This article needs to be updated. Although it is accurate as far as it goes, it no longer goes far enough, and lacks a modern perspective. The trouble with SSRI drugs is old news now, and focusing on them here overshadows more relevant, recent developments in treatment for depression. Evidence now shows that some anti-depressant medications, like escitalopram and sertraline, are probably more safe and effective than others.1 (Meanwhile, evidence accumulates that cognitive behavioural therapy, probably the most common modern form of psychotherapy, may not be as effective as once hoped.2 •sigh•) The article will remain available as-is until I can revise it, or for another year or two, whichever comes first. ~ Paul Ingraham, Oct 14, 2014
I believe that I have a professional and moral obligation to question the prescription and widespread use of old-generation (SSRI class) anti-depressant medications such as Prozac, Zoloft, Paxil, Celexa and Luvox. I cannot condemn it: I am not qualified to make that judgement. Condemnation must be left to the credible experts, and their interpretation of the evidence. However, I share my concerns: that the manufacture, marketing, excessive prescription, and sale of these drugs has probably been dangerous and negligent.
This position is well-supported by references to credible and recent scientific opinion and evidence. Credible criticism first came to public attention when David Healy, a professor of psychiatry who lost his job for speaking out about the undeniable risk that SSRIs cause a small percentage of patients to kill themselves, which had not yet been addressed in the scientific literature.3 In January 2008, New England Journal of Medicine reported that drug manufacturers failed to publish every FDA-registered study4 that didn’t make SSRI anti-depressants look good.5 Then PLos Medicine followed up in February with the largest review of SSRI studies to date — including6 all the previously unpublished FDA studies, as discussed by ArsTechnica.com. The effectiveness of anti-depressants has always been debatable, but this new analysis of all the evidence resulted in a particularly underwhelming picture of the efficacy of these drugs, which appear to be no more effective than sugar pills for most depression7 — though they may be modestly effective for severe depression.89 This is not a new expert opinion, but simply the most recent credible evidence to support an existing opinion. See the footnotes for full details, and please bear in mind the weight of this evidence as you read on.
A personal perspective
I have a personal history with so-called “clinical” depression and bipolar disorder. In 1991, a psychiatrist not only diagnosed me with manic-depression (probably a misdiagnosis), but told me that I would be dead by suicide “within a year” — yikes! — if I did not accept pharmaceutical treatment in the form of SSRI antidepressants. Prozac was three years old then, and had been the most prescribed drug in history as of 1990. I walked out of that psychiatrist’s office, and later recovered from my own depression and mood swings through personal development (which is not to say anyone can do that, but I was able to).
Fortunately, I recognized that “take this mood-altering drug or you’re dead within a year” was probably not the voice of compassionate wisdom. But, in fact, it was more dangerous than I knew.
Ely Lily is the manufacturer of Prozac. “The company’s internal documents, some dating to the mid-1980s, as well as government applications and patents, indicate that the pharmaceutical giant has known for years that its best-selling drug [Prozac] could cause suicidal reactions in a small but significant number of patients.”10
Taking Prozac could have induced my suicide rather than preventing it! The same is true for all the millions of people out there ingesting SSRI antidepressants. Scientific controversy about this allegation continues vigorously to this day, as any quick internet search can demonstrate (Google "SSRI suicide"). As long the truth remains elusive, there is a strong “better safe than sorry” case to be made against their use.
I have long condemned anti-depressants on the basis of general cynicism. I always knew or suspected that they have numerous alarming side effects, that they are marketed aggressively by some of the most profitable and unaccountable corporations in the world, and that their usage does not have a sound scientific rationale. These have been reason enough to suspect that they are more myth than medicine.
Yet, for all my cynicism, I foolishly had some faith that these drugs could not be all bad. I assumed that their side effects were more or less as reported in drug references, that the manufacturers’ power to obscure the facts is mitigated by government agencies, and that the physiological rationale for the drugs is at least intelligible.
As a health care professional, I have had the opportunity to learn otherwise. I have observed dozens of my own clients struggle with depression both with and without SSRI antidepressants, had numerous conversations with other complementary and conventional health care professionals on the subject, and read many articles and books.
Depression is the common cold of psychopathology. … On an incredibly simplistic level, [it occurs] when your cortex thinks an abstract negative thought & manages to convince the rest of the brain that this is as real as a physical stressor. In this view, people with chronic depressions are those whose cortex habitually whispers sad thoughts to the rest of the brain.
