Drugging Test Anxiety?

I suppose this can be the next grand adventure in “learning disability” pharmaceutical adjustments: taking drugs for “test anxiety.”  At some point people need to be able to get through life without being medicated for every stressful scenario unfolding in their lives.  Abstract:

Test anxiety is severely disabling to students whose fear of examinations causes cognitive dysfunction that paralyzes their thinking the way stage fright impairs actors ability to act. In studies using subjective evaluations among actors and musicians, beta-blockade relieved stage fright and has been used informally to treat test anxiety in students without objective measures of effectiveness. The Scholastic Aptitude Test (SAT) was chosen as an objective test instrument to confirm the effect of beta-blockade on test anxiety and performance. Thirty-two high school students who had already taken the SAT before enrolling in this study and who had stress-induced cognitive dysfunction on exams were given 40 mg of propranolol one hour before they retook those tests. Mean SAT scores with beta-blockade were 130 points higher than on the initial SAT done before entering the study without medication (p = less than .01). A single dose of propranolol immediately before the SAT permitted improved performance in students prone to cognitive dysfunction due to test anxiety.

Repurposing Old Drugs For New Roles

Here is an interesting article about expanding the use of old, approved drugs for new purposes.  In theory, this is a good idea, since the safety profile of the drug and its various side effects would already be known, and sometimes “side effects” can mean the drug can be useful against other disorders than originally intended.  However, this requires additional testing to determine if the drug is actually effective in the new role for which it is being proposed. The problem is that when you consider expensive drugs still under patent, pharmaceutical companies have a patent incentive to do such testing, but not for low-cost generic drugs. The author proposes some ways around this: government funding, prize funds, leveraging existing data.  Given the cost of new drugs and the uncertainty of side effects, particularly long-term side effects, once they are in clinical use, repurposing old drugs has promise in being more safe and efficient.  From the article:

US Food and Drug Administration (FDA) approval of a new drug typically coincides with a period of patent protection, during which the manufacturer will often apply for additional indications to expand the market for the product. For example, the tyrosine kinase inhibitor imatinib (Gleevec; Novartis) was originally approved to treat Philadelphia chromosome–positive chronic myelogenous leukemia, but has since been approved for treatment of other cancers. Many noncancer drugs also follow this pattern, including botulinum toxin A (Botox; Allergan), which was originally approved for the treatment of strabismus and blepharospasm and subsequently approved for treatment of cervical dystonia, cosmetic uses, and chronic migraine.

This pattern of additional testing and approvals is common for more expensive on-patent drugs, but new indications are rarely sought for less-expensive generic drugs, for which it is more difficult to profit from the research. This creates a policy conundrum: follow-on innovation for low-cost generic products offers a rare opportunity to simultaneously improve health outcomes and likely reduce health care expenditures, but how could such research be encouraged?

Big Pharma Disease Mongering?

Can’t say I’m surprised by this.  Related to that, if you work in an academic setting, you'll find plenty of students who suddenly are able to find a health care professional to diagnose them with a "learning disability" requiring "accommodation" (and medication - amphetamine stimulants - in many cases) once they fail some classes.  Interestingly, the same students who were straight-A students as college undergraduates mysteriously develop a "learning disability" in their early-mid 20s (or later) once they have problems with difficult courses in some sort of post-graduate education.

The pharmaceutical industry’s image has been significantly damaged in recent years as the public discovered the role its aggressive marketing played in fueling the opioid epidemic. But the American people are still largely in the dark about what may be pharma’s most effective tactic for pushing drugs — marketing diseases.

There’s a substantial body of medical literature dating back to the early ’90s about the practice known as “disease mongering.” Pharmaceutical companies regularly pathologize everyday experiences, convince doctors that they are serious problems, tell a hypochondriacal public it needs help and offers the cure: a new drug. Against the onslaught of billions of dollars in marketing campaigns each year, however, researchers’ warnings about these tactics have gone largely unheeded…

 …“Marketing for a drug can start seven to 10 years before they go on the market. Because it’s illegal to promote a drug before it goes on the market, what they’re promoting is the disease. That’s not illegal to do because there’s no regulation on creating diseases,” Fugh-Berman told Yahoo News.

Lisa Schwartz and Steven Woloshin, co-directors of the Center for Medicine and Media at Dartmouth Institute for Health Policy and Clinical Practice, said disease-awareness campaigns may seem caring or educational but are often just marketing in disguise. The campaigns often follow three basic steps: lower the bar for diagnosis, raise the stakes so people want to get tested and spin the evidence about a drug’s benefits and risks. These steps were seen in campaigns on testosterone deficiency, bipolar disorder and restless leg syndrome…

…Fugh-Berman recalled taking an online test with her coworkers at PharmedOut, a group she directs at Georgetown that exposes pharmaceutical marketing and promotes evidence-based prescribing. The test on pseudobulbar affect (PBA), which manifests when specific brain damage leads to laughing or crying that is inappropriate and unconnected to a person’s emotions, suggested that normal human expressions could be signs of PBA with questions like “Do you ever find things funny that other people don’t find funny?” and “Do you cry easily?”

“Almost every woman failed. Only one woman passed. Most of the men failed, but more of them passed. I would say that anyone who passed the test I was actually worried about,” Fugh-Berman said…

… “I feel that there are people involved in creating new diseases and promoting drugs that aren’t really needed who are pretty amoral. Their measurement of success for themselves is strictly sales,” Pearson said. “There are good-spirited and good-hearted people in companies who are proud of developing something that provides help to some people — and then their marketing department gets ahold of it and turns it into something else.”

