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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 36 to 60 of 143. Go back in thread:
Posted by Larry Hoover on May 9, 2006, at 17:21:21
In reply to Statistical question on SSRIs - Psychobabble says » linkadge, posted by Squiggles on May 9, 2006, at 16:57:46
> > "What was found was that there was a "significant change in slope" (a reduction) of the suicide rate, following the introduction of SSRI meds. A change in slope can only be caused by a change in the independant variables"
> >
>
> Sorry, is this a quote from the Healy paper?What you've got there is a me quoting the Sweden population study authors.
> And when you describe a slope ( i guess that
> is on a statistical graph ) as possible only
> by independent variables - what would those
> be? Are they typical of this clinical study
> alone?
>
> SquigglesA plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
Lar
Posted by linkadge on May 9, 2006, at 17:23:36
In reply to Statistical question on SSRIs - Psychobabble says » linkadge, posted by Squiggles on May 9, 2006, at 17:14:07
I certainly think it is a possibility. Akathesia, for instance may result from overactivation of certain serotonin receptors and a subsequent drop in dopamine release.
If an SSRI has a shorter half life, then the agonism would happen for a shorter length of time during the day. As serotonin levels drop, it might give opportunity for a bit of a dopamine rebound.
A longer half-life drug like fluoxetine, however, might cause more akathesia, since the serotonin agonism is longer lasting allowing less time for dopamine rebound.
Kind of like how seroquel tends to cause fewer movement problems based on the fact that it binds more loosely certain dopamine receptors.
Thats just a theory though.
Linkadge
Posted by Squiggles on May 9, 2006, at 17:24:57
In reply to Re: Statistical question on SSRIs - Psychobabble says, posted by linkadge on May 9, 2006, at 17:11:01
..............
> The reasons people kill themselves is based on too many variables to account for. To make an obersvation like that is just an observation. Weren't suicide rates lowest in this century during WWII, before SSRIs? Its all just a trend.
>
> If rates continued to drop consisntanty (which they won't) then we might be on to something.
>
> If anything, the drop is related to an increased awareness of the disorder, ie message boards like this.
>
> This board stopped me from off-ing myself from an acute suicidal reaction to zoloft.
>
>
> Linkadge
>
>Call me old-fashioned but I have always been
drawn to the "explanation" style of a case
be it suicide or an illness. Statistics will
tell you about something that the whole class
has in common, but scientific investigation will
point to the real cause(s). And in this case
as in others, a person commits suicide within
a particular multi-factoral context in which
he or she finds himself. If he has taken
a drug which after being stuporously depressed and lacking the vitality to pick up a gun, and that
drug suddenly energizes him, he may find a way out
of his misery at last. Another person, who has not been quite so depressed, may take the same
enervating drug and smash his car into a wall or take his anger out on something or someone.You get the picture - the drug CAN be the
necessary but not the final cause in his actions.
But the drug plays a very important role.
Squiggles
Posted by Larry Hoover on May 9, 2006, at 17:25:53
In reply to Re: Statistical question on SSRIs - Psychobabble says » Squiggles, posted by Larry Hoover on May 9, 2006, at 17:21:21
> A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
>
> The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
>
> LarI feel confused about this, so I'd ask for a moment to think about whether what I said is what I meant to say. It has been so long since I did this analysis as a matter of routine, I don't feel confident.
Lar
Posted by linkadge on May 9, 2006, at 17:31:30
In reply to Re: Statistical question on SSRIs - Psychobabble says » Squiggles, posted by Larry Hoover on May 9, 2006, at 17:21:21
The second chart on this page is usefull.
http://www.fathersforlife.org/US_suicide_rates_80-96.htm#ussuiral
I don't know if it is accurate, but if so, I'm not sure about the significance.
Linkadge
Posted by linkadge on May 9, 2006, at 17:38:39
In reply to Statistical question on SSRIs - L dL Statistics » linkadge, posted by Squiggles on May 9, 2006, at 17:24:57
I see what you are saying. Thats were a lot of people rest the case, that is that the drug provided the final umph for a person to commit suicide.
