In the interests of gaining a more balanced take on SSRI's after reading "Listening to Prozac" I've just started reading "Prozac Backlash"

http://www.amazon.com/Prozac-Backlas.../dp/0684860015

Joseph Glenmullen (psychiatrist) discusses evidence (and case reports) that Prozac (and other SSRI's) can cause side effects including permanent neurological damage and withdrawal syndromes. While he is a little unfair to Kramer in not seeing that he raises important ethical issues for (possible) future developments in pharmaceuticals he does offer a decent discussion of the evidence that is available for the dangers of SSRI's.

In particular, I was taken with the section entitled 'The 10-20-30 Year Pattern'.

'Unfortunately, the dangerous side effects emerging with Prozac, Zoloft, Paxil, and other serotonin boosters are right on schedule, appearing like clockwork in a 10-20-30 year pattern characteristic of popular psychiatric drugs. The first potent antidepressants of the modern era were cocaine elixirs, introduced in the late 1800's. At the turn of the century cocaine elixirs were the most popular prescription medications, prescribed for everything from depression to shyness, just as the Prozac group are today. Freud wrote three famous "cocaine papers" advocating the drug's use. Since cocaine elixirs, we have had numerous amphetamines, bromides, barbiturates, narcotics, and tranquilizers, all hailed as miracle cures until their dangerous side effects emerged.

Reviewing the history of these drugs, one finds a strikingly similar pattern: Initially, the drugs are aggressively marketed with claims they are revolutionary breakthroughs, remarkable scientific advances over predeccessors. Early on, a few doctors champion their cause, becoming celebrities along with the drugs. Often, a handful of celebrities step forward to endorse the miracle cure. As they gain momentum, use of the drugs spreads beyond the confines of psychiatry and they are prescribed by general practitioners for everyday maladies. Indeed, the burgeoning list of "conditions" they are used to treat, including everyday life, is often one of the first clues that one is looking at a general mood brightener that provides a quick fix.

In the typical life span of the drugs, the earliest signs of problems appear about ten years after introduction. Pharmaceutical companies and proponents deny the problems, adopting the strategy of defending the medication to the last. As we lack serious long-term monitoring of side effects and rely almost entirely on spontaneous, volountary reporting by doctors, it is typically only at the twenty-year mark that enough data has accrued for the problems to be undeniable and for a significant number of physicians to be sounding the alarm. Still another ten years or so elapse before professional organizations and regulatory agencies actively take steps to curtail overprescribing. Thus, the cycle from miracle to disaster typically takes thirty years or more. By then, even the most popular drugs are no longer covered by their patent and even their manufacturers have an incentive to abandon medications that have become passe and disreputable. Typically their energies are then focused on the next breakthrough: newly patented, more profitable agents, which can be promoted as "safer" because their hazards are not yet known". pp.12-13

I found his description of the see-saw relationship between the serotonin and dopamine systems to be interesting. The trouble I had with Breggin's 'Toxic Psychiatry' was that I didn't understand how he was able to claim that SSRI's were toxic similarly to anti-psychotics (which he made a fairly good case for). The idea here is that even if the drug has a 'selective action' (as SSRI's do in selectively boosting serotonin) the brain attempts to compensate / return to homeostasis by decreasing dopamine (resulting in 'extra-pyrimal' parkinson's symptoms (tardive dyskinesias and dementias) that one sees in response to anti-p's).

Desire to take SSRI's: Removed.

Another thing that I found interesting was this, however:

'Each year the FDA reviews about 25 new drugs for approval. For this task, the agency has a professional staff of 1,500 doctors, scientists, toxicologists, and statisticians. But to monitor the safety of the more than 3,000 drugs already on the market and being prescribed to millions, the agency has a professional staff of just 5 doctors and one epidemiologist. Because long-term monitoring is virtually nonexistent, in a 1993 article in the Journal of the American Medical Association, the then commissioner of the FDA, David Kessler, revealed that "only about 1% of serious events [side effects] are reported to the FDA. The FDA itself is not responsible for this state of affairs, says Thomas Moore, a leading authority on drug side effects at the George Washington Medical Centre. The FDA's budget is set by Congress.

So... Looks like the government is regulating the pharmaceutical industry (or allowing it to be dys-regulated) after all...