Exercise As An Anti-Depressant

Regular exercise can reduce depressive symptoms to an extent that can mimic chronic antidepressant treatment (of course, one likely won’t hear about this from most doctors or from the pharmaceutical companies pushing their samples onto those doctors), and there are molecular mechanisms for this, apparently involving the Wnt signaling pathway. Abstract:

Regular exercise reduces depressive-like behavior activation. In this study, we look for exact roles of exercise on molecular and neuronal mechanisms for antidepressant action by studying the hippocampal neuroplasticity and proliferation. Increased hippocampal neurogenesis with exercise has potential significance for depression. Exercise promotes brain health in the molecular levels in the hippocampus and also affects behavior in a similar way to chronic antidepressant treatment. Wingless (Wnt) and frizzled signaling system plays an important role in cell proliferation, growth, and differentiation during development. Our results demonstrate complicated, differential effects of antidepressants on Wnt signaling system, and assume a role for selected signaling molecules in the neurogenic activity of antidepressant care. Our review suggests that exercise may preserve brain function by increasing neurogenesis through activating Wnt signaling pathway in the psychiatric disorders, such as depression.

Maybe exercise rather than popping pills should be the first line treatment for many mental, as well as more directly physical, disorders?  First, ask you doctor about it - an informed doctor - and follow his or her advice.  Everyone is different.  Some people may require medication, others may only need exercise.  Get the medical consultation you require to figure out which category you may be in, if you require such help.

Antibodies To Watch In 2018

For those of you who like to keep track of such things, here is a list of clinically relevant antibodies that may prove therapeutically useful in 2018 and beyond. Abstract:

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018. Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 12 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 12 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 4 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab). Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application submissions in 2018. Brief summaries of these antibody therapeutics are provided in this installment of the 'Antibodies to watch' article series.

The FDA And Vasopressin

The FDA got involved in trying to regulate marketed previously unapproved drugs, with results perhaps not unexpected to those of us who have taken a MBA-level course in economics.  From the (publicly available) paper linked above:

In May 2017, the US Food and Drug Administration (FDA) announced a Drug Competition Action Plan, designed to address competition and pricing in the generic market and improve access to prescription drugs. One of FDA’s stated goals is to reexamine “places where its rules—including standards and procedures related to generic drug approvals—are being used in ways that may create obstacles to generic access,” instead of ensuring the vigorous competition Congress intended. In this Viewpoint, we examine FDA’s 2006 Unapproved Drugs Initiative (UDI), designed to strengthen the agency’s regulatory oversight related to unapproved marketed drugs. Using an illustrative example, we discuss this initiative’s unintended consequences, as it appears to have created obstacles to generic drug access, likely increasing prescription drug costs…On November 14, 2014, Par received FDA approval for Vasostrict, and on December 15, 2014, FDA instructed all other suppliers of unapproved intravenous vasopressin to stop manufacturing their products by January 30, 2015, leaving only Par with a marketed product. Subsequently, the average wholesale price of intravenous vasopressin increased from $4.27 to $138.40 per vial in November 2016, a 3141% increase. In 2013, when there were multiple competing suppliers, total sales from intravenous vasopressin approximated $4 million. As of November 2016, Vasostrict achieved annualized sales of nearly $400 million. As a result of the high cost, reports have surfaced of vasopressin being removed from code carts, making it unavailable in life-threatening situations.

I’ll leave it to the reader to ponder whether the vast increase per vial price for vasopressin was a justifiable change, and whether the unavailability of this drug for endangered patients is somehow compatible with the FDA’s ostensible mission.

The FDA and Big Pharm: a match made in heaven…or hell.  You decide.  Look at the facts reported in the paper and the other link and ponder well.

The New Blood Pressure Guidelines

The blood pressure guidelines for “high blood pressure” have been lowered once again. As America get fatter and fatter, it’s interesting that the cutoffs for things like blood pressure and cholesterol levels get lower and lower, and drug sales go higher and higher.

New guidelines lower the threshold for high blood pressure, adding 30 million Americans to those who have the condition, which now plagues nearly half of U.S. adults.

High pressure, which for decades has been a top reading of at least 140 or a bottom one of 90, drops to 130 over 80 in advice announced Monday by a dozen medical groups.

I’m skeptical of these new blood pressure standards.  If the ultimate outcome – regardless of what people are saying now – is really going to be an emphasis on losing weight, exercise, and good diets, then fine.  But I believe that the real ultimate outcome is going to be putting half of America, or more, on blood pressure medication, just like we’ll have half on statins, and a big percentage on attention deficit disorder medication, all leading to fat profits for pharmaceutical companies.

So, yes, get your blood pressure to healthy levels. But the specter of folks with 30+ BMIs taking blood pressure medications and statins seems to be self-defeating.

Psychotropic drugs

What do you think is more harmful to humanity: tobacco use or prescribed psychotropic drugs? After watching this documentary, I would say that both tobacco and psychotropic drugs might cause equal harm.

The difference is that no one prescribes you cigarettes, it is your own decision to use or not use tobacco.

However, the use of psychotropic drugs involves a criminal offense. It is an offense perpetrated by the pharmaceutical companies producing the drugs, the FDA approving the drugs, and the "doctors" who prescribe the drugs. You are simply the victim. Do not be one. Watch the documentary.

The drugging of our children is also discussed, and I have written about it earlier. Do not subject your kids to this injustice. Watch the documentary.