Are modern anti-depressants actually making people crazy? CLARE SWINNEY investigates the growing controversy over the side effects and withdrawal sympoms of the SSRIs:
Janet Frame touches on the association between doctors and patients in Faces In The Water, (1980) on page 28. ‘The doctor would pause sometimes to inquire, smiling in a friendly manner, but at the same time glancing hastily at his watch and perhaps wondering how in the hour before lunch he could possibly finish his rounds of all the women’s ward and get back to his office to deal with correspondence and interviews with demanding puzzled alarmed ashamed relatives.’ Although this was set in an asylum in New Zealand in between the First and Second World Wars, it bears a familiar flavour.
Propelled by a need for efficiency, psychiatry’s enthusiasm for symptomatic, push-button remedies, has led to life’s transient ‘symptoms’, such as forms of mild depression, to be clinically diagnosed and, once diagnosed, seemingly quickly alleviated, if not eliminated, by a pharmacological intervention. Many clinicians today consider it more practical, economical and speedier to prescribe medication than psychotherapy. But is dispensing tablets, such as the family of Selective Serotonin Reuptake Inhibitors (SSRIs), the best course of action for treating common ailments, such as mild to moderate depression? Or is it doing damage to those it is supposed to be helping?
Doctors have administered and prescribed a series of addictive drugs as sedatives for psychological distress since the early 1800’s, ascribing to the belief that they wouldn’t lead to dependence, and if they did, their patients were probably accountable in some way. Initially, there was opium and alcohol, then heroin, morphine and cocaine. Then in came the bromides, barbiturates and associated compounds. And an assortment of benzodiazepines ensued – including Librium and the iconic one, Valium, which was deceptively denoted ‘mother’s little helper.’
As a consequence of the relationships between governments, almighty drug companies, the medical profession and patients, it took over two decades of comprehensive use before benzodiazepines were accepted as addictive. When this occurred in the late 1980s, prescriptions for them went into sharp decline, but by then, thousands of addicts had been spawned worldwide, many for whom the sole motivation for continuing to take the drugs was that it was too distressing trying to cease using them. They were dependent upon them – in a similar manner some get hooked on drinking. It wasn’t an obvious addiction. Its effects were, for the most part, respectably concealed behind the white net curtains of suburbia. But the households were haunted.
A few weeks ago, an evening talkback show on Radio Pacific elicited calls from people who’d taken SSRIs, the antidepressants which soared in popularity when benzodiazepines lost favour. SSRI’s affect the brain’s ability to reabsorb serotonin, a neurotransmitter in the brain, which is supposed to affect mood, sleep and appetite. That night numerous people phoned the radio station. Said the program’s host: “We were inundated.” People related how difficult it was to come off SSRIs owing to a melange of atrocious withdrawal symptoms. Some divulging that they experienced anger, fierce rage and suicidal thoughts. A number regarded it as too difficult to give up, and regarded their medication as addictive.
Difficulties coming off the SSRIs are well documented. An Internet search of MEDLINEPlus using the search terms ‘SSRI’ and ‘withdrawal’ in combination drew out 278 entries and in Google, 51,900. Some experts stated that many patients, who go off the drugs, mistake their withdrawal symptoms for a return of the original symptoms they were using the drug to treat. They then commonly restart the medication. Other experts said that in many cases there may be a re-emergence of the symptoms people took the drug to alleviate, such as panic attacks for example, and that this was the deciding factor for some patients who restarted their SSRI medication.
Aropax, (paroxetine), which has a relatively intense impact and short duration of action, is associated with the most severe withdrawal reactions. It was approved for introduction into New Zealand in April 1992 and is now the most widely prescribed antidepressant in New Zealand – 209,054 prescriptions were written for it in 2003 alone. And this states Pharmac, the government-sponsored Pharmaceutical Management Agency of New Zealand, is in spite of it having come under scrutiny in Europe and North America, owing to reports linking it to an increased incidence of suicide and a heightened risk of dependence.
