Why we all should be concerned about how psychiatric drugs are researched, developed, and marketed

How psychiatric drugs are discovered or developed

In the 1940s, medically-oriented psychiatrists relied primarily on interventions like doctor-induced insulin coma, electroshock, and lobotomies, and had at their disposal very few chemical substances to administer to psychiatric patients. This would start to change in the 1950s. A surgeon named Henri Laborit noticed that chlorpromazine, an antihistamine that was being used to treat nausea, allergies and other conditions, seemed to alter mental states and induce calm in his patients before surgery. Word spread, and chlorpromazine was soon being given to psychiatric patients in U.S. mental institutions under the brand name Thorazine. The drug became one of the most widely prescribed early neuroleptics or tranquilizers – which today are more commonly called antipsychotics. Such accidental discoveries have been typical of the psychiatric drug industry. Unlike in certain areas of medicine where researchers are able to target a specific, biologically detectable pathology such as a bacterial infection, there are no biological markers of any kind for what are commonly called “mental disorders”. (Read more about this issue in ICI’s “How Mental Disorders are Diagnosed”.) Therefore, new psychiatric drug possibilities are not found by honing in on underlying biological abnormalities and working to eradicate or resolve them pharmacologically. New drugs are generally “stumbled upon” when researchers simply happen to observe a drug altering mental, emotional, or behavioral states in research subjects. Researchers sometimes subsequently develop a biological hypothesis about what the particular drug may be doing to help “treat” mental or emotional states and, if the drug becomes successful in the marketplace, other pharmaceutical companies may then develop chemically similar drugs and market them in similar ways. For example, the idea that depressed feelings were caused by low levels of the neurotransmitter serotonin was developed after it was observed that selective serotonin reuptake inhibitors (SSRIs) – drugs that in part temporarily increase the levels of serotonin re-circulating in the brain – seemed to slightly alleviate depressed feelings in some people. This biochemical hypothesis about depression was almost immediately disproven by subsequent research but, due to intensive marketing and public relations efforts by the pharmaceutical industry, the idea that low serotonin levels are related to depression has endured to this day in the media, among mental health organizations, and even in the minds of many average physicians and psychiatrists as if it were long-established fact. Similarly, when it was identified that many of the antipsychotic drugs in part disrupted dopamine activity in the brain, it was then that drug companies, the American Psychiatric Association, and many practicing psychiatrists began to promote the hypothesis that the experiences related to a diagnosis of schizophrenia or psychosis might be caused by a “chemical imbalance” of excessive dopamine. This hypothesis, too, has never been proven. Related reading: López-Muñoz, Francisco, Cecilio Alamo, Eduardo Cuenca, Winston W. Shen, Patrick Clervoy, and Gabriel Rubio. “History of the Discovery and Clinical Introduction of Chlorpromazine.” Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists 17, no. 3 (September 2005): 113–35. Hirschfeld, R. M. “History and Evolution of the Monoamine Hypothesis of Depression.” The Journal of Clinical Psychiatry 61 Suppl 6 (2000): 4–6.

A brief snapshot of the drug approval process in the United States and the risks of off-label prescribing

Before any new pharmaceutical drug can be sold in the United States by prescription, it must be approved as relatively safe and effective for its intended use by the U.S. Food and Drug Administration (FDA). But there’s a very large, commonly used loophole allowing circumvention of this entire process: The drug doesn’t actually have to be approved as safe or effective for all of the uses for which doctors may end up prescribing it. Physicians can prescribe “off-label” – meaning they can prescribe drugs for indications that are not approved by the FDA and are not listed on the official drug label. Many psychiatric drugs, in fact, fall into this category. They were approved as relatively safe and effective for very specific uses – in certain cases simply for short-term, non-psychiatric uses such as controlling epileptic seizures – yet now are being widely prescribed by doctors and psychiatrists for a wide range of psychiatric uses and for long periods of time. This common practice presents unknown risks to patients. However, even when a drug has been approved by the FDA for certain psychiatric uses, that doesn’t always mean it’s truly safe and effective for those uses, either. Let’s walk through the process of FDA approval to understand why that’s the case. Though physicians can prescribe whatever drugs they deem to be in the best interests of their patients, for a pharmaceutical company to be legally allowed to market a drug to doctors and to the public as relatively safe and effective for a particular, specific use, the pharmaceutical company must get FDA approval to do that. FDA approval can often mean billions of dollars in additional profits for a drug company, not only because it can lead to exclusive marketing rights, but also because FDA approval often is, in the minds of physicians and the public, a “stamp of approval” of safety and effectiveness. FDA approval involves a four-step process: During an initial trial (Phase 1), the drug company tests their drug – usually in animals – to see how well its active ingredient is tolerated and what if any adverse effects it causes.

In Phase 2, the drug company tests its drug on healthy human subjects in order to determine optimal doses of the drug and further assess its safety. None of the trial participants at this stage are diagnosed with the disease or condition that the drug is ultimately intended to treat.

