![[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 Seamus2 on May 27, 2000, at 11:14:16
Doc gave the go ahead to try Amisulpride.
Ordering from PharmaciaCerati.Will do two week washout of current Parnate just to be safe.
Anyone know of contraindications w/ amisulpride and other drugs?
Thanks,
Seamus
Posted by AndrewB on May 28, 2000, at 15:53:50
In reply to Amisulpride and MAOI -- AndrewB, posted by Seamus2 on May 27, 2000, at 11:14:16
Seamus,
I think you can take amisulpride and parnate together. I'll ask though and get back to you.
AndrewB
Posted by AndrewB on May 29, 2000, at 9:13:31
In reply to Re: Amisulpride and MAOI -- AndrewB, posted by AndrewB on May 28, 2000, at 15:53:50
Seamus,
The pharmacist at Farmacia Ceratti said that an internal paper on amisulpride urged caution when combining amisulpride with other antidepressants and that your doctor should be consulted before making such combinations.
I wonder what this advice means in practical terms!
Posted by michael on May 29, 2000, at 16:21:37
In reply to Re: Amisulpride and MAOI -- AndrewB, posted by AndrewB on May 29, 2000, at 9:13:31
> Seamus,
>
> The pharmacist at Farmacia Ceratti said that an internal paper on amisulpride urged caution when combining amisulpride with other antidepressants and that your doctor should be consulted before making such combinations.
>
> I wonder what this advice means in practical terms!
Clinical particulars
Therapeutic indications: Solian (AMISULPRIDE) is indicated for the treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent, including patients characterised by predominant negative symptoms.
Posology and method of administration: For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended. In individual cases, the daily dose may be increased up to 1200 mg/d. Doses above 1200 mg/d have not been extensively evaluated for safety and therefore should not be used. No specific titration is required when initiating the treatment with Solian. Doses should be adjusted according to individual response.For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive symptoms.
Maintenance treatment should be established individually with the minimally effective dose.
For patients characterised by predominant nega- tive symptoms, oral doses between 50 mg/d and 300 mg/d are recommended. Doses should be adjusted individually.
Solian can be administered once daily at oral doses up to 300 mg, higher doses should be administered bid.
Elderly: Solian should be used with particular caution because of a possible risk of hypotension or sedation.
Children: Solian is contra-indicated in childen under 15 years of age as its safety has not yet been established.
Renal insufficiency: Solian is eliminated by the renal route. In renal insufficiency, the dose should be reduced to half in patients with creatinine clearance (CRCL) between 30-60 ml/min and to a third in patients with CRCL between 10-30 ml/min.
As there is no experience in patients with severe renal impairment (CRCL65 years) show that a 10-30% rise occurs in Cmax, T1/2 and AUC after a single oral dose of 50 mg. No data are available after repeat dosing.
Preclinical safety data: An overall review of the completed safety studies indicates that Solian is devoid of any general, organ-specific, teratogenic, mutagenic or carcinogenic risk. Changes observed in rats and dogs at doses below the maximum tolerated dose are either pharmacological effects or are devoid of major toxicological significance under these conditions. Compared with the maximum recommended dosages in man, maximum tolerated doses are 2 and 7 times greater in the rat (200 mg/kg/d) and dog (120 mg/kg/d) respectively in terms of AUC. No carcinogenic risk, relevant to man, was identified in the rat at up to 1.5 to 4.5 times the expected human AUC.
A mouse carcinogenicity study (120 mg/kg/d) and reproductive studies (160, 300 and 500 mg/kg/d respectively in rat, rabbit and mouse) were performed. The exposure of the animals to amisulpride during these latter studies was not evaluated.
Incompatibilities: None known.Shelf life: Solian 50 and Solian 200: 3 years.
Special precautions for storage: Solian 50 and 200: Store in a dry place below 25°C in its original container.
Instructions for use/handling: No special precautions.Date of first authorisation/renewal of authorisation
11 August 1997.Date of (partial) revision of the text
August 1997.
Posted by michael on May 29, 2000, at 16:38:08
In reply to Re: Amisulpride and MAOI -- AndrewB, posted by michael on May 29, 2000, at 16:21:37
How about selegiline 10mg/day and low dose amisulpride?
I think both work to increase dopamine levels, although via different mechanisms?
Theoretically, would therefore potentiate/reinforce each other?
Any thoughts - or corrections, etc?
Posted by michael on May 29, 2000, at 17:10:52
In reply to Re: Amisulpride and MAOI -- AndrewB, posted by michael on May 29, 2000, at 16:21:37
I somehow lost some of the info I meant to post.... having difficulty getting the whole msg to post... this is most of the interesting stuff - plus some not so interesting stuff.
One comment - it seems to me that a lot of (most)the concerns/cautions raised below are more relevant to high-dosage use, rather than to the low-dose use that Andrew has referred to in the past.
Oh yeah - one more thing, check out this web site also: http://solian.com.ph/ Lots more info.
Here's what I meant to post originally:
Clinical particularsTherapeutic indications: Solian is indicated for the treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent, including patients characterised by predominant negative symptoms.
Posology and method of administration: For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended. In individual cases, the daily dose may be increased up to 1200 mg/d. Doses above 1200 mg/d have not been extensively evaluated for safety and therefore should not be used. No specific titration is required when initiating the treatment with Solian. Doses should be adjusted according to individual response.
For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive symptoms.
Maintenance treatment should be established individually with the minimally effective dose.
For patients characterised by predominant nega- tive symptoms, oral doses between 50 mg/d and 300 mg/d are recommended. Doses should be adjusted individually.