I would propose one step further, that in certain persons, an SSRI can initiate suicidal ideation where none previously existed.
The will to live (in my oppinion) is controlled by a delicate ballance between serotonin and dopamine neurotransmission. I believe that when you pharmachologically squelch dopamine you can run into big problems. Parkinsons patients have observable abnormailities in dopamine function. As a whole they tend to experience a fair share of depression. I don't think that parkinsons depression responds all that well to SSRIs. I think that sometimes, SSRI's can make both parkinsons depression, and parkinsons disorder significantly worse.
Linkadge
Posted by Larry Hoover on May 9, 2006, at 17:48:40
In reply to Re: Statistical question on SSRIs - Psychobabble says » Larry Hoover, posted by Larry Hoover on May 9, 2006, at 17:25:53
> > A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
> >
> > The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
> >
> > Lar
>
> I feel confused about this, so I'd ask for a moment to think about whether what I said is what I meant to say. It has been so long since I did this analysis as a matter of routine, I don't feel confident.
>
> LarSorry, I've hit the wall. Back at it, tomorrow.
Lar
Posted by Squiggles on May 9, 2006, at 17:51:23
In reply to Re: Statistical question on SSRIs - L dL Statistics » Squiggles, posted by linkadge on May 9, 2006, at 17:38:39
> The will to live (in my oppinion) is controlled by a delicate ballance between serotonin and dopamine neurotransmission. I believe that when you pharmachologically squelch dopamine you can run into big problems. Parkinsons patients have observable abnormailities in dopamine function............
off-topic question:
Do doctors give dopamine for depression?Squiggles
Posted by pseudoname on May 9, 2006, at 17:54:59
In reply to Statistical question on SSRIs - Psychobabble says » linkadge, posted by Squiggles on May 9, 2006, at 17:14:07
I'm glad Squiggles made that point about the AD giving oomph to pick up a gun or whatever.
The relationship between suicide and depression isn't linear. I've noticed that, over the last 4 months as I've been getting less depressed (mostly due to my med), I've also experienced increased anxiety and suicidality.
For myself, various projects and problems in my life (financial, legal, etc) have piled up over the years of depression. Although they were serious, I could ignore them while severely depressed because I didn't care and I was too depressed to fix them anyway. But as the drug removed depressive barriers, these problems suddenly became threatening and overwhelming in a wholly new, urgent way. I had my first panic attacks because I was getting less depressed.
Also, as I started getting better, I more often felt suicidal because I could now think things like, “Even though I'm not depressed, I can't handle all this. Clearly, my situation is hopeless. I have no choice but suicide.”
Plus, as people start getting better, family dynamics can change for the worse. As the patient gets more assertive with a partner or less dependent on a caregiver, the partner or caregiver may react badly and launch a new attack or withdraw support or start getting depressed.
With complex feedback systems like these, ironically the more *effective* an antidepressant initially is, the more likely it might be to result in suicidal action. I think that would be a higher risk in a situation where the patient is just getting the drug and isn't getting any other therapy or support.
Whereas if relief from depression comes from therapy, the client would have the ongoing support to turn to as the situation changes.
Posted by Squiggles on May 9, 2006, at 18:03:03
In reply to suicide and AD effect, posted by pseudoname on May 9, 2006, at 17:54:59
Interesting - it certainly points to
the advantage of being monitored while
on drugs. It's funny -- I was reading
Kraepelin again and in his chapter on
how to treat patients, he recommended
so much delicate care and attention with
the few drugs that they had - bromides and
opium, and such - and how if the person
seemed despondent to speak gently to him
and encourage him and direct his mind away
from dark thoughts. If he was suicidal
he was to be observed night and day until
the drug worked and to put him in a bath
to relax if agitated, and so on.I mean we are speaking of Victorian times.
