Psychopharmacology and Depression

Twelve years ago, I came across an article that changed my view of the pharmaceutical industry forever.  It appeared in the London Review of Books: Which came first, the condition or the drug?.  In it, Mikkel Borch-Jacobsen wrote a review of a book authored by David Healy titled “Mania: a Short History of Bipolar Disorder”.  The case was made that what was known as bipolar disorder seemed not to exist until a marketing campaign by the pharmaceutical industry produced a high level of diagnoses.  This condition was said to involve individuals who would switch between depressive states and manic states.  The work of Healy in inspecting the history of patient diagnoses over several decades, found that such a finding was extremely rare, but for some reason the diagnosis was now quite common.   Borch-Jacobsen provides this background information.

“…Healy arrives at a figure of ten cases per million each year, that is 0.001 per cent of the general population. This figure is striking, as today the incidence of bipolar disorder is supposed to be much higher. In 1994, for example, the US National Comorbidity Survey estimated that 1.3 per cent of the American population suffered from bipolar disorder. Four years later, the psychiatrist Jules Angst upped the figure to 5 per cent: 5000 times higher than the figure suggested by Healy.”

The implication was that the drug companies had created a new category of illness and proceeded to make it a popular medical diagnosis. 

“Healy tells the story of the launch of bipolar disorder at the end of the 1990s. A specialised journal, Bipolar Disorder, was established, along with the International Society for Bipolar Disorders and the European Bipolar Forum; conferences were inundated with papers commissioned by the industry; a swarm of publications appeared, many of them signed by important names in the psychiatric field but actually ghost-written by PR agencies. Once the medical elites were bought and sold on the new disease, armies of industry representatives descended on clinicians, to ‘educate’ them and teach them how to recognise the symptoms of bipolar disorder. Bipolar patient advocacy groups sprang up, generously supported by pharmaceutical companies; freelance journalists were hired to write magazine articles on the latest advances in psychiatric science; websites were created, such as IsItReallyDepression.com (sponsored by AstraZeneca), where you can fill out a ‘mood assessment questionnaire’ at the end of which you’ll inevitably be dispatched to the nearest doctor. As a British blogger noticed recently, the Wikipedia entries ‘Bipolar Disorder’ and ‘Bipolar Spectrum’ were edited from a computer belonging to AstraZeneca, ensuring that everyone is on the same diagnostic page as the industry.”

Depression is one of the most common features of life, easily recognized and apparently easily treated by medications—more on that later.  That market for antidepressant drugs was large and growing.  Apparently, the goal of establishing bipolar disorder as a common illness was to expand the depression market to allow the sale of stronger and more dangerous antipsychotic drugs—with the collaboration of the psychiatric community.  If one reads the list of symptoms in the psychiatrist created DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition) one finds almost exactly the same set of symptoms as normal depression, a set so broad that every human on Earth could be diagnosed with the condition.

“A series of prominent lawsuits has been brought over the past few years in the United States against the manufacturers of anticonvulsants and atypical antipsychotics for having hidden their side effects and for having marketed them ‘off label’ towards patient populations not approved by the FDA. The sums paid out in fines or settlements by the pharmaceutical companies involved are staggering, and they give an idea of how disastrous the effects of their medications have been: Warner-Lambert/Parke-Davis (now Pfizer) has paid more than $430 million for marketing Neurontin for bipolar disorder; Lilly had to pay a total of $2.6 billion for the illegal marketing of Zyprexa; Pfizer was forced to pay $301 million for the illegal marketing of the atypical antipsychotic Geodon. AstraZeneca has agreed to pay $520 million to settle federal investigations into its marketing of Seroquel and has already spent $593 million in legal fees defending itself against the 10,381 individual lawsuits brought by patients for the side effects caused by the drug. Johnson & Johnson and its subsidiary Janssen have been sued by nine American states for the off-label marketing of Risperdal.”

