![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by Jamal Spelling on June 27, 2008, at 15:45:50
I was just wondering what your opinion is on Cymbalta. Specifically its safety profile.
If you'd rather not comment, or if you don't have any particular thoughts on it, or whatever, that's fine. I don't mean to cause any trouble or anything.
Posted by linkadge on June 27, 2008, at 18:19:09
In reply to Hey Linkadge!, posted by Jamal Spelling on June 27, 2008, at 15:45:50
Its reasonably safe I suppose. The AD's are probably safer than other classes of meds.
Cymbalta hasn't been around as long as some of the other AD's so there is a degree of unknown.
As for whats known about it, you may want to watch:
Liver function (periodic testing if possable)
Heart function (BP, pulse etc)
Sleep quality / continuity.
Linkadge
Posted by Phillipa on June 28, 2008, at 0:46:20
In reply to Re: Hey Linkadge!, posted by linkadge on June 27, 2008, at 18:19:09
True as always have had low blood pressure but the three month on cymbalta it did go up and with working out at the gym and walking five miles a day. Helps with pain. Love Phillipa
Posted by Jamal Spelling on June 28, 2008, at 1:26:02
In reply to Re: Hey Linkadge! » linkadge, posted by Phillipa on June 28, 2008, at 0:46:20
Posted by Marty on June 28, 2008, at 10:11:48
In reply to Re: Hey Linkadge!, posted by linkadge on June 27, 2008, at 18:19:09
I know you didn't ask anyone but Linkadge but here's my 2 cents anyway...If you:
- suffering some neuropathic kind of pain
- are NOT doing much anxiety
- are WELL grounded into reality (no depersonalization, no derealization)
.. then Duloxetine (Cymbalta) may be worth trying.BUT if you're not suffering some neuropathy/fibromyalgia and didn't try Valenfaxine (Effexor XR) yet THEN this is hard to see any rationale go to with Cymbalta right away.
- Cymbalta side-effects are stonger than most SSRIs/SNRIs.
- Cymbalta is less effective (+ stronger side effects) than the SSRIs.
While I mostly agree with Linkadge about the relative safety of SSRIs/SNRIs AD, I feel Cymbalta may be one of the least safe modern AD. Which doesn't mean it is not safe... I wouldn't be scared to try it at all as a fact. BUT.. if it's true that some AD could induce permenant 'changes' (I do believe) in some (exemple: post-SSRI sexual dysfunction) then Duloxetine is one I would AVOID IF POSSIBLE. That's how I feel.
/\/\arty
Posted by Jamal Spelling on June 28, 2008, at 12:35:59
In reply to Re: Hey Linkadge!, posted by Marty on June 28, 2008, at 10:11:48
Thanks for your response Marty. Years ago I did try Effexor, but couldn't tolerate it. I felt unpleasantly overstimulated on it. Cymbalta so far has had few side effects, except for pain in my chest and heart palpitations. I think it's the most effective AD I've ever used, but I am concerned about what it may be doing to my body, especially my heart. I have no anxiety from it and my sleep is perfect. Also, I am concerned about the effect it has on blood sugar levels.
This is the first time I'm having therapy. In the past I only used ADs without getting any therapy. Maybe the AD response is not from the Cymbalta, but from the therapy. My therapist uses regressive hypnoanalysis. So maybe I don't need the Cymbalta.
One thing that concerns me is the brain damage from untreated depression. Maybe I'll quit the Cymbalta and go on to Zoloft or Celexa to avoid getting brain damage.
Thanks again Linkadge, Phillipa and Marty.
Posted by Marty on June 28, 2008, at 12:46:05
In reply to Re: Hey Linkadge! » Marty, posted by Jamal Spelling on June 28, 2008, at 12:35:59
I'm glad your doing well on it.
> One thing that concerns me is the brain damage from untreated depression. Maybe I'll quit the Cymbalta and go on to Zoloft or Celexa to avoid getting brain damage.
You may want to research Tianeptine (Stablon)since it's a pretty clean AD known to be a pretty good neurogenesis inducer able to reverse "brain damage" from untreated depression. Has it doesn't induce much side-effects: even if it doesn't help your depression symptoms as much as some other serotonergic AD, it may have a place in your 'cocktail' just to protect your brain from the 'brain degeneration' part of the disease. and who knows, maybe it could work wonders for your depressive symptoms too... it does for some.
/\/\arty
ps: Stablon is not in America but can be ordered easily and legally. about 100$ per month.
