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Dr. Bob is Robert Hsiung, MD,
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Posted by morgan miller on September 9, 2010, at 13:47:02
In reply to Re: Another semi failed trial » morgan miller, posted by conundrum on September 9, 2010, at 13:07:06
> Thanks for asking. I am currently taking 2.5 mg abilify. I went up to 5 mgs to see if it would help but it made my head feel really weird like some kind of pressure. Maybe two drugs that both work on post synaptic receptors don't mix so well. I don't know why though. So I went back down after 4 days to 2.5. Unfortunately it is too expensive for me to take anyway.
>
> I would like to try nortriptyline since its so cheap and it may increase norepinephrine better than mirtazapine. I could probably combine the two and maybe help with concentration and mood. Desipramine was a bit more expensive.
>
> I put zoloft on the back burner. Seems like it might help at a lose dose, but I don't have a good track record with SSRIs anymore. Having nortriptyline on board first might help with the headaches SSRIs give me.
>
> I'm also considering trying Wellbutrin XL the Watson version, since i'm not sure what my pdoc thinks about me taking a TCA yet. The generic Wellbutrin I had from Teva isn't supposed to be as good as the Watson or brand (if she has samples) and I respond better to longer acting drugs in general.Screw what the doc thinks about using a TCA, you need to do what's best for you, not what a conventional doctor influenced by the pharmaceutical industry thinks is best. We need doctors, but sometimes we just need to do our own research and may educated decisions on treatment options.
I'm assuming you have not discussed using Nortriptyline with your doctor yet. If you have not, you should.
Wellbutrin is worth a shot. Have you tried it before? My mother does very well on Wellbutrin. I couldn't handle it, it made me agitated and made my whole body tremble.
Posted by linkadge on September 9, 2010, at 14:04:00
In reply to Re: Another semi failed trial, posted by morgan miller on September 9, 2010, at 13:47:02
Well, here's my 2 cents:
The fact that people on revolution health find abilify effective doesn't really say a whole lot about its overall effectivness as an adjunct.
With sites like this, you often have non-response bias, i.e. you are not randomly seeking the experiences of a pool of *all* abilify users. Instead you are simply relying on the responses of those who respond on the site.
Those who have a positive response to a certain medication are more likely (to have the energy and motivation) to want to share their experiences (unless somebody has a *really* negative response). As a result, the responses from boards like revolution health are likely to be more positive than what would be obtained through random sampling of all users of Abilify.
This is why time is so important to the establishment of the utility of a particular medication. Things can really look great in the short term (i.e. remember the lamictal craze of 2004? - this is in spite of the fact that on the GSK trial registry, lamictal has failed something like 10x more psychiatric trials than it has ever proven useful for - and when it has proven useful it was not on the primary outcome measures)
Linkadge
Posted by morgan miller on September 9, 2010, at 14:31:04
In reply to Re: Another semi failed trial » morgan miller, posted by linkadge on September 9, 2010, at 14:04:00
Believe me, I abhor the marketing of things like Abilify. Still I wonder if it indeed would be a good option for me and others at a very low dose.
Posted by conundrum on September 9, 2010, at 14:44:29
In reply to Re: Another semi failed trial, posted by morgan miller on September 9, 2010, at 13:47:02
Wellbutrin only made me agitated for one day, but I did get tremors. I felt like I was full of adrenaline even though I was not nervous or anxious at all. I thought maybe the brand or watson generic might release at a slower rate and prevent those side effects. Like drinking 3 beers through out the day rather than all at once, less side effects.
Posted by conundrum on September 9, 2010, at 14:56:05
In reply to Re: Another semi failed trial » linkadge, posted by morgan miller on September 9, 2010, at 14:31:04
Abilify is worth a shot if you can afford it and other things have failed. To me its like a bigger caffeine buzz that fades. I know Emmanuel said it worked really well for him though. It probably is less likely to cause TD since it is a partial agonist at the D2 receptors, although TD has still occured. Its really expensive though.
Posted by morgan miller on September 9, 2010, at 15:14:30
In reply to Re: Another semi failed trial » morgan miller, posted by conundrum on September 9, 2010, at 14:56:05
Thanks for the input conundrum.
