![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by stjames on January 4, 2001, at 16:09:31
Glad to see you back posting often on the list. i would like to get your
opinions on some issues. Here goes:AD's take 6-8 weeks for true antidepressant effects to be felt. This is supported
by the facts of 50 years of people taking AD's, most drug monographs on specific AD's,
and my personal experience. AD effect builds over the first 2 months and can take 6 months
to max out, during which time dosage adjustments help max AD effects.When one feels something sooner (first few weeks) this is not the AD effect but sideeffects,
which can have positive effects, such as greater energy (as with many SSRI's) and sedation (which
helps with sleep and anxiety)So Cam, what say you ?
James
Posted by Cam W. on January 4, 2001, at 17:13:06
In reply to Cam...what say you., posted by stjames on January 4, 2001, at 16:09:31
James, buddy - I thought you might drag me into this one ;^)
You know that I totally back the 8 week rule. Man, if I could maintain the "start-up" side effects of Wellbutrin past the first couple of weeks, I'd be a happy man.
Unfortunately, all antidepressants have "start-up" side effects. This is because of the neurochemical changes that have occurred due to the breakdown of the body's stress defence system (in particular, but not exclusively, the HPA axis).
A breakdown of the HPA axis (hypothalamus-pituitary-adrenal axis) results in the symptoms we call depression. At the same time, the body is producing less serotonin (let's stick to this one subtype of depression for simplicity sake) as evinced by low levels of serotonin's metabolite in the CSF (cerebral spinal fluid - spinal taps = ouch; but a fairly funny mockumentary; not as good as Hardcore Logo, though....but I digress). Other neurotransmitters try to compensate for this lack of serotonin by altering their concentrations and the number of their receptors (the number of serotonin receptors also change). These other neurotransmitters (eg dopamine, norepinephrine, nitric oxide, glutamate, etc.) do not totally compensate for the lack of serotonin and the symptoms that we associate with depression are the result of this lack of compensation.
Now, when one starts taking a serotonergic antidepressant (SSRI - remember, for simplicity sake, we are talking about a subtype of depression that responds to a serotonergic antidepressant) the amount of serotonin in the brain (between nerve cells) increases. This causes a chain reaction of events to occur. Beta-receptors are downregulated; postsynaptic serotonin receptors are changed; amounts of different neurotransmitters begin to return to normal, etc. These changes take time to occur, as the body readjusts to a more "normal" complement of serotonin. In the meantime, the serotonin added to the system acts like excess serotonin, due to the compensatory changes of the other neurotransmitter systems, as well as changes to the complement of various serotonin receptors. The start-up side effects are caused by serotonin being added to a compensated (depressed) system (kinda like throwing gasoline on a fire - throw enough on and the fire goes out - I know it's a bad analogy, but I hope you get the picture). As time passes (2 to 8 weeks), the neurotransmitter systems readjust to pre-depressive levels and hopefully the depression has resolved. Then you need to stay on the antidepressant for another 9 months to retrain the body to work at this "normal" level, again.
The variation in time periods for these events to occur depends on how fast one's body can make these changes to the neurotransmitter systems. Everyone's neurochemistry is different, some being much slower than others. Therefore, it is unwise to give up too soon on an antidepressant. Research has shown that, if after 8 weeks, there is no noticeable improvement, perhaps a different class of antidepressants should be tried (in our example, a trial of a noradrenergic antidepressant or a dual action antidepressant may be in order). If there is partial response to an antidepressant by 8 weeks, augementation should be considered before changing classes (eg lithium, raising the dose, lowering the dose, etc.).
Full effect of an antidepressant, depending on one's body chemistry can take a long time. I believe that everyone taking an antidepressant will have ongoing improvement past the point of what is considered response, or even remission. Where this improvement stops is, at this point unknown (except that it is probably very individual in every person).
I will us an analogy from the treatment of tardive dyskinesia (TD). Treating TD with Clozaril can take from 6 months to a year to notice any substantial differences. I have seen Clozaril work in this manner. I encouraged the guy to keep taking the Clozaril after 5 months, but in my heart of hearts, I never expected it to work (if I was him I probably would have quit taking the med). Surprizingly, after 8 months the guy was riding his bicycle around town and you wouldn't know he has TD. At five months of Clozaril therapy he could even keep a hat on his head. The movements would only stop when he was in a deep sleep. I now have a much better appreciation for the body's biochemistry. It is absolutely facinating. So simple, yet so extremely complex. Let's not even start talking about second messenger systems and gene transcription.
I'm sorry, what was your question, again?
Start-up side effects do have both an upside (sedation in an agitated person) and a downside (nausea), but as the neurotransmitter systems adjust, these symptoms usually dissipate; but sometimes not completely. There are also longterm side effects that do not seem to resolve with time (lets pick on Paxil - insidious weight gain at 4-5 months and sexual dysfunction). If the drug is working to control depression, it is a shame to have to stop it due to longterm side effects. Most depressions (ie one's that are not chronic) will resolve, so one may have to put up with side effects for a year; at which point the body has retrained the neurotransmitter system to work at a certain level.
Also, during that year psychotherapy (which I also think is essential in "curing" a depression) can actually work because one is able to understand what the therapy is trying to do. Depression affects attention and cognition. In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.
That's enough for now. Sorry, I'm getting tired of typing. I hope this helps James - Cam
Posted by JahL on January 4, 2001, at 19:12:56
In reply to Re: Cam...what say you. » stjames, posted by Cam W. on January 4, 2001, at 17:13:06
> In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.
