![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 20 to 44 of 143. Go back in thread:
Posted by bassman on May 9, 2006, at 9:02:49
In reply to Re: Statistical question on SSRIs - Reboxetine » Squiggles, posted by SLS on May 9, 2006, at 8:55:04
Upjohn became Upjohn/Pharmacia and is now Pfizer (who laid a whole bunch of people off). So call Pfizer.
Posted by SLS on May 9, 2006, at 9:17:00
In reply to Re: Statistical question on SSRIs - Reboxetine, posted by bassman on May 9, 2006, at 9:02:49
> Upjohn became Upjohn/Pharmacia and is now Pfizer (who laid a whole bunch of people off). So call Pfizer.
I apologize for the misinformation.
I can't believe how large this company has become. Where's Teddy Roosevelt when you really need him?
- Scott
Posted by Squiggles on May 9, 2006, at 9:21:37
In reply to Re: Statistical question on SSRIs - Reboxetine, posted by SLS on May 9, 2006, at 9:17:00
I think it's very promiscuous behaviour;
i don't understand the Teddy Roosevelt
reference.Squiggles
Posted by bassman on May 9, 2006, at 9:31:45
In reply to Re: Statistical question on SSRIs - Reboxetine, posted by SLS on May 9, 2006, at 9:17:00
My theory is that Pfizer, GSK, BMS, etc. will become just one huge pharmaceutical company, so no one will every have to say, "who makes drug A?" or "you work for a pharmaceutical company, which one?". Marx would have been soooo happy. :>}
Posted by SLS on May 9, 2006, at 9:41:21
In reply to Statistical question on SSRIs - Psychobabble says, posted by Squiggles on May 9, 2006, at 9:21:37
> I think it's very promiscuous behaviour;
> i don't understand the Teddy Roosevelt
> reference.
>
> SquigglesT.R. was a "trust-buster" and began to administer a policy of preventing and dismantling monopolies.
- Scott
Posted by Squiggles on May 9, 2006, at 9:50:25
In reply to Re: Statistical question on SSRIs - Reboxetine, posted by bassman on May 9, 2006, at 9:31:45
Politics and drugs are a lethal combination.
Infact, politics alone can be dangerous, when
taken on an empty brain.Squiggles
Posted by Larry Hoover on May 9, 2006, at 13:56:01
In reply to Statistical question on SSRIs, posted by Squiggles on May 6, 2006, at 6:54:51
> Would anyone here know the statistical
> rates of AD-caused suicides, comparing
> different classes of drugs; or where I
> could find studies in such assertions?
> I am searching for evidence regarding
> the proposed unique ability of SSRIs to
> cause suicide, in exclusion of other
> causes and other classes of antidepressants.
>
> Thanks
>
> SquigglesI don't know of any such evidence. Clinical trials are not of much use, as the variables are controlled in such a way as to try to eliminate such an effect, if it existed.
What we need are studies of whole populations. Naturalistic or observational or ecological studies. There are very few studies which even try to answer that question. There was one issue of BMJ (I think) that was dedicated to articles attempting to answer that question, just a few months ago. As I recall, there was no such signal found. Healy, and a bunch of other "names", they all took a look, and found nothing to support that hypothesis. {with very specific exceptions, not germane to this review}
One of the limitations of studying populations is that you can't determine which independent variables are truly responsible for your supposedly dependent measurements. You must assume that you know what you're doing, I suppose.
If we refer to epidemiological findings, we may yet have the answer to your question. In the following study, the entire population of a country (Sweden) was being studied. In that study population, we presumably include all manner of people. Those at high risk for suicide, and those with low risk. People being given SSRIs for depression, but also those being given SSRIs who have comorbid conditions (generally excluded from clinical trials), those being given the drugs "off-label". But also, we include untreated depressed people not in contact with medical support, and so on. We include the lost souls, too. There are no restrictions on the study population, other than that they are all Swedes.
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. An independent variable was added, changed, or removed. In this case, the changed variable was (assumed to be) the introduction of SSRI meds. It is problematic to assign the nomenclature of experimental design to ecological data, so it may be more accurate to refer to the introduction of SSRIs as being a predictor variable, or a factor, rather than a true independent variable.
In real life, not in the artificial environment of a clinical trial, suicides decreased significantly when SSRIs became available in Sweden. It remains a possibility that some other independent variable or factor also changed at the same time as SSRIs were introduced, and that it is a coincidental finding to see the suicide rate change like this. Even with such a coincidence, though, we can still confidently say that SSRIs did not increase the rate of suicide in Sweden. As sales (and presumably consumption) increased, the suicide rate did not.
Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10(6):525-30.
Antidepressant medication and suicide in Sweden.
Carlsten A, Waern M, Ekedahl A, Ranstam J.
Department of Social Medicine, University of Goteborg, Sweden.
anders.carlsten@telia.comOBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.