[Rapunzel]

That's interesting too. I haven't had time to obtain and read this book, but meds scare me a little. I tend to avoid them. The FDA scares me a lot.

[ECHOES]

Thank you alex. This is something I"m interested in and I hadn't heard of this book. I did read Listening to Prozac years ago before starting on it myself.

[eskielover]

Prozac had some different side effects with me......I lost my appitite with it & ended up loosing 20 + lbs taking me down into the low 80's before anyone bother to care about what it was doing (& at the time, I didn't care either since I was very suicidal at the time anyway). I also think while on it, my suicidal feelings were higher than with other drugs also.

I was tired of being a guinea pig in the first place & having no drug help me feel better....the way I had felt before the situation that caused the anxiety & depression.

Information was coming out about prozac at the time (mid 1990's), so glad even more has come out about the drug.....It is sad that is takes so long to find out these things, but until they are actually used, there is no way to tell what they can do over the long term.

Debbie

Hey. The appetite loss is a common side effect with prozac. That is one of the socially desirable effects of the stuff - except, of course, when peoples weight dangerously deteriorates. And... No matter how thin you are (ideally by social standards) those tics and other Parkensonian symptoms just aren't socially appreciated...

Maybe in another 10 years... The extra pyramidal syndromes will be taken seriously enough such that prescribing practices will be restricted. That is about when the patient runs out... And that will be about when... The next 'wonder drug' will be about due to appear on the scene.

With another 10-15-20 years before that one gets restricted too...

And the drug companies get richer...

It is hard to know what to make of this... There are a lot of references to studies... But (sigh) I'm not much of a 'reading studied' kind of person.

We had this reading group the other week on the genetic basis of schizophrenia. There have been lots of studies on that one and popular headlines proclaim 'scientists discover the genetic basis of schizophrenia'. Except of course, they haven't.

Schizophrenia isn't to do with a single gene. If it was to do with a single gene then that would be obvious from looking at the pattern of affected people within a family. If you look at a family tree and mark the affected people then you should notice patterns that tell you that the condition is single gene dominant or single gene recessive etc etc. Basically... Those patterns aren't there, so we know that schizophrenia isn't to do with a single gene.

Geneticists use the term 'gene' in an ambiguous way to refer to two distinct things. Sometimes a 'gene' means a certain location on the chromosome (basically a string of t's and a's, and g's, and c's that are physically lined up next to one another and that code for - make - a single protein). We know schizophrenia isn't like that because of the family tree data.

The other use of the term 'gene' refers to different locations on the chromosome but the unity is in their united effort in coding for the protein. Sometimes physical genes (that are seperate in space) can act as a functional unit (in that they all contribte to making the protein). Researchers think that schizophrenia will be due to some complicated combination of physically located genes. So the million dollar question is 'which physically located genes?'

There have been many many many many many different candidates. The problem is lack of replicability. One study suggests one physical gene might be important... Another study finds that that physical gene isn't statistically significant in schizophrenia at all. Another study suggests another physical gene might be important... Another study finds that the physical gene isn't statistically significant in schizophrenia at all. And so it goes on...

People have similar 'success' in looking at the genetic basis of 'voting behaviour' or 'religion' or whatever. We read a lit review type paper which looked at all the candidates that had been shown to be implicated in MORE THAN ONE STUDY (because there are lots of papers that are lacking additional support). Still... Two studies isn't a very stringent criteria.

The statistical significance is low...

I wonder... What do we need to show us that schizophrenia ISN'T a genetic disorder? Do we just keep looking and eventually conclude that failure to find a robust genetic basis shows us that there isn't one? That isn't a very good inference... What would we need to find to rule that out? How do we prove that that is NOT the case? Even if we find social causal mechanisms... They aren't mutually exclusive...

I do think people are on a wild goose chase with this...

And with neurology too... I'm concerned about the reasoning processes used in psychiatry... I think... There is reason for concern. I never wanted to be such a sceptic... But I don't see how in good conscious I'm expected not to be...