Recall that the article discussed was published twelve years ago.  Time has not stood still.  The industry now refers to bipolar disorder as bipolar depression.  Perhaps the mania aspect was so rare that they had to change the strategy and focus on bipolar depression being a more serious form of depression requiring more serious medications.  And the drugs continued to fly off the shelves.

If one accumulates evidence that supports the notion that the pharmaceutical industry behaves in the manner described above when mental illness is involved, one is met with incredulous stares.  No one believes that such things can happen in our country.  One is viewed as some weird kind of conspiracy theorist. 

Two of the firmest tenets of psychopharmacology are that depression, and other mental illnesses, are caused by a chemical imbalance in our brains, and that medications act to control that chemical imbalance.  The chemical imbalance assumption began as an hypothesis.  It has never been proved, yet it has become dogma because both psychiatrists and the pharmaceutical companies found it profitable to assume it was true.  Evidence from depression drug trials indicate that almost as many participants who receive a placebo, perhaps a sugar pill, claim improved symptoms as do those who received the actual medication.  This demonstrates that a placebo effect is the dominant cause of most responses.  This fact has been known by both psychiatrists and drug companies for several decades.  Both can claim that the pills they give patients are often helpful at improving their symptoms, so what is the problem?  The problem is that the drugs alter brain function and often produce unpleasant side-effects and addiction. This source provides some perspective.

“The problem is that lots of people who do not need antidepressants are already on them, refilling prescriptions written years or even decades ago. They should be helped to get off the drugs. The side-effects are often life-limiting and, as people age, become life-threatening. They include sexual dysfunction (which sufferers describe as “genital anaesthesia”), lethargy, emotional numbness, increased risk of birth defects when taken during pregnancy, and, in older people, strokes, falls, seizures, heart problems and bleeding after surgery. This is a threat to health-care systems as long-term users age.”

In addition, patients who choose to stop their medications often face severe withdrawal symptoms.  This is yet another of the bizarre realities of the psychopharmacological industry that people find incredible.

A recent article in The Economist finally noticed data that had been around for over a decade and concluded that something should be done about it: How to make better use of antidepressants.  It details what is known about the most common antidepressant drugs: selective serotonin reuptake inhibitors (SSRIs).

“…new drugs called selective serotonin reuptake inhibitors (SSRI), which appeared in the 1980s, specifically block the serotonin transporters, so are much safer—so much so that by the 1990s they had become a lifestyle drug, prescribed widely for normal emotional reactions to events such as bereavement or work burnout.”

“For many years drug companies, the main source of research on SSRIs, tended not to publish in scientific journals the results of clinical trials that cast doubt on their products’ utility. That practice biased scientific reviews of the field in the drugs’ favour. But companies are nevertheless required by America’s medicines regulator, the Food and Drug Administration (FDA), to submit to that agency all the data collected during their trials, making them available for others to examine.”

“The most recent such analysis, published in the BMJ in June, combined the results of all trials of antidepressants filed to the FDA between 1979 and 2016. It found that the drugs had a substantial effect on depression beyond that of a placebo for only 15% of patients.”

“A study published in 2010, which examined research on two common SSRIs, estimated that for people with less severe depression the odds of improving by taking the drugs were just 6% higher than they were for taking a placebo. For those with more severe depression they were 25% higher.”

These studies confirm the claim that the majority of those benefiting from antidepressants are merely benefitting from a placebo effect.  More on this placebo effect can be found in Antidepressant Drugs versus Placebos.  The Economist also agrees there has not been any evidence to confirm a relationship between serotonin and depression. 

“Moreover, while all this has been going on the serotonin hypothesis has come crashing down. Researchers have looked from many directions for a relationship between serotonin and depression. They have found little or no evidence to link the two.”

So, if antidepressants provide no benefit other than as a placebo for most users, are the dangers of taking unnecessary brain-altering drugs sufficient to convince users that they are not worth the risk.  The potential side-effects have already been mentioned.  An equally important concern involves the difficulties associated with withdrawal symptoms experienced when quitting the drugs.