Solian can be administered once daily at oral doses up to 300 mg, higher doses should be administered bid.
Elderly: Solian should be used with particular caution because of a possible risk of hypotension or sedation.
Children: Solian is contra-indicated in childen under 15 years of age as its safety has not yet been established.
Renal insufficiency: Solian is eliminated by the renal route. In renal insufficiency, the dose should be reduced to half in patients with creatinine clearance (CRCL) between 30-60 ml/min and to a third in patients with CRCL between 10-30 ml/min.
As there is no experience in patients with severe renal impairment (CRCL<10 ml/min) particular care is recommended in these patients.
Hepatic insufficiency: Since the drug is weakly metabolised a dosage reduction should not be necessary.
Contra-indications: Hypersensitivity to the active ingredient or to other ingredients of the drug.
Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer.
Phaeochromocytoma.
Childen under 15 years of age.
Pregnancy or lactation.
Women of childbearing potential unless using adequate contraception.
Special warnings and special precautions for use: As with other neuroleptics, Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated CPK, may occur. In the event of hyperthermia, particularly with high daily doses, all antipsychotic drugs including Solian should be discontinued.
Solian is eliminated by the renal route. In cases of severe renal insufficiency, the dose should be decreased and intermittent treatment should be prescribed (see Posology and method of administration).
Solian can lower the seizure threshold. Therefore patients with a history of epilepsy should be closely monitored during Solian therapy.
In elderly patients, Solian, like other neuroleptics, should be used with particular caution because of a possible risk of hypotension or sedation.
As with other antidopaminergic agents, caution should be also exercised when prescribing Solian to patients with Parkinson's disease since it may cause worsening of the disease. Solian should be used only if neuroleptic treatment cannot be avoided.
Interaction with other medicaments and other forms of interaction: Solian may enhance the central effects of alcohol.
Caution should be exercised with the concomitant administration of drugs such as: CNS depressants including narcotics, anaesthetics, analgesics, sedative H1 antihistamines, barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives; antihypertensive drugs and other hypotensive medications; dopamine agonists (e.g. levodopa) since it may attenuate their action.
Pregnancy and lactation:
Pregnancy: In animals, Solian did not show direct reproductive toxicity. A decrease in fertility linked to the pharmacological effects of the drug (prolactin mediated effect) was observed. No teratogenic effects of Solian were noted.
The safety of Solian during human pregnancy has not been established. Therefore, use of the drug is contra-indicated during pregnancy and in women of child bearing potential unless using adequate contraception.
Lactation: It is not known whether Solian is excreted in breast milk, breast-feeding is therefore contra- indicated.
Effects on ability to drive and use machines: Even used as recommended, Solian may affect reaction time so that the ability to drive vehicles or operate machinery can be impaired.
Undesirable effects: The following adverse effects have been observed in controlled cinical trials. It should be noted that in some instances it can be difficult to differentiate adverse events from symptoms of the underlying disease.
Common adverse effects (5-10%): insomnia, anxiety, agitation.
Less common adverse effects (0.1-5%): somnolence, gastrointestinal disorders such as constipation, nausea, vomiting, dry mouth.
In common with other neuroleptics: Solian causes an increase in plasma prolactin levels which is reversible after drug discontinuation. This may result in galactorrhoea, amenorrhoea, gynaecomastia, breast pain, orgasmic dysfunction and impotence.
Weight gain may occur under therapy with Solian.
Acute dystonia (spasm torticolis, oculogyric crisis, trismus) may appear. This is reversible without discontinuation of Solian upon treatment with an antiparkinsonian agent.
Extrapyramidal symptoms may occur: tremor, rigidity, hypokinesia, hypersalivation, akathisia. These symptoms are generally mild at optimal dosages and partially reversible without discontinuation of Solian upon administration of antiparkinsonian medication. The incidence of extrapyramidal symptoms which is dose related, remains very low in the treatment of patients with predominantly negative symptoms with doses of 50-300 mg/day.
Tardive dyskinesia characterised by rhythmic, involuntary movements primarily of the tongue and/or face have been reported, usually after long term administration. Antiparkinsonian medication is ineffective or may induce aggravation of the symptoms.
Hypotension and bradycardia have been reported occasionally as well as an isolated case of QT prolongation.
Allergic reactions and cases of seizures have been reported occasionally.
Rare cases of Neuroleptic Malignant Syndrome have been reported (see Special warnings and special precautions for use).
Overdose: Experience with Solian in overdosage is limited. Exaggeration of the known pharmacological effects of the drug have been reported. These include drowsiness and sedation, coma, hypotension and extrapyramidal symptoms.
In cases of acute overdosage, the possibility of multiple drug intake should be considered. Since Solian is weakly dialysed, hemodialysis should not be used to eliminate the drug. There is no specific antidote to Solian. Appropriate supportive measures should therefore be instituted, close supervision of vital functions and cardiac monitoring is recommended until the patient recovers.
If severe extrapyramidal symptoms occur, anticholinergic agents should be administered.
Pharmacological properties
Pharmacodynamic properties: Amisulpride binds selectively with a high affinity to human dopaminergic D2/D3 receptor subtypes whereas it is devoid of affinity for D1, D4 and D5 receptor subtypes.
Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonin, ;in-adrenergic, histamine H1 and cholinergic receptors. In addition, amisulpride does not bind to sigma sites.In animal studies, at high doses, amisulpride blocks dopamine receptors located in the limbic structures in preference to those in the striatum. At low doses it preferentially blocks pre-synaptic D2/D3 receptors, producing dopamine release responsible for its disinhibitory effects.