Posted by linkadge on September 9, 2010, at 15:45:51
In reply to Re: Another semi failed trial » conundrum, posted by morgan miller on September 9, 2010, at 15:14:30
I'm not saying that Abilify is no good for anybody. I just hate to see when people start blaming themselves for failing medications which are promoted by the drug companies as god's gift to the mentally ill.
Linkadge
Posted by Conundrum on September 9, 2010, at 15:53:54
In reply to Re: Another semi failed trial, posted by linkadge on September 9, 2010, at 15:45:51
Good point Link. (I hope you don't mind that, the triforce be with you.)
I guess in a way I do blame myself. These new super selective drugs just don't seem to hold up over time to the older drugs. Speaking of revo-health and askapatient the highest rated drugs are the MAOis and stimulants. Even my pdoc admitted the MAOis were more effective. They just have more side effects they say. I just don't buy into that. She named one side effect of desipramine, constipation. Thats what prune juice and muscarinic agonists are for.
Abilify only works to increase dopamine in the prefrontal cortex. Not in the reward or mesolimbic emotional areas. If you wanna hit that hard your gonna need side effect ridden zyprexa or addictive stims. OR! Nardil or Parnate!
Hmm, I have some in the drawer from my grandmom... I'd have to ween off everything first...
I know all the diet restrictions...
hmm...
for now i'll stay the course, and try to be compliant, and I did mention TCAs but my pdoc is younger and doesn't seem to keen on them. Its my body though right?Oh I have some vics so I might try them tomorrow.
Posted by morgan miller on September 9, 2010, at 16:16:11
In reply to Re: Another semi failed trial, posted by linkadge on September 9, 2010, at 15:45:51
> I'm not saying that Abilify is no good for anybody. I just hate to see when people start blaming themselves for failing medications which are promoted by the drug companies as god's gift to the mentally ill.
>
> LinkadgeI hear ya
Posted by emme on September 9, 2010, at 16:16:20
In reply to Re: Another semi failed trial, posted by linkadge on September 9, 2010, at 11:51:23
> Its B.S. that these meds are good for TRD.Three plus years of success with Lamictal + Abilify for me for TRD! Of course I'm an "n" of one, and no combo will work for everyone. But I suspect "fads" start because at least some portion of the population has success.
Posted by morgan miller on September 9, 2010, at 16:25:58
In reply to Re: Another semi failed trial » linkadge, posted by Conundrum on September 9, 2010, at 15:53:54
>Hmm, I have some in the drawer from my grandmom... I'd have to ween off everything first...
I know all the diet restrictions...
hmm...You lost me, what do you have in your drawer?
>for now i'll stay the course, and try to be compliant, and I did mention TCAs but my pdoc is younger and doesn't seem to keen on them. Its my body though right?
Yes, it is your body. I would tell your pdoc that you are going to try Nortriptyline whether they approve or not. That is, if this is what you choose to do. Bring some literature on SSRI + Nortriptyline in to them and print out other's experiences on SSRI + Nortriptyline treatment, if you have access to some. We have to be our own advocates!
I have to say, the one drug that made me feel like I had enhanced response to rewards and pleasure was Zoloft. It may not do this for me anymore, but for a long long time, it did. That's why I really want to try combining Zoloft with Nortriptyline to see what happens.
I didn't know Zyprexa hit the reward and mesolimbic areas of the brain. Is this through 5ht2c antagonism? Or is it through another mechanism? I can't do Zyprexa anymore, it makes it too easy for me to sleep in and ruminate over negative conditions in my life.
Morgan
Posted by linkadge on September 9, 2010, at 18:44:00
In reply to Re: Another semi failed trial » linkadge, posted by Conundrum on September 9, 2010, at 15:53:54
I was on parnate and it was one of the cleanest medications I have ever taken.
