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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by ed_uk on January 23, 2005, at 12:07:55
Hello,
Jeroen said (in a post above) that he is feeling happier since starting amantadine a few days ago. A few of you have expressed recent interest in using memantine as an AD.
Have a look at this...........
Pol J Pharmacol. 2004 November-December;56(6):735-742.
(The full article can be obtained for free via PubMed!)
Effects of joint administration of imipramine and amantadine in patients with drug-resistant unipolar depression.Rogoz Z, Dziedzicka-Wasylewska M, Daniel WA, Wojcikowski J, Dudek D, Wrobel A, Zieba A.
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland. rogoz@if-pan.krakow.pl.
The paper describes the effect of amantadine (AMA) supplementation on imipramine (IMI) therapy in patients (with treatment-resistant unipolar depression) who fulfilled DSM IV criteria for major depression. Twelve patients were enrolled to the study on the basis of history of their illness and therapy. Following 2 weeks of washout period, the patients were treated with IMI twice daily (100-150 mg/day) for 6 weeks, and then AMA was introduced (twice daily, 100-150 mg/day) and administered jointly with IMI for further 6 weeks. Thereafter, AMA was withdrawn, and the patients were treated with IMI alone for 2 weeks. Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy. IMI changed neither HDRS nor BDI score after 3 or 6 weeks of treatment when compared with washout (before treatment). AMA supplementation significantly reduced both HDRS and BDI scores after 3- or 6-week supplementation. AMA augmentation of IMI treatment was beneficial and lasted even after AMA withdrawal. Moreover, pharmacokinetic data indicate that AMA did not influence significantly the plasma concentration of the IMI and its metabolite, desipramine, in the patients during joint treatment with AMA and IMI, what suggests the lack of pharmacokinetic interaction. These results suggest that joint therapy with IMI and AMA may be successful in the treatment-resistant unipolar depression.
Pol J Pharmacol. 2004 Mar-Apr;56(2):179-85.
Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies.Rogoz Z, Skuza G, Kusmider M, Wojcikowski J, Kot M, Daniel WA.
Department of Pharmacology, Institute of Pharmacology, Polsih Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland. rogoz@if-pan.krakow.pl
Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptor, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either of drugs given alone. Since it has been suggested that, in addition to their other functions, dopamine and alpha(1)-adrenergic receptors may play a role in behavioral response in the forced swimming test, in the present study we examined the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in combination with IMI in the forced swimming test in rats. We also measured the level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA (20 mg/kg) produced stronger antidepressant-like effect than either of agents given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the forced swimming test) inhibited an antidepressant-like effect induced by co-administration of IMI and AMA. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and AMA failed to enhance the locomotor activity of rats, measured in the open field test. Also sulpiride and prazosin did not decrease the exploratory activity induced by co-administration of IMI and AMA. The above result suggests that the dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism of synergistic action of IMI and AMA in the forced swimming test in rats. The pharmacokinetic interaction can be excluded, since AMA did not change significantly the antidepressant level in the rat plasma and brain, measured 1 h after exposure to the forced swimming test.
Int Clin Psychopharmacol. 2003 Mar;18(2):93-6.
Amantadine as augmentation therapy in the management of treatment-resistant depression.Stryjer R, Strous RD, Shaked G, Bar F, Feldman B, Kotler M, Polak L, Rosenzcwaig S, Weizman A.
Beer Yaakov Mental Health Center, Beer Yaakov, Israel. raels@post.tau.ac.il
Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry. While several strategies have been attempted, including medication switch, antidepressant polypharmacy and various augmentative regimens, success remains limited. Amantadine (AMN), an agent traditionally used in the treatment and prophylaxis of influenza, is now known to exhibit prominent effects at the level of dopaminergic, monoamine oxidase and N-methyl-D-aspartate systems. The present reports on the efficacy of AMN as augmentation to standard antidepressant treatment in patients with treatment-resistant depression. Eight patients with treatment-resistant depression consented to receive AMN, titrated up to a dose of 300 mg, over a period of 4 weeks in a non-blinded fashion. Improvement in both depression and anxiety scores were observed from week 1, with patients exhibiting improvement of depressive scores of up to 49% by study completion. Females appeared to exhibit a stronger response, and within a shorter period of time. Side-effects reported included dry mouth and sedation. AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression. Further studies are clearly mandated to test these preliminary observations in a double-blinded manner.
Neuropharmacology. 2002 Jun;42(8):1024-30.
Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats.
Rogoz Z, Skuza G, Maj J, Danysz W.
