The misprescribing of Prozac and the SSRIs.
NB. Any alteration to the use of a prescribed antidepressant ought be done in consultation with a well-informed medical practitioner. Ill-informed alterations or dose reductions can be dangerous.
(In this essay, certain personal details have been changed to protect the anonymity of friends and associates. The 'friend' referred to in the opening passages is a composite portrait.)
Something is not quite right.
He was told, like so many others, that his ‘depression’ was caused by a serotonin imbalance which the antidepressant was designed to fix.
I showed him a recent quote from Dr Wayne Goodman, Chair of the US Food and Drug Administration (FDA) “ Biological psychiatrists have looked very closely for a serotonin imbalance or dysfunction in patients with depression or obsessive compulsive disorder and, to date, it has been elusive.” That is to say, the oft made claim, very popular with prescribing doctors is not supported by science.
My friend’s doctor also said, as he handed over the script; ‘I think you’ll find this medicine makes a big difference’.
Whilst I appreciate that positive reinforcement can be an important part of medical practice, and yes, some people are helped by antidepressants, I puzzled at the wisdom of such an enthusiastic assurance when a cursory reading of the relevant literature and scientific research reveals that many patients cannot tolerate the side-effects of antidepressants, quite a percentage find the drugs unhelpful and for others they actually make things worse.
So my friend had been recommended a fashionable medicine on the back of a bogus claim and a dubious assurance. I consider he was poorly served.
He was not one of the relatively small percentage of people who suffer a distinct and profound depressive illness of the type which psychiatrist Mark Epstein, author of ‘Thoughts Without a Thinker’, describes as ‘chemical’ and for whom an antidepressant may be one of the treatments to consider, albeit carefully. Epstein characterises this chemical kind of illness by describing a patient who became ‘increasingly withdrawn and agitated, tired, anxious, weak, lethargic but unable to sleep, filled with hateful thoughts and obsessive ruminations, unable to concentrate on work or dharma practice. She took to her bed, lost interest in her friends and began to imagine she was already dead.’ This is a state wherein positive thoughts, energies and enthusiasms dramatically leave as though a bad fairy had cast a black spell over the sufferer’s physiological, mental and spiritual landscape.
No, my friend was not like that. Rather, he had found himself overwhelmed by the relentless demands of his young family, coupled with ongoing financial difficulties and then, the death of a workmate. He was very tired and anxious, he was grieving and run-down.
Not for a nanosecond do I wish to make light of his problems, or of the intense agony he was experiencing, however, I would suggest that what he was going through was a very normal life experience; he was doing it hard, very hard, but I do not think he was suffering from a supposed medical condition called ‘depression’.
With the advent of the new breed of antidepressants, Prozac and the SSRIs, we have been afforded an opportunity to dumb down our perception and understanding of a range of uncomfortable human experiences. A variety of unpleasant, sometimes horrible states, from guilt and ennui through to grief and despair, may now find themselves referred to as ‘depression’ : a lousy use of language, but quite marvellous for manufacturers of anti-depressants.
Had my friend’s situation been assessed more carefully, more wisely, he may have been presented with a variety of time proven, scientifically tested but poorly promoted non-drug resources and treatments which would perhaps have been more appropriate and useful.
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I quickly run out of fingers and toes for counting the numbers of my friends, acquaintances and work colleagues of recent years who have taken, are taking, or have on occasion been offered an SSRI antidepressant. I have a long-standing professional and personal interest in the use of such medicines so my ears prick up if I hear them mentioned and where appropriate I observe and ask questions.
Let me take you through some of what I’ve seen and heard.
In the case of one particular friend, and a couple of casual acquaintances, their lives appeared to change dramatically for the better once they were on the medication. However I know of a few for whom the pills appeared to make little difference one way or another, and others for whom the drug side-effects were so painful or scary that they threw the pills away.
An artist friend maintained that the antidepressants had kept him in a holding pattern so that he could manage his otherwise overwhelming life. Another friend found her attempts to cease taking the medication were frustratingly thwarted by the black hole she fell into whenever she stopped; she had no clue whether the black hole was an underlying ‘depression’ or a drug withdrawal syndrome.
One chap I worked with became disturbingly up-beat and sunny soon after commencing the medication while two women I know well, who had been prescribed Prozac and Zoloft respectively, both appeared to develop an agitation and a cold, utterly uncharacteristic lack of regard for the travails and worries of those close to them. I found these radical changes in personality traits particularly eerie.
An old, dear friend believes that the SSRI he was taking a few years ago drove him to the brink of a suicide attempt. Before commencing the medication he had felt despairing, heart-broken and quite lost after his marriage fell apart however he was not contemplating suicide. Once the drug action kicked in he found himself fiercely energised, uncharacteristically compelled to do something violent to stop the psychic pain. He drove his car to the Victorian coast in order to throw himself off a cliff: he stresses the unnatural nature of the fierce compulsion which was motivating him. By an effort of will my friend managed to keep himself from jumping, he drove home and threw the pills away. The extraordinary suicidal urge left him, never to return.