In 2003, the number of prescriptions for expensive antidepressants rose and cost taxpayers an additional $4.6 million from the year before. Clinicians’ preference for the SSRIs: Aropax, Fluox and Cipramil, over the old style of antidepressants, such as the tricyclics and monoamine oxidase inhibitors, accounted for most of this unwelcome gain.
One of the reasons for SSRIs popularity is that doctors do not regard SSRIs as addictive. Withdrawal from SSRI’s, such as Fluox and Aropax, can cause a range of unpleasant symptoms, such as dizziness, insomnia, virtual reality nightmares and headaches, but this in itself is not indicative of an addiction. According to Associate Prof Doug Sellman, a psychiatrist who specialises in addiction research at Christchurch, there is a crucial difference between a withdrawal syndrome associated with drugs taken for reward and attendant drug-seeking behaviour and a discontinuation syndrome from medications generally. He states: “There is no doubt that there is a discontinuation syndrome from SSRIs, such as Aropax, but not a withdrawal syndrome that will reignite drug-seeking behaviour.”
“Oh yeah?” responds Jane, one Auckland woman who tried to give up Aropax six weeks after starting. “By day five of climbing the walls, fighting the urge to kill yourself, fighting the urge to kill somebody else, feeling nauseous with the most horrific dreams I’ve ever experienced in my life – of course you go crawling back and start taking the drugs again! I suggest these doctors try taking these drugs themselves for a while, then try kicking the habit. Then you’d see their views change.”
Interestingly, a US clinician interviewed by Time magazine dismissed the link between SSRIs and suicides, saying a study of suicides failed to find evidence that an SSRI had been taken in the hours beforehand. But according to Jane and others, he missed the point – the suicidal thoughts come when you try to give up the drug, and you haven’t taken a pill.
Jane had gone to her doctor for exhaustion, and came away carrying a 20mg a day prescription for Aropax. When some of the side effects started to kick in after four weeks, she went back to the medic who decided to double Jane’s dose to 40mg a day. Things went from bad to worse – and the discovery that Aropax is one drug you can’t quit cold turkey.
“Once you’re on you can’t get off,” she says. “And that’s the most terrifying thing of all.”
The Diagnostic And Statistical Manual of Mental Disorders, 4th Ed., (DSM IV), is the clinicians’ bible. Amongst other things it categorises 307 different types of depression, other mental illnesses, the personality disorders, and substance abuse problems. According to this guidebook, ‘addiction’ requires at least 3 of 7 criteria to be met, (p. 181).
Offers Dr Alistair Dunn, a GP, who specialises in the field of addiction: “A withdrawal syndrome is but 1 of those 7 criteria. I don’t think taking an SSRI, such as Aropax, fulfils any of the others. And I don’t regard it as addictive because it may in some cases, require careful tapering off. If medication for blood pressure is stopped abruptly, a rebound rise in blood pressure can result, or in other cases, a return of angina may occur. Therefore, it must be tapered off slowly. But that doesn’t make it addictive. Addiction does not equal withdrawal syndrome. It’s much more complex, involving effects across a wide range of domains in someone’s life.”
A DSM IV diagnosis of addiction requires evidence of outright abuse. One of the 7 criteria assigned is self-destructiveness manifested in drug-seeking behaviour, such as visiting multiple doctors or driving long distances. Obviously, this would be most unlikely to occur with an SSRI, given that physicians readily prescribe and actively encourage their use. Asserts Dr Dunn: “It can sometimes take a long time for a GP to convince a patient to try a medication, even when the need is obvious to the doctor and the benefits are significant.” Dunn seemed quite annoyed this article was being written. “What about the benefits of the medication and the harm of someone stopping it because they have read an article stating it’s an addictive drug,” he queries.
