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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by SLS on June 19, 2009, at 12:19:46
According to this brief report, if accurate, either Valium interferes with the antidepressant effects of Prozac, or the neurogenesis model for the recovery from depression is wrong.
Personally, it is my suspicion that the reduction in the size of the hippocampus seen in MDD is the result of the atrophy due to its disuse rather than its being a site for the induction of the disease process. If this is true, we might see a clinical response to Prozac, but with the memory impairments sometimes attendant with the use of Valium. Actually, this might be a good model for the induction of memory impairments with benzodiazepine usage.
Just throwing some stuff out there.
- Scott
------------------------------------------
Biological Psychiatry
Volume 66, Issue 1, 1 July 2009, Pages 5-8Co-Treatment with Diazepam Prevents the Effects of Fluoxetine on the Proliferation and Survival of Hippocampal Dentate Granule Cells
Neuroscience Center, University of Helsinki, Helsinki, Finland
Received 29 April 2008;
revised 16 January 2009;
accepted 16 January 2009.
Available online 28 February 2009.Background
Selective serotonin reuptake inhibitors (SSRI) often produce increased anxiety during the first weeks of treatment before the clinical antidepressant response, and these symptoms are commonly treated with benzodiazepines. Selective serotonin reuptake inhibitors increase proliferation of neuronal progenitors in rodent hippocampus after a delay of approximately 2 weeks.
MethodsWe have used this delayed increase in neurogenesis, as detected with both a rapid dot-blot method and with immunostaining, as a model of the delayed clinical antidepressant effects.
ResultsWhereas the SSRI fluoxetine alone significantly increased both neurogenesis and survival of newborn cells when administered for 23 weeks, co-treatment with diazepam and fluoxetine completely blocked the increase in both neurogenesis and survival. Furthermore, neurogenesis was not increased when fluoxetine and diazepam were first co-administered for 2 weeks and then fluoxetine was given alone for 2 additional weeks. Moreover, we show that daily administration is necessary for neurogenesis, because injection of fluoxetine for up to 1 week failed to increase neurogenesis, when assayed at 14 days from the first injection.
ConclusionsThese results suggest that benzodiazepines might interfere with the clinical effects of fluoxetine or that increased neurogenesis is not a valid model for the delayed onset of the clinical antidepressant effects.
Posted by Phillipa on June 19, 2009, at 12:47:29
In reply to Valium defeats Prozac's antidepressant effects?, posted by SLS on June 19, 2009, at 12:19:46
Scott since don't have memory impairment from my years of benzos sounds like I've been right in not increasing ad use and sticking to 50mg of luvox. What's your take on this? Phillipa
Posted by West on June 19, 2009, at 16:45:11
In reply to Re: Valium defeats Prozac's antidepressant effects? » SLS, posted by Phillipa on June 19, 2009, at 12:47:29
A very thought-provoking piece Scott. Would one be able to make similar claims for other benzodiazepines do you think?
Posted by linkadge on June 19, 2009, at 17:05:47
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by West on June 19, 2009, at 16:45:11
Well, there have been studies in which mice responded to fluoxetine independant of neurogenesis. Also, some mice strains actually do not show neurogenesis in response to fluoxetine.
Valium could reduce the effect of fluoxetine for other reasons all together. Valium is a downer. In the absence of significant anxiety, it may just be a behavioral depressant.
Keep in mind though, that while fluoxetine does increase neurogenesis in non stressed animals, some studies show that it failes to protect animals agains the neurotoxic effects of stress. On the other hand, in the same study, tianeptine and a benzodiazapine did.
Linkadge
Posted by SLS on June 19, 2009, at 17:15:14
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by West on June 19, 2009, at 16:45:11
> A very thought-provoking piece Scott. Would one be able to make similar claims for other benzodiazepines do you think?
You know, it is tempting. I think that this should be the next question for these investigators to address. This phenomenon might be specific to diazepam. Perhaps there will be enough interest to perform an investigation using human subjects. If Prozac + Valium proves to be less effective than Prozac monotherapy, that might represent a clue as to how Prozac produces its therapeutic effect.
- Scott
Posted by linkadge on June 19, 2009, at 17:22:23
In reply to Re: Valium defeats Prozac's antidepressant effects? » West, posted by SLS on June 19, 2009, at 17:15:14
Prozac + klonazepam has been shown to be more effective that prozac alone for long term maintainence in certain depressed populations.
Linkadge
Posted by SLS on June 19, 2009, at 17:23:07
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by linkadge on June 19, 2009, at 17:05:47
> Well, there have been studies in which mice responded to fluoxetine independant of neurogenesis. Also, some mice strains actually do not show neurogenesis in response to fluoxetine.
