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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by TomG on April 9, 2006, at 13:49:21
I was on 25mgs for about 5 days and then took it up to 50mgs. I've been there for about 6 days. I got some mild energy in the beginning a maybe a little better focus and some insomnia. All that is gone now. Right now I have absolutely no effects from the drug. Is it a sugar pill? Someone give me some hope.
Tom
Posted by SLS on April 9, 2006, at 13:56:20
In reply to Amisulpride Sucks So Far...., posted by TomG on April 9, 2006, at 13:49:21
> I was on 25mgs for about 5 days and then took it up to 50mgs. I've been there for about 6 days. I got some mild energy in the beginning a maybe a little better focus and some insomnia. All that is gone now. Right now I have absolutely no effects from the drug. Is it a sugar pill? Someone give me some hope.
I had the same experience with sulpiride, a similar drug. I think if either of these drugs is going to work, it is going to work rather quickly. You should know one way or another within the first 2 weeks, provided you are taking the right dosage. I remember a few people here reporting that they needed 100mg of amisulpride to gain a sustained effect. I think 50mg is the average effective dose when treating depression or dysthymia.
I wish you luck.
- Scott
Posted by Tom Twilight on April 9, 2006, at 16:09:09
In reply to Re: Amisulpride Sucks So Far...., posted by SLS on April 9, 2006, at 13:56:20
High Tom
(I thought I was the only one!)
You probably don't want to hear this but I'm afraid I got nothing from Amisulpride, it was just like a sugar pill to me.
I'm really sorry........
Hope someone has a better experience
Posted by blueberry on April 9, 2006, at 17:42:55
In reply to Amisulpride Sucks So Far...., posted by TomG on April 9, 2006, at 13:49:21
Years ago I had great results with amisulpride, until my supply ran out and I couldn't get more in time.
The first few days are indeed energetic as that new dopamine rush kicks in. Then the dopamine receptors quickly adapt and you don't feel the rush anymore. It feels like nothing. But if you can wait for 4 weeks, that is when all the extra dopamine flow that is going on will cause a cascade of changes that results in a good antidepressant and anti-anxiety effect. Like all meds, it takes time. It's just that the initial dopamine rush can be misleading and a tease.
25mg probably is too low. 50mg to 100mg would be better.
Posted by ed_uk on April 9, 2006, at 18:10:22
In reply to Amisulpride Sucks So Far...., posted by TomG on April 9, 2006, at 13:49:21
Hi Tom
You might need a higher dose. Up to ~ 300mg is used to treat the negative symptoms of schizophrenia. Up to 1200mg for psychosis.
>Is it a sugar pill?
No! But it doesn't work for everyone.
Regards
Ed
Posted by ed_uk on April 9, 2006, at 18:12:19
In reply to Amisulpride Sucks So Far...., posted by TomG on April 9, 2006, at 13:49:21
>up to 50mgs. I've been there for about 6 days
6 days is not very long. You MIGHT need a higher dose, but you might not. Give it a little longer at 50mg before you come to a decision.
Ed
Posted by TomG on April 9, 2006, at 18:46:52
In reply to Re: Amisulpride Sucks So Far...., posted by ed_uk on April 9, 2006, at 18:10:22
I'll go as I as I need to. Scared I am not. Thanks for the replies. Patience is the hard part.
Tom
Posted by SLS on April 9, 2006, at 18:54:07
In reply to Re: Amisulpride Sucks So Far...., posted by blueberry on April 9, 2006, at 17:42:55
I wasn't aware that there should be such a latency of effect with amisulpride. It makes sense, though.
- Scott
> Years ago I had great results with amisulpride, until my supply ran out and I couldn't get more in time.
>
> The first few days are indeed energetic as that new dopamine rush kicks in. Then the dopamine receptors quickly adapt and you don't feel the rush anymore. It feels like nothing. But if you can wait for 4 weeks, that is when all the extra dopamine flow that is going on will cause a cascade of changes that results in a good antidepressant and anti-anxiety effect. Like all meds, it takes time. It's just that the initial dopamine rush can be misleading and a tease.
>
> 25mg probably is too low. 50mg to 100mg would be better.
Posted by linkadge on April 9, 2006, at 19:32:51
In reply to Re: Amisulpride Sucks So Far...., posted by SLS on April 9, 2006, at 18:54:07
I wouldn't think there would be latency either. The rational for this drug strange/mixed. It would not need time to desensitize dopamine autoreceptors like perhaps a MAO-B inhibitor. Wasn't it thought to work as dopamine autoreceptor antgonist ?
The other issue is that, it still is an antipsychotic. I think it has strong antagonistic affinity for D3 receptors (which are heavily located in the neucleus accumbens). So the net effect on dopaminergic neurotransmission, I don't know.