Try doing that now and you can cash in your
retirement savings for a day of group
therapy.Squiggles
Posted by pseudoname on May 9, 2006, at 18:13:15
In reply to Re: suicide and AD effect » pseudoname, posted by Squiggles on May 9, 2006, at 18:03:03
> I was reading Kraepelin again and in his chapter on how to treat patients, he recommended so much delicate care and attention […]
That sounds so very humane. Focused, taking the patient seriously.
> you can cash in your retirement savings for a day of group therapy
The last time I was offered group therapy with a TRAINEE therapist, it was $110 per session. Times 8 people... oh my gosh!
Posted by linkadge on May 9, 2006, at 18:24:15
In reply to Statistical question on SSRIs - L dL Statistics » linkadge, posted by Squiggles on May 9, 2006, at 17:51:23
The way I see the problem with antidepressant drugs that work via dopamine, is not that they lack efficacy, but is that they often posess potential for abuse.
Dopamine agonists used in parkinsons disease have antidepressant properties.
I think that a company is afraid to make a drug that has abuse potential, even if it is a very effective antidepressant, because it could be pulled from the market if people are abusing it.
Linkadge
Posted by linkadge on May 9, 2006, at 18:47:47
In reply to suicide and AD effect, posted by pseudoname on May 9, 2006, at 17:54:59
Those are good points. I think that sometimes messing with the monoamines can give a disorted preception of imminancy, and urgancy. I found that SSRI's "pushed me". They pushed me into feeling that things were more imparitive than they were.
I felt that sometimes SSRI's made me feel as if "I should know the answer right away".
Agonism at the 5-ht2c receptor for instance can make people feel very miserable, and agitated. They can shut down prefronal dopamine activity (which gives you the calmness to be able to complete tasks), and they can give you a feeling of needing to "pull out" or "pull back" or to "get out".
I have been reading about some of the activities of the 5-ht2c receptor. When you sit and concentrate and learn something there is low activity at 5-ht2c. But then once you've learned it 5-ht2c activation helps you to "do it without thinking about it" ie declaritive memory. But if you activate 5-ht2c when you're not supposed to you may feel compelled to know the answer before you have had time to think it though and really learn it.
Its the same thing with how the 5-ht2c receptor controlls eating and orgasm. 5-ht2c agonists can make you feel satiated or feel full without ever having eaten.
5-ht2a agonists like LSD, can really mess with your sence of time. SSRI's will indirectly activate 5-ht2a. That too can create anxiety.
The antiobsessive qualities of the SSRI's can often work at the expense of the ability to sit and calmly concentrate on one task. I found on SSRI's I started multitasking a million things at once, and I coudn't keep my mind on one task.
I guess what I am trying to say is that SSRI's can *really* put a spin on how your brain has learned to deal with its problems. For some, this may be leading up to an antidepressant effect, but for others it may just create more caos.
These are just some of my theories.
Linkadge
Posted by linkadge on May 9, 2006, at 18:52:21
In reply to Re: suicide and AD effect » pseudoname, posted by Squiggles on May 9, 2006, at 18:03:03
Thats true. We have lost the human component of this disease.
That is another reason I implicate dopamine. From www.hypercum.net, dopamine can "create positive feelings towards self and others".
I found SSRI's often made me hate myself, and hate other people. I also found myself iscolating more, and not wanting to work with other people. That was a bad spin on my recovery, since in school I need to work with other people in order to survive.
Linkadge
Posted by Squiggles on May 9, 2006, at 19:04:33
In reply to Re: suicide and AD effect, posted by linkadge on May 9, 2006, at 18:52:21
> That is another reason I implicate dopamine. From www.hypercum.net, dopamine can "create positive feelings towards self and others".
>
That's St. John's Wort or Mole.Squiggles
Posted by linkadge on May 9, 2006, at 19:43:55
In reply to Re: suicide and AD effect » linkadge, posted by Squiggles on May 9, 2006, at 19:04:33
Mole ? You'll need to explain.