This pharmacological profile explains the clinical efficacy of Solian against both negative and positive symptoms of schizophrenia.
Pharmacokinetic properties: In man, amisulpride shows two absorption peaks: one which is attained rapidly, one hour post-dose and a second between 3 and 4 hours after administration. Corresponding plasma concentrations are 39±3 and 54±4 ng/ml after a 50 mg dose.
The volume of distribution is 5.8 l/kg, plasma protein binding is low (16%) and no drug interactions are suspected.
Absolute bioavailability is 48%. Amisulpride is weakly metabolised: two inactive metabolites, accounting for approximately 4% of the dose, have been identified. There is no accumulation of amisulpride and its pharmacokinetics remain unchanged after the administration of repeated doses. The elimination half-life of amisulpride is approximately 12 hours after an oral dose.
Amisulpride is eliminated unchanged in the urine. Fifty percent of an intravenous dose is excreted via the urine, of which 90% is eliminated in the first 24 hours. Renal clearance is in the order of 20 l/h or 330 ml/min.
A carbohydrate rich meal (containing 68% fluids) significantly decreases the AUCs, Tmax and Cmax of amisulpride but no changes were seen after a high fat meal. However, the significance of these findings in routine clinical use is not known.
Hepatic insufficiency: since the drug is weakly metabolised a dosage reduction should not be necessary in patients with hepatic insufficiency.
Renal insufficiency: The elimination half-life is unchanged in patients with renal insufficiency while systemic clearance is reduced by a factor of 2.5 to 3. The AUC of amisulpride in mild renal failure increased two-fold and almost ten-fold in moderate renal failure (see Posology and method of administration). Experience is however limited and there is no data with doses greater than 50 mg.
Amisulpride is very weakly dialysed.
Preclinical safety data: An overall review of the completed safety studies indicates that Solian is devoid of any general, organ-specific, teratogenic, mutagenic or carcinogenic risk. Changes observed in rats and dogs at doses below the maximum tolerated dose are either pharmacological effects or are devoid of major toxicological significance under these conditions. Compared with the maximum recommended dosages in man, maximum tolerated doses are 2 and 7 times greater in the rat (200 mg/kg/d) and dog (120 mg/kg/d) respectively in terms of AUC. No carcinogenic risk, relevant to man, was identified in the rat at up to 1.5 to 4.5 times the expected human AUC.
Incompatibilities: None known.
Posted by AndrewB on May 30, 2000, at 1:57:39
In reply to Re: Amisulpride and Selegiline, posted by michael on May 29, 2000, at 16:38:08
> How about selegiline 10mg/day and low dose amisulpride?
>
> I think both work to increase dopamine levels, although via different mechanisms?
>
> Theoretically, would therefore potentiate/reinforce each other?
>
> Any thoughts - or corrections, etc?Michael,
I've thought about combining selegiline and amisulpride. They could potentiate one another. I remember someone saying that they had combined selegiline (low dose) with amineptine, another dopaminergic. It seems though from the posts I've read and other personal reports that selegiline has little or no noticeable psychological effect on people at low doses. With this is mind, I wonder just how effective a potentiator of amisulpride it might be. I am going to try entacapone, a COMT inhibitor that acts to increase dopamine at the synapse, as an augumentator to amisulpride. Hydergine, a smart drug, is also dopaminergic and another possible augmenting agent for those with mental slowness.
Michael, what have you decided on the adrafinil. Is it working for you? I might try it as my reboxetine pooped out.
Posted by michael on May 30, 2000, at 14:00:15
In reply to Re: Amisulpride and Selegiline, posted by AndrewB on May 30, 2000, at 1:57:39
> > How about selegiline 10mg/day and low dose amisulpride?
> >
> > I think both work to increase dopamine levels, although via different mechanisms?
> >
> > Theoretically, would therefore potentiate/reinforce each other?
> >
> > Any thoughts - or corrections, etc?
>
> Michael,
>
> I've thought about combining selegiline and amisulpride. They could potentiate one another. I remember someone saying that they had combined selegiline (low dose) with amineptine, another dopaminergic. It seems though from the posts I've read and other personal reports that selegiline has little or no noticeable psychological effect on people at low doses. With this is mind, I wonder just how effective a potentiator of amisulpride it might be. I am going to try entacapone, a COMT inhibitor that acts to increase dopamine at the synapse, as an augumentator to amisulpride. Hydergine, a smart drug, is also dopaminergic and another possible augmenting agent for those with mental slowness.
>
> Michael, what have you decided on the adrafinil. Is it working for you? I might try it as my reboxetine pooped out.Andrew -
I know that selegiline isn't thought to be an effective AD at those low doses. But if I understand correctly, 10mg selegiline/day is sufficient to inhibit all MAOI-B in the brain (read it on the clinical pharmacolog 2000 site), which is the one which works primarily on Dopamine. I was thinking that therefore, it might potentiate the amisulpride...
As for the adrafinil - I had a week or two when I didn't take anything. I then started taking the adrafinil, and noticed a subtle but significant effect - more energy, less social withdrawl... Didn't "feel" stimulated, just normal for a change - not constantly run-down, tired, etc.
This was the case for about a week. At that point I got sick - the cold from hell. The first week, I was miserable, the second, I started to feel human again. But while I was sick the adrafinil couldn't break through the misery.
About this time, I also re-started wellbutrin SR, at 400mg/day, to try and quit smoking - completely.