Institute of Pharmacology, Polish Academy of Sciences, PL 31-343 Krakow, Poland. rogoz@if-pan.krakow.pl
In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. The authors previously reported that combined administration of imipramine and the uncompetitive NMDA receptor antagonist amantadine reduced immobility time in the forced swimming test in rats to a much greater extent than either treatment alone. The present paper investigates the possibility of synergistic interactions between three antidepressants (imipramine, venlafaxine, fluoxetine) with three uncompetitive NMDA receptor antagonists (amantadine, memantine and neramexane). Most combinations resulted in synergistic (hyperadditive) antidepressive-like effects in the forced swim test. Most interesting was the observation that fluoxetine, which was inactive when given alone, showed a positive effect when combined with amantadine (10 and 20 mg/kg), memantine (2.5 and 5 mg/kg) or neramexane (2.5 and 5 mg/kg). The specificity of these observations is supported by control open field studies, which demonstrated no significant increase, or even a decrease in general locomotion after coadministration of the compounds. The present results suggest that the combination of traditional antidepressant drugs and NMDA receptor antagonists may produce enhanced antidepressive effects, and this is of particular relevance for antidepressant-resistant patients.
Pharmacopsychiatry. 1999 Mar;32(2):47-55.
Possible use of amantadine in depression.
Huber TJ, Dietrich DE, Emrich HM.
Department of Clinical Psychiatry, Medical School of Hanover, Germany.
Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.
Might amantadine be more effective in the treatment of depression than memantine?
Pharmacol Toxicol. 1993 Jun;72(6):394-7.Potential antidepressive properties of amantadine, memantine and bifemelane.
Moryl E, Danysz W, Quack G.
Merz+Co, Eckenheimer, Frankfurt, Germany.
The effects of amantadine, its dimethyl derivative, memantine and the chemically unrelated compound bifemelane were tested for antidepressant activity. Reserpine-induced hypothermia and the forced swim test (Porsolt test) were selected for this purpose. In the former test amantadine and bifemelane but not memantine were effective. In the forced swim test all three agents produced antidepressive-like activity (decreased immobility time), but in case of bifemelane it was less pronounced. The effect in the forced swim test was specific i.e. it was apparently not the result of an increase in general activity as evidenced by control experiments in the open field. The mechanism of amantadine and memantine action may involve indirect dopaminomimetic activity resulting from the blockade of NMDA receptors. However in reserpine-induced hypothermia this explanation is not valid considering the lack of effect of memantine and positive action of amantadine. Hence, amantadine may have an additional central sympathomimetic action that memantine is lacking. Bifemelane antidepressant-like activity might be attributed to an enhancement of noradrenergic transmission. We suggested that amantadine and bifemelane could be particularly useful therapeutically when depressive symptoms are present in patients suffering from Parkinson's disease and dementia.
Ed.
Posted by tensor on January 23, 2005, at 12:19:47
In reply to Amantadine for TRD. Anyone interested? SLS?, posted by ed_uk on January 23, 2005, at 12:07:55
Hi Ed,
Maybe this could be of interest:
http://www.bris.ac.uk/Depts/Synaptic/info/pharmacology/NMDA.html/Mattias
Posted by ed_uk on January 23, 2005, at 12:42:14
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » ed_uk, posted by tensor on January 23, 2005, at 12:19:47
Hi Matt,
Thank you for the link. In Finland, the brand name for amantadine is Atarin.
Ed.
Posted by SLS on January 23, 2005, at 12:47:25
In reply to Amantadine for TRD. Anyone interested? SLS?, posted by ed_uk on January 23, 2005, at 12:07:55
Hi Ed.
I tried combining amantadine with imipramine and Lamictal over the summer. It seemed to be neutral. After a few weeks, nothing was happening, so I stopped taking it. I don't have much of an idea as to how long it takes to see results with amantadine, but I was in a bit of a rush to try memantine once it became available. What do you think?
Thanks.
- Scott
Posted by ed_uk on January 23, 2005, at 13:19:28
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » ed_uk, posted by SLS on January 23, 2005, at 12:47:25
Hi Scott,
What dose did you try? Any side effects?
Ed.
Posted by SLS on January 24, 2005, at 8:39:13
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » SLS, posted by ed_uk on January 23, 2005, at 13:19:28
Hi Ed.
> What dose did you try?
I really don't remember. I'll have to track down the prescription bottle.
> Any side effects?
Not really. I might have felt a very slight flattening of affect and/or irritability.
Sorry I couldn't be more helpful on this one.
- Scott
Posted by ed_uk on January 24, 2005, at 8:55:52
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » ed_uk, posted by SLS on January 24, 2005, at 8:39:13
Hi Scott,
>I really don't remember.
Probably 100-200mg I would guess.
RE Nort...
Are you going to ask for Pamelor specifically? Have you had a plasma nort level done? Do you think it might help to try 80 or 90mg instead of 100mg?
Ed.
Posted by ed_uk on January 27, 2005, at 11:55:26
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » SLS, posted by ed_uk on January 24, 2005, at 8:55:52
Posted by SLS on January 27, 2005, at 16:04:14
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » SLS, posted by ed_uk on January 24, 2005, at 8:55:52
Hi Ed.
Sorry I didn't reply earlier, but I sort of reached my energy limit.
> RE Nort...
> Are you going to ask for Pamelor specifically? Have you had a plasma nort level done? Do you think it might help to try 80 or 90mg instead of 100mg?The last time I had a nortripyline blood test, I was taking 100mg. The level was 123 ng/ml.