Posted by Phillipa on June 28, 2008, at 19:53:43
In reply to Re: Hey Linkadge! » Jamal Spelling, posted by Marty on June 28, 2008, at 12:46:05
cymbalta is about the most popular ad in NC last pdoc had in Charlotte wanted me on 120mg in a month. Said manufacturer doesn't recommend over 60mg basically he scared me so much couldn't tolerate 30mg and before that I'd taken 60mg with benzos and nothing no side effects at all why? Love Phillipa
Posted by bleauberry on June 28, 2008, at 20:18:28
In reply to Re: Hey Linkadge!, posted by linkadge on June 27, 2008, at 18:19:09
> As for whats known about it, you may want to watch:
>
> Liver function (periodic testing if possable)
> Heart function (BP, pulse etc)
> Sleep quality / continuity.
>
>
> LinkadgeTo that I would add:
Large weight loss or large weight gain.
Unstable blood sugar or exacerbation of diabetes.
Digestive/intestinal problems.
>
Posted by linkadge on June 30, 2008, at 19:04:36
In reply to Re: Hey Linkadge! » Marty, posted by Jamal Spelling on June 28, 2008, at 12:35:59
While it is true that some studies have found certain forms of brain atrophy associated with long term, reccurent depression, there is unfortunately very little proof that antidepressants actually reduce this loss (tianeptine aside).
High blood pressure and high blood sugar are also associated with memory loss so..
Linkadge
Posted by Jamal Spelling on July 1, 2008, at 15:11:04
In reply to Re: Hey Linkadge!, posted by linkadge on June 30, 2008, at 19:04:36
Thanks Linkadge, and you too bleauberry.
So besides tianeptine, what other means are there to reverse depression-induced brain atrophy (assuming indeed that depression induces brain atrophy)?
Posted by Marty on July 1, 2008, at 15:31:06
In reply to Re: Hey Linkadge!, posted by linkadge on June 30, 2008, at 19:04:36
> While it is true that some studies have found >certain forms of brain atrophy associated with >long term, reccurent depression, there is >unfortunately very little proof that >antidepressants actually reduce this loss
>(Tianeptine aside).I'm surprised you say that "there is unfortunately very little proof that antidepressants actually reduce this loss
(Tianeptine aside)" ... Servier put most of their "marketting oriented research effort" on Tianeptine neurogenesis inducing properties and so it's true that this is an AD which has been documented extensively over this ability .. BUT .. is far from being the only AD which has been documented doing that .. most (all majors anyway) has been shown to induce neurogenesis (and other related "building" effects in the brain). Other class of meds also plays a role in reducing/reverting brain hippocampal atrophy... a short and -- VERY -- incomplete list just for the sake of example : tianeptine (affects structural plasticity in hippocampus and is an effective antidepressant); phenytoin (antiseizure and neuroprotective); fluoxetine (downregulates neurodegenerative enzyme and increases neuroprotective hippocampal S100 beta); lithium (neuroprotective and antiapoptotic); tricyclic antidepressants (increase hippocampal neurogenesis); antipsychotics (reduce hippocampal neuronal suppression) ...This list is from :
http://www.ncbi.nlm.nih.gov/pubmed/17098374?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum/\/\arty
Posted by linkadge on July 2, 2008, at 23:42:28
In reply to Re: Hey Linkadge! » linkadge, posted by Marty on July 1, 2008, at 15:31:06
Well, in response to the link I would still contend that there is no in vivo demonstration that the long term use of most psychotropic drugs actually protects or reverses the neurodegenerative effects of anxiety/depression.
Sure, certain antidepressants have been shown to *influence* neurogenesis, but we are still far from concluding that this will infact restore the damage done from depression.
For instance, certain studies on the effects of SSRI's on neurogenesis has revealed that the drugs may really be simply enhancing neuronal turnover (ie they also increase neuronal elimination) rather than neurogenesis.
See:
http://www.jneurosci.org/cgi/content/abstract/25/5/1089
The following studies show that while tianeptine has a clear ability to protect the hippocampus from the effects of stress, fluoxetine has no such protective effect.
http://www.tianeptine.com/stressmorphcog.html
http://www.ncbi.nlm.nih.gov/pubmed/17561824The following study showed that fluoxetine actually lowered long term potentiation in non stressed rats and did not pretect stress rats from the reduction in LTP. It also blocked the ability of tianeptine to restore stress induced LTP
http://www.ncbi.nlm.nih.gov/pubmed/11978839
The next study showed that tianeptine blocked stress induced neuronal atrophy but uptake inhibitors prozac or luvox did not.
