be written by paid consultants to the Pharma industry, that is just a given.
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This article notes, again and again, that “antidepressants” induce mania. At least the psychiatric establishment now openly admits this. But it’s fascinating, in a pathetic and frightening way, to see where the profession takes this observation. Antidepressant-induced mania, a toxic drug effect, is viewed by psychiatrists paid to act as spokespersons for drug companies as evidence of “mental illness” that should be treated with “antipsychotics” that produce additional, worse adverse effects. This is a brilliant strategy from the perspective of pharmaceutical company shareholders seeking to maximise their investment, and for the guild interests of psychiatry. But for the poor people whose antidepressant-induced mania leads to the use of additional and more toxic psychiatric drugs…well, the whole clinical guideline enterprise isn’t really about them, is it? The authors can add another line on their CV, confident that their publication will be highly cited and they will be viewed by their peers as key opinion leaders.
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You’re right. There’s no money or fame for proper treatment of these states. If you did treat them properly, you’d be likely to lose your license for using dangerous substances like B1, B3, B6, B12 and/or maybe desiccated thyroid (if you found signs of such disturbances- weight gain, sensitivity to cold, catatonic episodes). You definitely wouldn’t be invited to manufacturer sponsored conventions, even if you did keep your license (no more Florida conventions in mid January for you).
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The worst of it is, these guideline authors do not even admit that antidepressants cause mania! At any rate, not unless you have given them to “the wrong patient” — one of those “hidden bipolars” who has been mistaken for a person with simple depression. In that case, they say, you haven’t actually caused mania so much as unmasked it! It’s absurd, but it keeps the drugs flowing. The trouble is, this becomes a self-fulfilling prophecy. Unless the person is completely bedridden and lethargic, any sign of anxiety or agitation can be taken out of context as proof of this mysterious “mixed” bipolar state. Especially in 20-20 hindsight, after the antidepressant has made them worse. The moral of the story: Antidepressants don’t cause mania or agitation in general. They are simply the wrong drugs for people who “really” have bipolar disorder in some form, and should have been given an antipsychotic (preferably a pricey new one).
Stephen Stahl, the lead researcher, is kind of a poster boy for financial conflicts: Over $800K per year in promotional payments in 2015 and 2016; over $1.5 million in 2014!
https://openpaymentsdata.cms.gov/physician/77110/summary
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One of the guideline authors had nearly a page of disclosures. It is a pity the critical article in the BMJ doesn’t seem to be available to read.
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There are no “Antidepressants”. There are no “Antipsychotics”.
These are marketing concepts, not medicines.
Psycholeptic drugs all have non-specific effects on the brain. Most are detrimental, especially with prolonged use.
I have been practising and studying medicine continuously for almost half a century.
It seems beyond my comprehension that alleged doctors can be so influenced by pharma-marketing and its “incentives” that they can prescribe long term antipsychotics for alleged depression, “diagnosed” using drug company tick boxes.
These drugs have the potential to destroy lives.
The least professionals could do before prescribing is to become adequately informed about the real toxicity, and the devastating cost to persons and to society of the common, neuropsychiatric, metabolic, cardiac, endocrine, integumentary and sexual dysfunction – adverse psychiatric drug reactions.
Then they should inform All patients of All Toxicities in order to prescribe with informed consent.
Doctors have a duty both to know of, and to understand the adverse effects of the drugs which they prescribe. They have been denied such knowledge by both manufacturers and regulators. (Dolin v GSK 2017).
Doctors are responsible for the long term effects of the drugs they prescribe. This is unenforcible in psychiatric-drug long-term injuries as most precribers reject any patient/relative criticism – (or adverse drug reaction reporting by their patients) – often blaming all drug injuries on “emergent co-morbidities” and underlying, newly identified “psychiatric diseases”.
Psychiatry and its drugs means “Never Having To Say You’re Sorry”.
“Listen to your patients – they are telling you the diagnosis”. (Sir William Osler).
Listen to your drug reps and your pharma-funded “Continuing Medical Education” – and both practitioner and patient will be deceived.
TRM 123. Retired Consultant Physician.
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