Another woman I know had never in her life considered suicide. Shortly after she began taking Prozac, she lay down one afternoon and ‘as though a switch had been turned on’ her thought-scape suddenly filled with highly energised suicidal ideas. She was struck by the way the thoughts abruptly appeared out of nowhere. Plagued by this suicidal fever for a couple of days, she stopped taking the Prozac. The wild thoughts disappeared.
These are simply personal observations, of mine and of my acquaintances. I wonder what part the medicine may or may not have been playing in what I observed, in what they experienced.
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Back in 2001 my concern with the rather busy prescribing of these drugs to my friends and colleagues intensified when I commenced a voluntary phone counselling shift with Tranx (now known as 'Reconnexion'), a treatment agency in Melbourne which assists those recovering from prolonged use of tranquillisers and sleeping pills. I had last worked on the phones at Tranx several years earlier. On resuming this work I was struck by an increase in the number of callers who were describing problems with antidepressants. The calls made me uneasy. I decided to investigate.
Over the next few months, with the assistance of a philanthropic businessman in Sydney and the resources of Friends of the Earth in Melbourne I spent some time each week fossicking, reading and communicating with people who knew more about antidepressants than I did.
I was keen to know more about what was going on with these drugs and about what kinds of medicines they were.
Anti-depressants may have their place, but on the strength of what I discovered during my research into the history, marketing and prescribing of these drugs, and during many conversations with those who had taken them, I suspect that the extent of their appropriate, wise and effective use may be quite limited.
The degree to which these drugs may make matters worse (sometimes much worse) or be simply ineffective, or appear to be effective but create new problems for patients further down the track, is under-examined.
It seems to me the SSRIs are at present a highly problematic medicine which is being popularly treated like a super magic lolly, regardless of the portentous and poorly understood downside.
But that is nothing new.
During the early 1990’s I conducted a lengthy social research study with my colleagues at the Benzodiazepine Research Group (B.R.G.) in Melbourne.
The benzodiazepines, or ‘benzoes’ are tranquillisers and sleeping pills such as valium, Mogadon, Normison, Xanax etc. They are a different class of drug from the currently popular antidepressants. With the aid of funding from Consumers Health Forum in Canberra and the Lance Reichstein Charitable Trust, we founded the B.R.G. in an attempt to better understand a body of largely anecdotal information which claimed that prescribed benzo use was having harmful effects on the health and well-being of many patients. We were also keen to discover more about the nature of the withdrawal illness which so often accompanied cessation of these medications. Our qualitative research included lengthy interviews with patients who claimed they had come to grief whilst taking low doses of medically prescribed tranquillisers and sleeping pills.
During the 1970’s and 80’s the benzodiazepines were the most commonly prescribed medicines on the planet; valium for anxiety, Mogodon for insomnia, xanax for panic, Ducene, Normison, Ativan, Rohypnol for an ever increasing range of ‘ailments’.
For a good 30 years we drank from the yellow fountains of Roche, Wyeth et al. Growing numbers of us were progressively taught, and taught our children by example, that we humans lacked sufficient resources within ourselves (courage, patience, endurance, physical resilience, intuition, innate wisdom, ingenuity, faith) to cope with the emotional pains of life. We learnt to underestimate our families, friends and communities and their potential to assist us through various torments with kindness, compassion, physical contact, practical assistance, information and social services.
In the late 20th century we learnt, en-masse, to use mood medicines.
Undoubtedly such medicines can sometimes be valuable in general health care but their use ought be judicious. When the National Health and Medical Research Council of the Australian Government (NHMRC) finally issued cautious guidelines for benzodiazepine use in 1989 they recommended that in routine general practice, as a treatment for anxiety or insomnia, the benzodiazepines be henceforth prescribed only as a last resort and ideally for no longer than a week or two.
But since the 1960’s it had been commonplace to prescribe benzoes as a first resort and as a long term treatment.
Those pills didn’t actually dissolve the pain as had been promised, or at least implied. Rather, for many of us, the benzoes squashed our frightened feelings down so they might fester quietly within our physiology causing all manner of insidious damage. And often those feelings, submerged and distorted, would re-emerge fierce and strange, at an unpredictable, possibly shocking, later date.
Pill as Suppressive Agent. Feelings as Loch Ness Monster.
As we moved through the 1980’s, the benzoes began to fall from favour because more and more consumers of these pharmaceutical products were recognising the havoc the pill-monster was wreaking. Word spread. But the benzoes’ fall from favour during that decade left us with two glaring concerns:
Were we to be left floundering helplessly with our unruly feelings?
And
How were the pharmaceutical companies going to recover from the loss of their highest earners?
Never fear!
Prozac and the SSRIs were waiting in the wings.
So
bit by bit,
one by one,
we returned to the dance with newer, smarter partners.
(And anyway, the benzoes didn’t entirely disappear.)
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Unlike the benzoes and perhaps because of them, from the first public appearance of Prozac, with its attendant fanfare, certain voices were calling for caution. They’re still calling. We ought listen.