I would not be surprised to hear this. I think that neurogenesis occurs latent to the antidepressant response. Also, in order for there to be measurable neurogenesis, there might have to be atrophy in the first place. I believe that hippocampal atrophy is latent to the onset of depression, rather than being its cause.
Just a bunch of guesses.
- Scott
Posted by linkadge on June 19, 2009, at 22:35:00
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by SLS on June 19, 2009, at 17:23:07
I personally believe in the brain metabolism theory of depression. There are the 'depression circuits' that appear to dampen upon sucessful treatment with antidepressants.
Sleep deprivation, for instance, is not going to produce measurable neurogenesis in one night, but (in responders) it does lead to measurable alterations in regional metabolism.
They can also shut on and off depression in a matter of seconds with DBS. This also corresponds with alterations in brain metabolism.
Linkadge
Posted by SLS on June 20, 2009, at 6:05:16
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by linkadge on June 19, 2009, at 22:35:00
> I personally believe in the brain metabolism theory of depression.
Which one? Mitochondrial?
> There are the 'depression circuits' that appear to dampen upon sucessful treatment with antidepressants.
Yes.
> Sleep deprivation, for instance, is not going to produce measurable neurogenesis in one night, but (in responders) it does lead to measurable alterations in regional metabolism.
Perhaps, but then, couldn't there be a circuitry thing going on there with changes being exerted by the hypothalamus?
> They can also shut on and off depression in a matter of seconds with DBS. This also corresponds with alterations in brain metabolism.
How do you then separate out the metabolism, which might be a secondary effect, to a change in the activity of afferent circuits? Lightening is still faster than fire.
I am still all over the place when it comes to trying to find the target pathology for MDD or BD. Perhaps there needs to be a convergence of several pathological endophenotypes.
I don't know. Too much information and too little understanding.
- Scott
Posted by linkadge on June 20, 2009, at 19:06:28
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by SLS on June 20, 2009, at 6:05:16
All I am saying is that there are parts of the brain that generate depressive feelings. When these parts of the brain shut up, depression stops.
Linkadge
Posted by morganpmiller on June 20, 2009, at 23:12:08
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by SLS on June 19, 2009, at 17:23:07
> > Well, there have been studies in which mice responded to fluoxetine independant of neurogenesis. Also, some mice strains actually do not show neurogenesis in response to fluoxetine.
>
> I would not be surprised to hear this. I think that neurogenesis occurs latent to the antidepressant response. Also, in order for there to be measurable neurogenesis, there might have to be atrophy in the first place. I believe that hippocampal atrophy is latent to the onset of depression, rather than being its cause.
>
> Just a bunch of guesses.
>
>
> - ScottI agree with your hypothesis Scott..I don't think we are born with hippocampal atrophy. Then again, I don't think most of us are born with major chemical imbalances. These things happen over time with depression/emotional issues or other trauma. Yes, some of us are more predisposed to our chemicals being thrown out of balance and our hippocampus atrophying. So there are sensitivities/pedispositions that exist at birth.
I believe the damage to the hippocampus does contribute to making it much harder and harder to recover from depression.
I also do not think anyone should be on any benzo when starting an SSRI or other antidepressant unless the anxiety is so severe that it is preventing the person from functioning. And, if after 4 to 6 weeks, on the AD the anxiety has not begun to subside significantly, maybe add the benzo in cases of moderate anxiety. I just wonder if people are tolerating their anxiety as much as they could, and doing other things to help manage it.
Just like with alcohol, benzo(CNS depressant) does not mix well with AD. Sorry if I annoy or offend anyone with my opinion. I just think benzos are over prescribed and we need to give the AD a good try and suck it up for a little longer before settling for what I believe should be a last resort in many cases.
Posted by linkadge on June 21, 2009, at 7:43:17
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by morganpmiller on June 20, 2009, at 23:12:08
As I have said before, not all studies confirm the hypothesis that depression is associated with hippocampal atrophy.
Linkadge
Posted by SLS on June 21, 2009, at 9:25:22
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by linkadge on June 21, 2009, at 7:43:17
> As I have said before, not all studies confirm the hypothesis that depression is associated with hippocampal atrophy.
What about in humans with chronic or recurrent MDD or BD?
- Scott
Posted by SLS on June 21, 2009, at 9:58:56
In reply to Re: Valium defeats Prozac's antidepressant effects? » linkadge, posted by SLS on June 21, 2009, at 9:25:22
My memory was significantly impaired by the time I was age 20. Prior to that, who knows? I don't know what to think. My guess is that memory is affected immediately upon the onset of depression. I just don't think there is enough routing of messages making their way down to the hippocampus. Early on, the hippocampus is probably healthy enough to handle the volume, it is just that the volume is not there. It is being muted upstream because signal transduction is muffled. Without the normal amount of stimulation to keep it active, the hippocampus atrophies from disuse.