But you would accept that a depression can be entirely organic in origin? It is in my case (ie. suicidal ideation since age 7 despite idyllic upbringing, strong family history)
I can honestly say that my experience with various therapists has been deleterious towards my health (not to mention my wallet)
I find the blind devotion to an environmental model of depression displayed by EVERY therapist I have come across somehow invalidates/denies my v real suffering, the implication always being that merely by talking about non-existent problems I can resolve a serious organic disorder.
I'm not on yr case or anything Cam (!see "anergia") but I'd be interested to see if you agree that there are cases like my own that can be 'fixed' by medication alone. As you can tell, I think psychotherapy is deeply over-rated.
Rgds,
Jah.
Posted by SLS on January 4, 2001, at 21:49:17
In reply to Re: Cam...what say you. » Cam W., posted by JahL on January 4, 2001, at 19:12:56
Balance.
Spectrum.
Heterogeneity.
Chargoggagoggmanchauggagoggchaubunagungamaugg.
- Scott
Posted by Cam W. on January 5, 2001, at 0:13:12
In reply to Re: Cam...what say you. » Cam W., posted by JahL on January 4, 2001, at 19:12:56
Cam - I'd be the first to agree that the "causes" of depression are on a spectrum from genetically-based to environmentally-based. Just because a depression is purely genetic in origin does not preclude the use of psychotherapeutic interventions.
Especially relevant would be cognitive/behavioral therapy, in order to be able to live within the parameters of the disorder (ie coping mechanisms). Depending on the person (most probably not yourself) social skills training can help those who have gone too long without psychopharmaceutical modalities. I do not hold much faith in interpersonal therapies for purely genetically-based depressions, though.
Medications are a must in your type of depression and will probably be needed for life. Medications are only a bandage, not a cure. I try to never rule out any sort of help when it comes to dealing with a chronic illness.
Sincerely - Cam
Posted by stjames on January 5, 2001, at 1:50:06
In reply to Re: Cam...what say you. » stjames, posted by Cam W. on January 4, 2001, at 17:13:06
> James, buddy - I thought you might drag me into this one ;^)
Well, I could spend a lot of time finding primary supporting docs
or I could just ask you ! What is not important is that I am right or wrong.
What is important is that information I post is correct, this issue weighs on
me from time to time. This is a good post, I would like to use it in the tips
section.> Now, when one starts taking a serotonergic antidepressant (SSRI - remember, for simplicity sake, we are talking about a subtype of depression that responds to a serotonergic antidepressant) the amount of serotonin in the brain (between nerve cells) increases. This causes a chain reaction of events to occur. Beta-receptors are downregulated; postsynaptic serotonin receptors are changed; amounts of different neurotransmitters begin to return to normal, etc. These changes take time to occur, as the body readjusts to a more "normal" complement of serotonin. In the meantime, the serotonin added to the system acts like excess serotonin, due to the compensatory changes of the other neurotransmitter systems, as well as changes to the complement of various serotonin receptors. The start-up side effects are caused by serotonin being added to a compensated (depressed) system (kinda like throwing gasoline on a fire - throw enough on and the fire goes out - I know it's a bad analogy, but I hope you get the picture). As time passes (2 to 8 weeks), the neurotransmitter systems readjust to pre-depressive levels and hopefully the depression has resolved. Then you need to stay on the antidepressant for another 9 months to retrain the body to work at this "normal" level, again.
James here.....
I have read that reuptake happens almost at once after starting an AD, if this alone improved mood AD's would work by the first week. It is common to think you just need
more serotonin but the process to the end result is far more complex than that, which accounts for the time lag in improved mood.
> Full effect of an antidepressant, depending on one's body chemistry can take a long time. I believe that everyone taking an antidepressant will have ongoing improvement past the point of what is considered response, or even remission. Where this improvement stops is, at this point unknown (except that it is probably very individual in every person).James here.....
Over 16 years I have found some times you need less or more. Sometimes you need something different. There is no way to know how much is enough, therefor how normal you can feel, so I keep upping the dose till I discover the correct amount. Several times I thought I was doing excellent only to find an improvement at a higher dose. There is no way to know the full possible effect and side effects unless you have been there. There is also danger in being less than well. I have been through several breakthru depressions in the last 10 years that are significant as I do not leave the house. Looking at my chart my doc saw a pattern of 300 mgs Effexor after a depression, then over years the dose moved to 150 mgs with a depression a year or so after. Perhaps we ( I say we because I was mostly the one who lowered the dose; but my doc supports this) were helping cause these depressions. may only concern about Effexor is that it is a powerful SSRI, esp. at 300 mgs, which does me no good. My mood responds to meds than effect the noradergeneric system. I am waiting for the next SNRI to be on the market.
> Also, during that year psychotherapy (which I also think is essential in "curing" a depression) can actually work because one is able to understand what the therapy is trying to do. Depression affects attention and cognition. In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.
>James here....
With me I did psychotherapy first and then meds. I wish I would have done them together.
With me there is no doubt there is an underlying medical condition that needs to be treated for my mood, attention and cognition to function correctly. Also I have no doubt that the psychotherapy made a big difference. I now have better tools to works with now that I am not depressed. I fully believe that in some people psychotherapy alone may be enough. We also know short term use of meds and therapy is more effective than either alone for those that don't have chronic issues. I think everyone should do 3-6 months of therapy. Therapists have a global view of behavior than no one can hope to have.