~ Robert M Sapolsky, Why Zebras Don’t Get Ulcers, 2004 p. 271, 286
Worse than I’d feared
Contrary to what I once assumed, the side-effects of anti-depressants are actually numerous, severe, potentially life-threatening, and not widely known or even understood. They cause a low but measurable rate of psychotic mania, for instance — equal to millions of people who have been reduced to quivering wrecks, their behaviour drastically altered, careers, marriages and lives lost. Withdrawal symptoms from SSRIs are even more problematic.
The power of the SSRI manufacturers is quite unchecked by government institutions like the American FDA. Indeed, there are documented cases of these companies successfully:
- bribing plaintiffs to make an ineffective case,
- launching dummy lawsuits to create favourable legal precedents, feeding trial subjects Valium to hide severe side effects from the FDA.
This is no surprise given the amount of money and conflicts of interest involved. For instance, President George Bush Sr. was on the board of directors of Eli Lilly & Co. (Prozac), and the head of the FDA during the Prozac approval now works for the pharmaceutical industry as a consultant!
Finally, the scientific rationale for anti-depressants is not, it turns out, very good at all. It is as clumsy as the rationale for electroshock therapy and lobotomy was historically. The popularity of anti-depressants is a continuation of the historical tendency to use “brain-disabling treatments” in psychiatry.11
It is important to understand that SSRIs quite literally just “mess with your head,” specifically interfering with the function of a common messenger molecule (serotonin), one of thousands of others, whose purpose and broad significance to brain function in general is only vaguely understood, and whose particular significance to depression is completely unknown. Consider this 2010 article in New Scientist, emphasizing how recent research has only emphasized our ignorance:
If you thought depression was caused by low serotonin levels, think again. It looks as if the brain chemistry of a depressed person is much more complex, with mounting evidence suggesting that too much serotonin in some brain regions is to blame.
The most sophisticated method known for even measuring serotonin levels in the brain — never mind understanding the significance of these measurements — is to grind up a piece of brain, spin it in a centrifuge, and measure the sum total of serotonin relative to other substances. And how about our ability to measure the amount of serotonin in any given synapse at any time? Exactly zero. Yet the marketing of these drugs would have us believe that they are extremely specific in their effects. It is simply not so.
Despite the commercials — treating depression pharmacologically is not treating something as simple as a low level of a single neurotransmitter. Measuring serotonin levels, even if practical, would likely be of no clinical value. Depression is a result of poor emotional regulation among various brain regions. Drugs are a blunt tool by which we can nudge brain function in a direction which, for some people, can change this regulation and reduce depression. It’s not really about the levels.
Given these limitations, the idea that we can diagnose a “chemical imbalance” in the brain is pure nonsense — even if we could measure it, we don’t know what normal brain chemistry is. Bear in mind also that no psychiatrist actually attempts to measure your brain chemistry before prescribing SSRIs. They don’t do it, of course, because they have not the slightest idea how to diagnose allegedly dysfunctional neurochemistry. They infer the idea of dysfunctional neurochemistry from your subjective symptoms (i.e. depression). That idea has achieved an outrageously disproprotionate credibility, seeming like certain knowledge to the layperson, when it fact the reality is that the nature of sertonin and related neurotransmitters remain almost completely mysterious to medical science. “Chemical imbalance” is so imprecise it’s more poetry than science.
The concept of a “chemical imbalance” in the human brain is one of the most fantastic oversimplifications in science, and one of the worst legacies of the modern pharmaceutical industry. A bowl of soup could have a chemical imbalance …
We do not prescribe medicines to “treat” brain chemistry, we prescribe medications that mess with it — to rock the boat, stir the soup — not because we know what to do to brain chemistry, but because it is something that we can do to brain chemistry. The precision is in the mechanism of effect, and not the consequences.
Indeed, the scientific rationale for these drugs is so bankrupt that to even call them “antidepressants” has more to do with marketing than science, and various studies have shown that they simply do not work as advertised.12 Antidepressants are, in fact, closely related to amphetamines like ecstasy and cocaine. Cocaine essentially does exactly the same kinds of things to the brain, only it messes with serotonin plus a few other molecules. You can think of anti-depressants as “simplified cocaine.” And also “legal cocaine.” It’s an incredibly blunt medical instrument that does not do anything except generally interfere with normal brain function.
It is not necessarily a bad thing to carefully “tinker” with your brain. Humans have a long history of finding ways to mess with our own heads. There are times in life when almost any change in mental state feels like an upgrade. But we need to be more realistic and acknowledge that this is what we’re really doing with SSRIs.
All of the leading antidepressant drugs—the SSRIs, and older classes such as tricyclics or MAO inhibitors—work by altering the levels of one or more of these three neurotransmitters. At this point, there is nothing close to resembling a science as to which sort of person will respond best to which type of antidepressants.
