Its
content isn't exactly news, or hot off the presses, but its one of only a few
works that openly explores what medication creators simply have most avoided.
In the subtitle, the word 'addiction' is in inverted commas. As one finds out
in the book, this term is the one the lay population understands. When one
takes a substance that imposes suffering when it is withdrawn, a layperson
assumes that this implies they are addicted to it. Conversely, when one is
addicted, one cannot easily withdraw, as one is dependent on the constant
supply of the drug in order to avoid symptoms of withdrawal, so the three terms
are related as far as the lay public, to whom this book is addressed, are
concerned.
Pharmaceutical
information and conventional wisdom has held for many years that one cannot
become addicted to a medication for depression. If it were possible, this would
imply that the reward systems of the brain had responded dramatically and fast
to the drug's presence and then demanded a continued supply for more of the
drug. That is not the case with antidepressants, but from the lay point of
view, if I take a pill, and have to, rather than need to take it again and
again or otherwise suffer, then I am addicted, hence the emphasis around the
term "addiction".
For
the most part, an addictive drug targets the dopamine-based reward systems of
the brain, and when applied to the brain, changes take place in the brain that
lead to demand for the substance, sometimes in increasing doses. This is not
strictly true of the antidepressants, but Glenmullen explains that there are
changes in the brain that mean adaptation to supply or non-supply situations,
hence the gamut of medical and psychiatric symptoms which apply in both
scenarios.
Historically,
this confusion has arisen around the application of the germ theory, medical
model in psychiatry. If I have a disease, I take medication as an ameliorative
or restorative treatment, and when the disease entity has retreated, I can
stop. If depression is a disease, the cure is anti-depressants in the same way
that antihistamines are the cure for allergenic histamine responses to foreign
protein entering the body. Of course, this is not so, and mood disorders are
conditions, as in Major Mood Disorder, rather than major mood illness or
sickness, and testing for such conditions is rather more metaphysical and
esoteric.
We
also know that although antidepressants are found to have an effect on human
chemistry almost immediately, as with antipsychotic and other drugs and
medications, the benefit takes some time, perhaps two weeks or more, to be felt
by the recipient. Conjecture as to how this may occur includes the role of neurogenesis
via brain derived neurotrophic agencies, rather then the activities of the
neurotransmitters or their targets necessarily.
Indeed
there is emerging evidence to show that knocking out their neuroprotective and neurogenic
capacity in this regard, leaving the affinities for serotonin etc intact,
renders such medications fairly useless as antidepressants.
The
history of antidepressants includes the accidentally discovered and dirty drugs
(with regard to their affinities) that were the first to be stumbled upon (tricyclics
and MAOI's); the deliberately clean drugs (SSRI's in the Prozac- Paxil genre,
reversible MAOI's and so on) and the deliberately dirty (targeting more than
one neurotransmitter) drugs that we have today such as Effexor.
For
most of us exposed to patients in the sixties, ECT and the anticholinergic tricyclics
were all we knew, and patients had dry mouths, shaky hands, poor vision, constipation,
urinary retention, sedation, and so on, as we built their drugs up slowly until
remission of some symptoms of depression and anxiety. It was difficult though,
and so about 80% of patients just didn't take enough for long enough to get
really well, although there was no doubt these drugs worked well, perhaps
better than the ones that followed. However, they could kill, some were cardiotoxic,
and some, like the MAOI's, were downright dangerous in the face of dietary
mistakes and so on.
We
were all then introduced to the Prozac revolution, being sold on the issue that
this was a clean drug, free of any real capacity to kill, unlike the previous
overdose potential of the accidentally dirty. More convincingly, we were told
that one size fitted all, 20mg to start, and after that anyone would benefit.
