Anti-Depressants—Don’t Work For Depression Or Anything Else

    Do not think about, write about or deal with  human behavior without determining the effects of incentives.

    Wherein we see that, rather than developing a drug for a disease, there is the unseemly scrambling trying to shoehorn the disease into the drug.

Mad in America
SSRI ‘Indication Creep’ Relies on Negligent Doctors
Maria Bradshaw

A report on antidepressant consumption released on 18 February 2014 by the Organisation for Economic Cooperation and Development (OECD)[1] shows huge increases in prescribing of the drugs across most countries. According to the report a key factor driving this increase is the expansion of the off-label use of the drugs for a vastly increased number of indications. While this may not seem like news, I think it warrants some analysis because I think what we are seeing is something more complex than simple market expansion.

In my view what we are seeing is a strategic rebranding of antidepressants as treatments for non-psychiatric conditions which could only occur in an environment where doctors have a criminal disregard for patient safety while knowing they will not be held accountable for patient harm. While the development of a new product often entails sacrificing sales from an existing product, the willingness of doctors to prescribe off label in the absence of any evidence of their effectiveness or safety allows pharmaceutical companies to maintain and even expand their revenues from SSRIs while replacing them with newer drugs and biologics.


    Effectiveness and safety–one would think that would be paramount, wouldn’t one.

After a very long period in which the development of psychiatric drugs involved little in the way of identification of novel agents, pharmaceutical companies and leading universities are now publishing large numbers of studies and issuing media releases telling us they are working on developing, or have developed, a range of new treatments for depression. In a delicate balancing act, big pharma are highlighting the lack of efficacy of antidepressants as a way of promoting their new treatments but remaining silent on their adverse effects so as not to undermine their prescription for non-psychiatric conditions.


   Our drugs are super, but we need to develop better ones.

Dr. Rao, from Chicago’s Loyola and on the speakers bureau for Forest Pharmaceuticals[2] tells us, for example, that drugs such as Prozac, Zoloft and Paxil that target neurotransmitters succeed in inducing the remission of depression in fewer than half of all patients and that “new insights are leading to  treatments beyond common antidepressants such as Prozac and Zoloft.”[3]


    As the Reader knows, from these pages, if the placebo has a lot of  physiological effects, the drug is no better.

Similarly a Yale University/Astra-Zeneca partnership is questioning the value of SSRIs in favour of Ketamine-mimic Lanicemine[4],  a University of Pennsylvania/Takeda & Lundbeck partnership has developed and brought to market Brintellex, a new antidepressant with a markedly different  pharmacodynamic activity from that of SSRIS[5]. And Biohaven, which has a worldwide license from Yale University to use intellectual property relating to the use of certain glutamate modulating agents in the treatment of neuropsychiatric disorders has developed a candidate drug which targets the glutamatergic system.[6] All emphasise in their market communications the significant proportion of patients who experience no benefit from SSRIs, but do not promote the new drugs as having a superior adverse event profile.

The message is in both what they say – antidepressants don’t work effectively for depressed patients, so prescribe our new drugs – and what they don’t; keep prescribing antidepressants for other indications, as they are not harmful.

Recent studies show us this strategy appears to be working remarkably well.

A study published by Mercier at al in 2013 claims that between 25% and 60% of antidepressant prescriptions are issued for “health problems outside the field of psychiatry.”[7] An American analysis found that between 1996 and 2007, “the proportion of visits at which antidepressants were prescribed but no psychiatric diagnoses were noted increased from 59.5% to 72.7%.”[8]

The conditions for which Mercier et al found antidepressants were being prescribed included neuropathic pain, urinary stress incontinence, premature ejaculation, prevention of depression after stroke, emotionalism after stroke, smoking cessation, premenstrual syndrome, hot flashes, Irritable bowel syndrome, post herpetic neuralgia, trigeminal neuralgia, agitation in dementia, motor recovery after ischemic stroke, overactive bladder syndrome, tension-type headaches with drug abuse, sciatica, Parkinson’s disease, sleep disorders, pruritus, asthenia- fatigue-chronic fatigue syndrome, cancer-related fatigue, depression in physically ill people, unexplained complaints, somatoform disorders, treatment refusal, patient compliance, weight loss in adults with type 2 diabetes, HIV related neuropathy, phantom limb pain, burning mouth syndrome, non-specific low back pain, restless legs syndrome, other urinary incontinence conditions, erectile dysfunction, alcoholism, alcohol misuse, musculoskeletal symptoms, nocturnal enuresis, amphetamine withdrawal and cocaine dependence.[9]


   And yet, the drugs work for none of these conditions. I’m sure if patients have more faith, all will be well. Ask any cult master.

Among the 44 conditions, ADs were found to be potentially beneficial with a high level of evidence in treating 15 conditions and potentially beneficial with a lower level of evidence in treating 5 others. No proof of benefit was found for 15 conditions and proof of no benefit for 9.9 In other words, 55% of the conditions for which antidepressants were being prescribed had either no evidence of benefit or evidence of no benefit for patients.