~ Robert M Sapolsky, Why Zebras Don’t Get Ulcers, 2004 p. 284
My responsibility as a health care professional
If the allegations against them are correct — and they seem to be — the presence and typical usage of these drugs in our society is just as unconsciounable as any snake oil ever was, only worse because of the massive scale. Too often we think of our civilization as scientifically sophisticated in all fields. Yet neurophysiology is still primitive in many ways, lacking in testable theories with the power to explain many mental phenomena — yet touted (marketed) as advanced. Consequently, medical malpractice is still common. It’s my responsibility as a health care professional to raise these concerns, even though there are more credible voices to be heard.
Indeed, please do not take my word for it. Although under-reported in the past, lately all of this information is readily available from other and more credible sources. If you are considering antidepressant medication, please do your homework first. If you are already taking antidepressant medication and want to quit safely, it is not sufficient to simply ask your physician. You must educate yourself.
Get a massage! Get several!
Massage is pleasant (for most people), but its medical benefits are much less clear and proven than you might think. Myths about massage abound:13 it does not flush lactic acid out of cells, or increase circulation,14 or reduce inflammation.15 Maybe it reduces cortisol levels, but even that popular notion is far from proven, and there is actually evidence that it’s wrong. Even in the unlikely event that massage actually does reduce cortisol levels, the physiology of stress is much too complex to assume cortisol reduction is in itself a meaningful, good thing.16 There’s just too much going on.
While many benefits of massage are still disconcertingly uncertain and hotly debated (by some), there are two truly proven ones. Dr. Christopher Moyer, a psychologist and massage researcher, explains that the only truly confirmed benefits of massage are its effects on mood (“affect”),17 specifically:
- massage reduces depression
- massage reduces anxiety
And more massage is probably even better. Dr. Moyer:
We made an interesting discovery concerning the effect of the treatment on state anxiety. When a series of massage therapy sessions was administered, the first session in the series provided significant reductions in anxiety, but the last session in the same series provided reductions that were almost twice as large. This pattern was consistent across every study we were able to examine, which strongly suggests that experience with massage therapy is an important predictor of its success, at least where anxiety is concerned. To put it another way, it is possible that the greatest benefits come about only when a person has learned how to receive massage therapy.
So this should be a no-brainer: getting a massage is a better idea than taking meds in almost every possible way. It’s probably not cheaper. But it’s definitely better.
About Paul Ingraham
I am a science writer, former massage therapist, and I was the assistant editor at ScienceBasedMedicine.org for several years. I have had my share of injuries and pain challenges as a runner and ultimate player. My wife and I live in downtown Vancouver, Canada. See my full bio and qualifications, or my blog, Writerly. You might run into me on Facebook or Twitter.
- A very short but required read: Dr. Rob Tarzwell, a psychiatrist, explains the troubles with even defining depression, let alone treating it or trying to measure treatment efficacy. Much as I appreciate the perfectly good article he’s commenting on, Dr. Tarzwell’s observations steal the show.
- For those seeking help with depression or other emotional distress, perhaps the best resource in the world is a counselling and personal development school on Gabriola Island, BC, Canada, called The Haven Institute for Professional Training.
- In this article, I refer to my own A Short Story. It’s a cautionary tale with broad significance to anyone considering drug treatment for anything. It’s particularly relevant that I actually came full circle intellectually and, many years later, retracted my condemnation of a drug. It’s never, ever as simple as “pharmaceuticals are bad”!
- The medical journal The Lancet calls them “clinically proven,” but a new analysis of these new-generation anti-depressants published in January 2009 also concludes that there are “clinically important differences” between different drugs of this type “for both efficacy and acceptability.” The authors explains that past studies have had “inconsistent results.” This is the first meta-analysis (study of studies) to declare two fairly clear winners, two drugs that have shown better effectiveness and acceptability (lack of side effects) for major depression: escitalopram and sertraline.
- Johnsen TJ, Friborg O. The Effects of Cognitive Behavioral Therapy as an Anti-Depressive Treatment is Falling: A Meta-Analysis. Psychological Bulletin. 2015 May. PubMed #25961373. ❐
The evidence of the benefit of cognitive behavioural therapy for depression may be declining: “modern CBT clinical trials seemingly provided less relief from depressive symptoms as compared with the seminal trials.” (Or it may not be: the importance of the “decline effect” has probably been exaggerated.)
- The David Healy Affair (http://www.pharmapolitics.com/)
- What is an FDA-registered study? Drug companies are required by American law to study the effectiveness of their drugs, and to submit those studies to the FDA (to register them). The FDA uses them internally, but the drug companies independently decide whether or not to submit the papers for publication in scientific journals. So a study of a drug can be registered with the FDA … but never see the light of day!
- Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358(3):252–260.
BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio.
METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set.
RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.
CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.
- ArsTechnica.com [Internet]. Gitlin JM. Just how good are current antidepressants?; 2008 Feb 27 [cited 12 Feb 19].
- Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLos Medicine. 2008;5(2):e45. PubMed #18303940. ❐ PainSci #55898. ❐
From the abstract: “Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.”
Commenting on this paper, Ars Technica notes (see Just how good are current antidepressants?) that, “These trials include not just those that were published in peer-reviewed journals, but also unpublished trials that were registered with the FDA.” This is extremely important. Although it should be obvious, it helps that New England Journal of Medicine pointed it out recently: “Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased.” Yet they reported (see Turner) that the FDA has published studies of anti-depressants when they had positive outcomes, while studies with apparently negative results were “either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies)”!
- Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010 Jan;303(1):47–53. PubMed #20051569. ❐ PainSci #55569. ❐
This was a careful review of the evidence about how well antidepressant medications work. The results were refreshingly different from the usual “more research needed” (although doubtless more research is still needed). What they learned: the worse the depression is, the better antidepressant medications seem work. They really do not work at all for minor depression, but “for patients with very severe depression, the benefit of medications over placebo is substantial.”
The authors were not surprised by the basic pattern, but they were surprised by how strong it was:
What makes our findings both surprising and compelling is the high level of depression symptom severity that appears to be required for clinically meaningful drug/placebo differences to emerge, particularly given the evidence that the majority of patients receiving antidepressant medication in clinical practice present with scores below these levels.
- “Severity theory” is the now fairly well-established idea that anti-depressants only work for severe depression. This good, short article reviews an attempt to challenge severity theory — and rules in favour of severity theory.
- Garnett, Leah. Prozac revisited: As drug gets remade, concerns about suicides surface. Boston Globe May 7, 2000: A1, article.
- This is an idea borrowed from psychiatrist Dr. Peter Breggin, as expressed in his book The Antidepressant Fact Book: What your doctor won’t tell you about Prozac, Zoloft, Paxil, Celexa and Luvox. Unfortunately, Breggin is not generally a credible source, according to expert critic Dr. Stephen Barrett (whom I trust more). However, I think the idea in itself has merit: there certainly has been a strong tendency in psychiatry to attempt to treat ham-handedly with interventions that almost certainly change mental state by essentially changing neurology in an imprecise way. This isn’t necessarily as a sinister as it sounds: in many cases, perhaps most, such interventions have been tried in a genuinely earnest attempt to treat patients so sick that there was little left for them to lose. But the application of the principle into SSRIs, widely prescribed for only mildly depressed people, is of great concern.
- Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002 Apr 10;287(14):1807-14, abstract. This good quality study showed that “neither sertraline [Zoloft] nor H perforatum [St. John's Wort] was significantly different from placebo.” Judging from the number of letters published in JAMA about this study in subsequent issues, it’s fair to say the results are probably controversial.
- I discuss the myths of massage in great detail in Does Massage Therapy Work?
- Massage supposedly “increases circulation,” but the evidence shows that it probably doesn’t, especially when compared to even light exercise. Also, relaxation shunts blood away from muscles into the core. For more information, see Does Massage Increase Circulation? Probably not, and definitely not as much as a little exercise.
- A unreplicated and deeply flawed 2012 scientific study (Crane et al.) claimed to find that massage reduced inflammation in intensely exercised muscles. The profession of massage therapy took the conclusions at face value and claims that massage “reduces inflammation” are now common. For more information, see Massage Does Not Reduce Inflammation: The making of a new massage myth from a high-tech study of muscle samples after intense exercise.
- Cortisol levels after a massage do not give a meaningful picture of the organism, and there is no direct relationship between a temporary cortisol reduction and any health benefit. What matters is cortisol levels over time, but even that isn’t exactly straightforward: stress and cortisol have a complex and chaotic relationship regulated by many variables out of our control.
- Moyer CA. Affective massage therapy. Int J Ther Massage Bodywork. 2008;1(2):3–5. PubMed #21589715. ❐ PainSci #54758. ❐
Dr. Christopher Moyer explains that the only confirmed benefits of massage are its effects on mood (“affect”), specifically depression and anxiety. “Together, these effects on anxiety and depression are the most well-established effects in the MT research literature. They are especially important for us to understand not only for their own sake, but also because anxiety and depression exacerbate many other specific health problem.” He proposes that “the time is right to name a new subfield for massage therapy research and practice: affective massage therapy.”