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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by michael on May 17, 2008, at 23:01:23
Hello all -
I'm currently taking 450 mg wellbutrin xl, along with low dose (150 mg) sulpiride. The sulpiride seems to help, though rather subtly - I think maybe more with mood than with energy.
In the past I've tried low dose abilify (2.5 mg) abilify with the wellbutrin. The abilify was rather stimulating... I had a bit of akathisia/restlessness, and generally slept only 3 - 5 hours per night, (if I remember correctly) and some nights no sleep at all. The energy was helpful, but when I would get sleepy, I had difficulty getting to sleep - and as I mentioned, I would sleep only a few hours when I did sleep. When I increased the abilify to 5 mg, it flipped from stimulating, to sedating - a lot.
What I'm looking for is energy, or a stimulating effect.
I want to try the abilify again... however I'm trying to figure out if I should add it (@ only 1.25 mg) to the wellbutrin and sulpiride, or if I should stop the sulpiride first.
So, what I think I'm asking is, would the abilify be more likely to work with the sulpiride, in an additive fashion, in my search for more energy?
...or would it be more likely that adding the abilify to the wellbutrin & sulpiride combo would lead to sedation, along the lines of what I experienced at "higher" doses of abilify, (which I also experienced at higher doses of sulpiride)?
Or to put it another way... Given the methods of action suspected for sulpiride & abilify, I'm trying to figure out if I should stop the sulpiride or not, before trying the abilify again?
I hope that makes sense... Thanks for any thoughts or feedback that anyone may have to offer.
Michael
Posted by SLS on May 18, 2008, at 5:32:18
In reply to Sulpiride and Abilify questions..., posted by michael on May 17, 2008, at 23:01:23
Take a look at Geodon (ziprasidone). It is perhaps the most antidepressant-like of the atypical antipsychotics. A minority of people have unpleasant reactions to the drug, but I think it remains stimulating throughout its dosage range. I think it is worth trying.
- Scott
Posted by Phillipa on May 18, 2008, at 10:45:05
In reply to Re: Sulpiride and Abilify questions..., posted by SLS on May 18, 2008, at 5:32:18
Scott I have googled geodon and can't find a thing about it being good for depression can you provide a link? Thanks Phillipa
Posted by SLS on May 18, 2008, at 11:19:56
In reply to Re: Sulpiride and Abilify questions... » SLS, posted by Phillipa on May 18, 2008, at 10:45:05
> Scott I have googled geodon and can't find a thing about it being good for depression can you provide a link? Thanks Phillipa
1) Eye witness.
2) Speaking to doctors as to their clinical experience.
- Scott
Posted by undopaminergic on May 22, 2008, at 10:09:34
In reply to Sulpiride and Abilify questions..., posted by michael on May 17, 2008, at 23:01:23
I think aripiprazole (Abilify, APZ) is regarded as a full agonist at presynaptic dopamine (DA) (auto)receptors. This reduces DA synthesis and release, and is likely to be contrary to what you're looking for. Therfore, if sulpiride were to antagonise binding of APZ to autoreceptors, it would be expected to counter the sedative potential of the latter (APZ) and thus enhance stimulation. At higher doses, sulpiride might possibly block the partial agonism of APZ at postsynaptic DA receptors, and thus nullify the usefulness of the latter for dopaminergic enhancement.
In practice, you will have to test to determine the usefulness of the combination.
Posted by SLS on May 23, 2008, at 8:13:38
In reply to Re: Sulpiride and Abilify questions..., posted by undopaminergic on May 22, 2008, at 10:09:34
> I think aripiprazole (Abilify, APZ) is regarded as a full agonist at presynaptic dopamine (DA) (auto)receptors. This reduces DA synthesis and release, and is likely to be contrary to what you're looking for.
Not necessarily. One must look at all of the properties of aripiprazole. It is a dopamine system stabilizer (DSS). During times of excess synaptic DA, it acts as a full antagonist. During times of insufficient DA, it acts as an agonist at postsynaptic receptors. Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release. Aripiprazole has been known to produce psychosis, even at low dosages. This demonstrates the precedence that postsynaptic agonism has over presynaptic agonism.
http://www.medscape.com/viewarticle/468808_2
And let us not forget the ability of aripiprazole to block 5-HT2a receptors. It seems that this property has a synergistic effect as an antidepressant. The drug also binds to the serotonin transporter facilitating reuptake inhibition.
- Scott
Posted by SLS on May 23, 2008, at 10:13:22
In reply to Re: Sulpiride and Abilify questions..., posted by SLS on May 23, 2008, at 8:13:38
Here is an excerpt from the Medscape article for those who do not want to register for access of the site.