In addition, not all studies demonstrate that antidepressants actually do increase BDNF in any consistant fashion. This study found no effect of prozac on BDNF expression:
http://biopsychiatry.com/bdnfantidep.htm
This study found no effect of lithium on BDNF or BCL-2 levels:
http://www.ingentaconnect.com/content/mksg/pto/2007/00000100/00000005/art00012
Also, lithium is not always neuroprotective. In certain cases it can be highly neurotoxic. Sometimes this happens within theraputic levels, during certain affective states, or when combined with other drugs.
http://www.cogsci.ecs.soton.ac.uk/cgi/psyc/newpsy?7.32
We must be cautious on two counts. Antidepressant induced increase in neurogenesis has only been demonstrated in animals *and* it has not been consistantly demonstrated in animals.The following study shows that prozac did not increase neurogenesis in adult mice - only in adolecent mice *and* it did not produce any neurogenesis in mice with previous exposure to early life stress!:
This study discusses how prozac alters behavior but *not* neurogenesis in a certain mouse strain.
This study demonstrates that prozac works in this mouse strain without affecting neurogenesis:
I still contend that there is indeed very little proof that antidepressants actaully *correct the hippocampal atrophy seen in depression*. Like I said above, sure studies show that you can increase hippocampal turnover and perhaps cause certain cell forms to proliferate, but that doesn't necessarily equate to a larger hippocampus. Also, the acute stimulatory effects of serotonin on cell birth may not cary through after a few months. Other brain chemicals promote neurogenesis too - acetycholine, dopamine, norepinephrine etc. Hippocampal placticity may infact be impaired if the drug raises serotonin levels too high, at the cost of other brain chemicals.
The idea that all psychiatric meds induce neurogenesis is not true. Many psychiatric meds have questionable ability to induce neurogenesis and as mentioned above this does not necessarily equate to a reversal of atrophy.
This study found that lithium did not promote neurogenesis:
http://www3.interscience.wiley.com/journal/118870987/abstract?CRETRY=1&SRETRY=0
Some drugs like valrpoate are simultaniously neurotrophic and neurotoxic. (Who knows what the net long term effect will be?) Tegretol and lamotrigine are not neurotrophic but are neurotoxic. The benzodiazapines are not neurotrophic but are neurotoxic.
The word is certainly not out on antipsychotics. The typical AP's are associated with brain atrophy. The AP's are associated with faster decline of dementia and alzheimers patients despite initial hopes of cognative enhancement.
Risperidal downregulates BDNF.
http://www.ncbi.nlm.nih.gov/pubmed/12393228
Seroquel and olanzapine might have some mild benificial effect, but they both cause diabeties and metabolic disorders which is going to take a massive toll on brain health.
This study suggests that olanzapine does not have a major impact on neurogenesis, or neuronal survival.
http://cat.inist.fr/?aModele=afficheN&cpsidt=15892410
Also, dopamine signaling is neurotrophic so I would assume that long term blockade of dopamine receptors would lead to atrophy.
That leaves you with the antidepressants. As mentioned above not all studies demonstrate neurogenesis with the antidepressants, not all studies support the idea that antidepressants do infact lead to a net increase in number of surviving brain cells. In addition, many studies show that tianeptine but not the SSRI's has a preventative effect on stress induced hippocampal atrophy. Many studies find that antidepressants and lithium do not affect BDNF signalling in a consistant or prolonged way. Finally, virtually no studies (in humans) have infact demonstrated that antidepressant treatment leads any significant amelioration of brain atrophy associated with depression.
I.e. the link you gave refereneces a framework of potential benefits, based on certain mouse studies and some theorization.
The only reason I put tianeptine above the other treatments is that in any study I have seen that compares tianeptine to other AD's for their neuroprotective capacity, tianeptine always comes out far ahead. Its true that tianeptine's neuroprotective effects have not been done in humans but I believe the rodent studies are at least a little more consistent.
Linkadge
Posted by Marty on July 3, 2008, at 14:14:15
In reply to Re: Hey Linkadge!, posted by linkadge on July 2, 2008, at 23:42:28
Wow! Never thought you would reply me with such 'interest' in the subject... what a vigorous reply :)
And you know what ? I just deleted about 50 lines of argumentations I had wrote in the last couple minutes in reply to your reply ... because while writing them I somehow changed my opinion about the subject to a point where, while it doesn't 100% embrace yours, what I just wrote wasn't representative enough of what I now think ! ... I guess it's positioning me between my yesterday opinion and yours.