Phase 3 is the most important phase. During it, the drug company runs larger clinical trials involving patients who have been diagnosed with the targeted disease or disorder. The drug company typically hires outside researchers to conduct one or more “randomized, placebo-controlled trials” (RCTs) where all of the patients are randomly assigned to taking either the drug or a placebo or a comparison drug that is already approved. (A placebo is a pill that looks like the drug being studied, but that typically has no medical effects.) Often these are “double-blinded” studies, where neither the researchers nor patients are supposed to know until the end of the trial who was taking a drug or placebo. There are two basic types of Phase 3 trials – those that focus mainly on measuring the effectiveness of the drug for treating the targeted disease or disorder, and those that focus more specifically on monitoring for adverse effects of the drug. Finally, the pharmaceutical company presents the findings from these trials to the FDA for review.

The Phase 4 trials are post-market safety studies. If at the end of Phase 3 the FDA approves the drug for the new intended use, then the pharmaceutical company is expected to (but is often not forced to) collect reports of adverse events and notify the FDA of risks and harms that are becoming evident as the drug is being taken by many more people under real-world conditions. On the surface, this drug approval process might seem straightforward and reliable. In reality, this is far from the case. There are many points throughout the FDA drug approval process that leave a lot of room for important information about a drug to be missed entirely and for misleading or biased results to emerge. Phase 4 real-world surveillance of adverse effects, for example, is often not enforced by the FDA and drug companies simply never do it or do it only spottily. But since Phase 3 is the most important phase, in the next section we’ll explore in detail how even the medical “gold standard” research method of double-blinded, randomized, placebo-controlled clinical trials can easily be made to produce misleading, biased results favoring a psychiatric drug.

How clinical trials can easily produce falsely favorable findings about drugs – And how often it happens

How prescribers learn about drugs, and why we should be concerned about it

How psychiatric drugs are marketed through the news media

The United States is one of the only countries in the world that allows ‘direct-to-consumer’ advertising of pharmaceutical drugs. As a result, Americans are exposed to billions of dollars worth of prescription drug advertising in the media every year. But these ads aren’t the only channel through which drug companies influence us about their products. More subtle and arguably even more effective advertising for drugs comes through the regular programming and news stories of these same major media outlets. While it’s obvious that an advertisement will be biased and promotional in nature, many who hear about a particular illness or a drug’s safety and effectiveness on a TV program, read about it in a magazine or newspaper, or learn about it at a website like WebMD are more likely to regard the source as independent and trustworthy. News or media coverage of illnesses and drugs is, in effect, “free advertising” at its best for drug companies, because news stories come with a stamp of approval from an apparently independent source. Knowing this, the pharmaceutical industry cultivates relationships with news media, often by contracting third-party communications and media relations firms and working in collaboration with reputable researchers, universities and other institutions that they fund. How does it work? You can peer into the process yourself by looking at a widely used source of mental health-related news releases, the “Mind and Brain” section of the website ScienceDaily. First, a study is published that puts a positive light on the company’s drug or highlights the dangers of a disease, disorder or condition which the company’s drug treats, and then a news release highlighting the most dramatic or compelling aspects of the study’s findings are distributed. Professional reporters can usually obtain a more confidential “early view” of the news release and of the study itself. Typically the news release doesn’t look like it came from a pharmaceutical company or media relations firm but instead from a reputable university or research institute that was involved in the study. These news releases usually provide quotes, contact information for sources, and relevant background. Sometimes a quick call to the primary source listed also leads to contact information for celebrities or ordinary people who’ve been diagnosed with the condition or who’ve claimed to benefit from the drug. Notably, many medical journals now have policies asking authors to disclose their sources of funding and conflicts of interest, but if you follow health news, you have likely noticed that it is extremely rare for news reports to include any such disclosures from authors, experts, celebrities or any of the sources involved in the story. All of this helps busy health reporters produce quick and compelling stories that often serve to promote drug treatments, unless an individual reporter takes the time to actually read the entire study, dig more deeply, and contact independent expert sources and critics. Incorporating more sober voices and balance in this way, however, often makes for a longer, more complicated story.

The relationships between pharmaceutical companies and non-profit organizations

Non-profit mental health organizations play a key role in the marketing strategies of pharmaceutical companies. These organizations help promote public awareness of and concerns about mental disorders and support for the drugs aimed at treating them. Most prominent mental health non-profit organizations are heavily funded by the pharmaceutical industry, such as Mental Health America and the National Alliance on Mental Illness (NAMI). Even many much smaller groups around the country receive pharmaceutical funding. Secrecy about the exact amounts is common. NAMI, one of the largest and most politically influential U.S.-based mental health non-profits, became the target of a Congressional investigation in 2009, and it was revealed that 75% of NAMI’s tens of millions in funding was coming from pharmaceutical companies. Of course, accepting pharmaceutical industry funding does not necessarily mean an organization or its employees are not being honest about their views. What this widespread industry financial support definitely does, though, is strengthen and amplify the public voices and influence of people and organizations with views and opinions that tend to paint more positive pictures of the effectiveness and safety of psychiatric drugs, while further marginalizing voices and organizations that have more neutral or critical perspectives.

So where can we turn for independent information about psychiatric drugs?