The apparent worldwide anxiety epidemic of the 1970’s has been replaced (so we are told) by a worldwide epidemic of ‘depression’. Is it reasonable to suggest that global mental health epidemiology can alter so radically in a mere 30 years? Or are the same old human ailments simply going by different names? If so, is this choice of nomenclature, are these international diagnoses, being informed by scientific research and common-sense or by pharmaceutical marketing departments?
There is by now considerable discussion about the usefulness or otherwise of the highly fashionable SSRI antidepressants but this debate has had little effect on sales: the SSRIs are a resounding market success.
At what cost?
For clues, I suggest we might do worse than look back on the 45 year history of the benzoes.
From the beginning of the benzo craze there were signs that all was not as it should be for the millions of compliant patients. However, little heed was paid because the warning signs were largely missed, or misunderstood.
As a result, a massive, long-winded, medical tragedy has unfolded over decades, effecting the lives of millions of trusting patients, their families and health-workers.
Today I observe all-too-familiar warning signs in relation to the widespread and fashionable use of the SSRI antidepressants.
As with the benzoes, anecdotal reports have filtered out from the beginning suggesting all may not be well with these new wonder drugs.
As with the benzoes, the possible significance of those reports seems to be widely ignored. But people keep talking and if the sad tale of valium and the other benzoes is anything to go by, it is quite likely you will hear the truth about the safety or effectiveness of the new antidepressants via talk back radio, Oprah Winfrey, your next-door-neighbour or the internet before you hear it from your local doctor.
During the second half of the 1990s I left the benzo work behind for a time and returned to university to study creative arts therapy. Subsequently I began working as an arts therapist and counsellor. But I kept an eye on the Prozac phenomenon. Aware as I was of the tragic drama which had played out over the prior 3 decades with the tranquillisers, I watched the incoming tide of SSRIs with some concern. As far as I could see, warning lights were flashing.
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Prozac was an extraordinary cultural phenomenon. It came on the scene with unprecedented fan-fare. Not since the heyday of valium prescribing in the mid 1970's had a pharmaceutical product claimed so much media attention, nor had a prescription drug been such a popular topic, inspiration and reference point for artistic practice. Newspaper articles and cartoons, magazine features, television documentaries, song lyrics, paintings and performance art featured Prozac.
Hailed as a wonder drug, it was famously celebrated by psychiatrist Peter Kramer’s best selling homage ‘Listening to Prozac’ which sat on the New York Times best sellers’ list for ages. An informative and seductive read, it told of men and women who had apparently, perhaps for the first time in their lives, found peace, security, even self-confidence, thanks to a magical medicine.
Then Elizabeth Wurtzel appeared, young and glamorous in the jacket photo of her book "Prozac Nation: Young and depressed in America". Autobiography with pharmaceuticals; the book was a hit.
Wurtzel built a career for herself riding on the back of the green and white capsule. G.Q. magazine displayed mock-porn photos of Elizabeth-with-pills over text which told of her success as a commentator on her generation's angst. Hollywood bought the rights to Prozac Nation and made the film.
In 1994 maverick American psychiatrist Dr. Peter Breggin responded to Dr. Peter Kramer's persuasive ‘Listening to Prozac’ with his release, "Talking Back to Prozac."
Breggin tells stories of those who have been harmed by the drug, and other SSRIs. He outlines suspect and unethical steps allegedly taken by the manufacturer Eli-Lilly (including grand scale tinkering with research results) to ensure American Food and Drug Administration approval for Prozac. According to Breggin, the Prozac research trials, before being tampered with, did not indicate the drug to be particularly effective.
Shortly afterwards yet another book, "Living with Prozac", edited by Debra Elfenbein slipped quietly onto the bookshelves. In a way it was the most interesting of the lot.
It is simply a collection of personal stories from Americans who have used Prozac or it's cousins Zoloft and Paxil.
In her introduction, Ms. Elfenbein tells us, "Patients and their communities need to become educated consumers... and so... we share with one another what has happened to us."
These tales are diverse and intriguing, useful as a way of seeing the effects of these drugs under specific circumstances and enthralling as stories of human experience. Dr Peter Kramer warns us in his introduction to this book that because these are personal anecdotes we must be wary of the 'facts' reported. That is fair enough. On the other hand, as he acknowledges, another kind of all too rare 'fact' emerges simply because of the unscientific nature of these reports. We see how individuals are feeling and thinking and responding to all manner of things in their lives, including the medication. Some stories sing the praises of the SSRIs, others described the nasty, sometimes chilling downside.
By the mid 1990’s, with all this attention, and aided by a fascinating and unique gestalt in American popular culture, Prozac became the second most prescribed drug in the U.S.A.
The news media fed on the phenomenon as did the manufacturers of the drug and it’s, now proliferating, sister-substances with names like Paxil (Aropax in Australia), Zoloft, Cipramil, Effexor etc.