The FDA states that

Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.[10]

In another study conducted by Mercier et al a number of focus groups were convened to  “explore GPs’ viewpoints regarding their reasons for prescribing antidepressants and to determine what indications they reported using them for in daily practice.”[11]

The study showed that although the GPs stated that antidepressants were rarely prescribed for conditions other than those specified by the guidelines, they mentioned 24 unapproved “non-psychiatric” situations that might lead to a prescription.

The focus groups found that

ADs were seen as very useful, effective, safe and having few adverse effects, which gave the GPs a sense of self-confidence. The GPs were not afraid to prescribe antidepressants, which were seen as having little or no risk of addiction and as not harmful. Though antidepressants were sometimes assessed as useless, they were very rarely related to suicidal intentions.[11]

The researchers tell us that the GPs “harshly criticized the guideline criteria and agreed they were irrelevant in primary care settings” and had developed their own diagnostic tools including a ‘therapeutic test’ in which they gave a prescription for an antidepressant and assessed the patient a few days later as a way of reviewing their initial feelings about their diagnosis.

So much for evidence-based medicine.

In recent years there have been a constant stream of prosecutions and fines imposed on pharmaceutical companies for off-label promotion of drugs that have caused harm to consumers. And rightly so. In the end, though, these drugs are prescription only and it is doctors not pharmaceutical companies who supply them to patients. In all the stories we read of the harms arising from off-label promotion of drugs there is never a focus on the doctors who wrote the prescriptions. There is never a prosecution of a doctor for the kind of negligence described in the Mercier et al study.

Sometimes doctors are misled by members of their own profession who have sold out to the pharmaceutical industry. More often however, doctors are simply casual to the point of negligence when it comes to prescribing antidepressants. Pharmaceutical companies rely on doctors to ignore best practice and professional standards and evidence and the OECD data shows they don’t fail to deliver.

My son died as a result of off-label prescribing of an antidepressant and, while I recognize the role of the drug company who made the drug in his death, the fact is that no matter how hard Mylan Pharmaceuticals marketed their drugs, they would not have been in my son’s body had they not been prescribed by a doctor. Mylan did not sit with him and tell him he had a chemical imbalance that could be fixed by their drug. Mylan did not neglect to tell him of the adverse reactions he might suffer or that the drugs were being prescribed off-label. Mylan did not fail to report his death to the regulator. Those were the actions of his doctor, who since his death continues to prescribe the same drug off-label.

These drugs carry the FDA’s highest warning of lethality. They are potentially fatal. It’s time doctors started prescribing responsibly and were held to account when they don’t. My son’s case is currently being reviewed by the police who are assessing whether manslaughter charges should be laid. I have no doubt that they should be, not just for justice for my child but to provide a deterrent to the continued and casual expansion of off-label prescribing of antidepressants.

[1] OECD (2013), Health at a Glance 2013: OECD Indicators, OECD Publishing, November 21, 2013. DOI :10.1787/health_glance-2013-en
[2] Rao, M., A Mysterious Loss of Memory. Current Psychiatry, 8(4) April 2009
[3] New Depression Treatments Are on the Horizon. Loyola Medicine, February 14, 2014

[4] Fiddian, P., Antiepileptic is Effective Depression Treatment. Pharmaceutical International News. October 16, 2013
[5] Takeda and Lundbeck Announce FDA Approval of BrintellixTM (vortioxetine) for Treatment of Adults with Major Depressive Disorder. Takeda Pharmaceutical Company News Release. October 1, 2013
[6] United States: Portage Biotech Inc. Declares acquisition of 54% equity in Biohaven. 4-Traders News, January 7, 2014

[7] Mercier, A.,  Auger-Aubin, I., Lebeau, J.,  Schuers, M., et al.; Evidence of prescription of antidepressants for non-psychiatric conditions in primary care: an analysis of guidelines and systematic reviews. BMC Family Practice. 14(15) May 14, 2013. doi:10.1186/1471-2296-14-55

[8] Mojtabai R, Olfson M: Proportion of antidepressants prescribed without a psychiatric diagnosis is growing.  Health Aff 2011, 30:1434-1442

[9] Mercier, A.,  Auger-Aubin, I., Lebeau, J.,  Schuers, M., et al.; Evidence of prescription of antidepressants for non-psychiatric conditions in primary care: an analysis of guidelines and systematic reviews. BMC Family Practice. 14(15) May 14, 2013. doi:10.1186/1471-2296-14-55

[10] “Off-Label” and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices – Information Sheet. United States Food and Drug Administration.

[11] Mercier, A., Auger-Aubin, I., Lebeau, J., Van Royen, P., Peremans, L.; Understanding the prescription of antidepressants: a Qualitative study among French GPs. BMC Family Practice. 12(99) September 24, 2011. doi:10.1186/1471-2296-12-99


   Deaths, ineffectiveness–you’d think this was enough to stop this practice.

To order my novel, “Days of Songs and Mirrors: A Jacobite in the ‘45”, click here.

Government Job or Respect–Which’ll It Be?
Cheerio and ttfn,
Grant Coulson
Cui Bono–Cherchez les Contingencies


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s

%d bloggers like this: