![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 94 to 118 of 139. Go back in thread:
Posted by Phillipa on April 9, 2006, at 20:22:47
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by ed_uk on April 9, 2006, at 12:56:30
Ed I love you my adopted Son and listen to you most of the time. Love PJ XXXXXXXX
Posted by Caedmon on April 9, 2006, at 21:18:11
In reply to Re: Drugs versus Psychotherapy - Backlash? » Squiggles, posted by linkadge on April 9, 2006, at 19:51:39
> Its the same story with drugs like Aricept. Alzheimers is due to plaques and tangles isn't it? Acetylcholinsterase inhibitors only offer symptomatic improvement. If thats your only option then fine, but we do know that other (proactive strategies) can actually put off Alzheimer's onset. Thats more significant.
There is a way to significantly put off dementia? Although I should only think it will provide short-term (i.e. a few years) worth of protection.
Why is that *more* significant? Is it more significant when you are finally an Alzheimer's patient? I don't understand, the dichotomy seems false. Regards,
- C
Posted by ed_uk on April 10, 2006, at 13:44:09
In reply to Re: Drugs versus Psychotherapy - Backlash? » ed_uk, posted by Phillipa on April 9, 2006, at 20:22:47
Thanks PJ! But what did I do?
Ed xxx
Posted by Phillipa on April 10, 2006, at 19:17:56
In reply to Re: Drugs versus Psychotherapy - Backlash? » SLS, posted by ed_uk on April 7, 2006, at 17:24:29
Ed just agreed that excercise is a form of an antidepressant no biggie. Love PJ XXXXX
Posted by linkadge on April 11, 2006, at 15:43:24
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by Caedmon on April 9, 2006, at 21:18:11
(Don't really know what you are saying)
We do know that certain lifestyles seem to delay the onset of Alzheimer's disease. For instance, lifetime coffee drinkers apparently display lower rates, and less severe onset of dimentia and Alzheimers. Whether this habit has any ability to prevent the underlying structural abnormalities is not certain.
I guess what I am saying is that many of the current treatments do not seem to actually prevent and of the structural changes evident in Alzheimers.
Researchers are following certain leads to try and uncover why the plaques are forming. For instance, GSK-3b inhibitors appear influence some enzyme that is responsible for the formation of the plaques and tangles. Lithium (a GSK-3b inhibitor) appears to block the formation of plaques and tangles in a mouse model of Alzheimers) This would be a more significant treatment option since attacking the underlying progression should lead to less functional impariment.
There is no evidence that aceylcholinsterase is high in Alzheimers. The drugs boost cholinergic neurotransmission in attempts to kickstart remaining circutry.
The same arguments could be made about depression. We know it can be neurodegenertitive, ie involving loss of hippocampal volume, but we don't fully know why. Many studies attempting to link depression to the levels of the serotonin transporter (SERT) have not been conclusive. Same thing goes for the norepinephrine transporter (NET). Some studies actually show that the levels of these transporters are already low in depressive states.
I guess what I am saying is that, while I might believe an antidepressant will work temporarily, it would be more comforting and reassuring to know that the drug was correcting an idenified abnormality. That case might guarentee a more than temporary symtomatic improvement.
Would you not agree that a more satisfying answer is the right answer?
Linkadge
Posted by linkadge on April 11, 2006, at 15:51:59
In reply to Re: Drugs versus Psychotherapy - Backlash? » Caedmon, posted by linkadge on April 11, 2006, at 15:43:24
The same thing goes for schizophrenia. The idea that schizophrenia is due to too much d2 activation is interesting but not conclusive.
In addition, the drugs' usage can lead to increased number of d2 receptors and a loss of effect accompanied by rebound psychosis upon withdrawl. So it is evident that they are not fixing the problem. It would be more satisfying to actually cure schizophrenia.
How does that relate to drug use overall? If there is evidence to suggest that an antidepressant will only work for a certain period of time, and lead to subsequent dependance and significant withdrawl, in addition to only providing symptomatic improvement for a disease that often remits on its own has made some people carefully consider all treatment options.