Prozac, its promotion, and its attractiveness, was part of an extraordinary cultural shift. With this drug, an ages old stigma against certain manifestations of mental illness seemed to be biting the dust. Suddenly it was OK to be ‘down’ or ‘sad’, it was OK to call that ‘depression’, and it was totally fine to swallow the rather stylish grass-green and snow-white capsules that had such feel-good pre-publicity.
It had never, ever been chic to need Valium or Mogadon in the 60’s and 70’s. Quite the contrary. Users generally kept it quiet; anxiety and depression were not socially celebrated outside Woody Allen films. (Gwenda Cannard, Director of Australia's Tranx (now known as 'Reconnexion'), suggests that these pills may have been less stigmatised amongst women).
Prozac was born into a brave new America where the popular discourse had opened out. The social liberation movements of the 60’s and 70’s had fostered an acceptance of diversity, championing of the underdog, and respect for the individual’s personal concerns and ‘issues’. Then, as the 1980’s progressed, the so-called post-modernist trends in philosophy and cultural studies powerfully influenced a generation of tertiary students, progressively filtering through society. At a popular level these philosophies championed the varieties of human ‘difference’ and fostered a fresh, non-hierarchical curiosity regarding human achievements, failures, desires and being-ness at all strata of class and culture.
These fashions in the influential academies of learning were being mirrored at the less rarefied levels of popular culture where television and radio talk shows increasingly trawled the depths of the richly diverse social underbelly of the American cities and back-woods looking for peculiarity, stimulation and ratings.
Countless large and tiny closets were being opened, and as shocked as some of us were, age-old stigmas and fears around certain people and certain behaviours were dissolving somewhat. The feared ‘otherness’ was becoming a little more familiar as its essential, if sometimes unruly humanity was coaxed into the light.
Popular culture increasingly welcomed (at least the idea of) the marginalised, the strange and the sick, as having (almost) equivalent humanity, interest and cultural value as the successful, the healthy and the beautiful.
And in the midst of all this there were Twelve Step Programs. The cultural clout of Alcoholics Anonymous and its many off-shoots ought not be underestimated.
After decades of clandestine meetings in drafty church halls, these simple, powerful recovery programs, designed to help people with all manner of compulsions from alcohol abuse and over-eating to unmanageable family dynamics and unruly sexual appetites, were really coming into their own. With their zeal for confessional communication and non-judgmental ‘acceptance’, they flourished and were being increasingly sourced (read ‘validated’) by popular culture for pearls of wisdom. Those pearls were generously scattered, hither and yon, thanks to the pontifications of movie stars, pop stars, self-help books, children’s television and, of course, via ‘Oprah’ where we were regularly exhorted to ‘Get with the program!’.
So, parts of the society, and of the individual, which had been substantially silenced or shut out during the earlier years of the 20th century were being increasingly invited into the light, even the spot-light, with the unspoken but important proviso that they be at least reasonably well behaved.
Enter Prozac, right on cue!
The cultural ground had been well prepared within which the previously stigmatised and silenced territory of ‘Depression’, its unhappy sufferers, and most importantly its attendant magical medicines, might claim their 15 minutes of fame.
All of a sudden it was OK to be depressed, to chat about it, to wear your pills like heaven.
I reckon Prozac helped facilitate the vogue for public discussion (even celebration) of depression simply because the idea of such a drug set a reassuring limit to the potentially messy reality of depressive illness. It’s far more palatable, more relaxing, more enjoyable for Oprah’s audiences to hear of the heart-break, the grief, the tormented reality of depression, knowing that at the end of it all the camera will swing to the pretty girl on the podium: she displays a neat, green and white box between perfectly manicured fingers while a warm voice-over reminds us; ‘All You Need is Prozac’.
Go girl!
Warning Signs.
Prozac and the other SSRI antidepressants are different drugs from the benzodiazepines; they may turn out to be more, or less, benign and perhaps their efficacy and associated problems will be different. These drugs do appear to significantly assist an arguably small percentage of those who take them. I know they have saved lives and eased great pain. But, as it was with the benzoes, that’s hardly the complete story.
For some time now, our media outlets have been accessing and communicating worrying information about the SSRIs, information which is radically different from that which many of us might access through our GPs or psychiatrists. This is not a good sign.
It is very clear to me that warning lights are flashing.
Just what they are warning us about is still unclear - but that is what must be examined and discussed urgently, openly and impartially.
As I conducted my research into these medicines - following leads, fossicking, reading - I turned up various, persuasive, scientifically-based arguments which supported the use of antidepressants. I discovered equally convincing scientifically-based arguments supporting the avoidance of these medications. The area is complex and to some extent mysterious given that we are dealing with many unknowns: human feelings and behaviour, under-researched medicines, physical versus psychological responses to that medicine, scientific researchers with often vested interests, contentious research designs, and the less than transparent methodologies of some large pharmaceutical consortiums.
I could appreciate both sides of most arguments I encountered but certain pieces of information kept nagging at me. These were the warning lights. Let me share some of them with you.