Posted by JohnL on January 5, 2001, at 3:43:05
In reply to Cam...what say you., posted by stjames on January 4, 2001, at 16:09:31
> Glad to see you back posting often on the list. i would like to get your
> opinions on some issues. Here goes:
>
> AD's take 6-8 weeks for true antidepressant effects to be felt. This is supported
> by the facts of 50 years of people taking AD's, most drug monographs on specific AD's,
> and my personal experience. AD effect builds over the first 2 months and can take 6 months
> to max out, during which time dosage adjustments help max AD effects.
>
> When one feels something sooner (first few weeks) this is not the AD effect but sideeffects,
> which can have positive effects, such as greater energy (as with many SSRI's) and sedation (which
> helps with sleep and anxiety)
>
> So Cam, what say you ?
>
> JamesHi James and Cam,
I totally agree that full effects of medications usually (not always) take at least 8 weeks and longer. In my own experience, I remember years ago Paxil worked better at 2 months than at 1 month, better at 3 months than 2, and even better at 4 months than 3. Even now with my favorites Amisulpride and Adrafinil, I find the benefits continue to accrue slowly over time.In contrast to popular believe though, I do support the notion that a drug can work very fast, like one day to two weeks. Not completely of course. But definitely enough to give a hint at the drug was a good choice. Side effects? Maybe 30%. Placebo effects? Maybe 30%. The real thing? 30%.
Actually it's more than just a notion. If one examines clinical trials with this concept in mind, there are hundreds of documented studies where some patients responded very quickly and maintained the good response longterm. It happens. Even here at this board one can find dozens, maybe hundreds, of examples showing fast response times that were maintained longterm. They weren't side effects or placebo. One has to pick and choose which data he/she wants to back up one's theory, but if all the data is looked at then it becomes obvious that this is not an either/or issue. It's both. That is, fast responses do occur. Slow responses do occur. Neither one is abnormal or more valid than another. As further evidence that fast responses can and do occur, many medication labels specify that though the patient may feel some benefits in a few days, the most benefits will occur in 3 to 4 weeks. I'm sure millions of dollars and tons of research went into those labels. They didn't just print that haphazardly.
I believe chain reactions occur, as Cam described. I think what makes the difference between a fast response or a slow response (or no response) is how fast the body can make those changes, or how close those changes are to the real problem. For example, if low serotonin is the true problem, an SSRI will work fast. Serotonin is increased immediately. If instead receptors need to be down-regulated, then then response will be a bit slower. To take it further, perhaps the receptors need to be down regulated in order to again affect something else further down the chain. That will take even longer. A drug that would have targeted whatever it was further down the chain would have worked much faster, bypassing all the non-necessary sidesteps along the way.
Regardless, I haven't seen any facts to completely support any of our theories. It's probably a situation where there are no rights and no wrongs. Every theory is probably partially correct, but no theory is totally correct.
The one thing that continually puzzles me though is why we tend to WANT it to be so that these drugs take so long. I don't want ANYone to suffer more than one day. I would think that we would instead be wanting to find out how to hasten response, rather than believe that long responses times are fact and that's the end of the story. I believe there's a lot more to the story. As advanced as psychiatry is, I believe we've only nipped at the edges. It is still very very early in its evolutionary discovery, with only a few decades of hardcore research behind it.
John
Posted by SLS on January 5, 2001, at 6:59:02
In reply to Re: Cam...what say you., posted by stjames on January 5, 2001, at 1:50:06
Dear James,
I agree.
(I put a lot of time and effort into composing this post).
- Scott
----------------------------------------------
> Over 16 years I have found some times you need less or more. Sometimes you need something different. There is no way to know how much is enough, therefor how normal you can feel, so I keep upping the dose till I discover the correct amount. Several times I thought I was doing excellent only to find an improvement at a higher dose. There is no way to know the full possible effect and side effects unless you have been there. There is also danger in being less than well. I have been through several breakthru depressions in the last 10 years that are significant as I do not leave the house. Looking at my chart my doc saw a pattern of 300 mgs Effexor after a depression, then over years the dose moved to 150 mgs with a depression a year or so after. Perhaps we ( I say we because I was mostly the one who lowered the dose; but my doc supports this) were helping cause these depressions. may only concern about Effexor is that it is a powerful SSRI, esp. at 300 mgs, which does me no good. My mood responds to meds than effect the noradergeneric system. I am waiting for the next SNRI to be on the market.
> Also, during that year psychotherapy (which I also think is essential in "curing" a depression) can actually work because one is able to understand what the therapy is trying to do. Depression affects attention and cognition. In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.> With me I did psychotherapy first and then meds. I wish I would have done them together.
> With me there is no doubt there is an underlying medical condition that needs to be treated for my mood, attention and cognition to function correctly. Also I have no doubt that the psychotherapy made a big difference. I now have better tools to works with now that I am not depressed. I fully believe that in some people psychotherapy alone may be enough. We also know short term use of meds and therapy is more effective than either alone for those that don't have chronic issues. I think everyone should do 3-6 months of therapy. Therapists have a global view of behavior than no one can hope to have.
Posted by Cam W. on January 5, 2001, at 7:07:51
In reply to Re: Cam...what say you., posted by stjames on January 5, 2001, at 1:50:06
> > James, buddy - I thought you might drag me into this one ;^)
>
> Well, I could spend a lot of time finding primary supporting docs
> or I could just ask you ! What is not important is that I am right or wrong.