Linkadge
Posted by SLS on April 18, 2006, at 8:01:38
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by SLS on April 9, 2006, at 13:20:51
The following citation demonstrates what I have seen elsewhere in medical literature over the years.
This is the finding that leads me to the following hypothesis:
> It seems that if one limits the study population to those who have the severest of depressions that meet DSM criteria for MDD, antidepressants look more like wonder drugs. If, on the other hand, you were to give an antidepressant to a population of people whose mood depends entirely on how they think, a biological intervention will do little to affect them. In this case, the response rate is similar to placebo. Unfortunately, antidepressant trials in the past have included subjects with a psychologicaly driven depression. That's why the placebo rate is so high. Many of these people are very susceptible to suggestion.
>
> It is my guess that the preponderance of people with severe depression have a biological disorder while those with mild to moderate depressions are more likely to have a strong psychological component. This is why I keep questioning what we mean when we use the word "depression". People whose depression evolves from a psychogenic diathesis are far more apt to demonstrate a placebo effect because it is their expectation that they will be helped. I believe this expectation changes their outlook and therefore changes their mood. With psychogenic depressions, you can change the way you feel by changing the way you think. With biogenic depressions, this is not true. The way you think is determined by the way you feel.
>
> It would be ideal to identify the difference between an endogenous versus an exogenous depression when choosing a treatment modality. However, things are not that simple. I believe that there is an affective spectrum within which are an array of psychobiologies. At either end of the spectrum lie people whose depressions are either entirely biological or entirely psychological. In between lie those whose depressions are driven by a mix of both biological and psychological contributions. I find this framework appealing because it works well to explain the phenomenology of depression as a syndrome rather than a single illness. I find that the inferences that can be drawn from this model explains much about what we see happening in the diagnosis and treatment of depression.
Posted by zeugma on April 20, 2006, at 6:11:52
In reply to Re: Drugs versus Psychotherapy - Backlash? » Caedmon, posted by linkadge on April 11, 2006, at 15:43:24
Many studies attempting to link depression to the levels of the serotonin transporter (SERT) have not been conclusive. Same thing goes for the norepinephrine transporter (NET). Some studies actually show that the levels of these transporters are already low in depressive states.
>>Some have suggested that the transporters downregulate in an attempt to compensate for the pathological condition:
-z
Posted by SLS on April 20, 2006, at 6:53:04
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 6:11:52
"The decreased binding of [3H]nisoxetine to NETs in the LC in major depression may reflect a compensatory downregulation of this transporter protein in response to an insufficient availability of its substrate (norepinephrine) at the synapse."
That's very interesting. I would love to know if there is any biological precedence for their conclusion that the transporter would downregulate in the absence of neurotranmitter. Has this phenomenon been documented elsewhere? I can't imagine that no one has measured the amounts of NE to be found in the LC of suicide victims.
Can you think of a dynamic in circuitry that would explain this?
I gotta think about this one.
I see that the authors have published other papers studying NE and 5-HT function in major depression and Alzheimers. They all seem to corroborate each other and indicate that dimished neurotransmission is accompanied by reductions in transporter and increases in autoreceptors and the enzymes that produce neurtransmitter.
Ah. I get it. I suppose there must be a certain amount of neurotransmitter in the synaptic cleft to maintain a partial depolorization (prevent a static hyperpolarization) of the postsynaptic membrane.
- Scott
Posted by linkadge on April 20, 2006, at 8:09:44
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 6:11:52
Ok so suppose the NET transporter lowers itself to compensate for a deficiancy of norepinephrine. Then still, the pathelogical condition is not an abnormality in NET but rather an abnormality in norepinephrine availabilty.
Ie, I cant see how taking these depressed patients who's brains respond to low norepinephrine by decreasing NET, and exposing them to a drug that decreases it further, is going to remedy the situation, or make their brains function more like the contol brains.
Linakdge
Posted by linkadge on April 20, 2006, at 8:15:27
In reply to Re: Drugs versus Psychotherapy - Backlash? » zeugma, posted by SLS on April 20, 2006, at 6:53:04
In either case, I don't really see the problem as lying in a malfunctioning uptake system.
I remember reading somewhere that a fair portion of tested depressed patients had an abnormality in the TPH-2 gene (tryptophan hydroxylase)(or something like that) which coded for a much lower level of serotonin synthesis. That might explain things better.
Posted by zeugma on April 20, 2006, at 8:38:06
In reply to Re: Drugs versus Psychotherapy - Backlash? » zeugma, posted by linkadge on April 20, 2006, at 8:09:44
> Ok so suppose the NET transporter lowers itself to compensate for a deficiancy of norepinephrine. Then still, the pathelogical condition is not an abnormality in NET but rather an abnormality in norepinephrine availabilty.
>
> Ie, I cant see how taking these depressed patients who's brains respond to low norepinephrine by decreasing NET, and exposing them to a drug that decreases it further, is going to remedy the situation, or make their brains function more like the contol brains.
>
> Linakdgeif the downregulation of NET in response to abnormality in NE neurotransmission is a result of a homeostatic process, then amplifying the brain's own response with a NET inhibitor would be a strengthening of this response (possibly enough to compensate for the dysregulation).
The key is that 'normal' neurotransmission may be achieved by different routes. The brain is a highly 'degenerate' system; there are numerous ways to get the same functional result (definition of degeneracy i am using: "In physics two or more physical states are said to be degenerate if they are both at the same energy level." -Wikipedia). The use of a NET inhibitor might bring noradrenergic function in line with that of an individual who was unmedicated but euthymic despite the very different configurations of NET/NE systems in each.
-z
Posted by zeugma on April 20, 2006, at 9:02:56
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by linkadge on April 20, 2006, at 8:15:27
> In either case, I don't really see the problem as lying in a malfunctioning uptake system.>>
The evidence seems to be that the uptake systems are associated with drug response, if not with the disorder itself:
I suppose the key is the ability to attain a homeostatic state that has the same functionality as an euthymic individual's.
>
> I remember reading somewhere that a fair portion of tested depressed patients had an abnormality in the TPH-2 gene (tryptophan hydroxylase)(or something like that) which coded for a much lower level of serotonin synthesis. That might explain things better.>>
>There are likely abnormalities at all levels of neurotransmission. At some point psychiatrists will stop using trial and error and use genomic evidence to treat particular patients. I believe very strongly that the current pharmocopoeia is not used to maximum benefit because this information is not routinely used to guide treatment. It is certainly easier to study gene effects on treatment response, than to design new drugs.
-z
>
Posted by SLS on April 20, 2006, at 10:20:16
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 9:02:56
So, then, what's the deal?
Is the reduction in the numbers of NET reported in the previous study you cited the result of inadequate gene expression, or is it the result of a compensatory mechanism?
- Scott> > In either case, I don't really see the problem as lying in a malfunctioning uptake system.>>
>
> The evidence seems to be that the uptake systems are associated with drug response, if not with the disorder itself:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15939518&query_hl=211&itool=pubmed_docsum
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16005136&query_hl=212&itool=pubmed_docsum
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15993855&query_hl=215&itool=pubmed_docsum
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15337646&query_hl=230&itool=pubmed_docsum
>
>
> I suppose the key is the ability to attain a homeostatic state that has the same functionality as an euthymic individual's.
> >
> > I remember reading somewhere that a fair portion of tested depressed patients had an abnormality in the TPH-2 gene (tryptophan hydroxylase)(or something like that) which coded for a much lower level of serotonin synthesis. That might explain things better.>>
> >
>
> There are likely abnormalities at all levels of neurotransmission. At some point psychiatrists will stop using trial and error and use genomic evidence to treat particular patients. I believe very strongly that the current pharmocopoeia is not used to maximum benefit because this information is not routinely used to guide treatment. It is certainly easier to study gene effects on treatment response, than to design new drugs.
>
> -z
> >
>
>
Posted by zeugma on April 20, 2006, at 10:57:59
In reply to Re: Drugs versus Psychotherapy - Backlash? » zeugma, posted by SLS on April 20, 2006, at 10:20:16
So, then, what's the deal?