I have already mentioned maverick psychiatrist Dr. Peter Breggin who, early on, obtained and examined a more comprehensive body of Prozac research findings than the selectively edited version which Ely Lilly, Prozac’s manufacturer, submitted to the authorities in order to gain approval to release the medication onto the American market. On the basis of the more complete research data, Breggin concluded that the FDA had been misled, that Prozac was possibly no more effective than placebo, that is to say, than a sugar pill. In certain of those primary research studies the drug was actually shown to be less useful than placebo.
And because most of the initial Prozac research trials lasted only a matter of weeks - we knew nothing, absolutely nothing about the long term effects of Prozac on the body, on the mind, on behaviour, on society.
Certainly, since the SSRIs first appeared, lengthier trials have been carried out but none of them has been long enough, nor sufficiently sensitively monitored, to reveal the real potential effects of prolonged use of this medication. As with the benzoes, the long term effects are being discovered, for good or ill, by patients themselves. In a drug with such dubious beginnings, can that be considered good medicine?
Dr. Peter Breggin also suggested, way back in 1994, that there were indications in the research that the use of SSRIs to treat a depressive episode may actually damage a patient’s natural ability to respond effectively to subsequent episodes of depression. When I asked British psychopharmacologist and antidepressant expert Dr. David Healy for a comment on this recently, he remarked that there was validity in such concerns but that it was hard to disentangle this possibility from the drug withdrawal phenomena. Similar concerns have been echoed elsewhere and I would like to see them adequately examined.
As the years have gone by, medical researchers have begun to implicate certain SSRIs in a higher rate of health problems in the new-born. Then in 2003 most SSRIs were banned for use by children and teenagers in Britain due to the implication of the drugs in suicidal and aggressive behaviours. Now the use of these drugs by kids is being re-assessed in the USA in response to similar concerns. Yet for years and years they were cheerily prescribed to kids and to pregnant women who were comforted by the medical assurances that the drugs were ‘safe’. That enthusiastically proclaimed ‘safety’ was not supported by good science! Are there further dangers yet to be revealed?
Is this good medicine?
After Prozac came onto the market, anecdotal reports began filtering out from people who had experienced a nasty withdrawal syndrome when they tried to come off the antidepressant. Reportedly, some folk found the withdrawal illness so severe they had to go back on the pills. They no longer wanted to take them but could not come off.
Other SSRI patients, becoming highly anxious and deeply depressed shortly after coming off the medication, concluded that this was the re-emergence of their original depressive/anxious problem. Their doctors agreed with them and so the medication was resumed. But I heard expert voices like that of Charles Medewar of Social Audit in the U.K. and Welsh antidepressant expert Dr. David Healy suggesting that such severe post-pill symptoms may also be part of a withdrawal illness caused by the medicine, not by the pre-existing condition.
So we have the possibility that some patients are being forced back on pills because the withdrawal illness is unendurable while others may be going back on pills because the withdrawal illness has been misdiagnosed as evidence of their pre-existing depression or anxiety. This is exactly what happened with the benzoes; millions of benzo users were trapped for months or years on unhealthy medication (which would only make them sicker) due to misdiagnosis of its harmful effects. I wonder about the torment endured by patients who are thus trapped on SSRIs. What will become of them?
In the early 1990’s The Citizens Commission on Human Rights in the U.S. alleged incidences of heightened agitation, aggression, violence, suicidal ideation and even homicidal acts associated with SSRI use. I heard scoffing. The claims were easily discredited because the CCHR was affiliated with the Church of Scientology.
Before long similar claims were being made by reputable scientists and, as the years have gone by, claims of SSRI induced murder and suicide have on occasion been verified by the courts.
And it was in fact a very similar list of side-effects (excepting homicidality) which led to the ban on prescribing most SSRIs for kids in the U.K. in 2003. So what about the adults? Are we being cautious enough?
You might suppose that with my particular personal history I would have it in for the large pharmaceutical manufacturers (see 'A Slice of Benzo History'). I’ve certainly had my moments over the years but in many ways I’ve given them the benefit of the doubt, tending to consider that the benzo debacle may have been more about misguided enthusiasm and ignorance than blatant deceit and greed.
However, about 5 years ago I began receiving regular emails from the Alliance for Human Research Protection (AHRP) based in New York. AHRP operates as a watchdog regarding ethics in medical research and on average I receive three posts a week.
The tone of their posts can sometimes be overly strident however their assertions of possible breaches of ethics are generally carefully documented and cross-referenced. Most weeks there will be at least one notice regarding suspected breaches of ethics and human rights in the operations of large pharmaceutical companies.
I have read these posts over the years in amazement, often disbelief. The cumulative picture shocks me. (John LeCarre, author of ‘The Constant Gardener’ a 2001 novel (later a movie) which portrays monstrous behaviour by pharmaceutical companies in Africa, notes at the end of his book that the real life stories he uncovered while writing the book were far worse than anything portrayed in his fiction.)