> What is important is that information I post is correct, this issue weighs on
> me from time to time. This is a good post, I would like to use it in the tips
> section.
>
• James, feel free to use any of my posts in the tips section; except the one's where Dr.Bob is giving me sh**.
;^)
>
> > Now, when one starts taking a serotonergic antidepressant (SSRI - remember, for simplicity sake, we are talking about a subtype of depression that responds to a serotonergic antidepressant) the amount of serotonin in the brain (between nerve cells) increases. This causes a chain reaction of events to occur. Beta-receptors are downregulated; postsynaptic serotonin receptors are changed; amounts of different neurotransmitters begin to return to normal, etc. These changes take time to occur, as the body readjusts to a more "normal" complement of serotonin. In the meantime, the serotonin added to the system acts like excess serotonin, due to the compensatory changes of the other neurotransmitter systems, as well as changes to the complement of various serotonin receptors. The start-up side effects are caused by serotonin being added to a compensated (depressed) system (kinda like throwing gasoline on a fire - throw enough on and the fire goes out - I know it's a bad analogy, but I hope you get the picture). As time passes (2 to 8 weeks), the neurotransmitter systems readjust to pre-depressive levels and hopefully the depression has resolved. Then you need to stay on the antidepressant for another 9 months to retrain the body to work at this "normal" level, again.
>
> James here.....
>
> I have read that reuptake happens almost at once after starting an AD, if this alone improved mood AD's would work by the first week. It is common to think you just need
> more serotonin but the process to the end result is far more complex than that, which accounts for the time lag in improved mood.
>
• Then you start adding in the hormone axis and the 50 to 100 other neurotransmitters (neuomodulators, neuropeptides, transcription factors, secondary messengers, receptor subtypes, etc, etc). All of these systems (and some that have not be elucidated, yet) must be taken as a whole to see the entire picture. A reductionist view, whereby you look at one or two neurotransmitters &/or receptors (eg serotonin, norepinephrine reuptake) tells you very little of what is actually happening. This is what the drug companies peddle, though; I believe for simplicity sake (and lack of full scientific knowledge).
>
> > Full effect of an antidepressant, depending on one's body chemistry can take a long time. I believe that everyone taking an antidepressant will have ongoing improvement past the point of what is considered response, or even remission. Where this improvement stops is, at this point unknown (except that it is probably very individual in every person).
>
> James here.....
>
> Over 16 years I have found some times you need less or more. Sometimes you need something different. There is no way to know how much is enough, therefor how normal you can feel, so I keep upping the dose till I discover the correct amount. Several times I thought I was doing excellent only to find an improvement at a higher dose. There is no way to know the full possible effect and side effects unless you have been there. There is also danger in being less than well. I have been through several breakthru depressions in the last 10 years that are significant as I do not leave the house. Looking at my chart my doc saw a pattern of 300 mgs Effexor after a depression, then over years the dose moved to 150 mgs with a depression a year or so after. Perhaps we ( I say we because I was mostly the one who lowered the dose; but my doc supports this) were helping cause these depressions. may only concern about Effexor is that it is a powerful SSRI, esp. at 300 mgs, which does me no good. My mood responds to meds than effect the noradergeneric system. I am waiting for the next SNRI to be on the market.
>
• Maybe also wait for a drug that effectively regulates CRH (CRF) or some other component of the HPA axis. Or, better still, a drug that can directly modify aspects gene transmission. I believe that the next ten years are going to be exciting. I have all but given up on the serotonin/norepinephrine interactions as mechanisms for antidepressant action (but then again, I seem to have a short attention span). Currently, these drugs are the best we have and without them depressed people did worse, so I guess we should be lucky we have them.
>
> > Also, during that year psychotherapy (which I also think is essential in "curing" a depression) can actually work because one is able to understand what the therapy is trying to do. Depression affects attention and cognition. In most cases, antidepressants are need to "put the floor under one's feet" (as was so aptly said by someone on this board) so that the depressed person is able to work with the therapist on what caused the depression in the first place.
> >
>
> James here....
>
> With me I did psychotherapy first and then meds. I wish I would have done them together.
> With me there is no doubt there is an underlying medical condition that needs to be treated for my mood, attention and cognition to function correctly. Also I have no doubt that the psychotherapy made a big difference. I now have better tools to works with now that I am not depressed. I fully believe that in some people psychotherapy alone may be enough. We also know short term use of meds and therapy is more effective than either alone for those that don't have chronic issues. I think everyone should do 3-6 months of therapy. Therapists have a global view of behavior than no one can hope to have.
>
• Too true, my friend.•Keep me thinking guys; you're the best thing to happen to my career since a research prof took me under his wing 18 years ago (Dr.David F. Biggs, a therapeutics prof, taught me how to think). - Cam
Posted by shar on January 5, 2001, at 9:27:26
In reply to Re: Cam...what say you., posted by Cam W. on January 5, 2001, at 7:07:51
This is an interesting topic. The only AD I've ever felt true relief from is Zoloft. It was a very fast reaction to the AD, and then a pretty quick poop-out (about 4 months later). I've always wondered how that worked.
It would make sense that what I felt early on had something to do with the "domino effect" of neurochem. changes taking place. And, that when it came to the effect of the AD itself, not much help was really there.
It makes me wonder though if I gave it up to quickly. The example of the fellow with TD really caught my eye.