Here's something to think about. My pharmacy used a different generic manufacturer to fill my most recent prescription. I deteriorated quite a bit over the next week or so before I became suspicious that the new generic was responsible for this. Well, all I did was to increase the dosage to 100mg. I felt better within 12 hours. It is my feeling that this is an example of the lack of bioequivalence of different preparations of the same drug. So far so good.
- Scott
Posted by zeugma on January 27, 2005, at 18:36:26
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » ed_uk, posted by SLS on January 27, 2005, at 16:04:14
Scott,
which brands of nortriptyline were you using? I've been using Watson for the last year, and used either 75 or 100 mg depending on whether I was augmenting with a stimulant. recently I have gone down to 50 mg, and experienced a relapse of depression as well as other problems. I'm going back up to 75 mg tonight, and adding 25 mg strattera tomorrow.
Very glad to hear you are feeling better! If anyone deserves some relief from relentless depression, it's you!
-z
Posted by ed_uk on January 28, 2005, at 13:48:31
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » ed_uk, posted by SLS on January 27, 2005, at 16:04:14
Hi,
>Sorry I didn't reply earlier, but I sort of reached my energy limit.
It's not a problem at all- I just thought you might not have seen the post.
>It is my feeling that this is an example of the lack of bioequivalence of different preparations of the same drug.
It sounds like it, perhaps you can ask to have the same generic each time you get your prescription filled.
Ed.
Posted by SLS on January 28, 2005, at 17:01:28
In reply to Re: Amantadine for TRD. Anyone interested? SLS?, posted by zeugma on January 27, 2005, at 18:36:26
Hi Z.
> which brands of nortriptyline were you using?I forgot to ask, but I'll be sure to next time I have my prescription renewed.
> I've been using Watson for the last year, and used either 75 or 100 mg depending on whether I was augmenting with a stimulant.
Does the stimulant affect the kinetics of nortriptyline, or do you feel their mechanisms of action are too synergistic for you to remain at the higher dosage?
> recently I have gone down to 50 mg, and experienced a relapse of depression as well as other problems. I'm going back up to 75 mg tonight, and adding 25 mg strattera tomorrow.
Good luck. Anything good to report so far?
> Very glad to hear you are feeling better!A little, but I'll take all I can get. My combo manages to give me a bit more mental and physical energy, but is not really attacking the depression itself. I am still anergic with anhedonia and cognitive and memory deficits. But at least I vacuumed my apartment today. That is a big deal!
> If anyone deserves some relief from relentless depression, it's you!
:-)
- Scott
Posted by zeugma on January 29, 2005, at 10:58:22
In reply to Re: Amantadine for TRD. Anyone interested? SLS? » zeugma, posted by SLS on January 28, 2005, at 17:01:28
Hi Scott.
>
>
> > >
> Does the stimulant affect the kinetics of nortriptyline, or do you feel their mechanisms of action are too synergistic for you to remain at the higher dosage?
>I suspect both. The synergism in terms of sympathomimetic stimulation was too much. I had a constant case of mydriasis when on an effective dose of Ritalin, and my heart rate was elevated, so I had to lower the nortriptyline. it's noteworthy that Provigil did not cause either of these effects. I first raised the nor dose to 100 mg when I experienced insomnia early in Provigil treatment, and was able to keep it there throughout the course of my Provigil trial without any of the symptoms I later encounter with Ritalin. It's a shame because I think the higher dose of nortriptyline was countering some of the anxiety from ritalin.
> Good luck. Anything good to report so far?
>
The raising of nortrip from 50 to 75 mg has caused me to wake up in a better mood. the strattera also has had an antidepressant effect that wears off by early evening. It's also been confounded by the terrible drowsiness from stopping the ritalin, per my dr.'s orders, suddenly. The real problem with the ritalin was that it was causing terrible jitteriness, irritability, and a constant feeling of being 'on edge.' So I'm relying on caffeine to maintain wakefulness, and while it's far less effective, it also causes less anxiety. Obviously the situation is not optimal, but hopefully the strattera will control enough of the ADD for me to figure out how to distribute my energy in a more productive way. It's a difficult situation.
> > Very glad to hear you are feeling better!
>
> A little, but I'll take all I can get. My combo manages to give me a bit more mental and physical energy, but is not really attacking the depression itself. I am still anergic with anhedonia and cognitive and memory deficits. But at least I vacuumed my apartment today. That is a big deal!
>
that is. I did the dishes and took out the garbage last night. the ritalin would leave me comatose by the end of the day and nothing got done around the house. and i was depressed because of the lowered nortriptyline, so my energy level was down anyway. We'll see if I can manage the situation without stims. My goal is to keep the nortrip at 75 mg and get the strattera to 40 mg BID morning and noon. Since strattera is not anxiogenic I can keep the clonazepam at no higher than .5 mg BID, and maybe I can add 15 mg buspirone back in the AM (I currently take 15 mg hs to help with sleep induction).Hopefully, a lot of little things, like cleaning house etc., will add up to something beneficial for both of us, although given the chronicity and multifariousness of our symptoms I am quite realistic about the limitations of both of our current therapies. A little will have to go a long way.
-z
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