“A review of the research published on that topic, carried out in 2019, found that between 27% and 86% of people attempting to come off antidepressants experienced withdrawal symptoms, and that nearly half of them described those symptoms as severe. The variation in these results may have several causes. How long people took the drugs for, and the dose they took, are two.”

Little attention has been paid to the issue of antidepressant drug withdrawal.  Drug companies have no interest in it, and psychiatrists mostly assumed quitting drugs was easy.  It was also convenient to confuse withdrawal symptoms with relapse of the original problem.  This situation seems to be changing, in the UK at least, as healthcare systems ponder the cost effects of aging antidepressant users. 

“Dr Taylor and Mark Horowitz, of University College, London, began the research that led to what has become known as the Horowitz-Taylor method. Drawing on brain images of serotonin-transporter blockage by SSRIs, they proposed a biological explanation for this difference in withdrawal symptoms. Their study found that the effect of the drug on the brain increases steeply at small doses but levels off at higher ones…In other words, reducing SSRIs more slowly at lower doses is needed to produce a gradual decline in their effect—and thus minimise withdrawal symptoms.”

If the requirement is that over time small decreases in the drug level, how does the patient accomplish that?  Pills only come in a few discrete dosage levels.  Liquid drugs could fill the need if they were available.  Some external assistance is needed by most sufferers to ease the transition.

“As things stand, doctors rarely suggest to patients that they should stop taking the drugs. ‘It’s a systems issue. We just don’t have systems to start de-prescribing,’ says Dee Mangin of McMaster University, in Canada. Such cessation is usually initiated by patients who…decide that the side-effects are no longer worth it. The sexual-dysfunction problem is one of the reasons most commonly cited, particularly when people meet a new partner. ‘There is really no way of combating the sexual side-effects other than stopping the drug,’ says Dr Turner. Another is people realising, because of the scary effects on their brain after they have accidentally missed a dose (by forgetting to order a refill, for example), that they have developed a strong physical dependency on them.”

“…the liquid formulations of antidepressants needed for the preparation of small doses are expensive—a month’s worth may cost as much as an annual supply of the pills. And not all antidepressants are available in liquid form, because there are no incentives for drug companies to produce something that will help people stop taking their drugs.”

“’Tapering strips’—prescriptions of pills that contain smaller and smaller amounts of a drug—are available in the Netherlands and have been shown to result in a 70% quit rate. But the Netherlands is an exception, and the strips are too expensive for a lot of those in other countries who try to import the Dutch versions. An alternative is to obtain tapering doses from a compounding pharmacy (a business which can measure out minuscule amounts of the pills). But that, too, is expensive—and not usually covered by health insurance. So patients are stuck.”

Too much short-term thinking has hindered a concerted effort to address antidepressant drug addiction and withdrawal effects.

“Nor do the economic incentives stack in favour of cessation. Most SSRIs are off-patent and therefore cheap. In Britain, a year’s supply of the pills may cost around £40-50 ($35-44). ‘Getting people off them doesn’t save the NHS much in terms of the cost of the drugs,’ says Dr Kendrick. ‘The problem is that when people try to come off if you get only one or two people to have a severe relapse and end up in hospital, that would cost an awful lot,’ he says. This leads to a reluctance to promote quitting.”

“This unwillingness to ante-up is, though, short-sighted. Health-care systems face a risk of there being growing numbers of ageing patients who start to experience the worst side-effects of the long-term use of antidepressants. There will be extra falls, strokes, seizures, heart problems, surgery complications and more. Pay now. Or pay double later.” 

What is startling about depression is the strength of the placebo effect, which is essentially just the power of suggestion.  This suggests that there should be other, less dangerous methods for changing peoples’ view of their lives.  In Treating Depression: It’s Free, It’s Healthy, and It Works, it was pointed out that exercise seems to work better at combating depression than at least one popular antidepressant.  Perhaps therein lies a clue.