I am "dysthymic" (chronic depression with severe episodes whenever my body feels like it) so I wonder if there is some fundamental neurochem. thing going on all my life. Oh, to find the right dip switch in that computer in my head.
FWIW, I've also been doing therapy for many years. More therapy years than AD years. And, even though I don't expect a "cure" I still am able to learn and grow and develop new coping mechanisms, because, in fact, I am dealing with depression regardless of the cause.
This is a great series of posts. Thanks ya'll.
Shar
Posted by Cam W. on January 5, 2001, at 10:22:38
In reply to Re: Cam...what say you., posted by JohnL on January 5, 2001, at 3:43:05
John - There is merit in what you say about early responders. We agree that depression (as with most, if not all psychiatric disorders) is a very heterogeneous set of neuronal dysregulations. Depending on the biochemical breakdown, some instances a drug may work from the start. To me, this would indicate that compensatory mechanisms (eg. changes in concentrations of neurotransmitters and receptors) had not occurred, which theoretically, is entirely possible.
I still believe that in the vast majority of depressions, compensatory neurochemical alterations do occur, so Dr.Jensen's method of many rapidfire drug trials would not have universal applicability. Of course, this is just my opinion.
Some of the studies that I have been reading lately have been facinating. In one, these researchers have shown that although there may be a genetic mutation in a key protein, the protein that is formed is identical to that made by a non-mutated gene. What this means is that epigenetic factors may be at work. Could the protein's release factors be changed? Could specific transporter mechanisms be altered? The area or genetics in psychiatry is just starting to open up. What about "junk" DNA? Does the body really have DNA that does nothing? I sincerely doubt it.
Anyway, I better get back to work before someone catches me playing here. - Cam
Posted by SLS on January 5, 2001, at 12:15:17
In reply to Re: Cam...what say you. » JohnL, posted by Cam W. on January 5, 2001, at 10:22:38
> John - There is merit in what you say about early responders. We agree that depression (as with most, if not all psychiatric disorders) is a very heterogeneous set of neuronal dysregulations. Depending on the biochemical breakdown, some instances a drug may work from the start. To me, this would indicate that compensatory mechanisms (eg. changes in concentrations of neurotransmitters and receptors) had not occurred, which theoretically, is entirely possible.
>
> I still believe that in the vast majority of depressions, compensatory neurochemical alterations do occur, so Dr.Jensen's method of many rapidfire drug trials would not have universal applicability. Of course, this is just my opinion.
>
> Some of the studies that I have been reading lately have been facinating. In one, these researchers have shown that although there may be a genetic mutation in a key protein, the protein that is formed is identical to that made by a non-mutated gene. What this means is that epigenetic factors may be at work. Could the protein's release factors be changed? Could specific transporter mechanisms be altered? The area or genetics in psychiatry is just starting to open up. What about "junk" DNA? Does the body really have DNA that does nothing? I sincerely doubt it.
>
> Anyway, I better get back to work before someone catches me playing here. - Cam
Some of the old timers of psychopharmacology considered a slow, gradual response to antidepressants to indicate a better long-term prognosis.
- Scott
Posted by JohnL on January 6, 2001, at 5:07:50
In reply to Re: Cam...what say you., posted by SLS on January 5, 2001, at 12:15:17
> Some of the old timers of psychopharmacology considered a slow, gradual response to antidepressants to indicate a better long-term prognosis.
>
>
> - ScottBased primarily on the opinions of my most recent and favorite psychiatrist in Maine (an old timer, in his 70's, seen it all), the best prognosis he saw in his lifetime was a rather rapid response. Sure, sometimes those pooped out, or were confused with side effects or placebo effects. But more often than not, a good early response was predictive of a superior longterm response. Others here have verified their own doctors hold the same belief.
It almost sounds like some people actually want antidepressants to take a long time. They somehow like that idea and accept it to be a fact. I can never understand that. If we were talking about curing freckles or something, that would be a different story. But depression. Yikes. That's serious stuff. Every hour of every day is torture. Every moment is crucial. 10% of depression victims take their own lives. Eight weeks is totally unacceptable. 6 weeks is a stretch. Even 4 weeks is an eternity. I would think those who really care would be obsessed with finding methods and theories to speed response, rather than accepting supposed fact that there is not and never will be a better way. I don't know about you, but I want to see the depression sufferer get well fast. I will never cling to a theory that has flaws, holes, unexplainable mysteries, and slow response times. In other words, conventional psychiatry as I see it is way too primitive, way to narrow-sighted, biased, and in need of pioneering experts rather than go-with-the-flow experts.
John
Posted by SLS on January 6, 2001, at 9:55:13
In reply to Re: Cam...what say you., posted by JohnL on January 6, 2001, at 5:07:50
John,
You are going to have to take your debate directly to the people who have said such things. You may want to start with Nathan Klein.
I am not committed to their opinions and purported observations. However, this is consistent with *my* experience, as the only thing that worked for me that lasted more than a week took 2-3 months to produce a robust improvement. I felt well. n=1
As far as drugs often taking 4-8 weeks to work, well, things are the way they are. I am sorry. I'm sure so are the doctors who are treating desperately ill people. What is the motivation for so many neuroscientists and clinical investigators to invest so much money, time, and energy searching for better treatments? I don't think they feel any less disappointed in the current state of affairs as do you. I trust them. I gave up enough cerebrospinal fluid for medical science to pursue treatments that work better, faster, and with fewer side effects. If you are so indignant at the current state of psychiatry, help psychiatry out by taking experimental drugs and potent biological probes, being hooked up to EEGs every few days, giving pints of blood, collecting all urine over 24 hours periods, being forced to ingesting vomitous shakes devoid of specific amino-acids as your diet, going through several nights' total sleep deprivation, sleeping with EEG cups stuck to your head and face, subjecting yourself to P.E.T. scans while your head has been immobilized in a cast, having radioactive molecules coursing through your body, and consenting to multiple spinal taps. We could really use your help here.