Linkadge
Posted by Squiggles on May 9, 2006, at 20:15:42
In reply to Re: suicide and AD effect, posted by linkadge on May 9, 2006, at 19:43:55
> Mole ? You'll need to explain.
>
> LinkadgeWort, Mole - it's a pun; bipolars are
known to pun a lot. :-)Squiggles
Posted by bassman on May 9, 2006, at 20:33:11
In reply to Re: suicide and AD effect, posted by Squiggles on May 9, 2006, at 20:15:42
Gulp, I hope that's not really true...
Posted by Larry Hoover on May 10, 2006, at 8:31:37
In reply to Re: Statistical question on SSRIs - Psychobabble says » Squiggles, posted by Larry Hoover on May 9, 2006, at 17:21:21
> > > "What was found was that there was a "significant change in slope" (a reduction) of the suicide rate, following the introduction of SSRI meds. A change in slope can only be caused by a change in the independant variables"
> > >
> >
> > Sorry, is this a quote from the Healy paper?
>
> What you've got there is a me quoting the Sweden population study authors.
>
> > And when you describe a slope ( i guess that
> > is on a statistical graph ) as possible only
> > by independent variables - what would those
> > be? Are they typical of this clinical study
> > alone?
> >
> > Squiggles
>
> A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
>
> The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
>
> LarSorry for the interuptions, Squiggles. I had a medical test done Saturday and it's still messing me up.
My quick summary of the methodology for gaining the measure of the slope, i.e. the rate, was incomplete. I skipped one step. I do it all the time in my brain, but I forgot how to describe it.
The revised version:
A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative of the best fit line, the slope, is equal to the rate. In this case, plots from two periods eighteen years apart yielded different best fit lines (i.e. different rates). Statistical testing showed that the difference between the two rates was significant. The rate during a period of high sales of antidepressants (including SSRIs) was significantly lower than a period when antidepressants were prescribed less often.
Then I went into blather, which is why my brain called a halt to the proceedings. I have a weird brain.
I know very well that there are alternate explanations for the significant inverse correlation (i.e. I'm not trying to say SSRIs brought it down). The fact that it is inverse, and significantly so, places an upper bound on the effect size for your hypothetical SSRI-mediated suicide induction process.
As it happens, on reloading the pages I was working from last night, I found another more recent Scandinavian report.
Therein, it is stated that, "In all four countries decreases in suicide rates appeared to precede the widespread use of SSRIs."
As my intent here has been to show that SSRI-induction hypothesis has an upper bound, this new evidence is also consistent with my earlier conclusions.
If I had evidence to support your hypothesis, Squiggles, I'd show you. I haven't found any, yet.
Lar
Posted by Squiggles on May 10, 2006, at 9:05:07
In reply to Re: Statistical question on SSRIs - Psychobabble says » Larry Hoover, posted by Larry Hoover on May 10, 2006, at 8:31:37
First, sorry about your medical problem. Best
of luck..........
> > > And when you describe a slope ( i guess that
> > > is on a statistical graph ) as possible only
> > > by independent variables - what would those
> > > be? Are they typical of this clinical study
> > > alone?
> > >
> > > Squiggles
> >
> > A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
> >OK - i will try to follow this; i hope you will
be patient; i really am innumerate:The rate of suicide = the number of suicides over
"consecutive years" from all causes?
> > The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
> >
> > Lar
>A stable rate before the introduction of Prozac
in the market, could be a low rate of suicide or
a high rate of suicide.
> .......
> The revised version:
>
> A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative of the best fit line, the slope, is equal to the rate. In this case, plots from two periods eighteen years apart yielded different best fit lines (i.e. different rates). Statistical testing showed that the difference between the two rates was significant. [The rate during a period of high sales of antidepressants (including SSRIs) was significantly lower than a period when antidepressants were prescribed less often.]
>
> Then I went into blather, which is why my brain called a halt to the proceedings. I have a weird brain.
>Well, it seems to be functioning better than mine.