- Scott
Posted by Phillipa on June 21, 2009, at 19:34:43
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by morganpmiller on June 20, 2009, at 23:12:08
Another analogy what if you were put on benzos back in the 70's for panic attacks and no ssri's snri's existed and you had little kids to care for and they make you "normal". Now 40 years later I'm stuck and need less and less of benzos but feel horrible anyway. What would you do? As I don't know? Phillipa
Posted by morganpmiller on June 22, 2009, at 0:23:31
In reply to Re: Valium defeats Prozac's antidepressant effects? » morganpmiller, posted by Phillipa on June 21, 2009, at 19:34:43
Yeah who knows..the brain and psyche are so complex. Was that you that was but on benzos in the 70's?
I only say what I say about benzos based on my experience and others I have spoken to. I have had a few discussions with doctors and psychiatrists that were not crazy about benzos either. If I were healthy and working out the way I used to and in a better place in my life, benzos would not even be a consideration. That is why I tell people, if you can avoid starting them and wait to see if the AD alone helps, do it. I easily could have gotten back on klonopin several times recently. But I threw that bottle away and I am waiting till I get stabilized on an AD/mood stabilizer combo..if there is one out there that can get rid of this constant headache, muscle stiffness and fatigue. ugh..I fear the worst.
I know medications have helped me tremendously in thee past. I also know that they have played a major role in mind currently being a complete train wreck.
As far as the hippocampus goes, I have no doubt that chronic depression and anxiety take their toll.
Posted by Phillipa on June 22, 2009, at 20:07:26
In reply to Re: Valium defeats Prozac's antidepressant effects?, posted by morganpmiller on June 22, 2009, at 0:23:31
Yes that was me Phillipa
Posted by morganpmiller on June 22, 2009, at 23:59:47
In reply to Re: Valium defeats Prozac's antidepressant effects? » morganpmiller, posted by Phillipa on June 22, 2009, at 20:07:26
Yeah that sucks that there were not better solutions back then. Sorry to hear that
Posted by Amelia_in_StPaul on June 23, 2009, at 11:03:12
In reply to Valium defeats Prozac's antidepressant effects?, posted by SLS on June 19, 2009, at 12:19:46
WOW. I wonder if this is true of Lorazepam as well. It would explain a LOT. Thanks, Scott
> According to this brief report, if accurate, either Valium interferes with the antidepressant effects of Prozac, or the neurogenesis model for the recovery from depression is wrong.
>
> Personally, it is my suspicion that the reduction in the size of the hippocampus seen in MDD is the result of the atrophy due to its disuse rather than its being a site for the induction of the disease process. If this is true, we might see a clinical response to Prozac, but with the memory impairments sometimes attendant with the use of Valium. Actually, this might be a good model for the induction of memory impairments with benzodiazepine usage.
>
> Just throwing some stuff out there.
>
>
> - Scott
>
>
> ------------------------------------------
>
>
> Biological Psychiatry
> Volume 66, Issue 1, 1 July 2009, Pages 5-8
>
> Co-Treatment with Diazepam Prevents the Effects of Fluoxetine on the Proliferation and Survival of Hippocampal Dentate Granule Cells
>
> Neuroscience Center, University of Helsinki, Helsinki, Finland
>
> Received 29 April 2008;
> revised 16 January 2009;
> accepted 16 January 2009.
> Available online 28 February 2009.
>
> Background
>
> Selective serotonin reuptake inhibitors (SSRI) often produce increased anxiety during the first weeks of treatment before the clinical antidepressant response, and these symptoms are commonly treated with benzodiazepines. Selective serotonin reuptake inhibitors increase proliferation of neuronal progenitors in rodent hippocampus after a delay of approximately 2 weeks.
> Methods
>
> We have used this delayed increase in neurogenesis, as detected with both a rapid dot-blot method and with immunostaining, as a model of the delayed clinical antidepressant effects.
> Results
>
> Whereas the SSRI fluoxetine alone significantly increased both neurogenesis and survival of newborn cells when administered for 23 weeks, co-treatment with diazepam and fluoxetine completely blocked the increase in both neurogenesis and survival. Furthermore, neurogenesis was not increased when fluoxetine and diazepam were first co-administered for 2 weeks and then fluoxetine was given alone for 2 additional weeks. Moreover, we show that daily administration is necessary for neurogenesis, because injection of fluoxetine for up to 1 week failed to increase neurogenesis, when assayed at 14 days from the first injection.
> Conclusions
>
> These results suggest that benzodiazepines might interfere with the clinical effects of fluoxetine or that increased neurogenesis is not a valid model for the delayed onset of the clinical antidepressant effects.
>
>
This is the end of the thread.
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