I dont have the motivation today to start from zero and expose you all my fresh and more moderated arguments but I can summarize with:
1- You're right about the fact that, as being at the edge of the neuroscience research subject, we're not sure of ANYTHING related to depression<->neurogenesis<->antidepressants and friends. And yes Tianeptine is the most studied and 'agreed on' at this point.
2- I'm not convince of the quality of some (high majority) of your argumentations which lay upon the fact that some says "No" and some says "Yes"... if it only takes about this level of "Nayers" to discredit a theory, well I can't think of ANY neuroscience theory which would be considered by you as being credible.
MUCH MORE (70% + ?) results IN THE LAST COUPLES YEARS point to the theory that most AD drugs induce/stimule SOME KIND OF BRAIN PLASTICITY MECHANISM/PHENOMENON and that it would be that effect which brings *MOST* -ALLIVIATED- DEPRESSED PATIENT out of their misery. While this is not quite what I would call a scientific concensus (!!) it's seems this theory is already as good as the other ! .. and at this pace, will surpass the infamous monoamine theory and others in the next decade. In fact, it's already a more respected/elegant theory that any other.
Btw, Here's how I see the whole thing: (oversimplified version)
Depression is a biological mechanism which kicks in when the brain evaluate (RIGHTFULLY OR WRONGLY !) solely based on HIS PERCEPTION OF RESULTS (which has MANY point-of-failure and evoluated in a world QUITE DIFFERENT that the one we are living in in 2008 ! and so is often maladapted) that the organism, which he's part of, behaviours/strategies are badly performing to the point where it become a viable/acceptable risk, from a evolutionism point of view, TO FORCE THE ORGANISM TO ADOPT A "SICKNESS BEHAVIOURS" STRATEGY (WITHDRAWAL AND AVOIDANCE, ECONOMY OF RESOURCES ETC ETC) TO PROTECT ITSELF WHILE HE PROGRESSIVELY *UNBUILD/UNLINK* IN A *BRUTEFORCE* KIND OF WAY SOME NEUROLOGICAL COMPONENTS (neurons, intraneuronal Unknows, dentrites, glials etc etc) IN SOME BRAIN ORGANS (ie. hypotalamus. hypocampus, amygdala etc) WHICH ARE SUITABBLE/VIABLE TARGETS FOR POSSIBLY INHIBITING, IN THIS *BRUTEFORCED* MATTER (some randomness/luck, some more somehow calculated moves), THE PROBLEMATIC UNVIABLE BEHAVIOURS/STRATEGIES.
Now 1 of 2 things could happen and both are viewed from OKAY to BEST from this strategy point of view:
1- BEST = the brain evaluated (again, RIGHTFULLY or WRONGFULLY by the up mentioned, PARTLY OBSOLETED by mordern day, "Organism objectives/results evaluation mechanism") that ENOUGH UNVIABLE behaviours/strategy are OUT and/or ENOUGH NEW (Coping? Adapting?) VIABLE behaviours/strategy came IN .. and so the brain GRADUALLY STOP (fadeout) this mecanism to start another one (fadein) which kick in to REBUILD to some extent the implicated (and so impaired) neurological organs base on NEW experiences...
2- OKAY= the operation has failed and the organism die OR doesn't reproduce (at all, or as much) because of the unviable/failing behaviours/strategy + the sickness behaviour induced by the 'depression' mechanism. And the whole thing is OKAY from an evolutionary point-of-view because it STATISTICALLY serves well the familly/clan by allowing the resources to go to the 'stronger' member AND serves well the species by helping getting pulling some unviable/inferior genes out of the species pool. Species > Clan > Organism (member) .. what's important is the GENES survival at the biggest scale, a single organism entity/instance (and his genes) has not much value in the big scheme.. in doubt one can spread some bad genes (combinaison etc) -> sacrifice is OKAY.
So.. at least 3 strategy/mechanisms is involved in this obviously oversimplified theory:1- Sickness behaviour : kicks in, in part, for a safer depression.
2- Depression : WANTED Partial-Bruteforce (semi-dumb, random) neurodegeneressance in some brain organs well suited (evoluated/ready for this operation)
3- Growth : increased but prudent neurological growth (structural, operational, etc etc.. neurogenesis is of the bunch) to the organs implicated in the depression. That mechanism COULD BE activated at the same time as the 'depression' in order to help find some coping/adaptating strategy ? .. kicks in from the start VERY WEAKLY and then goes from prudent to confident as the depression fadeout ?