A review of the medical literature on the SSRI withdrawal syndrome by Tamam and Ozpoyraz, concludes that the best approach for a doctor in dealing with patients experiencing withdrawal symptoms is to educate them, reassuring them that it is a reversible condition, while reinstating the original SSRI, and further slowing the rate of tapering off the drug. (Source: Adv. Ther, 2002).
Anna De Jonge of Hamilton is the Liaison Officer for the Patients’ Rights Advocacy Waikato Inc, (PRAWI), a group of 570, that advocates having will power over pill power. PRAWI’s principal aim is to empower people with information and knowledge. And it, amongst other activities, assists victims of medical misadventure to make formal complaints. Says De Jonge, who is opposed to the use of the SSRI’s because she says they’ve been associated with “suicide, murder, self-harm and mental turmoil,” if in time SSRI’s turn out to be no improvement on latter-day antidepressants, this will be owing to and in spite of the minimisation of the risks of taking them. “If SSRI’s were in some regard, drugs of dependence, but not being categorised as such, it will increase the element of risk of self-harm using them, and their effectiveness will naturally be over-estimated,” maintains De Jonge.
Is their effectiveness being over-estimated? Effectiveness of numerous drugs is. Although it’s seems baffling given the drug industry’s culture of maximum possible sales for maximum possible profit, Dr Allen Roses, an employee of GlaxoSmithKline, (GSK), which is Britain’s largest drugs empire, publicly disclosed that most prescription medicines don’t work on most of those who take them. Amongst those working in the pharmaceutical industry, this was no secret. Seemingly paradoxically, Roses, worldwide Vice-President of genetics at GSK, stated late in 2003 that most drugs only work in 30-50% of people – a substantial proportion prescribed some of the most expensive drugs do not derive any benefit from them at all.
Could this be a reason why the SSRI, Prozac, which is the most widely prescribed antidepressant drug in history, made a fortune for the company, Eli Lilly, yet couldn’t save the CEO’s own spouse? In May 1994, Mrs Marilyn Tobias, the wife of Randall L Tobias, chief of Eli Lilly, committed suicide. Tobias told a magazine in 1995 that his wife was depressed and had tried Prozac.
Prozac was approved for use in New Zealand in February 1988. Eli Lilly’s www.prozac.com website states: “…since its introduction in 1986, Prozac has helped over 40 million patients worldwide, including those suffering from depression…”. Yet, as Charles Medawar, who has worked in consumer protection in the UK and held appointments with the World Health Organisation, pointed out “there has been no discernible effect on suicide rates, since the start of the new war on depression.” Suicide rates in the USA, where SSRIs have been most used, and in England, provided no evidence of any national dose-response. (Source: ‘The Antidepressant Web – Marketing Depression and Making Medicines Work,’ in International Journal of Risk and Safety in Medicine, 1997, p.23).
And now the 24,500 or so anti-depressant prescriptions provided for treating children and adolescents each year in New Zealand are under scrutiny as researchers look for a possible link between SSRIs and suicide. SSRIs are not registered for use here in children, but some doctors prescribe them to youngsters. In Britain, authorities have advised doctors not to prescribe the SSRIs Lustral, Cipramil, Cipralex, and Faverin to young depressed people as clinical trials found a higher rate of insomnia, agitation, weight loss, headache, tremor, loss of appetite, self-harm, and suicidal thoughts in children taking the drugs.
For years, drug manufacturers and regulators in the UK and US maintained that antidepressants would reduce the risk of suicide. Perhaps most notably, Dr David Healy, Director, North Wales Department of Psychological Medicine, a psychiatrist with an international reputation, having authored 12 books and over 120 peer-reviewed articles, strongly disputes this claim. Healy has examined many confidential internal drug company documents, to which he gained access in his capacity as an expert witness in a lawsuit against GSK. These internal documents, Healy states, show the results of the company’s own clinical trials testing the SSRI, paroxetine (Aropax). The evidence, he alleges, shows that rather than reducing the risk of suicide, the drug increases it. He told the BBC that the evidence indicates that roughly 1 in 60 people who go on this drug makes a suicide attempt, whereas only 1 in 550 on a placebo or sugar pill do. Dr Healy says both the drug company and the regulators in the UK and US knew this data for 13 years.