Linkadge
Posted by linkadge on September 9, 2010, at 18:47:00
In reply to Re: Another semi failed trial, posted by morgan miller on September 9, 2010, at 16:25:58
The overall effect of zyprexa on dopamine function is not clear. It does antagonize 5-ht2c receptors, which enhances dopamine release in certain brain regions, but it also blocks dopamine receptors. So the net effect on dopamine receptor mediated events? Who knows..
Linkadge
Posted by emmanuel98 on September 9, 2010, at 19:12:59
In reply to Re: Another semi failed trial, posted by linkadge on September 9, 2010, at 18:47:00
Well I'm just and n of one but abilify worked like magic for me. It's a shame it's still under patent and ridiculously expensive. But if you can't afford it, you can't afford it. Parnate worked like magic for me as well and that's cheap, generic (I think). It requires a two-week washout of other meds, but if the other meds aren't working,, who cares? Might be worth a shot.
Posted by SLS on September 10, 2010, at 5:03:58
In reply to Re: Another semi failed trial » linkadge, posted by Conundrum on September 9, 2010, at 15:53:54
> Abilify only works to increase dopamine in the prefrontal cortex.What about its partial D2 and D3 agonist activity? Do you know where I can find information affirming your statement here?
Thanks.
- Scott
Posted by SLS on September 10, 2010, at 5:15:35
In reply to Re: Another semi failed trial, posted by linkadge on September 9, 2010, at 18:47:00
> The overall effect of zyprexa on dopamine function is not clear. It does antagonize 5-ht2c receptors, which enhances dopamine release in certain brain regions, but it also blocks dopamine receptors. So the net effect on dopamine receptor mediated events? Who knows..
>
> LinkadgeWhat would be the effect of the partial 5-HT1a autoreceptor (somatodendritic?) agonism Abilify exhibits?
- Scott
Posted by Conundrum on September 10, 2010, at 6:41:48
In reply to Re: Another semi failed trial » Conundrum, posted by SLS on September 10, 2010, at 5:03:58
"Moreover, aripiprazole, 0.3 mg/kg, slightly but significantly increased dopamine release in the medial PREFRONTAL CORTEX but not in the NUCLEUS ACCUMBENS.(Nac) These increases were significantly inhibited by WAY100635. By contrast, aripiprazole, 3.0 mg/kg and 10 mg/kg, significantly decreased dopamine release in the nucleus accumbens but not the medical prefrontal cortex. "
It actually can decrease dopamine in the Nac.
"However, aripiprazole 10 mg/kg significantly decreased dopamine release in the both regions. Aripiprazole had no effect on acetylcholine release in the medial prefrontal cortex, hippocampus, or nucleus accumbens at any dose, except for 3.0 mg/kg, which decreased acetylcholine release in the nucleus accumbens only. "
Abilify is actually a 5 HT2C antagonist/agonist so that be part of the reason why there is no increase in the NAC.
http://www.ncbi.nlm.nih.gov/pubmed/16336943This seems to be the effect of the atypical drugs with 5HT2a antagonism and weak 5HT2C antagonism.
(may have to delete spaces in link for it to work)
Abilify is actually a 5 HT2C antagonist/agonist so that be part of the reason why there is no dopamine increase in the NAC.
http://www.ncbi.nlm.nih.gov/pubmed/16336943Zyprexa which is a stronger 5 HT2C antagonist the Nac.
http://www.springerlink.com/content/lmcjhp01pqf34jxy/
Here is a link to the binding affinities of Atypical Antipsychotics
http://www.nature.com/npp/journal/v28/n3/fig_tab/1300027t1.html#figure-title
Thats it before this gets moved to Neurotransmitters. :D
Posted by SLS on September 10, 2010, at 7:11:42
In reply to Re: Another semi failed trial, posted by Conundrum on September 10, 2010, at 6:41:48
Posted by linkadge on September 10, 2010, at 7:52:20
In reply to Re: Another semi failed trial » linkadge, posted by SLS on September 10, 2010, at 5:15:35
>What would be the effect of the partial 5-HT1a >autoreceptor (somatodendritic?) agonism Abilify >exhibits?
I'm not sure. Does it have any post synaptic efficacy at 5-ht1a?