Anyway, still taking the adrafinil. It helps somewhat - not to the degree it did that first week. (I tried skipping it, and it does still help) I'm wondering if it might be more effective again by itself, when I stop the wellbutrin (which unfortunately won't be for a while), or if it just "pooped-out", or if it's just an issue of building tolerance. (tolerance isn't supposed to be as much of a problem w/adrafinil as it is w/other stim's, since it's so focused on alpha-1 receptors - I believe)
I'm going to expirement with increasing the dose, to try to determine if it is a tolerance issue (ie: if I need increasing doses to get the same effect it had initially), or if maybe the wellbutrin makes a higher dose necessary...? or if it's just "pooped-out"...
I've been away for a while - what has been JohnL's experience - is it still working? JohnL...?
I'm also experimenting w/LOW dose amisulpride, as you suggested, since the 50mg/day made me sleep sooo much (like you mentioned, that seems to be a side effect more associated w/higher doses/overdose - if I've read the research correctly...?) So 1/4 of a tablet/day (approximately 12.5 mg/day). I did it for about a week, and the most noticeable effect was increased libido, and elimination of problems with erection which the adrafinil had induced.
I'm planning on trying it again for another week, to see if I get the same results, and pay more attention for any other, more subtle results.
And as I mentioned initially, I'm also interested in experimenting a bit w/low dose selegiline, both in place of, as well as in in addition to the amisulpride.
I'm trying to just change one variable at a time - difficult to be patient enough, now that I finally have some ideas that I want to try... Oh yeah, I also have some reboxetine, but haven't had the time to give it a try yet, w/all the other "trials" I'm trying.
Hope that ramble is coherent/makes sense... As always, I'd be interested in any comments/insights, suggestions, etc. that anyone may have... michael
Posted by AndrewB on May 31, 2000, at 17:54:15
In reply to Re: Amisulpride and Selegiline, posted by michael on May 30, 2000, at 14:00:15
Michael,It sounds like you are taking a reasonable approach with your drug trials. One at a time is definitely the way to go.
Tell me how did you respond to Wellbutrin before? Did it increase your energy? Did it give you side effects?
Be careful when combining Wellbutrin and Adrafinil. Both work on NE. For example if you add a full dose of Wellbutrin to an already significant dose of Adrafinil, you might find yourself over agitated and with a rapid pulse and high blood pressure when the Wellbutrin fully kicks in.
If you haven’t experienced increased arousal either with Wellbutrin alone or this combo of Wellbutrin and Adrafinil, you may not be responsive to NE meds.
You can try a higher dose of Adrafinil, but only after you’ve given your system time (2 weeks) to stabilize on Wellbutrin. Also make sure your pulse and BP is not excessive.
Adrafinil receptors shouldn’t become tolerant after a week. I don’t think NE tolerance can work that fast. Sometimes though the increased energy might last only a week if there is an underlying metabolic insufficiency.
With the amisulpride I suggest that, yes, you do another 12.5 mg. trial for a week. If all goes well then do a 25mg. trial for a week. Hopefully this dose will give you a fuller response without the sleepiness. If this goes well you can try a 37.5mg. dose.
I reviewed some literature and I think that your idea of augmenting with selegiline is worth a try. You may experience increased energy and mood at a dose of 5 to 15 mg. I forget how long the effect takes to kick in. Again, don’t do this trial until you have stopped fiddling with the other meds.
Phenylalanine sometimes can be added onto selegiline with good results. I would give it a try. The trial need only take four days and it is available at the health food store.
St. John’s Wort also has some dopamine inhibition. I like what it has done for me. It seems to be gently uplifting of energy and mood.
Please let me know how it goes with your amisulpride trials and your selegiline augmentation.
Do you have a couple of favorite international pharmacies that you haven't already told me about. If so, drop me a line. I'm going to put together a list. Of course, non prescript. sources are of the most interest.
Best wishes,
AndrewB
Posted by michael on May 31, 2000, at 20:10:25
In reply to Re: Amisulpride and Selegiline, posted by AndrewB on May 31, 2000, at 17:54:15
Hey Andrew -
As always, thanks for the input...
And as for wellbutrin, never did much for me, except help w/smoking - even at 400mgSR/day. I may have gotten a little boost from it temporarily, which passed quickly, or it may have just been a placebo type of thing... it was a couple years ago. I've been on it roughly a month now.
This time it made me a bit edgy for a while, which I attribute to the fact that I went up to 400mgSR/day so quickly, which I did because from my previous experience, I knew I need to go that high (I was taking 300mg before I took my 2 week break), and that I had essentially no side effects in the past - except, now that I think back, I believe it increased my libido some. No apparent problems, so far, with the adrafinil/wellbutrin combo.
I tried St. John's before I tried wellbutrin - no effect that I could notice. I'll be interested to hear about your experiments/trials.
One more item, re: the adrafinil... It may not have faded after just the first week - I was really clobbered by that cold during weeks 2 & 3, and I don't think I would've noticed any difference - but I wanted to continue, since the effect is supposed to be cumulative - or at least vary as time goes by. That's also roughly the time I started again w/the wellbutrin... so I thought that may have been a factor as well...? Too many variables already.
Just for the record - I do know of at least one other person who claims it faded on them after a week, during which they noticed a significant improvement... Who knows - the YMMV motto is the only aboslute w/this stuff.
I'll let you know what I come up with, with the amisulpride and selegiline... That's it for the moment... michael
>
> Michael,
>
> It sounds like you are taking a reasonable approach with your drug trials. One at a time is definitely the way to go.