At the heart of the problem, Healy believes is that SSRIs cause akathisia, a syndrome involving motor restlessness, and it is this that causes some patients to commit suicide. GSK’s own studies, and Healy’s, show that SSRIs can cause 1 in 4 healthy volunteers to become agitated. Healy, who is also involved in legal action against Pfizer, following the suicide of the 13-year old American called Matthew Miller, who hanged himself after taking the SSRI sertraline for a week, carried out a trial in healthy human volunteers comparing sertraline with Pharmacia’s Edronax, which does not work on the serotonin system.
The results showed that one third did not respond well to sertraline at all. Of this third, 2 volunteers became acutely and seriously suicidal just being on a normal clinical dose for 2 weeks. They were absolutely normal people. Healy claimed that the archives of the 2 companies contained evidence supporting his own findings.
In excess of 30 studies on sertraline carried out before the drug was licensed, showed that 1 in 4 people taking the drug became agitated. The healthy volunteer studies carried out by the company showed that about 50% of patients suffered withdrawal problems when they came off the drug. Healy claimed this suggested that some patients had become physically dependent on the drug. But instead of warning patients and doctors, he said the company argued that the patients with problems coming off drugs were suffering a recurrence of depression and needed to resume medication.
It can be difficult to conceive of what could be going through someone’s mind when they consider suicide. According to 31-year old, Ashburton mother of two, Diane Blakemore, of how she felt while taking an SSRI: “My life was totally miserable. I wasn’t living – I was surviving. I had horrific nightmares, usually quite satanic. Irrational fears on the drug, were the norm too.
She continues: “I would lie on the couch, too lethargic to move and felt suicidal, as I was highly anxious and depressed. My whole body had inner shakes, I was sweating all over and I had headaches and unbearable muscle tension. My nervous system was overstimulated to the max.
“I felt suicidal because I felt like this and really didn’t like it. I didn’t know how to handle it. The doctor told me to keep taking the tablets, saying that these side effects would go away after 4 weeks. But they didn’t.
“I’d never had any of these symptoms prior to taking the drug. I recently had a bladder and uterine prolapse with terrible backache as a result of giving birth, which made me feel very tired. And as my child had colic, I had to walk the floor, and this walking made my backache worsen. The longer I was on my feet, whether I be sitting or standing later, the worse the pressure and resultant pain would be. And it affected my legs too, as they felt heavy. My backache would ease if I lay down and I took my body weight off my sacrum – so I knew it wasn’t a psychological problem. And I was aware that prolapses might cause this pressure pain. But unfortunately, I just did what the doctor told me and took the medication for the ‘chemical imbalance’ I was told I had.” In this case, the chemical imbalance her doctor referred to was a diagnosis of depression. Blakemore wrote to members of parliament in March 2004 regarding her experiences. In her opinion the medical profession is too ready to categorise behaviour as indicative of depression and far too disposed to prescribe antidepressants.
As with the withdrawal syndrome, problems such as Blakemore’s SSRI experiences have been documented, yet SSRI popularity continues to soar worldwide. For example, in the UK in 1992, 500,000 prescriptions were written for SSRIs. A decade later, the figure was 15 million. Likewise, in 1993 in New Zealand approximately 50,000 scripts were written for SSRI’s and by 2003, this mushroomed to almost 450,000.