Now where does the AD fits in this theory ? What about:
1- SOME would initially increase mechanism #1(sick.Behav) + #2(depres) and somehow after ~2 weeks forces the brain to promote #3 (Growth)in order to compensate or something ? (Increased Turnover Link ?) Prozac and Cie (SSRIs/SNRIs etc)2- SOME would just promote #3(Growth) and leave the other alone... but after awhile indirectly (by way of recovery) inhibits #2 and so #1 ? SSRE like Tianeptine ?
3- SOME would JUST kill the pain of the process and so in 'adjusted relieving' would allow the organism to NOT be paralized too much by the sickness behaviour and so find more easily what's working for him .. completing the process with success .. AND so in 'TOO MUCH relieving' would deprive the organism of some helpful (to some extent) CUES IN FORM OF PSYCHOLOGICAL PAIN and so would leave the organism with LESS CHANCES of completing succesfully the process than a more 'adjusted relieving' .. or not relieving at all in case of not-paralyzing-already-okay psychological pain... (Benzo style? .. which are, of course, not ADs in the strict sense)
Anyway this whole theory (which Neurogenesis is part of and support) makes ALOT of senses from an engineering/evolutionist point of view.. don't you think ?Any toughts ? .. wow what happened to the "I dont have the motivation today to start from zero and expose you all my fresh and more moderated arguments but I can summarize with" from the beginning of this post ? XD
/\/\arty
Posted by linkadge on July 4, 2008, at 10:57:46
In reply to Re: Hey Linkadge! » linkadge, posted by Marty on July 3, 2008, at 14:14:15
>MUCH MORE (70% + ?) results IN THE LAST COUPLES >YEARS point to the theory that most AD drugs >induce/stimule SOME KIND OF BRAIN PLASTICITY >MECHANISM/PHENOMENON and that it would be that >effect which brings *MOST* -ALLIVIATED- >DEPRESSED PATIENT out of their misery.
Again, I don't necessarily think so. I think recovery is probably associated with a recovery of normal hippocampal placticity, but I don't think enhancment of hippocampal placiticity is critical for the theraputic effect. The one study I provided is an example of this (ie prozac still had an antidepressant effect in these mice without affecting neurogenesis). Lamotrigine is another example. It has a robust antidepressant effect in some users but does have any neurotrophic effect that we can detect. There is of course the glutamatergic model of antidepressants (I.e. ketamine can aleviate depression in hours, far too short a timeframe to cause any significant hippocampal growth). I (personally) think the lag more required to produce the long term adaptations in regional NMDA function.
>While this is not quite what I would call a >scientific concensus (!!) it's seems this theory >is already as good as the other !
I think its a good idea, but ketamine seems to demonstrate that neurogenesis is not really critical for alleviation of certain forms of depression. I think that the restoration of placticity is a marker of recovery, but not critical for recovery.
>which he's part of, behaviours/strategies are >badly performing to the point where it become a >viable/acceptable risk, from a evolutionism >point of view, TO FORCE THE ORGANISM TO ADOPT >A "SICKNESS BEHAVIOURS" STRATEGY (WITHDRAWAL AND >AVOIDANCE, ECONOMY OF RESOURCES ETC ETC) TO >PROTECT ITSELF WHILE HE PROGRESSIVELY >*UNBUILD/UNLINK* IN A *BRUTEFORCE* KIND OF WAY >SOME NEUROLOGICAL COMPONENTS (neurons, >intraneuronal Unknows, dentrites, glials etc >etc) IN SOME BRAIN ORGANS (ie. hypotalamus. >hypocampus, amygdala etc) WHICH ARE >SUITABBLE/VIABLE TARGETS FOR POSSIBLY >INHIBITING, IN THIS *BRUTEFORCED* MATTER (some >randomness/luck, some more somehow calculated >moves), THE PROBLEMATIC UNVIABLE >BEHAVIOURS/STRATEGIES.
Some depression is associated with reduced hippocampal volume, but there is the possability that reduced hippocampal volume is a risk factor for depression. I think that stress can cause depression through with a variety of mechanisms: hormonal, immune, monoamine, bloodflow changes, intracellular alteration, HPA axis abormalities etc. Antidepressants may not necessarily need to produce neurotrophic effects in order to quell the pain of depression IMO.