My
colleagues very soon were giving valium with the 20 mg to avoid akathisia and a
host of nasty overarousal features. We learned that fluoxetine was powerfully
stimulating, to the extent that for two weeks the patient might feel worse than
before treatment started, leaving them desperate to avoid the stimulation side
effects. The rapid introductions of a liquid medication helped us a lot, as we
could initially titrate the dose and reduce the weight of symptoms, instead of
dissolving the drug in orange juice and varying doses that way. With Prozac,
when we stopped the side effects were long lasting. When paroxetine (Paxil, Aropax
etc) was introduced, we were told it was much quicker to metabolise, and so the
side effects lasted barely 24 hours. We didn't cotton on to the fact that this
might mean that withdrawal side effects would launch more rapidly and severely.
What
this failed to reinforce was that if you missed a day with paroxetine, it felt
far worse than if you skipped a fluoxetine, and this wasn't rapid onset of
depression again, this was, well, withdrawal, something which our paradigm said
should not happen. Sedation, sexual side effects, loss of sleep and appetite,
restlessness and agitation, aggression related to overstimulation, 'zaps' in
the head like electricity, cycling moods, a host of side effects attended the
drug, changing the dose, and going off it. Nothing was to be seen in the
literature, just something we all realised. And it wasn't in everyone, and
neither was improvement necessarily at 20mg, or even 80mg. Safer, yes, better,
no, clear of problems and issues, absolutely not. Stephen Stahl was quick to
point out that these SSRI's were not five similar drugs in one class, but thanks
to varying affinities, quite substantially different from one another. My
colleagues Les Koopowitz and Mike Berk wrote of the withdrawal problems in paroxetine
in 1995 in Human Pharmacology after observing this for years (it came to
their attention in 1992-1993, and Tom Gualtieri had noted problems with Prozac
in 1991). They noted that the drugs with the shortest elimination half-lives
were the worst, as this made withdrawal symptom onset much more sudden and
likely. This was 10 years before this book was published.
By
2000, Glenmullen had produced his book Prozac Backlash (reviewed in Metapsychology
5: 26). Many others, like Peter Breggin for instance, found themselves on Quackwatch
websites, but authors such as Glenmullen, a clinical instructor in psychiatry
at Harvard Medical School, were harder to challenge. Glenmullen won the 2001
Annual Achievement Award from the American Academy for the Advancement of
Medicine for his book.
The
BBC documentary about paroxetine was sensationalist stuff (2002), but even
Thomas Gualtierri in 1991 had warned of the paradoxical effects one might
encounter with Prozac, let alone the faster metabolised Paxil, as noted by Koopowitz
and Berk, often cited by Glenmullen.
And
so the book enters the fray with the FDA and others, driven by a need to
buttress drug company and federal agency poverty of information on what might
occur in some, sometimes most, of those patients who try to get off their
antidepressants.
At
first a warning: this book teaches by repetition, based, I think, on his worry,
sometimes expressed, that people will dive in to specific chapters without
reading others, such as first going to the children's section, rather than
reading what came prior to this. Case histories and tick-box forms with rating
scales are the books finest features, painstakingly describing a thorough and
commonsense approach to assisting patients escape from the trap of medication.
Overall he is trying to reach the consumers themselves, and hence his tendency
to repeat and restate his case in a serial fashion.
The
first and sharpest lesson is that symptoms that mimic depression but which
occur in the hours, minutes and perhaps days that follow a reduction or change
in dosing. This must be considered withdrawal, not the re-presenting of the
original illness or an exacerbation: that can take weeks and even months to
emerge. Moreover, such withdrawal can occur even when the patient has only been
on the medication for a month or so. The faster the elimination half-life, the
more likely is the withdrawal to rapidly occur after altering the dose, and
more severely in some cases, with a confusion of medical symptoms interspersed
with psychiatric. Effexor may be one of the worst, with a case described of
severe withdrawal after just a single missed dose. Some patients are known to
have opened capsules of slow release antidepressants, counting out 280
granules, and taking off just two at a time, in order to avoid withdrawal. Sertraline,
escitalopram, fluoxetene, these may be less violent in terms of potential for
withdrawal effects.
Given
that children metabolize faster than adults, the chances of withdrawal appear
to effectively double in this patient group.
Glenmullen
thus embarks on a teaching exercise for professionals and patients alike that
is a solid How-To book on taking oneself or others off of the offending drug.