The picture which has emerged of the expedient or perhaps simply ignorant operations of some of the major antidepressant manufacturers should be of grave concern. Information about serious harmful effects of medicines is suppressed so that the medicines can still be vigorously promoted. Drugs which do not meet ethical standards for testing or selling in Europe or the U.S. are shipped off to Asia or Africa. And much promotional advertising is ludicrously manipulative or misleading.
I will give you a rather minor example of the kind of amoral behaviour which goes on, choosing this one because it has a local aspect (my daily newspaper, The Melbourne Age, became a vehicle) and shows how a ‘small’ deceit can spread potentially dangerous misinformation around the planet.
At the beginning of June 2004 there was a front page article in the New York Times headed “Antidepressant Seen as Effective for Adolescents”. A version of this misleading article appeared in the Melbourne Age a couple of days later.
Both pieces suggested that the antidepressant Prozac may be the most useful treatment for depressed children.
Un-named ‘experts’ quoted in the NYT article informed us that the research under discussion was ‘notable because it was carried out...without financing by drug manufacturers.’ In The Age report this became ‘ The U.S. study... unlike many other trials, did not have drug company backing.’ Such comments would doubtless reassure many parents and young people who are trying to get a handle on the pros and cons in the rather muddy and tedious antidepressant debate.
However, subsequent to the appearance of the New York Times article, Vera Sharav who heads the AHRP issued a statement informing us that the claims of the ‘experts’ quoted in the New York Times report were misleading.
According to Ms. Sharav, although the funding to carry out the study came from American tax-payers, the lead authors of the reported study, Dr. John March and Dr. Graham Emslie had substantial, ongoing financial ties to antidepressant drug companies, including Eli Lilly the manufacturer of Prozac. According to Ms. Sharav, Dr. Emslie, amongst other things, is a consultant for, and receives research support from Eli Lilly. Dr March receives research support from Eli-Lilly and other drug manufacturers, and is a speaker/consultant for various pharmaceutical giants. These men are hardly free agents.
Ms Sharav notes that two previous studies of Prozac use in adolescents authored by Dr. Emslie claimed beneficial findings which the U.S. Food and Drug Administration’s statistical analysts subsequently questioned, concluding; “based on the primary endpoint, there was no evidence of treatment effect.”
Vera Sharav wonders why the U.S. government’s National Institute of Mental Health, which spent $17 million of tax-payers money sponsoring this new study, did not employ independent psychiatrists to carry out the work.
But the average reader of the Melbourne Age, not privy to Vera Sharav’s information, was likely to be reassured that Prozac is safe and useful for teenagers thanks to this erroneous report in a reputable, widely circulated broadsheet.
It is also problematic that both the NYT and Age reports were based on partial, preliminary findings of research which had not yet been completely analysed and which had not yet been through a peer assessment process. Vera Sharav tells us that over recent years, claims made for antidepressants in drug-company funded studies, or studies authored by medicos who have financial/employment links to such companies, have regularly been challenged when closely examined by independent analysts.
Another news item which appeared in The Age a couple of days later highlighted this very point: the New York State Attorney General had filed a lawsuit alleging that Glaxo-Smith-Kline, manufacturer of one of the most popular, Prozac-class antidepressants Paxil (Aropax), had engaged in ‘repeated and persistent fraud’, concealing from the regulatory bodies information from clinical trials which indicated that this drug caused suicidal behaviour amongst children and teenagers.
The case was eventually settled out of court.
These are relatively small examples from a litany of suspect dealings which we ignore at our peril.
I have watched in dismay as worrying reports about SSRIs were promptly refuted and pushed aside. Oughtn’t we err on the side of caution?
As with the benzoes, the medical profession, by and large, have appeared to be avoiding engaging sincerely and openly with either the anecdotal evidence of possible SSRI problems, or the growing debate amongst allied health professionals and in the media.
Too often I’ve observed a medico, either in public sound-bites or in private conversation, responding with dismissive, defensive and sometimes aggressive comments when confronted with information critical of this fashionable medication - regardless of the source of that information. A very unscientific response and not at all helpful.
This was evident in comments attributed to Australian Professor Ian Hickie in a cover story on the SSRIs in The Age ‘Good Weekend’ magazine on June 19, 2004.
I suppose it is possible he was quoted out of context, but as the ‘Good Weekend’ report stands, Prof. Hickie, director of the Brain and Mind Research Institute at the University of Sydney, previous head of Beyondblue (Jeff Kennett’s Victorian depression research initiative) responds inadequately to the serious concerns raised by British antidepressant authority Dr. David Healy regarding the widespread use of SSRIs.
Dr. David Healy is a leading psychopharmacologist, based in the Department of Psychological Medicine at the University of Wales. He is very concerned about the misprescribing of antidepressants, their potential to produce dependence and a withdrawal illness, and the possibility that the SSRIs may actually be causing suicides.
When commenting on Healy’s concerns, Prof. Hickie contributes to the discussion by taking a cheap shot at Dr Healy (whose painstaking investigation of the antidepressants strikes me as well reasoned, un-hysterical and important). Rather than carefully engaging with the substance of Healy’s claims, Hickie has a go at him, referring to him as a ‘hired gun’ who helps people sue drug companies. This kind of response is not particularly unusual. It’s only when such a man as Prof. Hickie engages seriously with the concerns raised that the debate can progress.
