Undoing Depression, my book from 1997, will be coming out in a completely revised edition in 2010. There have been a great many developments in the field and in my thinking about depression that have begged for an update. But some things had to be left out of the book, both because of space and because I occasionally strayed from the narrow focus of the book.
Here’s a section I had to omit, reluctantly; but I had to agree with my editor that it wasn’t really necessary for a self-help book on depression. If you read on, though, I think that you’ll agree it’s really important news both about depression and the whole field of pharmaceutical research.
Antidepressant medication is of great help to many people; I want my severely depressed people to be taking something, because it can often relieve their distress and mobilize them to start to take action against their depression. But the drug industry, which underwrites most studies, has drastically and dishonestly manipulated formal academic research to the extent that we really can’t trust anything much of what respected journals say about antidepressants—especially SSRIs like Prozac, Zoloft, Celexa, and Lexapro, and the SNRIs like Effexor and Cymbalta. In some cases, they have simply bribed researchers, some of them the most respected in the field.
Here’s one example: the original research that got FDA approval and set off the craze for these drugs had very low standards, which were not revealed to the public. They were generally two- or three-month trials, very short over the lifetime course of depression, and the definition of cure was simply no longer meeting all the criteria for major depression. You might still be feeling suicidal and wracked with guilt, but if your sleeping had improved, as far as the FDA was concerned, the drug had demonstrated its effectiveness. Then there was the fact that in all these trials the drugs proved only slightly better than placebo—in most cases, about 40 percent of people got better with a sugar pill, and about 50-60 percent improved with an SSRI.[i] Added to that is the fact that many of these studies stacked the deck by excluding people who were most responsive to placebo.[ii]
Subsequent studies, with larger groups over longer periods of time, have shown about the same disappointing results. The STAR*D study, with a large sample of real-world patients, without excluding placebo responders, found that about 50 percent of patients had a significant response to medication, but only about 30 percent met the researchers’ definition of remission.[iii] During follow-up, a significant number of patients relapsed. Overall, the recovery rate was only slightly better than chance alone. STAR*D was sponsored by the National Institute of Mental Health and should be considered relatively free of drug company influence.
More and more news keeps coming out about hidden payments from drug companies to the supposedly objective researchers investigating their drugs—especially antidepressants. Frequently, these researchers have national reputations and carry great respect; they’ve published articles on other subjects that are objectively excellent, some of which I’ve cited in my books. But their greed has resulted in their downfall. In one case, it was Dr. Charles Nemeroff of Emory University, the drug company was GlaxoSmithKline, and the drug was Paxil. According to Senator Charles Grassley’s Finance Committee, Nemeroff received a total of $2.8 million from Glaxo and other Big Pharma companies, all of which he sought to hide from his employers and the publishers of his articles. Senator Grassley has found a tree with some very low-hanging fruit, because this pattern seems to be increasingly the rule, not the exception, among leading academic researchers. Another, even more shocking, case is that of Dr. Frederick K. Goodwin, the retired director of the National Institutes of Mental Health, who hosted public radio’s series “The Infinite Mind” for many years, during which time he earned at least $1.3 million from drug companies, which he did not disclose to NPR. Many of the programs covered subjects relating to the same drug companies. For instance, in one broadcast Dr. Goodwin stated that children with bipolar disorder who are left untreated could suffer brain damage, which is not a common opinion. He then went on to recommend mood stabilizers as both safe and effective. According to the New York Times, on the very same day as the broadcast Dr. Goodwin earned $2500 from GlaxoSmithKline for giving a lecture touting the benefits of Lamictal, a drug considered less effective than other mood stabilizers.
On May 15, 2008, Newsweek’s cover feature was “The Bipolar Child,” the culmination of the exponential growth in the diagnosis of pediatric bipolar disorder over the last few years—a forty-fold increase from 1994 to 2003. Much of this growth can be attributed to the work of Dr. Joseph Biederman, a Harvard child psychiatrist who has published multiple articles pointing with alarm to his own discoveries of the high incidence of pediatric bipolar disorder and the need for treatment with strong antipsychotic drugs. Three weeks after the Newsweek feature, Sen. Grassley revealed that Dr. Biederman had received $1.6 million in consulting fees from drug makers, income which he had gone to great lengths to hide from his employer and from the journals that published his articles. Essentially, Dr. Biederman both created an epidemic and found a cure for it—by turning a generation of children into guinea pigs—though it must be said that his “cure” was often worse than the disease, creating a lot of drug-dependent, fat, unhealthy kids completely unable to control themselves. In this case, Dr. Biederman and his colleagues, Dr. Timothy Willens and Dr. Thomas Spencer, were employed by Harvard and Mass General; the drug company was Janssen, and the drug was Risperdal, a powerful antipsychotic; though the trio also received funds from many other drug companies.