Linkadge
Posted by SLS on April 9, 2006, at 19:50:18
In reply to Re: Amisulpride Sucks So Far.... » SLS, posted by linkadge on April 9, 2006, at 19:32:51
> I wouldn't think there would be latency either. The rational for this drug strange/mixed. It would not need time to desensitize dopamine autoreceptors like perhaps a MAO-B inhibitor. Wasn't it thought to work as dopamine autoreceptor antgonist ?
>
> The other issue is that, it still is an antipsychotic. I think it has strong antagonistic affinity for D3 receptors (which are heavily located in the neucleus accumbens). So the net effect on dopaminergic neurotransmission, I don't know.Me neither.
I didn't know about the D3 antagonism. I wonder what would happen if one were to mix amisulpride with either pramipexole or ropinirole. I guess it would depend upon the relative binding affinities of each drug to the pre- and post- synaptic receptors. One would hope that amisulpride would be stronger at the presynaptic D2 and the agonists stronger at the postsynaptic D3.
- Scott
Posted by TomG on April 9, 2006, at 21:45:29
In reply to Re: Amisulpride Sucks So Far.... » linkadge, posted by SLS on April 9, 2006, at 19:50:18
Have you known anyone to combine pramipexole with amisulpride? Should the amisulpride fail on its own I thought it a good place to start for augmenting agents. That or a stimulant. I've got a lonley bottle of modafinil in my medicine drawer too.
Tom
Posted by Questionmark on April 10, 2006, at 3:12:34
In reply to Re: Amisulpride Sucks So Far.... » linkadge, posted by SLS on April 9, 2006, at 19:50:18
> > I wouldn't think there would be latency either. The rational for this drug strange/mixed. It would not need time to desensitize dopamine autoreceptors like perhaps a MAO-B inhibitor. Wasn't it thought to work as dopamine autoreceptor antgonist ?
> >
> > The other issue is that, it still is an antipsychotic. I think it has strong antagonistic affinity for D3 receptors (which are heavily located in the neucleus accumbens). So the net effect on dopaminergic neurotransmission, I don't know.
>
> Me neither.
>
> I didn't know about the D3 antagonism. I wonder what would happen if one were to mix amisulpride with either pramipexole or ropinirole. I guess it would depend upon the relative binding affinities of each drug to the pre- and post- synaptic receptors. One would hope that amisulpride would be stronger at the presynaptic D2 and the agonists stronger at the postsynaptic D3.
>
>
> - ScottAccording to the first abstract below, amisulpride supposedly should be primarily antagonistic at D2 & D3 autoreceptors (and therefore enhances dopamine transmission) in the frontal cortex, and it supposedly should have primary agonistic actions at D2 & D3 postsynaptic receptors (and therefore inhibit dopamine transmission) in the limbic system. The specific consequences of these actions-- i'm not sure.
Of course, these pharmacological characteristics might only exist at certain doses. Maybe the opposite occurs at, say, lower doses. It would seem like this should be the case at least in regard to the limbic system effects, since i would suspect "dopamine rush"-like effects to come through DA stimulation in the limbic areas and antipsychotic properties to result from DA inhibition there. But heck, i don't know.
Interesting drug though._Amisulpride: Progress and Outcomes._
Lecrubier Y.
The French Institute of Health and Medical Research.
Hjpital La Salpetriere, Paris, France.
Curr Med Res Opin 2002;18 Suppl 3:s18-22
[Not sure what that journal title is.]ABSTRACT
Amisulpride is a unique atypical antipsychotic that selectively blocks D2 and D3 receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission, and postsynaptically in the limbic areas, possibly reducing it. Thus dopaminergic over-activity in the frontal cortex, and under-activity in the limbic areas, can be treated simultaneously, alleviating both positive and negative symptoms of schizophrenia, respectively. In acute schizophrenia, amisulpride is at least as effective as haloperidol, with a greater number of patients responding to treatment as determined by Clinical Global Impression (CGI scores (p = 0.014). In addition, amisulpride is associated with a lower incidence of extrapyramidal symptoms (EPS) as determined by Simpson-Angus scores (SAS) when compared with haloperidol (p = 0.0053). Amisulpride showed similar efficacy to risperidone as determined by the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptom Score (PANSS) positive subscale; a trend towards greater improvement of negative symptoms as determined by PANSS negative subscale compared with risperidone; and similar levels of EPS. Amisulpride uniquely benefits patients with negative symptoms and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/long-term treatment as demonstrated in studies of up to 12 months. Amisulpride demonstrates greater improvement in controlling symptoms compared to haloperidol. In terms of the relevance of the effects, a superiority is observed for quality of life, social adaptation and functioning as measured by the Quality of Life Scale (QLS), Clinical Glocal Impression scale (CGI) and Functional Status Questionnaire (FSQ) scales. Amisulpride also has one of the lowest potentials of all the antipsychotic agents for weight gain. The clinical evidence for amisulpride supports its earlier pre-clinical potential, showing it to be an atypical antipsychotic agent with specific clinical advantages.