By the way, you are right. I want my antidepressants to take 2 to 3 months to work. I wouldn't have it any other way!
>:-/
- Scott
Posted by SLS on January 6, 2001, at 13:19:00
In reply to Re: Cam...what say you., posted by JohnL on January 6, 2001, at 5:07:50
Spelling...
Nathan S. Kline
Dr. Kline was the mentor of several of the most notable personages in the field, including one of my previous physicians, Baron Shopsin.
Nathan S. Kline Institute
for Psychiatric Research"Nathan S. Kline, MD (1916-1982) was a man of diverse talents and interests whose mind was ever open to new ideas. He was best known for his pioneering work with psychopharmacologic drugs.
In 1952, with a few associates, he started a research unit at Rockland Psychiatric Center (then called Rockland State Hospital), which in 1975 became the Rockland Research Institute.
At that time, the national inpatient population in public hospitals was approaching the half-million mark, and traditional therapies appeared inadequate to treat the growing number of mentally ill patients in hospitals.
Taking an unorthodox approach, Kline and his colleagues at the institute investigated the properties of reserpine, a derivative of Rauwolfia serpentine. Rauwolfia was commonly used in India to treat many somatic complaints, and reserpine was being used in the US to treat high blood pressure. For two years, the researchers conducted trials with hospitalized patients and found that 70% of those suffering from schizophrenia obtained marked relief from symptoms.
Encouraged by his success with tranquilizers, Kline and his colleagues began to investigate the properties of antidepressants. lproniazid, used to treat tuberculosis, also appeared to elevate the patients' moods and Kline used it successfully with psychiatric patients who suffered from depression.
Within a year, patients in psychiatric centers throughout the states were receiving antidepressant medication. The use of drugs to treat two of the major categories of psychiatric illness led to the release of thousands who were able to rejoin society.
Kline's work has been acknowledged as a major factor in opening a new era in psychiatry. For his work with tranquilizers and antidepressants, he was twice awarded the prestigious Albert Lasker Medical Research Award.
During the 1960's the Rockland Research Institute grew to more than 300 staff. Dr. Kline's reputation drew biomedical researchers from around the world. Psychopharmacology was emphasized and numbers of new drugs were given clinical trials, as well as investigations made of the safety and utility of long-term drug use.
Many laboratory techniques were developed to determine safe, effective doses of frequently used medications.
Kline foresaw the potential of applying computer technology to psychiatry, believing that it could be used in large scale epidemiological studies and could streamline the administration of complex health facilities.
He oversaw the installation at Rockland in 1968 of a major computer center, funded by the Federal government, and guided the development of computerized medical systems, many of which led to improvements in the quality of patient care.
As an advisor to international health agencies such as the World Health Organization (WHO) and CARE-Medco, Kline was aware of the dearth of medical treatment for mental disorders in developing countries. He traveled widely and devoted much time to establishing and visiting mental health clinics and programs in other parts of the world.
Kline was founder and director of the International Committee Against Mental Illness. He was also a prolific writer, authoring nearly 500 scientific publications, magazine and newspaper articles for the general public, and a book, From Sad to Glad. He made frequent appearances as a guest on radio and television shows in his attempt to educate the public about mental illness and research.
Upon his untimely death in 1982, the Rockland Research Institute was renamed in memory of Dr. Kline.
Posted by stjames on January 6, 2001, at 16:15:56
In reply to Re: Cam...what say you., posted by JohnL on January 6, 2001, at 5:07:50
>
> It almost sounds like some people actually want antidepressants to take a long time. They somehow like that idea and accept it to be a fact. I can never understand that.James here....
Or some people, despite 50 + years of medical history and plenty of supporting information, chose to ignore the facts and go with "a wish".
james
Posted by Neal on January 6, 2001, at 20:06:42
In reply to Re: Cam...what say you., posted by Cam W. on January 5, 2001, at 7:07:51
Cam- re your comment: "• Then you start adding in the hormone axis and the 50 to 100 other neurotransmitters (neuromodulators, neuropeptides, transcription factors, secondary messengers, receptor subtypes, etc, etc). All of these systems (and some that have not be elucidated, yet) must be taken as a whole to see the entire picture. A reductionist view, whereby you look at one or two neurotransmitters &/or receptors (eg serotonin, norepinephrine reuptake) tells you very little of what is actually happening. This is what the drug companies peddle, though; I believe for simplicity sake (and lack of full scientific knowledge)."
I've read so many tantalizing comments in the popular press re depression; "on the brink of a breakthrough" here, "strong possibility", "may be the key to", etc., etc., but nothing ever seems to come of it. As you said, all we ever seem to get officially is the SSRI/TCA/MAO axis -year after year. I've read that some of the biotech companies have things in the works, but of course just blurbs in the press. Yes, the mechanisms are not simple, FDA requires years of testing, costing millions, but to be, say in one's 40's, watching the best part of your life go by while reading this stuff is frustrating, to say then least. Maybe the next big breakthrough will be, like so many in the past, be found by accident.