Is the reduction in the numbers of NET reported in the previous study you cited the result of inadequate gene expression, or is it the result of a compensatory mechanism?>>
Definitely not inadequate NET gene expression, but compensation for inadequate gene expression downstream:
Daily treatment of rats with DMI (10 mg/kg, i.p.) for 3 or 14 days significantly increased postmortem cerebral TH mRNA in the locus coeruleus (LC) area by 47-68%. Again, TH protein concentrations in LC decreased at 3 and 14 days, by 25-40%, with transient significant reduction in amygdala tissue after 3 days of treatment that were not sustained. These findings indicate that DMI exerts complex, typically opposite and perhaps compensatory, gradually evolving effects on the expression of TH protein (decreases) and its message (increases), possibly in response to increased synaptic availability of NE.
it is possible that the reduction of NET in the other studies is an attempt to upregulate inadequate gene expression (of tyrosine hydroxylase), and that the inhibitor facilitates this process. I think that antidepressants, when they work, probably build on the brain's own compensatory mechanisms.then again, I am just speculating. What do you think?
-z
Posted by linkadge on April 20, 2006, at 17:55:02
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 8:38:06
"The use of a NET inhibitor might bring noradrenergic function in line with that of an individual who was unmedicated but euthymic despite the very different configurations of NET/NE systems in each."
Maybe, or it may even further serve to mask/ intensify an additional, yet unidentified predisposing factor.
Some people even think that the TCA's work independantly of their effects on monoamines. For instance the TCA surmontil has no effect on monoamine reuptake, yet is an effective antidepressant in animal models. It also leads to identical adaptive changes in monoamine receptor sites as other TCA's.
Another argument is that we have drugs such as straterra, which are NRI's but display only weak, negligable effect in depression.
One would think that if the if NET inhibition was the key mechanism, then any drug which inhibited it would be an antidepressnat.
Linkadge
Posted by linkadge on April 20, 2006, at 18:06:26
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 9:02:56
These studies are great, but you can probably find just as many others which suggest that drug responce is not really associated with any abnormalities in the SERT genes.
For instance, in this study, which has been replicated in different populations, some researchers found that the double-short varient of the serotonin transporter was associated with a higher lifetime occurance of depression and anxiety disorders. But heres the thing, The SS varient of the serotonin transporter gene codes for a lower reuptake of serotonin.
http://www.futurepundit.com/archives/001611.html
Some people mistakenly site this as an argument for SSRI use, without noting that this gene actually codes for a lower reuptake of serotonin than those with one or two long varients. So it doesn't make sence to have these people taking SSRI's. Perhaps Tianeptine would bring them to a better homeostasis.
Linkadge
Posted by linkadge on April 20, 2006, at 18:11:21
In reply to Re: Drugs versus Psychotherapy - Backlash? » SLS, posted by zeugma on April 20, 2006, at 10:57:59
I was under the impression that a high level norepinephine firing in the locus coeruleus corresponded to high anxiety states, and that drugs like clonidine relieved anxiety by reducing firing.
Linkadge
Posted by zeugma on April 20, 2006, at 18:44:25
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by linkadge on April 20, 2006, at 18:06:26
>
>
> For instance, in this study, which has been replicated in different populations, some researchers found that the double-short varient of the serotonin transporter was associated with a higher lifetime occurance of depression and anxiety disorders. But heres the thing, The SS varient of the serotonin transporter gene codes for a lower reuptake of serotonin.
>
> http://www.futurepundit.com/archives/001611.html
>
> Some people mistakenly site this as an argument for SSRI use, without noting that this gene actually codes for a lower reuptake of serotonin than those with one or two long varients. So it doesn't make sence to have these people taking SSRI's. Perhaps Tianeptine would bring them to a better homeostasis.
>
I agree completely that the double-short variant of the serotonin transporter is associated with a poorer response to SSRI's. This study bears it out:Buspirone or more selective 5-HT1A agonists might be effective in this population, or the new antidepressant (stil in phase III) vilazodone, which is a combined SRI/5-HT1A agonist.