Overall, his tone is cautionary, but effective, warning the world at large that
there is a science to this, and patient and doctor alike have to be alert and
aware, or lives can be dominated by unnecessary symptoms, with undetermined
causes if the appropriate stance is not taken. In order to do this, he repeats
and repeats, restates and reworks, and each citation given is repeated often in
most chapters, as he comes back to the same issues, again and again. However,
this is not boring, just perhaps a little tedious, but he is serious about this
information and wants it conveyed in each and every chapter nuance.
At
about US$25 it is pretty much recommended as absolutely necessary for every GP
I know, and for many psychiatrists at resident or registrar level, as well as
every psychologist and helping profession member on the planet: its just too
important a set of data to ignore.
This
doesn't mean everyone will suffer withdrawal. It does however makes the point
that those who do are as diverse as those who don't, and so each package has to
be tapered according. This results in a method similar to that now being
revealed by the NIHM CATIE study into novel antipsychotic medication, which is
finding similarly that we are far from being predictably equal in terms of
response to medication. Individual treatment plans have to consider individual
withdrawal scenarios, using the many forms and tables he puts forward here.
Reading
between the lines, it is clear that Glenmullen spends a lot of time with his
patients, and that each client is in receipt of an individually tailored plan
for both treatment and termination.
In
his afterword, he notes that this book should never have had to be written.
Most drugs were released with comments that withdrawal was in the order of
.01%, not the over 60% which has been found subsequently. So bad is this for
drug companies that they have tried to reframe this phenomenon as "antidepressant
discontinuation syndrome" which reformulation Glenmullen attributes to
Lilly Pharmaceuticals. Glenmullen focuses on what he calls deceptive processes
and semantic gamesmanship, and elaborates on what these have been like within
the Paxil and Prozac stables. The longsuffering FDA also comes under scrutiny,
and as we all now know, it has been found sorely lacking in credibility and
neutrality. It is well that he writes with anger only at the end of the book,
as if this was in the beginning, one would wonder how objective he was being,
given the sorry state of affairs he elaborates on at the end. To his credit,
he notes that he has avoided the murky politics of why doctors and patients do
not know more about this subject until the end of the book. He makes some
suggestions as to how the situation can be addressed.
Reading
this book, and its more saddening end section, the snake oil salesman of the
past come to mind. We all work on fairly intimate terms with pharmaceutical
companies and their representatives, and some of us benefit financially from
honoraria. I do notice however that many companies that I work with are much
more cautious in their sponsorship and marketing, keen to avoid the slur that
they are influence peddling and lobbying their products into use. Large scale
studies such as the antipsychotic CATIE that look at antidepressants, their
efficacy and outcomes on a large scale may clear the scientific air as to what
these drugs really accomplish.
The
difficulty for all of us that work with what we cannot see, or measure directly
will continue to hamper our efforts to provide accurate information on
medication and its efficacy and utility. Beating placebo effects, namely
rising in a statistical way beyond the drug and examiner interactions with
human clients is always a challenge. Glenmullen however is making the point
that the prior ignorance or downright avoidance of the symptoms of withdrawal
when medication is changed or discontinued was and is closely related to the
vested interests of pharmaceutical companies and the doctors and researchers
that make their living off of them. Stereotypical statements about the
impossibility of dependence had a long half-life of their own, and have taken
years to be challenged. Books like this however do largely stand out on their
own even though there is peer-reviewed literature to support them: Glenmullen's
is an unpopular position take even though he seldom advocates for an end to
such medication attempts, let's say as in the partisan scientology approach to
life.
He
does however make a stronger stand when children are involved, as in his
previous book, and directs parents and doctors to take a closer look at safer
alternatives.
Overall,
he is advocating for an honest and commonsense approach to antidepressants and
their priests, and the highest form of science, human observation with an open
mind, but with purpose.
© 2006 Roy Sugarman
Roy Sugarman
PhD, Acting Director of Psychology Royal Rehabilitation Centre Sydney; Conjoint
Senior Lecturer in Psychiatry University of New South Wales, Australia