The acute effects of agonizing 5-ht1a autoreceptors would be to decrease overall serotoninergic firing. This might be expected to increase dopamine release in certain brain regions which are under inhibitory control by serotonin.
OHOT, chronic administration might desensitize the autoreceptors, thus increasing serotonergic functioning and producing the reverse action.
It really depends on the brain region and the serotonin receptor involved. For instance, in the frontal cortex, post synaptic 5-ht1a agonism increases dopamine release, wheras 5-ht2c agonism decreases it.
Linkadge
Posted by linkadge on September 10, 2010, at 7:55:41
In reply to Re: Another semi failed trial, posted by Conundrum on September 10, 2010, at 6:41:48
Well, if abilify only slightly increases dopamine in the prefrontal cortex, then I would suspect that its otherwise potent (non d2) dopamine receptor antagonism would counteract this.
Linkadge
Posted by Conundrum on September 10, 2010, at 7:59:33
In reply to Re: Another semi failed trial, posted by linkadge on September 10, 2010, at 7:55:41
So basically it is like you said a newer drug but not as good as older drugs. The dirtier the drug the better the response right?
Thirty tablets of 2 mg, 5 mg and 10mg cost a good $440.
nortripytline $3.50 from a canadian pharmacy. 7.50 from adam's discount pharmacy.
Posted by SLS on September 10, 2010, at 8:03:54
In reply to Re: Another semi failed trial » SLS, posted by linkadge on September 10, 2010, at 7:52:20
> > What would be the effect of the partial 5-HT1a autoreceptor (somatodendritic?) agonism Abilify exhibits?
> I'm not sure. Does it have any post synaptic efficacy at 5-ht1a?From what I've read, it does. However, I don't know what the net effect on PFC activity would be.
> The acute effects of agonizing 5-ht1a autoreceptors would be to decrease overall serotoninergic firing. This might be expected to increase dopamine release in certain brain regions which are under inhibitory control by serotonin.
Okay. I understand.
> OHOT, chronic administration might desensitize the autoreceptors, thus increasing serotonergic functioning and producing the reverse action.
>
> It really depends on the brain region and the serotonin receptor involved. For instance, in the frontal cortex, post synaptic 5-ht1a agonism increases dopamine release, wheras 5-ht2c agonism decreases it.Interesting.
Thanks for replying.
- Scott
Posted by linkadge on September 10, 2010, at 8:04:30
In reply to Re: Another semi failed trial, posted by Conundrum on September 10, 2010, at 6:41:48
And again, if abilify is a potent d3 antagonist, this would be expected to block some / all the pleasurable effects of dopamine release in the NAc.
Linkadge
Posted by Conundrum on September 10, 2010, at 8:08:35
In reply to Re: Another semi failed trial, posted by linkadge on September 10, 2010, at 8:04:30
> And again, if abilify is a potent d3 antagonist, this would be expected to block some / all the pleasurable effects of dopamine release in the NAc.
>
> LinkadgeEff that shiz, anhedonia is one of my core symptoms.
Posted by linkadge on September 10, 2010, at 10:42:41
In reply to Re: Another semi failed trial » linkadge, posted by Conundrum on September 10, 2010, at 7:59:33
>So basically it is like you said a newer drug >but not as good as older drugs. The dirtier the >drug the better the response right?
Well I don't know if dirty directly equates to efficacy. I just think that there are fads in psychiatry. Sure, some will respond to abilify augmentation just as some respond to lithium augmentation or thyroid augmentation or nortriptyline augmentation. The key idea is that there is money to be made off of abilify at the moment.
The big thing 10 years ago was risperdal / olanzapine augmentation. There were all sorts of fancy studies demonstrating superior efficacy of SSRI + atypical. Overall attitudes have changed towards atypicals however, since the demonstration (in CATIE) that the atypicals are really not more effective than the typicals (in positive or negative symptoms) and that they have more metabolic side effects.
Can't you remember 10 years back everybody being on paxil + zyprexa.
I would think that perphenazine augmentation would be as effective as abilify augmentation. But significantly more doctors use abilify because it is the drug du jour.
Linkadge
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