CGPR: Why is it important for psychiatrists to be aware of company marketing strategies?

Dr. Healy: Pharmaceutical companies use randomized controlled trials (RCTs) and evidence-based medicine as key strategies to influence doctors. They also engage in apparent conflicts of interest through interactions with sales reps, free lunches, and control over continuing medical education. However, these conflicts are nothing compared to industry influence on published studies. Medical journals frequently carry articles that endorse drugs and minimize their risks, even reporting negative studies as positive. These ghostwritten articles are the true advertisements, going unquestioned. Psychiatry, historically at the forefront with its specialist journals, hospitals, and early RCTs, has not been immune to pharma’s influence.

CGPR: What’s the scale of pharma marketing to physicians versus the public?

Dr. Healy: Once our drugs became prescription only, doctors became the primary consumers for pharmaceuticals, prescribing medications without personal cost or health risks. This unique consumer status means that the industry targets physicians intensely: In the US, there is roughly one physician per 329 people, a small consumer base with a huge financial return. Data from the US show that the average number of prescriptions per person has increased over the past few years (www.cbo.gov/publication/57772). That’s potentially thousands of pills per person each year. Some medications cost as much as a cell phone, making doctors the critical gateway to this lucrative market. Researchers have tried to find good data on the proportion of industry spending on marketing to doctors compared to industry-funded scientific research spending (Schwartz LM and Woloshin S, JAMA 2019;321(1):80–96). It’s hard to nail down, but the consensus is that much more goes into marketing. But we really should ask “What does industry spend on research other than market research?”

CGPR: Can you speak about the influence of pharmaceutical companies on clinical trials?

Dr. Healy: The post-thalidomide 1962 amendments to the Food and Drugs Act, which were intended to regulate the pharmaceutical industry, instead resulted in greater industry control of medicine. These regulations, which remain in place today, state that before marketing a drug, companies have to prove that their drugs are not only safe but efficacious. Companies now only need two positive placebo-controlled trials to get a license (one positive trial if the medication is granted accelerated approval). Roughly half of the antidepressant trials submitted for approval between 1990 and 2008 were negative (Turner EH et al, N Engl J Med 2008;358(3):252–260). Alarmingly, although some trials remain unpublished, many negative trials were published as positive.

CGPR: Do you have an example?

Dr. Healy: Pediatric depression trials were universally negative but published as positive. In 2012, GlaxoSmithKline submitted three depression trials to the FDA and told the FDA that these trials were negative. However, Study 329, the main trial, had already been published as glowingly positive. In the adult trials leading to market approval, 11 studies were published in a way that conveyed a positive outcome, even though the FDA viewed these studies as having negative or questionable results. These examples are all listed in an appendix to Erick Turner’s 2008 article (Turner et al, 2008).

CGPR: How can understanding the limitations of published data help us improve our care?

Dr. Healy: As doctors, we tend to believe medical experts and publication journals like the New England Journal of Medicine. We may benefit from increasing our skepticism and closely watching our patients—they may not show the benefits that the articles claim, or they may experience hazards that an article denies—but we should believe the patient. (Editor’s note: We recommend taking a patient seriously when they think a medication causes side effects, even if it’s not due to a published drug reaction. Work collaboratively to come up with a plan that may involve decreasing the dose or discontinuing the medication.)

CGPR: Are there specific issues with older patients?

Dr. Healy: There are. Pharmaceutical companies and regulators set low benchmarks for drug approval, like slight improvements (two or three points) on activities of daily living scales for antidementia drugs, without providing real clinical benefits or improving survival rates. Often, these drugs show increased mortality and serious adverse events with active treatment. Psychotropic drug trials in older people are rare, with companies using adult trials for marketing. An unpublished company trial I led compared paroxetine against a tricyclic in older adults (OAs), designed to investigate cognitive function; paroxetine’s unfavorable results kept it out of journals. Industry practices among the elderly have also misbranded anticholinergic drugs as causing antidepressant side effects actually triggered by serotonergic or catecholaminergic effects (Healy D, Ther Adv Psychopharmacol 2023;13:20451253231176375). This has led to misrepresentation of many drugs as anticholinergic, resulting in the unnecessary discontinuation of effective, cheaper drugs.