Senator Grassley also ran across Dr. Melissa DelBello of the University of Cincinnati. She touted Seroquel, a powerful antipsychotic drug, as effective for treating depression in children. Let me just quote from the Times:
Dr. DelBello’s studies of Seroquel in children have helped to fuel the widespread pediatric use of antipsychotic medicines. Those studies were inconclusive, but she has described them as demonstrating that Seroquel is effective in some children.
Asked in a past newspaper interview how much she was paid by AstraZeneca [the manufacturer] to help market Seroquel, she had said, “Trust me, I don’t make much.” Mr. Grassley said this week that her disclosure forms at the University of Cincinnati show she received $100,000 from AstraZeneca in 2003 and $80,000 in 2004. Dr. DelBello consults for seven other drug makers as well.[iv]
The hospitals, universities, and publishers who work with these researchers all have clear conflict-of-interest policies, which were all violated in every case. The researchers usually went to great lengths to cover up their outside income, which certainly suggests they all had the guilty knowledge that they were doing something unethical.
Some of these people may have their wrists slapped by their employers, but they don’t have to worry about money. They also don’t have to worry unduly about their professional reputations, because the professional community tends to ignore these things. An earlier, similar scandal makes that point: In 1999 the Boston Globe revealed that Dr. Martin Keller of Brown University had received $550,000 in unreported consulting fees from the makers of antidepressants that had been touted in his published research.[v] In 2009 you could do a computer search of all psychiatric literature since 1999, looking for an editorial or letter that mentions Dr. Keller, and you would find nothing. That means that all his published research is still accepted at face value, unless you happen to have read the Globe. That will most likely also be the fate of all this new tainted research.
But it’s not just the big names who are involved in this. It’s quite likely that your psychiatrist has been invited to speak at conferences which can earn him or her $10,000 a year or more for reading a speech written by a drug manufacturer. He may be given the opportunity to add his name to a published research study they have ghost-written. At the very least he will be invited to attend “educational conferences” at resorts and vacation spas, all expenses paid. One such conference took place at Yankee Stadium during a game. Big Pharma wouldn’t be doing things like this if they didn’t have evidence that such payments will influence what drugs your doctor prescribes. Dr. Stephen Sharfstein, past president of the American Psychiatric Association, questions why Celexa is currently the most-prescribed SSRI, when Prozac, equally effective, has gone generic.[vi]
This is all the result of hubris, of course, except for some cases that may just be greed at work. The big-name researchers and the psychiatrist in your neighborhood probably believe that their research and prescribing habits are objective and not swayed by the money they take; they are so vain they think they’re immune to influence. They need to look at decades of social psychology research showing how easily influenced we are: finding a dime on the sidewalk influences our mood, reading about older people makes us walk slower, and monetary rewards affect our decisions.
Objective studies of antidepressants, funded by governments with larger groups over longer periods of time, have shown disappointing results. The STAR*D study, with a large sample of real-world patients, without a placebo washout phase, found that about 50 percent of patients had a significant response, but only about 30 percent met the researchers’ definition of remission.[vii] During follow-up, a significant number of patients relapsed. Overall, the recovery rate was only slightly better than chance alone. STAR*D was sponsored by the National Institute of Mental Health and should be considered relatively free of drug company influence.
The effects of stopping SSRIs have also been minimized. There can be significant withdrawal problems when you stop taking SSRIs—“SSRI Withdrawal Syndrome”—including extreme anxiety, skin crawling, confusion, GI distress, insomnia, and agitation. For some individuals these symptoms are excruciating. I had a patient who went through pure hell—fever, nausea, chills, extreme depression, and the certainty she was losing her mind—going off a pill I had encouraged her to take. The best advice is to discontinue any of these medications by tapering off slowly and under a physician's care.