****************************************************
Clinical Pharmacology
Aripiprazole (Abilify; Bristol-Myers Squibb, Princeton, NJ) is chemically characterized as a quinolinone derivative (Figure 1).[9] Drug therapies developed to treat schizophrenia traditionally have targeted positive symptoms of the disease -- hallucinations and delusions. Dopamine neurotransmission appears to be important in psychosis; the D2 receptor plays the clearest role. All previously available antipsy-chotics are antagonists at D2 receptors.[10, 11] Aripiprazole is a partial agonist at these receptors.[12] Under conditions of dopamine excess, aripiprazole acts as a D2 receptor antagonist, since its intrinsic activity at the receptor is less than that of endogenous dopamine. This is its likely action at postsynaptic D2 receptors in patients with schizophrenia.
Figure 1. Chemical structure of aripiprazole.
Autoreceptors are receptors present on neurons that regulate the synthesis and release of ligands by positive and negative feedback processes. Generally, they provide negative feedback and thus downregulate neurotransmission. The intrinsic activity of partial dopamine agonists at presynaptic D2 autoreceptors is thought to reduce the synthesis and release of dopamine at the synapse.[13] The slight measure of agonist activity at autoreceptors lowers the tendency of the partial agonist to upregulate the receptors as a true antagonist would.[13] Aripiprazole has an affinity about 100 times higher for D2 than D1 receptors in rat striatum in vitro,[11] and has a high affinity for the D2 receptor.[14, 15] However, it caused minimal upregulation of D2 receptors in contrast to other high-affinity compounds, such as haloperidol.[11] High-affinity blockade of D2 receptors and increases in D2 receptor density are thought to be associated not only with untoward extrapyramidal symptoms but also with the development of tardive dyskinesia.[16]
In animal models, under hyperdopaminergic conditions, binding of aripiprazole resulted in decreased activation of D2 receptors, whereas in hypodopaminergic states, administration resulted in activation of D2 receptors.[15] Several models have been postulated regarding treatment of negative symptoms and focus on the dysregulation of dopamine in the prefrontal cortex. Improvement of negative symptoms through alleviating hypodopaminergic function in the prefrontal cortex with dopamine agonists or partial agonists has been hypothesized.[17, 18] The clinical benefits of aripiprazole in treating schizophrenia could be attributed in part to the drug's unique mechanism of action on dopamine and serotonergic receptors.
Aripiprazole is also an antagonist at the serotonin 5-HT2A receptors, a common trait of all atypical antipsychotics. The 5-HT2A antagonism is one potential mechanism by which atypical antipsychotic agents help alleviate negative symptoms associated with schizophrenia -- flattened affect, alogia, anhedonia, avolition, and emotional and social withdrawal.[19, 20] Therapy with agents that inhibit serotonergic function may increase dopaminergic transmission in the prefrontal cortex, and may result in improvement of negative symptoms.[19] It has also been asserted that 5-HT2A blockade may offer limited protection from the extrapyramidal symptomatology associated with extensive D2 blockade.[19]
Aripiprazole is also an agonist at 5-HT1A receptors.[21] The 5-HT1A agonists and their actions on somatodendritic autoreceptors may offer extra help in mediating extrapyramidal effects when D2 blockade is complete. This is accomplished through their inhibitory actions on serotonergic neurons, which leads to an increase in dopaminergic transmission in the striatum, thus decreasing EPS.[21] The pharmacologic actions of aripiprazole on these receptor types have led some specialists to describe the drug as the first of a new class of atypical antipsychotic agents, termed dopamine-serotonin system stabilizers.[22]
In addition to the actions mentioned above, aripiprazole is an antagonist at α1-adrenergic receptors. It also exhibits high affinity for D3 receptors, moderate affinity for D4, 5-HT2C and 5-HT7, histamine H1 receptors, and the presynaptic serotonin transporter site. However, the functionality of aripiprazole on these neuroreceptor subtypes is unclear.[23]
Posted by undopaminergic on May 23, 2008, at 15:37:34
In reply to Re: Sulpiride and Abilify questions..., posted by SLS on May 23, 2008, at 8:13:38
> > I think aripiprazole (Abilify, APZ) is regarded as a full agonist at presynaptic dopamine (DA) (auto)receptors. This reduces DA synthesis and release, and is likely to be contrary to what you're looking for.
>
> Not necessarily. One must look at all of the properties of aripiprazole.
>Right, so why do you quote - out of context - only one part of a message that looks at the properties most relevant to predicting how it will it will interact with sulpiride?
> Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
>That is dose dependent. At low doses of sulpiride/amisulpride and dopamine direct agonists, the presynaptic effects predominate.
Posted by SLS on May 23, 2008, at 15:45:11
In reply to Re: Sulpiride and Abilify questions..., posted by undopaminergic on May 23, 2008, at 15:37:34
> > > I think aripiprazole (Abilify, APZ) is regarded as a full agonist at presynaptic dopamine (DA) (auto)receptors. This reduces DA synthesis and release, and is likely to be contrary to what you're looking for.