Some studies find reduced hippocampal volume only in *chronic / prolonged* depression.
http://www.jneurosci.org/cgi/content/abstract/19/12/5034
This means that depression can exist without hippocampal atrophy and that the atrophy might be a *result* of prolonged depression, not the cause. Alternatively, those with the lowest hippocampal volume may be the ones that are the least responsive to treatment.
For instance, this study found that those with the smallet hippocampal volumes are the ones that are more likely to relapse:
http://bjp.rcpsych.org/cgi/content/abstract/192/6/472
This would suggest that low hippocampal volume is not necessary for depression, but it is sufficiant to worsen the course of depression.
But even the mechanisms of this are unclear. For instance, the smaller hippocampal volume might not directly cause the depression, but it might do so indirectly. For instance smaller hippocampal volume => poorer memories for coping mechanisms. Ie a person with smaller volume may have fewer relative connections with regards to how to cope with certain stressors etc.
>3
>Now where does the AD fits in this theory ? What >about:
>1- SOME would initially increase mechanism #1
>(sick.Behav) + #2(depres) and somehow after ~2 >weeks forces the brain to promote #3 (Growth)in >order to compensate or something ? (Increased >Turnover Link ?) Prozac and Cie (SSRIs/SNRIs etc)The SSRI's might also may more provide symptomatic treatment. For instance, many of the SSRI's (fluoxetine included) have some sort of opioid mechanism. Some also have an ability to ehance the function of reward circutry. These effects may produce the behavioral effects independant of neurotrophic effects.
>2- SOME would just promote #3(Growth) and leave >the other alone... but after awhile indirectly
>(by way of recovery) inhibits #2 and so #1 ? >SSRE like Tianeptine ?I think the neurotropic and neuroprotective effects may enhance recovery and reduce relapse by way of positive cognative restructuring. I.e. increased neruogenesis helps establish memories which are critical for more effective coping strategies. *But* there are many drugs which enhance cognition and promote neurogenesis which are not antidepressants. For instance, nootropics and smart drugs are usually not effective antidepressants, some actually *increase* depression (cholinsterase inhibitors etc).
>3- SOME would JUST kill the pain of the process >and so in 'adjusted relieving' would allow the >organism to NOT be paralized too much by the >sickness behaviour and so find more easily >what's working for him
Depression is a vicious cycle. Sometimes symptomatic improvement is all thats needed. Every brain is built with the capacity for depression. Everybody has the *hell* circutry. Chronic stress in mice causes depression through a number of mechanisms. For instance, reward circutry becomes less active. Cholinergic systems also become supersensitive producing superactive memory for negative events. The stress is simply altering a number of emotional switches which tells the brain which circutry to use. The antidepressant combats these effects and attemts to turn off the switches turned on by stress. In doing so, it tries to restore a more balanced functionality of the pain/pleasure circutry.
I think those with lower hippocampal volume may find general day to day adaptation more difficult. Everyday stressors are harder to cope with. This causes an increase is subjective stress which again turns on the depressive switches. Drugs like Ketamine work so quickly because it is able to more quickly target the hyperactive/hypoactive brain circutry and metabolism. An SSRI may take weeks to dampen and enhance certain regional bloodflow wheras ketamine can do it rather quickly.
Ketamine appears capable of produceing longer lasting (weeks) relief from depression. After its influence wears off though, the effects of life and stress may start to resenstize the 'hell' circutry etc. At this point any agent which can help the patient process life events in a more postive way or help the patient change their life in a way that is that will allow the patient to make their life subjectively more managable, may be what prevents relapse - this may be through neurogenesis,
*but* keep in mind anything that can make the patient more active and capable of interacting with their environment is likely to enhance neurogenesis. Learning, physical activity, decreased iscolation, increased sociability, etc are all capable of promoting neurogenesis. So, even if the drug doesn't directly enhance plactiity, it may do so indirectly by simply reducing depression.
>not-paralyzing-already-okay psychological >pain... (Benzo style? .. which are, of course, >not ADs in the strict sense)
Yes, but benzo's tent to dampen neuronal activity in general. They can also dampen pysical activity too, ie they can abolish more adaptive behaviors. So, the reason they are not antidepressants is not necessarily that they don't produce neurogenesis.
>Anyway this whole theory (which Neurogenesis is >part of and support) makes ALOT of senses from >an engineering/evolutionist point of view.. >don't you think ?
Partially. Again, I think it may be part of the picture, but I don't think it is necessarily the *core* issue.