You can never prove the absence of something. You can't prove what didn't happen. However, we can show that there was not a population-wide increase in completed suicides that can be attributed to SSRI medication. We see no such signal in a broad population. One that is completely and thoroughly documented by its government. For whatever reason, these people write everything down. That provides us with an historical record of a population as it undergoes changes. And when we look at that record, we find no evidence for your hypothesized effect.
One possible explanation for that failure, though, is that the observed suicides are actually all SSRI-induced suicides. That would be very difficult to demonstrate unambiguously. That we have all these new and induced suicides, nested into the background rate, and yet the rate itself has not increased proportionately. Another possible limitation to this study is that Swedes might not be like other people.
I don't see the signal you seek evidence for. I've looked, and I can't find it.
That does not invalidate anecdote. That there are unambiguous cases of SSRI-induced suicide is not something that I am trying to refute. The evidence suggests that it is a fairly uncommon occurrence.
I'd tell you if I knew of the evidence you seek. I've looked, and I've looked hard. I can't find it anywhere.
Lar
Posted by Larry Hoover on May 9, 2006, at 13:58:51
In reply to Statistical question on SSRIs, posted by Squiggles on May 7, 2006, at 6:22:17
> I think that should be long half-life. The
> longer the half-life of the drug, the longer
> it takes to start effecting, upon first
> taking it, right?
>
> SquigglesA drug's effects are not influenced by its half-life. Half-life determines both dose and dosing schedule. A drug's effects are absolutely independent of half-life, unless it leads to poor medical management.
Lar
Posted by Squiggles on May 9, 2006, at 14:52:44
In reply to Re: Statistical question on SSRIs » Squiggles, posted by Larry Hoover on May 9, 2006, at 13:56:01
In Sweden, that is correct. And who knows
what variables change from large population
studies to small controlled groups;However, I have found some counterexamples,
looking at PubMed articles:---------
Antidepressant drug use in Italy since the introduction of SSRIs: national trends, regional differences and impact on suicide rates.Barbui C, Campomori A, D'Avanzo B, Negri E, Garattini S.
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. barbui@irfmn.mnegri.it
Little is known about the use of antidepressant drugs in Italy since the introduction of selective serotonin reuptake inhibitors (SSRIs). To fill this gap, we examined antidepressant drug sales data from 1988 to 1996 for the whole country, and for the years 1995 and 1996 on the regional level. National suicide trends from 1988 to 1994 were also examined to assess whether the increasing use of SSRI antidepressants was associated with changes in suicide rates. From 1988 to 1996 an increase of antidepressant sales of 53% was recorded. This increase reflected increasing use of SSRIs, which in 1996 accounted for more than 30% of total antidepressants sold. The analysis of regional differences demonstrated heterogeneity between north, center, and south. In the south prescriptions of antidepressants and use of SSRIs were lower than in the rest of the country. In the 7-year period over which SSRI use increased, male suicide rates increased from 9.8 to 10.2 per 100,000 inhabitants, and female suicide rates declined from 3.9 to 3.2 per 100,000. These data suggest that SSRIs gave a new impetus to antidepressant sales. However, possible public health benefits related to the shift from old to new antidepressants have yet to be demonstrated.
A large-population study where 50% of
takers reported suicidal thoughts or
inclinations:Top-selling drug linked to increased suicide risk - Britain ... [New Window]
ONE of Britain’s most widely prescribed antidepressants has been linked to a seven-fold increase in suicide attempts. An analysis of trials for Seroxat ...
http://www.timesonline.co.uk/article/0,,2-1741916,
00.html------
But as you have probably studied, there are
countless other articles with studies supporting
no increase in suicidality over years in SSRI
sales, and infact many which point to a *decrease*.But I think that Healy's point is that comparing
SSRI-takers who commit suicide to those taking other anti-depressants, does not imply that SSRIs
*do not* cause suicides. A comparative study
is something that *I* consider meaningful, not
a court of law. As far as Healy's case is concerned, that SSRIs cause suicide in a significant enough number of the population is enough to regulate the drug. If Reboxetine, for example, or another class of ADs cause a greater number of suicides than Prozac, then there is no
medically sound reason to sell SSRIs competitively to them. Healy is not trying to propose what is the best drug in this light. And so there is no good reason NOT to sell SSRIs, nor does he propose that.I am asking for a comparison because I am
suggesting that in comparing drugs that have
dangerous side effects, the one with the greatest
safety margine (according to the most comprehensive studies), should take precedence
over the inferior ones. Furthermore, the ones
that do cause harm, should be not only restricted
but taken off the market - heck we sure have
enough of them to make that ecomomically feasible.As for the half-life of a drug goes, I guess what
you are saying is that the pharmacology of it
is that any drug will have an immediate effect
regarless of its half-life?Squiggles
Posted by Larry Hoover on May 9, 2006, at 15:30:55
In reply to Statistical question on SSRIs - Psychobabble says » Larry Hoover, posted by Squiggles on May 9, 2006, at 14:52:44
> And so there is no good reason NOT to sell SSRIs, nor does he propose that.