>
> Tell me how did you respond to Wellbutrin before? Did it increase your energy? Did it give you side effects?
>
> Be careful when combining Wellbutrin and Adrafinil. Both work on NE. For example if you add a full dose of Wellbutrin to an already significant dose of Adrafinil, you might find yourself over agitated and with a rapid pulse and high blood pressure when the Wellbutrin fully kicks in.
>
> If you haven’t experienced increased arousal either with Wellbutrin alone or this combo of Wellbutrin and Adrafinil, you may not be responsive to NE meds.
>
> You can try a higher dose of Adrafinil, but only after you’ve given your system time (2 weeks) to stabilize on Wellbutrin. Also make sure your pulse and BP is not excessive.
>
> Adrafinil receptors shouldn’t become tolerant after a week. I don’t think NE tolerance can work that fast. Sometimes though the increased energy might last only a week if there is an underlying metabolic insufficiency.
>
> With the amisulpride I suggest that, yes, you do another 12.5 mg. trial for a week. If all goes well then do a 25mg. trial for a week. Hopefully this dose will give you a fuller response without the sleepiness. If this goes well you can try a 37.5mg. dose.
>
> I reviewed some literature and I think that your idea of augmenting with selegiline is worth a try. You may experience increased energy and mood at a dose of 5 to 15 mg. I forget how long the effect takes to kick in. Again, don’t do this trial until you have stopped fiddling with the other meds.
>
> Phenylalanine sometimes can be added onto selegiline with good results. I would give it a try. The trial need only take four days and it is available at the health food store.
>
> St. John’s Wort also has some dopamine inhibition. I like what it has done for me. It seems to be gently uplifting of energy and mood.
>
> Please let me know how it goes with your amisulpride trials and your selegiline augmentation.
>
> Do you have a couple of favorite international pharmacies that you haven't already told me about. If so, drop me a line. I'm going to put together a list. Of course, non prescript. sources are of the most interest.
>
> Best wishes,
>
> AndrewB
Posted by AndrewB on June 1, 2000, at 1:37:42
In reply to Re: Amisulpride and Selegiline » AndrewB, posted by michael on May 31, 2000, at 20:10:25
Michael,
Yes , I too have heard of the arousal effect fading after a week. I just want to say that I would think that such a fade out isn't due to receptor tolerance. Rather it may be due to an underlying metabolic insufficiency. In other words, the body itself wouldn't be producing enough energy, say, at the cellular level. Anyway I've read of that line of reasoning. Just be aware that there are some people who don't respond to NE meds apparently because they don't have any energy reserves to stimulate. People with Chronic Fatigue Syndrome sometimes react this way to NEs. There are some often effective ways to deal with low metablolic energy supposedly.
My amineptine is on order.
Posted by Anna P. on June 1, 2000, at 18:34:23
In reply to Re: Amisulpride and Selegiline, posted by AndrewB on June 1, 2000, at 1:37:42
People with Chronic Fatigue Syndrome sometimes react this way to NEs. There are some often effective ways to deal with low metablolic energy supposedly.
>
> My amineptine is on order.> I responded to Amineptine when in a severe episode of my seasonal depression, but not to the amisulpride.
I can't tolerate any more stimulating drugs, although I need them. What's wrong with me?
SLS - what is the problem with the autonomic system?On Amineptine on 5th day I got:
-severe heart pain for 10 hours
- problems with breathing at the end of it
I didn't go to the doctor, as my physician doesn't care. So I conclude one may die here, and nobody
move a finger.
My husband would discourage me of going to the emergency room, as we don't have a good insurance.ANY INPUT?
Anna P.
Posted by AndrewB on June 2, 2000, at 1:43:27
In reply to Re: Amisulpride, Amineptine, posted by Anna P. on June 1, 2000, at 18:34:23
Anna,
I'm so glad to see your post. I haven't heard from you in a long time and I was so worried.
You sound so down. Try to be hopeful. I know it can seem hard or not make much sense at times but, you know, when one believes that good tiding are imminent, the wind can bring miraculous gifts in the guise of a helping hand from an old friend or some other earthly guise.
Your reaction to amineptine must have been scary. You've had similar reactions to stimulants haven't you? Amineptine increases dopamine (in the synaptic cleft) but this isn’t what caused your reaction. Through dopamine, amineptine has a cascade effect on the activity of norepinephrine. It sounds like some of your receptors that respond to norepinephrine caused your side effects, specifically, your beta andrenergic receptors. Antagonism of the beta 1 andrenergic receptor can cause side effects such as heartburn, shortness of breath, dizziness, tiredness, bradycardia and heart failure.
This does not necessarily mean you can’t take stimulants. But is does mean that you have NE dysregulation that will have to be dealt with first. Tell me, have you had a similar reaction to other stimulants? If so, you should consult your doctor, or better yet a cardiologist, about appropriate beta receptor medicines to deal with your side effects.
Sorry the amisulpride didn’t help. Did you have any reaction to it at all?
AndrewB
Posted by JohnL on June 2, 2000, at 3:24:57
In reply to Re: Amisulpride, Amineptine....Anna, posted by AndrewB on June 2, 2000, at 1:43:27
Anna,
I'm very sorry about Amineptine. That must have been a scary frustration. I hope you're feeling a little better now.
I was reading in the Physician's Desk Reference about the narcolepsy stimulant Provigil (Modafinil). Have you tried this one yet? The reason I ask is because it is described as having dopamine reuptake action without increasing the output of dopamine. Though it has other modes of action which may or may not be good for you--don't know--I thought the part about dopamine reuptake inhibition was worth noting.