I mean... The reasoning goes a little like this:

- we gave drug x to people with disorder y and those people seemed to improve.
- drug x boosts serotonin
therefore - disorder y is caused by too little serotonin

Part of the trouble is that we don't know enough about what else the drug does. Just because SSRI'S selectively TARGET serotonin doesn't mean that the brain doesn't adjust other things as a DIRECT CONSEQUENCE of the drug. I mean... I have feet injuries. Those feet injuries result in me adjusting my posture to compensate. Now I get a sore back too. Similarly... one could raise serotonin and the result could be in the brain adjusting dopamine to compensate.

We don't know that the change in serotonin vs the change in dopamine is responsible for the benefits people find in anti-d's. And... Major tranquilisers (old generation anti-p's) USED to be prescribed (with reasonably good effect) for people with depression. They only stopped that because... The extra-pyramidal side effects.

That was meant to be the link between SSRI's and the extra-pyramidal side-effects.

Thats frigging horrifying... The extra-pyramidal side-effects. I really can't believe that the drug companies aren't required to more robustly test the effects of medications in animals. Neurodegeneration...

I've had a bit of a discussion about this before... But... Who should be responsible for setting the standards on what the drug companies have to do to gain FDA approval? I really... Well... The way things work currently... I really find it beyond belief.

Thalydomide... How have things changed to prevent that? Basically... They haven't... Have they?

And... Maybe... The psychotic / mood disorder distinction breaks down (YAY!) if you don't see that the evidence really does support that psychosis is to do with dopamine and mood is to do with serotonin...

[Rapunzel]

I like the serotonin as police theory. Serotonin is involved in so many things. I think that what it really does is regulates other neurotransmitters, which in turn regulate other substances, processes, feelings, and indirectly actions. But the whole process can operate from the reverse too. Actions can affect feelings and change the substances and proportions and activity in the brain. Exposure to environmental conditions is important too.

It seems to be established that light exposure regulates serotonin, and serotonin regulates melatonin and the sleep/wake cycle. Light and dark can be used effectively to treat depression, mania, and sleep or circadian rhythm disorders, as long as you control the light exposure in the right ways. Mood is connected somehow to serotonin, and to this cycle.

We can also establish that dopamine is connected somehow with mood and perception, maybe in a different way. Too much dopamine is associated with schizophrenia, and too little with Parkinson's disease. We also know that medications that control schizophrenia symptoms can cause Parkinson's-like symptoms. I wonder if Parkinson's meds could trigger schizophrenia too?

There is so much that we don't know. I find the connections between one thing and another to be very interesting.

i'm not sure how much L-dopa etc (treatments for Parkinson's) are related to amphetamines. if people go on an amphetamine binge then they start to develop symptoms that are indistinguishable from paranoid psychosis..

[Doh2007]

Wow alexandra_k, you have such interesting information to share. I'm so glad you're sharing.

I don't really have an opinion, just that we sure are complicated. My father and his mother and my sister and I have all experienced psychosis. It's a chicken-egg thing. Did the illness cause the crummy parenting, or vice versa.

Fascinating stuff.

Hey. I think we sure are complicated!

One thing I'm interested in is what entitles us to say that some people are disordered whereas other people aren't.

The standard justification is that some people have a 'dysfunction' and when they are harmed by their 'dysfunction' then they have a disorder.

So... psychosis is supposed to be caused by some kind of dysfunction and we consider that people are harmed by their psychosis (or that other people are harmed by their psychosis).

If you look to other cultures... Then people with psychosis might be revered as holy people, prophets, seers etc. The person doesn't seem to be harmed in those societies (whether or not they have a dysfunction).

Yet mental health professions often advocate us medicating these poor people who don't even realise they are dysfunctional! BUT THEY AREN'T HARMED. Looks like... Colonisation of values to me...

What entitles us to say that people with psychosis are dysfunctional? We might find that people with psychosis have inner state x that people without psychosis lack. That doesn't tell us that x is a dysfunction, however. We might find that conservative voters have inner state x that people who aren't conservative voters lack. Similarly, that doesn't tell us that x is a dysfunction.

Studies have shown that people with a disposition to psychosis tend to be more creative than people without a disposition to psychosis. Sometimes people say 'well yes, but psychosis is surely malfunctional because people clearly aren't creative when they are in the grip of psychosis!' Except that... Notably... People can be. Painters and musicians and poets etc seem to be MOST creative while they are in the grip of psychosis (manic psychosis, notably). Maybe... It is about learning to focus the psychosis...

;-)