AROPAX NATION: A HARD HABIT TO BREAK, APR 2004
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.