JohnL
Posted by SLS on June 2, 2000, at 9:50:58
In reply to Re: Amisulpride, Amineptine....Anna, posted by JohnL on June 2, 2000, at 3:24:57
> Anna,
>
> I'm very sorry about Amineptine. That must have been a scary frustration. I hope you're feeling a little better now.
>
> I was reading in the Physician's Desk Reference about the narcolepsy stimulant Provigil (Modafinil). Have you tried this one yet? The reason I ask is because it is described as having dopamine reuptake action without increasing the output of dopamine. Though it has other modes of action which may or may not be good for you--don't know--I thought the part about dopamine reuptake inhibition was worth noting.
> JohnL
I really like JohnL's suggestion.Andrew made a good comment regarding Chronic Fatigue Syndrome. Has anyone ever suggested to you that you might have Mitral Valve Prolapse?
John - Someone told me about the Provigil package insert describing that it exerted some dopaminergic activity. I have not seen this cited on Medline. The studies I have seen concluded quite emphatically that it does not affect dopamine reuptake at the synapse. What's the deal? Would you be kind enough to summarize its pharmacology to me. If it is dopaminergic, I would really like to know this before my next doctor's visit on Wednesday. Does adrafinil do the same thing? If I were a cynic, I would say that the drug company is full of crap and just wants to cover all bases for treating narcolepsy.
Does the PDR give a bibliography?
On the contrary, it seems that modafinil *does* induce the release of dopamine in limbic structures through the inhibition of GABAergic neurotransmission.
Amineptine:Along with its ability to inhibit the reuptake of dopamine (DA), amineptine also inhibits the reuptake of (NE). This is probably the more likely explanation for such an acute autonomic response.
---------------------------------------------
For Anna and other person =>
Who wrote the following? I'm sorry I never saw it."> I responded to Amineptine when in a severe episode of my seasonal depression, but not to the amisulpride.
I can't tolerate any more stimulating drugs, although I need them. What's wrong with me?
SLS - what is the problem with the autonomic system?"What is your diagnosis?
Can you list the drugs or drug combinations you have tried?
Which gave you some improvement? How long did it take to feel the improvement? How long did last? What were the side effects?
Which stimulants have you tried? What were the side effects?
Without medication-induced side effects, which of these do you experience:
- dry mouth
- constipation
- heart palpitations
- sweating
- dizziness when you stand up
- unexplained changes in heart rate
- sudden breathlessness
- TMJ
- fibromyalgia
- tinnitus (ringing or buzzing in the ears)
- indigestion
- irritable bowel
- chronic fatigue/weakness
- panic attacks
Is there any history of cardiac disease/arrhythmia in your family? Irritable bowel? Mitral-Valve Prolapse? Diabetes? Anything?
Have you ever tried either a tricyclic or MAO inhibitor?
- Scott
Posted by S.D. on June 2, 2000, at 15:25:38
In reply to Re: Amisulpride, Amineptine....Anna and JohnL, posted by SLS on June 2, 2000, at 9:50:58
> On the contrary, it seems that modafinil *does* induce the release of dopamine in limbic structures through the inhibition of GABAergic neurotransmission.
>I'm kinda dense on the biochemistry stuff, but I always take note of stuff relating to GABA due to it's relevence to Social Anxiety. Does your above statement mean it inhibits GABA receptors? Why does inhibition of GABAergic neurotransmission induce the release of dopamine?
Thanks
peace and health,
S.D.
Posted by SLS on June 2, 2000, at 18:37:19
In reply to Re: seems that modafinil *does* induce... » SLS, posted by S.D. on June 2, 2000, at 15:25:38
> > On the contrary, it seems that modafinil *does* induce the release of dopamine in limbic structures through the inhibition of GABAergic neurotransmission.
> >
>
> I'm kinda dense on the biochemistry stuff, but I always take note of stuff relating to GABA due to it's relevence to Social Anxiety. Does your above statement mean it inhibits GABA receptors? Why does inhibition of GABAergic neurotransmission induce the release of dopamine?
>
> Thanks
>
> peace and health,
>
> S.D.
Hi S.D.How's it goin'?
Modafinil (Provigil) does not block (antagonize) GABA receptors. It decreases the level of GABA within the synapse due to a reduction of its release. These GABAergic neurons are designed to inhibit dopaminergic neurons and pathways, along with other excitatory pathways.
So...more GABA = less dopamine
less GABA = more dopaminemore GABA = less norepinephrine (noradrenaline)
less GABA = more norepinephrine (noradrenaline)more GABA = less excitation
less GABA = more excitationmore GABA = less anxiety
less GABA = more anxietyModafinil => less GABA => more anxiety
Neurontin => more GABA => less anxietyMany of the anticonvulsant mood stabilizers increase GABAergic neurotransmission. This may be the reason why Neurontin seems to be effective for treating anxiety and social-phobia.
Now, are you less excited or more excited for having read this?
Sincerely,
Scott
Posted by S.D. on June 4, 2000, at 22:19:31
In reply to Re: seems that modafinil *does* induce... » S.D., posted by SLS on June 2, 2000, at 18:37:19
>Hi S.D.
>
> How's it goin'?Hi SLS, thanks for asking. I guess it's goin' pretty swimmingly. I've got antidepressants that have eventually worked for me (at least for a while, but long enough to lift me out of The Pit) and at least one med that seems to work decently for Social Anxiety. The main reasons it's not exactly cool as a moose are that
A) while I feel less anxiety when I'm "put on the spot", I haven't the 1st clue about proactively acquiring friends or breaking into particular social groups.
and
2) ...well, it's non-psycho stuff so I'll spare everyone ;^)> So...