> I know very well that there are alternate explanations for the significant inverse correlation (i.e. I'm not trying to say SSRIs brought it down). The fact that it is inverse, and significantly so, places an upper bound on the effect size for your hypothetical SSRI-mediated suicide induction process.
>
> As it happens, on reloading the pages I was working from last night, I found another more recent Scandinavian report.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16582062
>
> Therein, it is stated that, "In all four countries decreases in suicide rates appeared to precede the widespread use...Is a suicide rate decrease preceding widespread
use of ADs (incl. SSRIs) equivalent to an
increase in suicide rate in the increase rate
of SSRI use? It's a statistical inference
that does not seem to take into account the
counterexample studies, as well as other possible factors in the country, age, social events, and
personal circumstances. Wow, is this the way
science is done?...........
> As my intent here has been to show that SSRI-induction hypothesis has an upper bound, this new evidence is also consistent with my earlier conclusions.
>
> If I had evidence to support your hypothesis, Squiggles, I'd show you. I haven't found any, yet.
>
> Lar
>Thank you. I am really sorry that i am
past my level of incompetence now. Maybe
others can understand the meaning of these
stastical studies better than I.Good luck recovering from your medical test.
Squiggles
Posted by pseudoname on May 10, 2006, at 9:55:55
In reply to Re: suicide and AD effect » pseudoname, posted by linkadge on May 9, 2006, at 18:47:47
> These are just some of my theories.
*I* like them, FWIW. I like the overall picture that messing with neurotransmitters leads to diverse effects. I'm finding the imagery helpful too. I woke up today freaked about the supposed urgency of some things. Then I thought, “Maybe recent neurochemical changes just favor a perception of urgency… It's a chemical perception…” Not necessarily phony, but also not so overwhelming.
Posted by Larry Hoover on May 10, 2006, at 11:28:31
In reply to Re: Statistical question on SSRIs - Psychobabble s » Larry Hoover, posted by Squiggles on May 10, 2006, at 9:05:07
> First, sorry about your medical problem. Best
> of luck.Thank you.
> > > A plot of "all cause suicide deaths" against "total population" for consecutive time periods would yield a graph where the first derivative, the slope, is equal to the rate.
> > >
>
> OK - i will try to follow this; i hope you will
> be patient; i really am innumerate:
>
> The rate of suicide = the number of suicides over
> "consecutive years" from all causes?Divided by the population, which yields numbers such as 22 suicides per 100,000 population, per year.
> > > The rate was stable over two periods of time, but different, one from the other. One time period of stable rate preceded the stable rate seen around the time of the SSRIs. Inferences were drawn.
> > >
> > > Lar
> >
>
> A stable rate before the introduction of Prozac
> in the market, could be a low rate of suicide or
> a high rate of suicide.Exactly so. And we might call that stable rate the baseline rate.
> > Then I went into blather, which is why my brain called a halt to the proceedings. I have a weird brain.
> >
> Well, it seems to be functioning better than mine.We trained in different things.
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16582062
> >
> > Therein, it is stated that, "In all four countries decreases in suicide rates appeared to precede the widespread use...
>
> Is a suicide rate decrease preceding widespread
> use of ADs (incl. SSRIs) equivalent to an
> increase in suicide rate in the increase rate
> of SSRI use?It seems to suggest that other social factors also changed. However, SSRI use did not seem to change that existing stable regime, even during the period of astronomical increase in prescription rates for the SSRI drugs as a class. In other words, we must look elsewhere than SSRIs for the change in baseline suicide rate over the comparative periods.
> It's a statistical inference
> that does not seem to take into account the
> counterexample studies, as well as other possible factors in the country, age, social events, and
> personal circumstances. Wow, is this the way
> science is done?This sort of science is nothing more than the equivalent of going through your old files, and only then noticing that your phone bill changed dramatically, or whatever. These specific studies examined records which already existed, and that were collected independently of each other (suicide records vs. drug sale records). Then, restrospectively, somebody compared the data in the files.
> ...........