Again (in summary) mainly for the following reasons:
1) Not all studies show AD's promote neurogenesis
2) Some studies show the AD effect does not require neurogenesis.
3) Many compounds with AD effect have no influence on neurogenesis, ketamine, lamotrigine, etc.
4) Some studies show that only *chronic* depression is assocaited with reduced hippocampal volume.
5) There are many neurotrophic agents which are not antidepressant.
Linkadge
Posted by Jamal Spelling on July 6, 2008, at 14:28:56
In reply to Re: Hey Linkadge!, posted by linkadge on July 4, 2008, at 10:57:46
I am going to stop taking Cymbalta. Even the FDA patient information sheet warns of possible liver damage!?!
http://www.fda.gov/cder/drug/InfoSheets/patient/duloxetinePIS.pdf
That's more than I'm comfortable with.
Posted by Marty on July 6, 2008, at 22:22:55
In reply to Re: Hey Linkadge!, posted by Jamal Spelling on July 6, 2008, at 14:28:56
> I am going to stop taking Cymbalta.
My 2 cents: If it works well and you can cope with the side effects I suggest you continue with it and don't touch anything. The chances for you having those liver issues are about THE SAME AS GETTING HIT BY A CAR CROSSING ANY STREET IN A CITY... and maybe even less likely ! Will you stop crossing streets tomorow now that I'm telling you this ? ;)
BUT.. if it doesn't help much .. then I agree with you: Cymbalta isn't a clean drug enough for taking it while having only some small benefits.
Only my opinion ;) .. you may want to read again the first post I wrote you after you ask Linkadge what he though of Cymbalta.
Good luck!
/\/\arty
Posted by Jamal Spelling on July 7, 2008, at 10:54:40
In reply to Re: Hey Linkadge! » Jamal Spelling, posted by Marty on July 6, 2008, at 22:22:55
Thanks for your response Marty.
Cymbalta does seem to be working quite well for me. I'm a bit confused about what to do now. There are also conflicting studies on PubMed about the effect of Cymbalta on liver function. Maybe I'll first have my liver function tested and then decide. The good thing about SRIs is you can't do anything suddenly, otherwise you get withdrawal. So I'm still a long way away from quitting completely.
Thanks!
Posted by Marty on July 7, 2008, at 15:48:09
In reply to Re: Hey Linkadge! » Marty, posted by Jamal Spelling on July 7, 2008, at 10:54:40
> Thanks for your response Marty.
My pleasure.
> Cymbalta does seem to be working quite well for me.
I'm glad to hear that. I'm also glad you decided to take your time and think about it. Keep us posted about your decision.
/\/\arty
Posted by 49er on July 8, 2008, at 7:25:38
In reply to Re: Hey Linkadge! » Jamal Spelling, posted by Marty on July 6, 2008, at 22:22:55
> > I am going to stop taking Cymbalta.
>
> My 2 cents: If it works well and you can cope with the side effects I suggest you continue with it and don't touch anything. The chances for you having those liver issues are about THE SAME AS GETTING HIT BY A CAR CROSSING ANY STREET IN A CITY... and maybe even less likely ! Will you stop crossing streets tomorow now that I'm telling you this ? ;)
>
Marty,As one who developed a hearing loss from Remeron and cognitive side effects from the rest of my med cocktail, I have a different view.
First of all, what may seem like a rare side effect is based on what is reported and not what actually exists. I read somewhere that only about 10% of actual side effects are ever reported to the FDA.
Also, if doctors don't take it seriously when patients report side effects, in my opinion, you can't really trust the reports of how often side effects really occur.
Yes, the drug may be working great for Jamal Spelling now but all drugs eventually poop out. Then what?
Finally, everyone talks about how if you don't stay on your med, your depression will get out of control, etc. But no one talks about the cure being worse than the disease.
Having a hearing loss and cognitive issues on top of an already existing learning disability is devastating. The only reason I don't allow myself to get depressed is I am tapering off all my meds and I know that if I succumbed to it, I would go down a path that would keep me on meds forever. So I don't go there. But it hurts.
49er
Posted by 49er on July 8, 2008, at 7:28:33
In reply to Re: Hey Linkadge!, posted by Jamal Spelling on July 6, 2008, at 14:28:56
> I am going to stop taking Cymbalta. Even the FDA patient information sheet warns of possible liver damage!?!
>
> http://www.fda.gov/cder/drug/InfoSheets/patient/duloxetinePIS.pdf
>
> That's more than I'm comfortable with.Jamal,
See my response to Marty. Obviously, only you can make the decision but if it were me, I would definitely get off it.