-z
>
>
>
Posted by zeugma on April 20, 2006, at 18:49:59
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by linkadge on April 20, 2006, at 17:55:02
Another argument is that we have drugs such as straterra, which are NRI's but display only weak, negligable effect in depression.
One would think that if the if NET inhibition was the key mechanism, then any drug which inhibited it would be an antidepressnat.>>
I don't know the answer to this. In the case of Strattera, I have supposed that since Strattera's metabolite is a kappa opiod partial agonist, a depressogenic effect counteracts its NRI-based antidepressant effect.
Even reboxetine is not a pure NRI: it blocks nicotinic ACh receptors. Reboxetine seems to be an effective antidepressant from numerous studies, and yet it doesn't seem to work for anybody who posts here. Maybe everyone who has taken reboxetine and gotten a positive result is so deliriously happy that they have no need to post here.
-z
Posted by linkadge on April 20, 2006, at 18:52:48
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by zeugma on April 20, 2006, at 18:44:25
I mean, if you said that SS varient represented only a minority of depressed persons, then the theory would still look good on paper. But if the majority of depressed people actually posess the SS varient then it would be an arguement against the purported mechanism.
Its great to say that SSRI's work well for people with the L/S or L/L varients, but if they only represent the minority of depressed persons, then it might not look so good.
Linkadge
Posted by zeugma on April 20, 2006, at 19:27:58
In reply to Re: Drugs versus Psychotherapy - Backlash? » zeugma, posted by linkadge on April 20, 2006, at 18:52:48
> I mean, if you said that SS varient represented only a minority of depressed persons, then the theory would still look good on paper. But if the majority of depressed people actually posess the SS varient then it would be an arguement against the purported mechanism.
>
> Its great to say that SSRI's work well for people with the L/S or L/L varients, but if they only represent the minority of depressed persons, then it might not look so good.
>
> Linkadge
This is actually quite fascinating. The link you posted connected the s/s serotonin transporter with stress/anxiety and reactive depression. In generalized anxiety disorder it seems that it breaks down this way:Psychopharmacology (Berl). 2006 Mar 9; [Epub ahead of print]
Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder.Stein MB, Seedat S, Gelernter J.
Departments of Psychiatry and Family & Preventive Medicine, University of California, 9500 Gilman Drive (0985), La Jolla, San Diego, CA, 92093-0985, USA, mstein@ucsd.edu.
OBJECTIVES: To determine whether variation in the serotonin transporter gene promoter (5HTTLPR) influences the efficacy of selective serotonin reuptake inhibitors (SSRIs) in generalized social anxiety disorder (GSAD). METHODS: Consecutive series of N=32 patients with DSM-IV GSAD for whom DNA and standardized outcome data from a 12-week SSRI trial were available. After ensuring that neither clinical response [clinical global impression of change scale (CGI-C)] nor 5HTTLPR genotype was confounded by ethnicity or sex, we determined whether the number of copies (0, 1, or 2) of hi-risk alleles using either the diallelic L-S system or the triallelic La-Lg-S system, predicted response and change in Liebowitz social anxiety scale (LSAS) and brief social phobia scale (BSPS) scores during SSRI treatment. RESULTS: Twenty-one patients (66%) were responders to SSRI (i.e., CGI-C much or very much improved). A trend was seen for a linear association between 5HTTLPR genotype and likelihood of response to SSRI: diallelic classification L/L 7/8 (88%), L/S 12/18 (67%), S/S 2/6 (33%), p=0.051; triallelic classification L'/L' 4/5 (80%), L'/S' 14/19 (74%), S'/S' 3/8 (38%), p=0.093. Reduction in LSAS (and BSPS) scores during SSRI treatment was significantly (p<0.02) associated with 5HTTLPR genotype using either the diallelic or triallelic classification. CONCLUSIONS: Variation in a functional polymorphism known to influence serotonin reuptake is associated with SSRI response in patients with GSAD. Independent replication in larger samples is required before the predictive utility of this information can be confirmed and generalized to clinical settings.