Investigate asked GlaxoSmithKline how many packs of Aropax – a drug subsidised by the government – they sold in 2003, in New Zealand. Neil Jarvis, the sales manager responded: “Unfortunately the information you have requested cannot be provided. As you appreciate, sales data is confidential and is not readily available from a majority of pharma [sic] companies.” While GlaxoSmithKline regarded this as classified information, it is in the public arena that in 2003, doctors wrote 203,636 prescriptions for Aropax and that the Ministry of Health paid $19,269,716 for it. Pacific Pharmaceuticals, which supplies the Prozac equivalent, Fluox, a drug which is also subsidised by the government, told Investigate that the company sold 193,000 packs of capsules in New Zealand in 2003. Each pack contains 90 capsules.
In light of the show-stopping number of these drugs being sold each year, it is little wonder the Radio Pacific talkback session on SSRIs became deluged with callers a few weeks ago. When the BBC broadcast a show on SSRIs in the UK in late-2002, it also received a huge response from viewers – 1,374 e-mails and over 5,000 telephone calls. A published medical paper presents an analysis of these e-mails and finds that 17% rated paroxetine as “very positive to worth taking”, 48% rated paroxetine negatively, from not worth taking to severely disabling, and 35% were uncertain, giving no or insufficient evidence of having taken the drug.
Investigate went to a pharmacy to take photos of SSRI packs. The pharmacist, who does not wish to be named, regarded the number of people he knew who were taking it as “sad.” Although not being handed out like sweets by the medical profession, because of restrictions, he knew of people taking it because their friends were.
According to Dr Jay M. Pomerantz of Harvard University, since antidepressants have severe adverse side effects, most patients stop taking them before they might have any positive effect. Investigate found evidence that SSRIs aren’t being swallowed according to doctors’ orders. A near full pack of Aropax was found in a skip outside someone’s apartment. A friend handed me 35 Fluox tablets to take photos of, saying he didn’t ask his doctor for anything for depression, but was prescribed them. He took the medication for 15 days, before deciding it more prudent to address the cause of his unhappiness. In addition, there were packs of Prozac 20 located at a relation’s residence, abandoned in a kitchen drawer.
It is not difficult to fathom that the medical profession is eager to promote these drugs’ use.
The British government is now cracking down on reckless over-prescribing of SSRI drugs, which are depleting public health care budgets. New draft guidelines from the UK’s National Institute of Clinical Excellence (NICE), the British government agency that decides which drugs should be available through the National Health Service, state that antidepressants are not recommended for the initial treatment of mild depression in adults “because the risk–benefit ratio is poor.” NICE will publish guidelines for the treatment of depression in children in 2005.
Investigate asked Pharmac’s Medical Director, Dr Peter Moodie, if there were any plans to curtail the burgeoning sum being spent on SSRIs here. Moodie advised that a cheaper source of paroxetine was in the process of being sourced, as the patent for the drug had expired. However, he said it would take some time before a cheaper, generic equivalent to Aropax could be obtained, as its producer is fighting tooth and nail to keep its market share. He said it would help reduce costs to taxpayers if doctors were more prepared to look at the basic causes of depression, before reaching for a prescription pad.
Do SSRI’s work? They inhibit serotonin reuptake. They inhibit the action of receptors on cells near neurons, thus making the serotonin stay in the synapse longer and consequently activate the next neuron for a longer duration than would otherwise occur. However, it is merely hypothesised that depression and anxiety are related to abnormal levels of serotonin and altering its effectiveness with an SSRI may alleviate the symptoms.
Depression, which, as mentioned, falls into 307 categories in the DSM IV, is also believed to be associated with abnormal levels of other neurotransmitters, such as norepinephrine and dopamine, which can, some experts say, be regulated by other drugs. A problem with prescribing the ‘right’ drug to treat depression, is that there is no scientific way to prove that a person has a low or high level of a specific neurotransmitter – so finding the appropriate drug for someone is deemed to be on a trial basis.