If you do decide to get off of Cymbalta, please do it slowly. Paxil Progress recommends 10% of the current dose every 3 to 6 weeks. You might have to go even more slowly since this drug has one of the shortest half lives.
Good luck.
49er
Posted by Marty on July 8, 2008, at 16:00:26
In reply to Re: Hey Linkadge! » Marty, posted by 49er on July 8, 2008, at 7:25:38
> As one who developed a hearing loss from Remeron and cognitive side effects from the rest of my med cocktail, I have a different view.
I'm sorry to hear that 49er. That's terrible. I too am living with some sequels from meds (tried ~30 meds):
1- Permanent Tinnitus (but only when it's calm, no sound around me.. after a couple year not that bad .. I dont notice it often, strangely) .. think it started on Nardil.
2- Unspecified Facial pain that doesn't fit in any Dx .. this began after withdrawing from Clonazepam a couple years ago. Even if I tempered my withdrawal and the dose was only .5mg/day ...
3- Partial POST-SSRI Genital anesthesia and partial anorgasmia, again POST-SSRI. Paxil seems to be the worst offender.
So as you can see I'm well aware of the possible consequences of some meds. But I know it's not everyone that is so much predisposed to those kind of sequel. I keep that in mind when I give others advice because the man who is one of the few which got hit by a car while crossing the street is sure to have a different point of view on the danger/odds of getting hit !
> First of all, what may seem like a rare side effect is based on what is reported and not what actually exists. I read somewhere that only about 10% of actual side effects are ever reported to the FDA.I know but we got a good enough feeling to know that those meds are SAFE ENOUGH to prescribe it to someone suffering depression/anxiety. It would NOT be safe enough as an headache pill BUT depression is a potentially fatal disease just like cancer ... would you tell a man with cancer to NOT follow chemotherapy because of the associated risk ? ... Without the same meds that f*cked my face, ears and p*nis, I wouldn't be here in 2008. YMMV
> Also, if doctors don't take it seriously when patients report side effects, in my opinion, you can't really trust the reports of how often side effects really occur.Yes, but again we have a feeling of the occurence and we know it's relatively safe compared to many other class of meds and also in relation to the decree of severity of the disease they treat (depression/anxiety etc).
> Yes, the drug may be working great for Jamal Spelling now but all drugs eventually poop out. Then what?
I have to disagree. Not all drugs poop out at some point. This perception you have could be encouraged your own experience and by going to some forum like Dr-Bob where there's a MUCH higher of "treatment resistant" people. People for who meds work great and long time don't come here often.. why would they ? ... too busy living there life and I'm happy for them.
> Finally, everyone talks about how if you don't stay on your med, your depression will get out of control, etc. But no one talks about the cure being worse than the disease.
I understand how you feel and I know what you know and yes that is true that we don't hear often of the darkside of those meds. BUT for MOST PEOPLE.. the treatment (ADs aren't CURE.. I'm sure you agree with me on this!) isn't worse than the disease. But that's true for many people.. especially the one that comes on this kind of forum.
> Having a hearing loss and cognitive issues on top of an already existing learning disability is devastating. The only reason I don't allow myself to get depressed is I am tapering off all my meds and I know that if I succumbed to it, I would go down a path that would keep me on meds forever. So I don't go there. But it hurts.
I feel you. That's very hard to live the appearance of a disability/sequel/disease coming from a med which was supposed to help our depression, not f*ck our body and our quality of life .... I, for one, feel you on this.
/\/\arty
Posted by linkadge on July 10, 2008, at 13:06:51
In reply to Re: Hey Linkadge! » 49er, posted by Marty on July 8, 2008, at 16:00:26
I agree. Meds do have side effects but it does need to be taken in perspective.
Some medication side effects are idosyncratic whereas some are exposure/dose dependant.
I am taking straterra because it really helps me and I can't find too many functional alternatives. I am concenred about the potential liver problems. I don't know if periodic testing would help.If this reaction is ideosyncratic, where only certain people have liver reactions, then that would be ok. If atomoxatine is hepatotoxic in geneeral and damages most livers in a dose / exposure dependant way (like alcohol), then I am not so sure I want to be taking it for any length of time.
I have post SSRI persistant sexual dysfunction too. But to be honest, I'd rather have this than liver damage. Anyhow, its hard to find somebody who can put the side effects into proper perspective.Linkadge
This is the end of the thread.
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