As far as I'm concerned, that's all there is to it.
These drugs have had harder scrutiny than any substances ever synthesized by man. You are at far greater risk every time you swallow an aspirin, but you do that without fear for your life. Put it all into context, and you'll see that there is no evidence to support further restrictions on these meds. Proper medical management of depression does not stop at prescription. I think doctors get that, now. They need to properly monitor and inform their patients, as elements of a standard of care that is evolving as we go.
> I am asking for a comparison because I am
> suggesting that in comparing drugs that have
> dangerous side effects, the one with the greatest
> safety margine (according to the most comprehensive studies), should take precedence
> over the inferior ones. Furthermore, the ones
> that do cause harm, should be not only restricted
> but taken off the market - heck we sure have
> enough of them to make that ecomomically feasible.I have no argument, there.
> As for the half-life of a drug goes, I guess what
> you are saying is that the pharmacology of it
> is that any drug will have an immediate effect
> regarless of its half-life?
>
> SquigglesIt's a property of only certain chemicals, certain selected chemicals, that we classify them as drugs. We call them that because they have physiological influences on us. Some act quickly. Some slowly. That is a unique property of each drug. Solubility. Half-life. Other properties of any drug. They are independent properties. Like the colour of the pill. There is no link between these properties.
Half-life affects dose and dose schedule, as I said. But those are medical management decisions based on a single and specific drug property, called half-life.
Lar
Posted by Squiggles on May 9, 2006, at 15:50:58
In reply to Re: Statistical question on SSRIs - Psychobabble says » Squiggles, posted by Larry Hoover on May 9, 2006, at 15:30:55
> > And so there is no good reason NOT to sell SSRIs, nor does he propose that.
>
> As far as I'm concerned, that's all there is to it.
..............From a legal point of view, yes, but
from a social point of view, I do think
there is some fall-out here that has
affected people, perhaps adversely. If
I am right in this, I think Dr. Healy got
himself in a bad spot and chose a damaging
way to get out. Pity, only in Canada.> Half-life affects dose and dose schedule, as I said. But those are medical management decisions based on a single and specific drug property, called half-life.
>I think that in cases of addiction, half-life
is important for benzos, and also for washout
of the drug.Thanks for all your info.
Squiggles
Posted by linkadge on May 9, 2006, at 16:52:26
In reply to Re: Statistical question on SSRIs » Squiggles, posted by Larry Hoover on May 9, 2006, at 13:56:01
"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"
That is to assume that you are taking into account all variables. Correlation does not imply causation. In addition, the mild decrease in suicides after the introduction of SSRI's means nothing in my opinion. Suicide rates have been lower within the century, before SSRI's. Suicide can be trendy, and I think it will go back up sooner or later.
Linkadge
Posted by Squiggles on May 9, 2006, at 16:57:46
In reply to Re: Statistical question on SSRIs, posted by linkadge on May 9, 2006, at 16:52:26
> "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?
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
Posted by linkadge on May 9, 2006, at 17:00:23
In reply to Re: Statistical question on SSRIs - Psychobabble says » Squiggles, posted by Larry Hoover on May 9, 2006, at 15:30:55
Different halflives of drugs may affect the system differently.
Although paxil and prozac are both taken once a day, the short half life of paxil makes it likely that the user will experience a greater fluctuation in the activity of the serotonin transporter throughout the day. This may result in a more, or less desireable outcome. Ie, a paxil user may get more yin and yang with the system.
Linkadge
Posted by linkadge on May 9, 2006, at 17:11:01
In reply to Re: Statistical question on SSRIs - Psychobabble says, posted by linkadge on May 9, 2006, at 17:00:23
It was just from the post above.
http://www.dr-bob.org/babble/20060504/msgs/641794.html
I guess what I am saying is that it is nonsensicle to say that the very modest decrease in suicides recently is directly related to the increasing use of SSRI medications.
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
Posted by Squiggles on May 9, 2006, at 17:14:07
In reply to Re: Statistical question on SSRIs - Psychobabble says, posted by linkadge on May 9, 2006, at 17:00:23
> Different halflives of drugs may affect the system differently.
>
> Although paxil and prozac are both taken once a day, the short half life of paxil makes it likely that the user will experience a greater fluctuation in the activity of the serotonin transporter throughout the day. This may result in a more, or less desireable outcome. Ie, a paxil user may get more yin and yang with the system.
>
> Linkadge
I wonder if this difference may not have
contributed to the slight propensity for
agitated depression, contributing to the
desire for suicide in the case of one SSRI
versus another.Looking at the Merck, under Psychopharmacology,
i see that I am really out of my depth - there
are so many biological transformations of the
drug - absorption, elimination, plasma concentration plasma, renal clearance,
receptor binding (wonder if there is unbinding
in clonazepam :-))
etc. etc. - this is a difficult area for me. But
a psychopharmacologist would know. They would
know if one SSRI could have an ennervating or
lasting effect or not in the first few days, depending on half-life.Squiggles
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.
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