Ironically, while doctors continue to give SSRIs the red carpet treatment, numerous studies have demonstrated that drugs are not required to treat depression. Placebos or dummy tablets, such as disguised sugar pills, can do just as good a job. Indeed, numerous reputable studies have found that patients may respond to placebos, in much the same way they respond to antidepressants. One such study, a major government-funded study in the US, found that neither Zoloft, nor St. John’s wort are any more effective than a placebo in patients with major depression. (See: JAMA, Vol. 287, No. 14, April 10, 2002).
Similarly, research by a team led by University of Connecticut psychologist, Irving Kirsch, did an analysis of clinical trial data submitted to the US FDA for the 6 most widely prescribed antidepressants in the US, that were approved between 1987 and 1999. Namely fluoxetine, paroxetine, sertraline, venlafaxine, nefazodone and citalopram.
The group found that 80% of the response to medication was duplicated in placebo control groups. Thus, those who received only the pretend pills felt better to about the same degree than those who took the SSRI drug did. The average difference in improvement was only 2 points on the Hamilton Depression Scale, which produces scores up to 50 or 62 points, depending on the version used. The difference was so small that it was obvious the people got well because they expected to.
Kirsch et al concluded that if the drug affect is as small as it appears when drug-placebo differences are estimated, then there is little justification for the clinical use of SSRIs. (Source: ‘The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration,’ published by American Psychological Association, 2002).
These studies raise very serious questions about whether SSRIs should be the treatment of choice for depression -questions that seem to be falling on deaf ears.
A placebo poses no risk and costs next to nothing, and research findings have demonstrated repeatedly that they work as well as antidepressant medication. So why do psychiatrists prescribe expensive SSRI drugs despite the serious risks and side effects? The risks associated with highly prescribed antidepressants can be severe: in some patients they produce suicidal thoughts.
Investigate asked Pharmac if the many studies that have shown a placebo is as effective in treating depression as an SSRI, have influenced any decisions Pharmac has made? Dr Moodie said: “No. We are aware of those papers. How quickly doctors prescribe SSRIs is up to good medical practice. If Pharmac perceives that there is something obviously going awry in the prescribing of various drugs, then there is a responsibility to promote responsible use.”
Aropax is repeatedly advertised in full-page ads in the New Ethicals Catalogue, a handbook used by GPs to select medications, as ‘more than just an antidepressant.’ Indeed, SSRI antidepressants are advertised and prescribed as safe for a myriad of complaints that have nothing to do with severe, clinical depression for which they were approved.
Dr. Pomerantz notes that “SSRIs in particular, have replaced benzodiazepines as the drugs of choice when the physician is at a loss for what to do to get a patient out of the office.” And: “If what we are seeing is a pattern of widespread antidepressant prescribing for a multitude of subsyndromal, amorphous, patient complaints, it suggests that antidepressants have become the modern-day sugar pill, or placebo. It is quite likely that antidepressants have largely replaced benzodiazepines in this regard.” (Source: Antidepressants Used as Placebos: Is That Good Practice? in Drug Benefit Trends 15 (8), 2003).
If antidepressants are being prescribed as a placebo, New Zealand taxpayers are paying the pharmaceutical companies a ridiculously high price. It is a joke and a telling one. We would be misguided blaming the drug industry for this state of affairs. Effective corporate monsters like GSK and Eli Lilly exist to make a profit for shareholders, not to help provide premium health care for people. Providing good health care is the job of the medical profession.
When Coming Off Antidepressants:
Work closely with your doctor.
Taper the medication. Experts agree that the best way to avoid withdrawal side effects is to wean off the medication. By reducing the dosage in small increments, the brain can adjust to the change in chemical balance and slowly adapt to living without the drug. For some people, experts say, this process may take up to a year.
Get psychotherapy or counselling. While drugs can often mask problems, therapy can help address underlying causes. Psychotherapy is far superior to medication in the long term.
Exercise. Even if you don’t feel like it. Force yourself to. There’s strong evidence exercise plays a major role in lifting one’s mood and reducing stress.
Eat a healthy diet.
Laugh. Laughter is one of the best medicines.