> > As my intent here has been to show that SSRI-induction hypothesis has an upper bound, this new evidence is also consistent with my earlier conclusions.
> >
> > If I had evidence to support your hypothesis, Squiggles, I'd show you. I haven't found any, yet.
> >
> > Lar
> >
>
> Thank you. I am really sorry that i am
> past my level of incompetence now. Maybe
> others can understand the meaning of these
> stastical studies better than I.It's always worth the effort, to try.
> Good luck recovering from your medical test.
>
> SquigglesThanks.
Lar
Posted by Larry Hoover on May 10, 2006, at 11:39:18
In reply to Re: suicide and AD effect » pseudoname, posted by linkadge on May 9, 2006, at 18:47:47
> I guess what I am trying to say is that SSRI's can *really* put a spin on how your brain has learned to deal with its problems. For some, this may be leading up to an antidepressant effect, but for others it may just create more caos.
>
> These are just some of my theories.
>
> LinkadgeI'm very impressed by your ability to lay out these details of receptor function so cleanly.
I have no doubt that SSRIs are powerful meds. Behaviourally, on SSRIs, I did things that are not part of my normal. I thought thoughts that were not part of my normal. I entered a psychotic mania, under their influence. I am not naive.
What was missing, though, was proper medical management. There was a society-wide subliminal decision to simply think of SSRIs as benign medication. Even the doctors got hoodwinked. I remember seeing Prozac on the cover of Time magazine. Nobody was talking about sexual dysfunction, or any of that. No, these pills were different.
I think we, collectively, have begun to abolish the misrepresentation of these meds. In the spirit of getting it right, though, I also want to ensure that we don't substitute another erroneous belief system for the existing miracle drug 'chemical imbalance' propaganda. Let's make sure that what we say is founded on data. Science, the knowing, is in the data.
Lar
Posted by Squiggles on May 10, 2006, at 12:46:59
In reply to Re: suicide and AD effect » linkadge, posted by Larry Hoover on May 10, 2006, at 11:39:18
Perhaps if Dr. Healy had said that the
statistics show that caution in the form
of very close monitoring in the first two
weeks or so of taking Prozac, is necessary,
to avoid the high probability of akathisia-
related suicide, the U of T would not have
reacted so negatively. After all, there would
be no harm in keeping a professor who was
queasy about these new drugs. Or did they
perceive there was?As for as I am concerned I don't find such scandals very good for the public. We have to cope with miserable side effects and experiment after experiment.
I find the psychiatric drug life, far wilder
and unpredictable, and dangerous, than smoking
a joint at a party when i was young. But kids are
watched like a hawk by parents for taking
"drugz". The difference of course is that most
kids then smoked a joint or dropped acid once in a year or every few months, then they graduated and went on to conforming lives. Prescription drugs are for life. The "counterfeit" drug crisis i
recently went through almost killed me, but
if it had, it would have been a clean, legal
death with the stats to back up the safety of the drug from some medical journal. A suicide in
a state of agitated mania is not a universal
cause for suicide after all. But I did have to
fight the urge with all my might and play with
the lithium caps so as to rise above the urge -- something that left my brain burning for weeks.So, I may have to reconsider just how much harm would have been done if Dr. Healy was kept at the U of T with his radical notions, because even if there was a dent in the sales of Prozac on account of his polemics, another SSRI could easily have taken its place. I did consider the possibility that his actions were self-centered and that he may have contributed to mass suffering for people taking Prozac. I am not 100% sure there was no harm done there, but I think it may not have been an irreversible harm. So, I suppose they could have reacted differently if they wanted to. It must have been embarrassing and stressful for all concerned.
Thank God I take Lithium :-)
Squiggles
Posted by Squiggles on May 10, 2006, at 15:16:31
In reply to Re: Statistical question on SSRIs - tolerance » Larry Hoover, posted by Squiggles on May 10, 2006, at 12:46:59
on Healy:
http://absolutad.com/absolut_gallery/singles/pictures/?id=1822&_s=singles
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