Posted by SLS on January 7, 2001, at 11:15:36
In reply to Re: Cam...what say you., posted by JohnL on January 6, 2001, at 5:07:50
Hi John.
I hope you read the previous post regarding Dr. Kline. It contained more than just a spelling correction.
I thought you might want to read an excerpt from a post I came across while I was searching the archives to compile a list.
--------------------------------------------------------
http://www.dr-bob.org/babble/20000411/msgs/30533.html
"I noticed immediate effects of Adrafinil in terms of great mood and energy. But that faded in two days.It returned GRADUALLY OVER A PERIOD OF TWO WEEKS IN A SLOW BUT STEADY IMPROVEMENT.
MY MOOD ACTUALLY IS NOT AS GOOD AS IT WAS THE FIRST DAY (THREE WEEKS LATER)."
--------------------------------------------------------
I believe you posted several times that the full antidepressant effect of adrafinil took 1-2 months to evolve.What say you?
- Scott
Posted by JohnL on January 7, 2001, at 17:47:20
In reply to Re: JohnL...what say you. » JohnL, posted by SLS on January 7, 2001, at 11:15:36
Hi all,
A couple months ago I sat down for a morning and searched www.mentalhealth.com for any and all abstracts that indicated early response to medication. I take a lot of abuse here for believing in quick response times. Some people turn their noses up to me and even become downright hostile that I would have the gall to question the almighty psychiatric myths. So I wanted to see if I could gather evidence from the very same psychiatric pool that everyone else was basing their own opinions.Obviously hardly any clinical trials focus on the aspect of quick response times. They instead are looking for response rates at 6 weeks or whatever. So finding what I was looking for seemed like it was going to be hard. But as it turned out, there was tons of evidence showing quick responses. Many of these clinical trials had patients who responded anywhere from 3 days to 2 weeks. They weren't placebo or side effects, because the responses were still sound at the end of the trial. I was planning on saving the evidence I found to defend myself here. But as it turned out, it was too overwhelming. It would have taken a couple weeks, not one morning, to gather the amounts of evidence out there. The problem is, it's buried in fine print. Unless one is actively seeking it, one might overlook it. One might think it to be inconsequencial, since they were looking for something else. But it's there. The same clinical trials going back to the 1970s that many here use to form their beliefs also show that there is always a certain percentage of patients that respond quickly. I would venture a guess that if all clinical trials took note of it, it would occur in every single trial.
My own response to Adrafinil and Amisulpride took a full two months to plateau. However, there were good early signs, even as early as day one, that these drugs might actually work. At two weeks there was no doubt they were working. Obviously not as much as I would like, but they were working. There was no doubt. So unlike many other meds that didn't seem to do anything at 2 weeks except make me numb or make me worse, I had good reason to hang in there. If there was no good sign by 2 weeks, I might have stopped. Not sure. At 4 weeks I definitely would have stopped.
I was reading the labels on all these medications I have leftover. Lots of antidepressants. Just about any you can think of. The labels all say about the same thing, in different words. What they say is that "it may take a week before you feel the effects of the medication...it may take 4 weeks before the medication takes full effect...blah blah blah". Or, "It may take several weeks...blah blah blah". Generally when most people think of 'several', they probably think of 3, 4, or 5. Not 8. Not 6. Not 7. I think those labels indicate patients should feel better in 1 to 4 weeks for a reason...because that's what happens if it's the right medicine. Simple as that.
Anyway, the debate goes on. All I know is that if you look for proof that only long response times are valid, you will have to ignore a lot of evidence that proves otherwise. 50 years of psychiatry is not as one sided as some read it to be, that is, unless they purposely or accidentally ignore contrary evidence. 50 years does not prove that medications should take a long time. The label right on the bottle, the local pharmacist, and the local doctor all agree. That is, if it's working somewhat at 4 weeks, stay with it. If it's not, the doctor should prescribe a different medicine. That's what they all say. I guess your mentors and your doctors feel differently. Personally I don't think someone should have to continue suffering if a medication isn't helping them at 4 weeks. That's insane, and rather cruel. Much better to start the patient on another medication.
John
Posted by natg on January 8, 2001, at 1:14:20
In reply to Re: JohnL...what say you..SLS, StJames, posted by JohnL on January 7, 2001, at 17:47:20
> I'm no expert but based on my personal experience with AD's in the last 7 years I have to agree with John.
I had almost immediate relief with Paxil and then with Risperdal-- as in 5-7 days. I took Paxil for 3 years and it worked great.
Risperdal worked on the 2 nd day.
I felt awful on Wellbutrin, Effexor and Prozac and I took those drugs for as long as 7-8 months.
It was insane and inhumane.This is just my personal experience and opinion. I'm not taking sides just wanted to share with all of you.
My Doctor says it takes 6 weeks to get the full AD effect.Great posts, thanks!
Nat
> Hi all,
> A couple months ago I sat down for a morning and searched www.mentalhealth.com for any and all abstracts that indicated early response to medication. I take a lot of abuse here for believing in quick response times. Some people turn their noses up to me and even become downright hostile that I would have the gall to question the almighty psychiatric myths. So I wanted to see if I could gather evidence from the very same psychiatric pool that everyone else was basing their own opinions.