Prof. Hickie goes on to support SSRI use by claiming that since their appearance, the incidence of suicide in elderly Australians has fallen. This also strikes me as a peculiarly naive response to the issues under discussion.
Has research proven clearly that the SSRIs are responsible for a fall in elderly suicide in Australia? If the elderly suicide rates have actually fallen, in the absence of sound research which has determined precise causation I would think that many factors may be involved and it is somewhat naive, let alone expedient, to lay the bouquet at the door of the SSRIs.
Vera Sharav of AHRP noted recently that the incidence of suicide in the USA has in fact risen since the SSRIs came along. Neither Hickie’s nor Sharav’s statements are proof in themselves of a causal link between the drug and the behaviour. They are interesting observations each requiring closer examination. (Incidentally, Dr. David Healy, in recent private correspondence, maintained that the Australian figures on suicide are in fact relatively unchanged now compared to pre SSRI times.)
But even if a clear causal link is established between the taking of SSRIs and a reduction in suicide amongst the elderly, in the climate of the current debate it doesn’t automatically follow that the SSRIs are a good thing.
There are still very important questions to be considered. A 2001 meta-analysis of the body of reliable research into the efficacy of antidepressants, was carried out by Irving Kirsch and his associates at the University of Connecticut. This study echoed concerns raised by Dr. Peter Breggin in the early 1990’s; Kirsch found that overall SSRI antidepressants are only marginally more effective than placebo, if that. In fact Kirsch claims that despite hundreds of trial participants, 57% of trials funded by the pharmaceutical industry failed to show a significant difference between drug and placebo. Certainly Kirsch’s results have been challenged by some commentators and some earlier meta-analyses have in fact shown some advantage for antidepressants. However, Dr. David Antonuccio, who has written about the over-use of antidepressants for people with nonbipolar, non-psychotic depression, refers to those earlier meta-analyses in his January 1999 article in the journal Psychotherapy and Psychosomatics. He notes that ‘some problems with the publication process and the research paradigm [used in those studies]’ may diminish the strength of the apparent advantage of antidepressants.
Antonuccio suggested that the results of such meta-analyses may be skewed because individual antidepressant studies in which the drug performs poorly are likely to be delayed or not published in an attempt to withhold unfavourable results. These results are therefore less likely to be considered in a meta-analysis. Antonnucio cites evidence that drug companies appear to terminate studies at an early stage when they do not seem to be producing results which support their product. He tells us that as many as 10 to 20% of antidepressant studies aren’t published. Further, it has been documented hither and yon that drug research which is funded by the antidepressant manufacturers themselves is questionable because of the obvious conflict of interest.
It is also commonplace to employ a placebo washout period in antidepressant trials i.e. would-be trial participants who have previously been on another antidepressant are switched onto a placebo for 2 weeks so that the previous drug has time to wash out of the body and doesn’t interact with the new one to be tested. But patients who improve during the placebo washout period are removed from the drug trial as ‘placebo-responders’ i.e. people who respond too favourably to the taking of a pill which has no actual chemical efficacy. It is considered that such folk will confuse the findings of the trial. Potential participants whose condition was worsened by their previous antidepressant and who therefore improved once they were off it (i.e. during the placebo washout phase) will also likely be excluded as ‘placebo responders’. As many as 20% of trial participants are excluded from a drug trial in this fashion.
Thus, non-drug responders and placebo-responders may be eliminated from a study before it begins. Patients with a history of non-response to the drug being studied are also routinely excluded. Since each of these groups would be liberally represented in the general population, Antonuccio is concerned that such exclusionary practices would skew research results in favour of the drug being studied.
On the basis of information such as that outlined by Kirsch and Antonuccio there are now many commentators suggesting that the SSRI antidepressants may be no more, or minutely more effective, than placebo. (Dr J. Salamane in his article "Antidepressants and Placebos: Conceptual Problems and Research Strategies" in the journal 'Prevention and Treatment' Vol 5 July 2002, makes the point that even though SSRIs may not be as useful as we've been led to believe, it is important not to forget that for some people they may still be highly efficacious.)
Dr. Antonuccio wonders, somewhat incredulously, in a 2002 article in the Journal of Prevention and Treatment; “How is it that with such a weak advantage over placebo, antidepressants have apparently become the most popular treatment for depression in the United States and in many parts of the world? Does the small advantage of antidepressants over placebo justify the risks and side-effects associated with these medications?”
To my knowledge, such worrying questions and concerns have not been adequately explored or refuted.
And if there is truth to such claims, many of the elderly Australians who, according to Ian Hickie, are turning from suicide due to SSRI use, may be largely responding to a placebo effect, not a true antidepressant effect.