>
> more GABA = less dopamine
> less GABA = more dopamine
>
> more GABA = less norepinephrine (noradrenaline)
> less GABA = more norepinephrine (noradrenaline)
>
> more GABA = less excitation
> less GABA = more excitation
>
> more GABA = less anxiety
> less GABA = more anxiety
>
> Modafinil => less GABA => more anxiety
> Neurontin => more GABA => less anxiety
>
> Many of the anticonvulsant mood stabilizers increase GABAergic neurotransmission. This may be the reason why Neurontin seems to be effective for treating anxiety and social-phobia.
>
> Now, are you less excited or more excited for having read this?
>More perplexed mainly. Not about your answer, which was great. Rather about how increasing GABA has been associated with an anti-social-anxiety effect, yet so have MAOIs which result in the opposite effect on dopamine and norepinephrine. Oh well, I don't care so much anymore 'cuz I've been spending too much time studying this stuff as it is (instead of what I'm supposed to be studying - right now in fact - which is what my problem "2" above was about, the details of which I promised to spare you).
> Sincerely,
> Scottback atcha
peace and health,
S.D.
Posted by CarolAnn on June 5, 2000, at 9:37:08
In reply to thanks / how it's goin' / supplementary whining » SLS, posted by S.D. on June 4, 2000, at 22:19:31
>
> A) while I feel less anxiety when I'm "put on the spot", I haven't the 1st clue about proactively acquiring friends or breaking into particular social groups.>>Hi S.D., I hope you don't mind, my butting in, but I really feel for anyone who, like me, has trouble acquiring friends. I have exactly two, after years of actively looking. Unfortunatly, all I can offer are the same old cliches; church, volunteering, special interest classes(Gourmet Cooking?,ect.). I made my first friend in a theatre class, and the second at a writing workshop. From my experience, the only way to break into a social group, is to join one that has a purpose and is looking for members. Sometimes, making one friend can lead to making others 'through' that friend (his or her friends become your friends). Good luck and best wishes! CarolAnn
p.s. I'd love to hear how you progress, if you feel like posting about it.
Posted by SLS on June 6, 2000, at 10:30:13
In reply to thanks / how it's goin' / supplementary whining » SLS, posted by S.D. on June 4, 2000, at 22:19:31
> Hi SLS, thanks for asking. I guess it's goin' pretty swimmingly. I've got antidepressants that have eventually worked for me (at least for a while, but long enough to lift me out of The Pit) and at least one med that seems to work decently for Social Anxiety.
Would you be kind enough to give some details regarding your medication regimen? I’m still looking for ideas.
> The main reasons it's not exactly cool as a moose are that
> A) while I feel less anxiety when I'm "put on the spot", I haven't the 1st clue about proactively acquiring friends or breaking into particular social groups.
Carol Ann’s suggestions:
Hi S.D., I hope you don't mind, my butting in, but I really feel for anyone who, like me, has trouble acquiring friends. I have exactly two, after years of actively looking. Unfortunatly, all I can offer are the same old cliches; church, volunteering, special interest classes(Gourmet Cooking?,ect.). I made my first friend in a theatre class, and the second at a writing workshop. From my experience, the only way to break into a social group, is to join one that has a purpose and is looking for members. Sometimes, making one friend can lead to making others 'through' that friend (his or her friends become your friends). Good luck and best wishes! CarolAnn
p.s. I'd love to hear how you progress, if you feel like posting about it.Carol Ann – Those are wonderful suggestions. When (if) I get better, I think I’ll follow them.
> and
> 2) ...well, it's non-psycho stuff so I'll spare everyone ;^)
Thanks.
-------------------------------------------------------------
> > So...
> >
> > more GABA = less dopamine
> > less GABA = more dopamine
> >
> > more GABA = less norepinephrine (noradrenaline)
> > less GABA = more norepinephrine (noradrenaline)
> >
> > more GABA = less excitation
> > less GABA = more excitation
> >
> > more GABA = less anxiety
> > less GABA = more anxiety
> >
> > Modafinil => less GABA => more anxiety
> > Neurontin => more GABA => less anxiety
> >
> > Many of the anticonvulsant mood stabilizers increase GABAergic neurotransmission. This may be the reason why Neurontin seems to be effective for treating anxiety and social-phobia.
> >
> > Now, are you less excited or more excited for having read this?
> More perplexed mainly. Not about your answer, which was great. Rather about how increasing GABA has been associated with an anti-social-anxiety effect, yet so have MAOIs which result in the opposite effect on dopamine and norepinephrine.Ah… This is what makes neuroscience such a frontier of endeavor.
I like to remind people every now and then that the brain is not so simple as to be able to determine the net effect a drug will produce based simply upon what they do in test-tubes and in petri dishes filled with brain slices. I will ignore my own caveat make a comment regarding MAOIs. Most of them are capable of inhibiting the breakdown of serotonin, presumably increasing synaptic levels of this neurotransmitter. Serotonin and serotonergic pathways are generally *inhibitory*. They tend to *reduce* the activity of dopamine and norepinephrine neurons. Perhaps this will take some of the paradox out of the equation.
Good luck with psycho and non-psycho stuff.
- Scott
Posted by S.D. on June 6, 2000, at 19:08:19
In reply to Re: thanks / how it's goin' / supplementary whining, posted by SLS on June 6, 2000, at 10:30:13
>>I've got antidepressants that have eventually worked for me (at least for a while, but long enough to lift me out of The Pit) and at least one med that seems to work decently for Social Anxiety.