This is exactly what I would have thought from reading your link. But consider this:
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar 30; [Epub ahead of print]
Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.Ng CH, Easteal S, Tan S, Schweitzer I, Ho BK, Aziz S.
Professorial Unit, The Melbourne Clinic, University of Melbourne, Australia.
The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.
Who knows? I'm inclined to say that the s/s genotype is more prone to anxiety, and that the serotonin transporter polymorphisms might have a closer bearing on anxiety states than depression. But it is obviously complex and also there are so many other variables (MAO, COMT, etc.). But I am pretty sure that the s/s polymorphism really is associated with a a poorer response to conventional antidepressants, despite the study above. It's also worth noting that the l/l and l/s genotypes were more common in the Causcasian patients in that study.
-z
Posted by zeugma on April 20, 2006, at 19:34:02
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 19:27:58
also, the Stein et al. study used a 12-week duration which is surely more adequate than a six-week study if you are trying to pick up possibly subtle effects/ screen for placebo effects. The Mulder/Joyce et al. studies are very trustworthy because they have done extensive work on drug response, and they have worked with Cloninger, who is one of the leading theorists of temperament (which is the dimension that your link was really concerned with).
-z
Posted by zeugma on April 20, 2006, at 20:08:27
In reply to Re: Drugs versus Psychotherapy - Backlash?, posted by zeugma on April 20, 2006, at 19:34:02
I found this article on how clonazepam upregulates the serotonin transporter:
Neuropharmacology. 1995 Oct;34(10):1327-33.
Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in the hippocampus of rats subchronically treated with clonazepam.Lima L, Trejo E, Urbina M.
Laboratorio de Neuroquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
Selective central benzodiazepine agonists, such as clonazepam, are known to modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to further study the effect of this benzodiazepine on serotonin turnover rate, rats received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin and 5-hydroxyindoleacetic acid were determined in the hippocampus after inhibition of monoamineoxidase with pargyline. The results indicate a reduction in the turnover rate of the monoamine. In addition, the systemic administration of clonazepam produced a decrease in the Bmax of [3H]DPAT binding to 5-HT1A sites in the hippocampus. By contrast, this effect was not observed if clonazepam was delivered into the dorsal raphe nucleus by osmotic minipumps. The binding of [3H]paroxetine to 5-HT reuptake sites was increased by the treatment with clonazepam. The present observations indicate that clonazepam produces a reduction of serotonin turnover rate in the hippocampus of the rat concomitant with a down-regulation of 5-HT1A binding sites, probably by an effect at the forebrain projections. There is also an up-regulation of the serotonin transporter, which might contribute to a reduction in the synaptic availability of serotonin during clonazepam treatment.
This might make clonazepam an option similar to tianeptine in its effect on the 5-HT transporter. And it is consonant with the idea that the s/s genotype is prone to anxiety/stress.
-z
Posted by linkadge on April 20, 2006, at 20:52:10
In reply to Re: Drugs versus Psychotherapy - Backlash? » linkadge, posted by zeugma on April 20, 2006, at 19:27:58
Interesting. Another thing to consider is that all of the currently available SSRI's increase the synthesis of a very potent gabergic neurosteriod called allopregnanalone. I believe that it is an intrinsic effect of the molecule, and not an effect of an SSRI in general.
This could definately confound some of the responces. Ie a person could respond to this
mechanism but perhaps still have a s/s transporter gene.SSRI's often made my anxiety much much worse. They also had minimal effect on my depression.
They helped my depression a little when things weren't stresfull, but heavy stress + SSRI's always made me near psychotic.Heres what I never understood. They don't discover these drugs by doing all of these advanced biochemical studies in humans. They discover all of the antidepressants by throwing regular mice in a vat of water and seeing which ones keep the mice swimming longer. They don't base their presumptions on the ability of the drugs to fix any rat's bad biochemisty, so why all of a sudden are these drugs supposedly fixing humans at the biochemical level? Oh sure, some of these drugs can keep you "swimming" a little longer, but they're a far cry from feeling good.
Linkadge
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