__A Review of the Pharmacokinetics, Tolerability and Pharmacodynamics of Amisulpride in Healthy Volunteers.__
Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G.
Department of Internal Medicine-Clinical Development.
Sanofi-Synthelabo, Chilly-Mazarin, France.
Human Psychopharmacology, 2002, Jan, 17(1):1-13.ABSTRACT
Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50-300 mg/day), and also on the positive symptoms of the disease at high dosages (400-800 mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of approximately 12 h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400 mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (/= 50 mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4 mg/day and is consistent with a weak blocking effect on striatal D(2) receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered.
Posted by SLS on April 10, 2006, at 6:05:54
In reply to Re: Amisulpride Sucks So Far.... » SLS, posted by Questionmark on April 10, 2006, at 3:12:34
Thanks!
These abstracts are very helpful.
- Scott
Posted by SLS on April 10, 2006, at 6:35:34
In reply to Re: Amisulpride Sucks So Far.... » SLS, posted by TomG on April 9, 2006, at 21:45:29
> Have you known anyone to combine pramipexole with amisulpride?
No, I haven't. It is an interesting proposition, though.
> Should the amisulpride fail on its own I thought it a good place to start for augmenting agents. That or a stimulant. I've got a lonley bottle of modafinil in my medicine drawer too.
You never know what's going to do what. Linkadge might have some insight into how the drug pairings might interact.
Ideally, one might profit from combining amisulpride with a dopamine reuptake inhibitor like amineptine. Unfortunately, it is no longer available. Ritalin works as a DA reuptake inhibitor, but I'm not sure it exerts this action where it is most needed.
Modafinil is a drug with multiple actions. It does not seem to affect directly NE or DA neurotransmission. However, it does stimulate the release of glutamate in the thalamus, which then stimulates the release of DA in the nucleus accumbens.
Amphetamine acts primarily as a DA and NE releaser, although it also inhibits reuptake. I'd be inclined to try this first. The amisulpride would induce an increase in the synthesis of DA with the amphetamine inducing its release. It's just a guess, though.
I would also consider adding selegiline somewhere in there.
- Scott
Posted by linkadge on April 10, 2006, at 12:31:20
In reply to Re: Amisulpride Sucks So Far.... » linkadge, posted by SLS on April 9, 2006, at 19:50:18
Yeah, I think I got the d3 antagonism idea from your site :) But I do think it is true.
Linkadge
Posted by linkadge on April 10, 2006, at 12:32:05
In reply to Re: Amisulpride Sucks So Far.... » linkadge, posted by SLS on April 9, 2006, at 19:50:18
It would probably block the rewarding effects of say nicotine, which seems to depend on the functionality of d3 receptors.
Linkadge
Posted by linkadge on April 10, 2006, at 12:34:21
In reply to Re: Amisulpride Sucks So Far.... » SLS, posted by Questionmark on April 10, 2006, at 3:12:34
I guess it is necessary to ask weather dysthemia is more a disorder of reduced frontal cortex dopaminergic neurotransmission or limbic dopamine.
Linkadge
Posted by Caedmon on April 11, 2006, at 23:51:18
In reply to Re: Amisulpride Sucks So Far...., posted by linkadge on April 10, 2006, at 12:34:21
Amisulpride is such a weird drug!
> I guess it is necessary to ask weather dysthemia is more a disorder of reduced frontal cortex dopaminergic neurotransmission or limbic dopamine.>
I should think limbic? I would associate frontal cortex DA dysregulation would involve more cognitive deficits, such as occur with MDD. But I could be wrong, that's just what I understand, and I'm sure some manifestations of dysthymia involve cognitive issues. I believe that prefrontal cortical dysregulation is involved in a lot of mood disorders.
- C
Posted by linkadge on April 12, 2006, at 9:05:52
In reply to Re: Amisulpride Sucks So Far...., posted by Caedmon on April 11, 2006, at 23:51:18
I think prefrontal deficits can turn into lack of drive or motivation, but lack of limbic dopamine might reflect absence of reward (?).
Its not really about feeling great about sitting and doing nothing, I think its about finding motivation and reward in previously enjoyed activities.
Linkadge
This is the end of the thread.
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