Last but not least, there are worries that antidepressants interfere with emotional vitality. One study of non-depressed volunteers found that taking an SSRI for only a week interfered with their ability to read facial expressions, especially of anger and fear.[viii] Another study of normal volunteers found that four weeks of Paxil significantly reduced their ability to feel sad or angry when appropriate.[ix] A group of patients who were experiencing sexual side effects also developed significantly less ability to cry or care about others’ feelings. They also lost erotic dreaming, surprise, creativity, anger, and ability to express their feelings.[x]
Therapists who take SSRIs themselves were very disturbed by these findings, wondering if it meant they were losing their ability to be empathic; many of us have stopped medications as a result. I know a musician who tried Lexapro for his social anxiety and asthma. He noticed that he stopped getting chills and goose bumps when he was really moved by music. When he stopped Lexapro, he was able to get goose bumps again. Another male patient, who was prone to picking up girls for one-night stands, reported that with Paxil he stopped feeling guilty. At least he recognized this was a problem.
It seems quite possible that SSRIs (and other antidepressants, for all I know) get some of their effect from an overall emotional blunting, especially of negative feelings. Their use may make us temporarily a little shallow or insensitive. That’s a good thing if you’re seriously depressed, but a problem otherwise. As far back as Listening to Prozac (1993),[xi] Peter Kramer was advancing the theory that people with depression may be especially sensitive to signs of rejection, and that SSRIs helped them cope better. This is one of the reasons why I’m so against the use of antidepressants by people without severe depression who simply want to feel better. They may worry less, but it can damage their relationships, reduce their enthusiasm, make them more shallow and unrealistically complacent. This may be why, in this age of stress, so many people are using antidepressants—the drugs can help people put up with things they should not put up with.
Bottom line on SSRIs? Depression is a serious illness, and these are serious medications. No one should ever take them lightly. They definitely can do harm, but the harm depression can do can be much worse. If you have a severe depression, you owe it to yourself to give medication a genuine try. But it needs to be part of a balanced plan that includes good psychotherapy and a lot of self-care. One thing medication can do is let you have the energy or hope to follow through.
[i] Irving Kirsch, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls, “The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration,” Prevention and Treatment 5 (article 23) http://journals.apa.org/prevention/volume5/pre0050023a.html. 2002.
[ii] W. A. Brown, “Placebo as a Treatment for Depression,” Neuropsychopharmacology 10:4, 265–288 (1994).
[iii] Madhukar H. Trivedi, A. John Rush, Stephen R. Wisniewski, et al., “Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice,” American Journal of Psychiatry 163, 28-40 (2006).
[iv] Gardiner Harris, Benedict Carey, and Janet Roberts, “Psychiatrists, Children and Drug Industry’s Role
.” New York Times, May 10, 2007.
[v] Alison Bass, “Drug Companies Enrich Brown Professor
.” Boston Globe, p. A1 (Oct. 14, 1999).
[vi] Harris, Carey, and Roberts, New York Times, May 10, 2007.
[vii] Madhukar H. Trivedi, A. John Rush, Stephen R. Wisniewski, et al., “Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice
.” American Journal of Psychiatry 163, 28-40 (2006).
[viii] Catherine J. Harmer, Nicholas C. Shelley, Philip J. Cowen, and Guy M. Goodwin. “Increased positive Versus negative Perception and Memory in Healthy Volunteers Following Selective Serotonin and Norepinephrine Reuptake Inhibition,” American Journal of Psychiatry 161, 1256–1263 (2004).
[ix] Brian Knutson, Owen M. Wolkowitz, Steve W. Cole, Theresa Chan, et al., “Selective Alteration of Personality and Social Behavior by Serotonergic Intervention,” American Journal of Psychiatry 155, 373–379 (1998).
[x] Adam Opbroek, Pedro L. Delgado, Cindi Laukes, et al., “Emotional Blunting Associated with SSRI-Induced Sexual Dysfunction. Do SSRIs Inhibit Emotional Responses?” International Journal of Neuropsychopharmacology 5, 147–151 (2002).
[xi] Peter Kramer, Listening to Prozac. (New York: Penguin, 1993).