>
> Would you be kind enough to give some details regarding your medication regimen? I’m still looking for ideas.
>
------Absolutely. The first part is uneremarkable, but it gets a little more interesting at the end.
I'm not on an antidepressant currently, but I'll outline what I've been on in the past 20 months. (Note that this was not a highly severe/debilitating depression during this time.)Zoloft worked for me, starting to kick in after a few weeks. I don't think it did any good against SAD but I was given clonazepam (low dose) for a while to treat anxiety side effects, and I noticed that the stuff did reduce my inhibitions about speaking to my boss or in confrontational situations.
I quit the Zoloft and went with Parnate, which took I guess 3 months, including time to ramp up to 60mg/day. Again worked for depression, and no "apathy effect" setting in which was partly why I quit Zoloft. Quit it 12 weeks ago.
Here's the more interesting part, pharmaceutically speaking.
Was going to take the plunge with clonazepam/Klonopin but thought of Kava Kava. Maybe it was a Sign, that GNC had a bunch marked about 80% off.
It works! For me. YMMV of course. Side effects mainly were sleepiness for first few days, and itchy eyes. Supposedly doesn't have negative cognitive effects. 1000mg/day of 30% kavalactones preparation.
You can search for my posts a few weeks ago about kava kava if interested. Some more dosage info and links to more info sources.
It didn't transform me lightning-bolt style, or like Kramer wrote about in Listening To Prozac; maybe eventually it could. Hard to say how much it works because I have to experiment for a while with anxiety-inducing situations to really know, and I've trained all my life to avoid such situations in the first place.I would have stayed with Kava Kava except for an appt. I already had scheduled to talk w/ psychopharmocologist about Neurontin. So I started taking that (1200mg/day) and I think it too works. It's been about 10 days. Nearly zero side effects. I have a history of epilepsy and shyness/undiagnosed SAD in my family and this connection is why I was interested in Neurontin. You can search for my previous posts about epilepsy/SAD/anticonvulsant-med connection, and the one published study on Neurontin for SAD.
peace and health,
S.D.
Posted by S.D. on June 6, 2000, at 19:55:02
In reply to Re: a note to S.D., posted by CarolAnn on June 5, 2000, at 9:37:08
> Hi S.D., I hope you don't mind, my butting in,
but I really feel for anyone who, like me, has trouble acquiring friends. I have exactly two, after years of actively looking. Unfortunatly, all I can offer are the same old cliches; church, volunteering, special interest classes(Gourmet Cooking?
-----They may be cliches but I'm sure they are good ideas (Though for me, it'd have to be can opener-microwave-spoon cooking instead of gourmet cooking). No doubt they are better venues for socializing than the programming and network technology classes which are the only places lately that I've been among a group of people. I think it was Woody Allen who said 80% of life is just showing up, but maybe all the good stuff is in the other 20% because my problem is the next few steps after showing up.
I've read what to do: Approach someone who appears receptive (this is a tough one and someone with SAD is going to worry too much about determining whether someone is indicating receptiveness); ask ritualistic questions or questions based on the situation; follow up with open-ended questions; follow up on "free information" that the other person reveals when responding to you; reveal free information about yourself. Later (when??), offer an invitation that is likely to be accepted.BTW the foregoing is a goodly chunk of the essence of "Conversationally Speaking" by Alan Garner, a very worthy book on this topic even though it is not specifically written for those of us with severe social anxiety.
So I know what the professionals say to do, but I've not been able to. And so what happens is I may have a couple superficial conversations with someone and it never goes beyond that. Strangely I think dating is in a way easier (if I can get a woman to accept in the first place) because it is normal for dates to be accepted without the parties knowing each other much, and because the rituals are so well established that you can be more sure of what you are supposed to do.
peace and health,
S.D.
Posted by Kath on June 7, 2000, at 13:49:54
In reply to Re: a note to S.D. (acquiring friends, etc.) » CarolAnn, posted by S.D. on June 6, 2000, at 19:55:02
> > Hi S.D., I hope you don't mind, my butting in,
> but I really feel for anyone who, like me, has trouble acquiring friends. I have exactly two, after years of actively looking. Unfortunatly, all I can offer are the same old cliches..................
Hope you don't mind me butting in on this conversation. Different things work for different people. I'd like to share what's recently worked for me in getting to know more people & beginning to make a few more friends.Two & a half months ago I attended an Al-Anon meeting to see if it would help me in dealing with my son's drug use (no Narcotics Anonymous meetings nearby). I didn't feel comfortable there, & discovered a CoDA (CoDependents Anon.) meeting which I attended. From the second I walked in the door, I felt totally welcome; it was a wonderful feeling. It turns out that I have numerous "co-dependent" traits including an overwhelming drive to take care of others, often at my own expense; a need to "control" situations, events, ways things are done in order to feel "safe", to name a couple. One of the goals of the group is to help people have healthy relationships with themselves & with others. Part of a CoDA meeting is those who wish to share how they are feeling have a chance to do so with no comments or feedback from the group. This makes it a very safe place to simply share and know that one is accepted. People often get together after the meeting & can obtain wonderful ideas & support if they wish.
As in any group, there are some people who I feel more in tune with than others, but there are 2 people in particular, who I'm getting to know better & those 2 friendships are developing.
I think I can truly say, that at 53 years of age, this group is one of the very best things that has happened to me in my whole life.
Hope this might be of use to someone.
Kath
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