> >
> > Not necessarily. One must look at all of the properties of aripiprazole.> Right, so why do you quote - out of context - only one part of a message that looks at the properties most relevant to predicting how it will it will interact with sulpiride?
Feel free to post the entire article. You can use the link I provided.
> > Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
> That is dose dependent.No. It is DA concentration dependent. I thought the article was clear about that. This is a well known property of this drug. Check out what Stephen Stahl, MD has to say about it.
Try reading the article. It won't take that long.
- Scott
Posted by undopaminergic on May 23, 2008, at 16:11:02
In reply to Re: Sulpiride and Abilify questions..., posted by undopaminergic on May 23, 2008, at 15:37:34
>
> > Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
> >
>
> That is dose dependent. At low doses of sulpiride/amisulpride and dopamine direct agonists, the presynaptic effects predominate.
>Furthermore, with the possible exception of some ergot-based dopamine agonists, they don't stimulate D1-receptors even at high concentrations, and hence fail to make up for the deleterious effects of reduced synthesis and release of endogenous DA. Insufficient (or excessive) stimulation of D1-receptors disturbs working memory, among other things. Fortunately in the case of aripiprazole, antagonism of serotonin 5-HT2A and 5-HT2C antagonism may possibly mitigate this problem.
Posted by SLS on May 23, 2008, at 16:21:27
In reply to Re: Sulpiride and Abilify questions..., posted by undopaminergic on May 23, 2008, at 16:11:02
> >
> > > Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
> > >
> >
> > That is dose dependent. At low doses of sulpiride/amisulpride and dopamine direct agonists, the presynaptic effects predominate.
> >
>
> Furthermore, with the possible exception of some ergot-based dopamine agonists, they don't stimulate D1-receptors even at high concentrations, and hence fail to make up for the deleterious effects of reduced synthesis and release of endogenous DA. Insufficient (or excessive) stimulation of D1-receptors disturbs working memory, among other things. Fortunately in the case of aripiprazole, antagonism of serotonin 5-HT2A and 5-HT2C antagonism may possibly mitigate this problem.
Why is D1 so important to mood illnesses? I should think that D2 and D3 are more important, as they facilitate the activities of limbic structures, primarily, the nucleus accumbens. Reward, motivation, and all of that stuff. Apomorphine, an unselective DA receptor agonist (including D1), does not appear to have antidepressant properties.The key might not be which DA receptors are affected, but in what tracts they are affected.
- Scott
Posted by undopaminergic on May 24, 2008, at 16:21:48
In reply to Re: Sulpiride and Abilify questions... » undopaminergic, posted by SLS on May 23, 2008, at 16:21:27
>
> Why is D1 so important to mood illnesses? I should think that D2 and D3 are more important, as they facilitate the activities of limbic structures, primarily, the nucleus accumbens. Reward, motivation, and all of that stuff.
>At least some dopamine actions in that region require the simultaneous activation of both D1- and D2-receptor subtypes. Drugs that accomplish that, typically by enhancing the production or release of DA - such as cocaine, heroin, or L-dopa - generally produce effects that are more desirable - especially subjectively - than do synthetic direct agonists or partial agonists.
> Apomorphine, an unselective DA receptor agonist (including D1), does not appear to have antidepressant properties.
>On the other hand, the fact that apomorphine remains in use despite its unfavourable technical properties - such as a short half-life and the necessity to administer it by injection - suggests that it is superior to alternatives in other respects, including a more complete or natural receptor binding profile.
> The key might not be which DA receptors are affected, but in what tracts they are affected.
>The place is indeed of significance. The relative importance of different types of receptors may also vary between regions.
Posted by undopaminergic on May 24, 2008, at 16:31:12
In reply to Re: Sulpiride and Abilify questions... » undopaminergic, posted by SLS on May 23, 2008, at 15:45:11
> > > > I think aripiprazole (Abilify, APZ) is regarded as a full agonist at presynaptic dopamine (DA) (auto)receptors. This reduces DA synthesis and release, and is likely to be contrary to what you're looking for.
> > >
> > > Not necessarily. One must look at all of the properties of aripiprazole.
>
> > Right, so why do you quote - out of context - only one part of a message that looks at the properties most relevant to predicting how it will it will interact with sulpiride?
>
> Feel free to post the entire article. You can use the link I provided.
>I was referring to your quotation of my message, not the aripiprazole article.
> > > Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
>
>
> > That is dose dependent.
>
> No. It is DA concentration dependent. I thought the article was clear about that. This is a well known property of this drug.
>Both agonist concentration and endogenous DA tone are (almost certainly) of significance, and the article does not contradict that. In any case, I was not referring to APZ exclusively, but to other agents as well.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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