But there’s the rub: these elderly Australians are not taking a placebo, they’re not taking a harmless sugar pill. They are taking a drug which has many possible side-effects and which is alleged to sometimes cause illness, dependence, a severe withdrawal syndrome, agitation, suicidal ideation and aggressive behaviour. We also know very little about the potential long term harmful affects of this medication on the human body, let alone a thorough profile of interactions with other medications.
Are the sometimes harmful SSRIs little more effective than placebos? If so, can their widespread use be considered good medicine?
I was interested to discover through my research that even though science has not thoroughly investigated non-drug treatments for depression, various studies have nevertheless shown that there are good, reliable, non-pharmaceutical, treatment options.
According to Antonuccio’s 1999 article ‘Raising Questions about Antidepressants’ several meta-analyses had, by that date, evaluated the relative worth of pills, psychotherapy, and the two combined. According to Antonuccio, those studies indicated that psychotherapy is as good as, or better than, antidepressants as a treatment for depression. When the patient drop-out rate is taken into account the pills show a substantially worse outcome than psychotherapy and are inferior to both treatments combined. And psychotherapy, like other non-drug treatments, hasn’t the worrying side-effect profile, the potential for chemical dependence or the likelihood of a nasty withdrawal illness.
It is argued that certain studies show that combining SSRIs with cognitive therapy is the most effective method for treating depression. I recently asked Dr. David Healy to comment on this approach. Healy suggests there is minimal research on this, that it’s certainly not the best approach for the severest depressions (which, he says, seem to respond better to older, non-SSRI antidepressants, and ECT) and that arguably in the milder depressions the best thing would be to let the person recover under their own steam.
Dr. I Kirsch (who authored the 1999 meta-analysis referred to above) reminds us that studies have shown regular exercise produces a response almost as great as SSRIs but with more positive side-effects. Bibliotherapy (reading and informing oneself about the condition and its management) performs similarly.
Information like this demands our attention and might curb our overblown enthusiasm for favouring a treatment which is often problematic and arguably not the most effective.
In recent times, friends or associates have happily told me they had been prescribed a ‘really low dose’ of some SSRI which they were told had ‘fewer side-effects’ than last year’s model. I grit my teeth at the familiarity of those recycled, spurious reassurances. During the 1960’s and 70’s each new benzo was claimed to have fewer side-effects: the claims weren’t true but they were reiterated over and over, and the famous ‘child’s dose’ left countless people dependent and sick.
Now, each new SSRI is claimed to have fewer side-effects than the last. Where are the grounds for believing such claims when the true list of side-effects is still being discovered, drug by drug, person by person - its a work-in-progress unfolding in the lives of millions of patients world-wide.
Meanwhile we watch the recommended uses of SSRIs proliferate, just as they did with the benzoes.
Fifteen or twenty years ago, when the benzoes were falling from favour, the SSRIs made their initial entrance as antidepressants. We have seen them gradually progress to being prescribed as anti-anxiety medications, sleeping agents, treatments for grief, for relationship difficulties, for social anxiety, for chronic fatigue syndrome, irritable bladder etc. The drugs may have some efficacy in some conditions but the obscene haste to claim new and sometimes dubious territory for a quite possibly tainted medicine is likely to end in tears. Recently, Prof. Ronald Kessler from Harvard Medical School announced his research into ‘intermittent explosive disorder’. This ‘disorder’ appears to be what lay people call outbursts of anger. Kessler and his co-investigator, both of whom have received grants from major antidepressant manufacturers in the past, wish to inform us that such outbursts are in fact an illness. But don’t be alarmed, the condition is apparently treatable. Dr. Kessler reassured us that all we require is, you guessed it, a prescription for an SSRI!
Too many doctors are finding too many ‘appropriate’ uses for a still poorly understood voguish chemical. And possibly too many of the rest of us are complying.
At one point in the 1990’s, as a logical extension of our overly infatuated misuse of these medicines, one of the big pharmaceutical manufacturers in the U.S. lobbied the F.D.A. to add ‘absence of joy’ to the list of conditions treatable with an SSRI. Absence of joy? That’s many people much of the time! That’s some folk’s lives!
‘Absence of joy’ is definitely not an illness. But boy, what a market!
We are being prescribed these drugs at the drop of a hat as though we had no other tools in our mind-bogglingly rich and various human inheritance - as though we had nothing else, innate, scientific, psychological, sociological, theological, creative or common-sensical to help us through difficult times.
For those of us who have experienced or studied the benzo debacle, the key questions here are: Why, once again, are we freely prescribing medications which we don’t fully understand? Why have these drugs become a first line treatment for depression when other treatments are as effective, sometimes more effective, time proven, and much safer? Why are we suggesting millions of patients take a drug long-term when we have little idea of the true long-term effects and possible dangers of that drug? Why are we widely using medicines which cause dependence and which can produce a very painful withdrawal illness which is easily misdiagnosed?
Why are the warning signs being swept aside or ignored?
Why are we continuing to re-define normal, albeit uncomfortable human experiences as ‘illness’ and prescribe pills which have no relevance at all to the problem or its solution?