CGPR: Do you have any examples?

Dr. Healy: Absolutely. One example is oxybutynin, which is now often replaced by mirabegron due to concerns about oxybutynin’s anticholinergic activity. Over half the drugs listed to reduce anticholinergic burden don’t affect cholinergic systems (Lavrador M et al, Pharmaceutics 2023;15(1):230). When selective serotonin reuptake inhibitors or anticonvulsants cause problems, for example, it is commonly incorrectly attributed to their anticholinergic actions.

CGPR: Are there other ways marketing has influenced the rise of polypharmacy in OAs?

Dr. Healy: Yes indeed. In the 1980s, company marketing led doctors to treat risk factors like minimally raised blood pressure or glucose levels, dramatically impacting polypharmacy among OAs. We no longer accept natural age-related increases in blood pressure and glucose—and we now have more hospital admissions because of drugs used to manage risks than we have from osteoporosis, hypertension, or diabetes. Ironically, older people are often wary of polypharmacy, preferring to reduce their medication burden with their doctor’s approval (Rubin R, JAMA 2023. Epub ahead of print). However, aligning medical advice with this preference is challenging. Clinicians, aiming to adhere to guidelines for various risk factors, find themselves in a legally defensible position, yet this stance conflicts with more person-centered guidelines, which advise limiting patients to no more than three medications when possible. (Editor’s note: For more information, see article on “Addressing Polypharmacy in Older Adults” in this issue.)

CGPR: You have often mentioned rating scales as a marketing tool—do these affect diagnosis and treatment among OAs?

Dr. Healy: ADHD drugs offer an extreme example. The ADHD drugs for children brought ADHD rating scales in their wake. While there is a clear disorder we call ADHD, scales asking about abilities to focus led to an overdiagnosis of adult ADHD (Harrison AG and Edwards MJ, J Atten Disord 2023;27(12):1343–1359). Now, if people in their 60s report concentration problems, their doctor might give them an ADHD scale with a high score leading to an ADHD diagnosis and medication, when until recently ADHD often resolved in the teenage years. A high score on a screening tool now trumps clinical judgment.

CGPR: What use do companies make of other indirect strategies to inform clinicians about their products?

Dr. Healy: In addition to rating scales, companies have long been adept at selling diseases in order to sell the product. It’s only later that their drug turns up as the “solution” to that problem. These strategies are common and shape our perspectives and treatment choices. Examples include elevated blood pressure, cholesterol, and glucose levels—they are all risk factors of minimal importance if the rest of a patient’s risk profile is relatively safe, but companies aggressively market them as serious problems.

CGPR: How can clinicians best communicate with OAs about their medication choices?

Dr. Healy: As with everyone these days, OAs access guidelines but may be unaware that these are based primarily on commercial exercises companies carry out. Even real RCTs only reveal average drug effects; they do not tell us how to treat the person in front of us. All science, particularly in clinical practice, relies on building a consensus that includes the patient’s perspective, especially when their experiences diverge from established evidence. The critical question isn’t just about communicating effectively with patients. Rather, it’s asking “Can we create a situation where we hear what our patients have to say?”

CGPR: Where can we find unbiased medication information?

Dr. Healy: The only point today at which we have full access to the data in giving a pharmaceutical is when we have a patient in front of us. The patient has no reason to mislead us, particularly if the patient is having problems. If at the end of the day the consensus is that the drug has caused the problem, then this is the scientific method in operation in clinical practice.

CGPR: Thank you for your time, Dr. Healy.

Related content: The Other Side of Psych Meds: An Interview with David Healy