>
> Obviously hardly any clinical trials focus on the aspect of quick response times. They instead are looking for response rates at 6 weeks or whatever. So finding what I was looking for seemed like it was going to be hard. But as it turned out, there was tons of evidence showing quick responses. Many of these clinical trials had patients who responded anywhere from 3 days to 2 weeks. They weren't placebo or side effects, because the responses were still sound at the end of the trial. I was planning on saving the evidence I found to defend myself here. But as it turned out, it was too overwhelming. It would have taken a couple weeks, not one morning, to gather the amounts of evidence out there. The problem is, it's buried in fine print. Unless one is actively seeking it, one might overlook it. One might think it to be inconsequencial, since they were looking for something else. But it's there. The same clinical trials going back to the 1970s that many here use to form their beliefs also show that there is always a certain percentage of patients that respond quickly. I would venture a guess that if all clinical trials took note of it, it would occur in every single trial.
>
> My own response to Adrafinil and Amisulpride took a full two months to plateau. However, there were good early signs, even as early as day one, that these drugs might actually work. At two weeks there was no doubt they were working. Obviously not as much as I would like, but they were working. There was no doubt. So unlike many other meds that didn't seem to do anything at 2 weeks except make me numb or make me worse, I had good reason to hang in there. If there was no good sign by 2 weeks, I might have stopped. Not sure. At 4 weeks I definitely would have stopped.
>
> I was reading the labels on all these medications I have leftover. Lots of antidepressants. Just about any you can think of. The labels all say about the same thing, in different words. What they say is that "it may take a week before you feel the effects of the medication...it may take 4 weeks before the medication takes full effect...blah blah blah". Or, "It may take several weeks...blah blah blah". Generally when most people think of 'several', they probably think of 3, 4, or 5. Not 8. Not 6. Not 7. I think those labels indicate patients should feel better in 1 to 4 weeks for a reason...because that's what happens if it's the right medicine. Simple as that.
>
> Anyway, the debate goes on. All I know is that if you look for proof that only long response times are valid, you will have to ignore a lot of evidence that proves otherwise. 50 years of psychiatry is not as one sided as some read it to be, that is, unless they purposely or accidentally ignore contrary evidence. 50 years does not prove that medications should take a long time. The label right on the bottle, the local pharmacist, and the local doctor all agree. That is, if it's working somewhat at 4 weeks, stay with it. If it's not, the doctor should prescribe a different medicine. That's what they all say. I guess your mentors and your doctors feel differently. Personally I don't think someone should have to continue suffering if a medication isn't helping them at 4 weeks. That's insane, and rather cruel. Much better to start the patient on another medication.
> John
Posted by stjames on January 8, 2001, at 1:49:13
In reply to Re: JohnL...what say you..SLS, StJames, posted by natg on January 8, 2001, at 1:14:20
> I had almost immediate relief with Paxil and then with Risperdal-- as in 5-7 days. I took Paxil for 3 years and it worked great.
> Risperdal worked on the 2 nd day.
> I felt awful on Wellbutrin, Effexor and Prozac and I took those drugs for as long as 7-8 months.
> It was insane and inhumane.
james here.....I would agree that staying on something that does not work for more that 2 months is insane. Sorry you had to go thru that. I am not saying that some may have quick resonce but years of treating patients indicates for most 6-8 weeks is the norm.
Do keep in mind Risperdal is a different class and should work quickly. Given that some only get help from 1 of 2 AD's and the rest don't work or cannot be tolerated,if you find an AD that you tolerate, give it a good trial.James
Posted by SLS on January 8, 2001, at 8:23:24
In reply to Re: JohnL...what say you..SLS, StJames, posted by JohnL on January 7, 2001, at 17:47:20
JohnL,
You are too funny.
First of all, I think you should have taken the time to read more closely the statement I posted that you felt so impelled to reply to.
http://www.dr-bob.org/babble/20001231/msgs/50972.html
"Some of the old timers of psychopharmacology considered a slow, gradual response to antidepressants to indicate a better long-term prognosis."What word, words, or phrases in the above statement indicate to you that I was referring to "latency of onset"?
Slow down. You don't want to pick fights by accident with such cavalier and pompous tones. You have a lot to learn about medical science before you are in a position to make such comments of condemnation about it. You make it sound like a conspiracy.
I've said it a million times.
What in the hell is so complicated about recognizing that there is a heterogeneity of phenomology that is both genetic and epigenetic? One size doesn't fit all. If one feels the necessity to assume a position at either end of a polarized spectrum, when it comes to mood illness, he will manage to find examples of what he is looking for. In my opinion, he will also fail to successfully treat many individuals. In my second opinion, I believe that it is the goal to successfully treat as many people as possible without missing any. Robert M. Post does too.
You may not want to continue to throw your doctors' credentials around to bolster your arguments. You are barking up the wrong tree with that one.
- Scott
Slow down.
Posted by JohnL on January 10, 2001, at 5:56:43
In reply to Re: JohnL...what say you..SLS, StJames » JohnL, posted by SLS on January 8, 2001, at 8:23:24
> JohnL,
>
> You are too funny.Thank you. :-)
Sorry you totally misunderstood me though. Sorry you are offended if someone else's views don't qualify to fit into your world.
Go take your medicine and calm down. Better yet, ask one of your respected mentors for a medicine that works.
(just kidding, but you do seem a bit edgy)
John
Posted by SLS on January 10, 2001, at 6:32:14
In reply to Re: JohnL...what say you..SLS, posted by JohnL on January 10, 2001, at 5:56:43
Good work.
This is the end of the thread.
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