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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Jackd on May 4, 2004, at 14:57:13
Is this combination safe? Namenda (Memantine HCl) is in a trial for treatment of depression so I am thinking of trying it with Remeron.
Posted by SLS on May 4, 2004, at 15:17:24
In reply to Namenda and Remeron, posted by Jackd on May 4, 2004, at 14:57:13
> Is this combination safe? Namenda (Memantine HCl) is in a trial for treatment of depression so I am thinking of trying it with Remeron.
I can't think of any reason why there would be a problem. I am even considering combining it with an MAOI. I hope my doctor is receptive to the idea. I am currently taking:
Lamictal 300mg
imipramine 300mg
Zoloft 250mg
Abilify 10mg
Namenda 20mg
I added Namenda about 6 weeks ago. I have seen some encouraging signs, but I cannot report a trend towards improvement yet. Hopefully, I'll be able to soon.
- Scott
Posted by Jackd on May 4, 2004, at 15:25:56
In reply to Re: Namenda and Remeron, posted by SLS on May 4, 2004, at 15:17:24
Supposedly it can help eliminate tolerance to opiates, and if you do a search on medline on mirtazapine and opioid receptors it appears that mirtazapine has some prominent action on delta and kappa opioid receptors.
I tried a bit of Namenda 20mg BID last week for a few days, and I experienced a tightness in my chest and shortness of breath. I have no cardiovascular conditions. Is that common? Should I be worried about it in the future?
Posted by SLS on May 4, 2004, at 15:42:08
In reply to Re: Namenda and Remeron, posted by Jackd on May 4, 2004, at 15:25:56
> Supposedly it can help eliminate tolerance to opiates, and if you do a search on medline on mirtazapine and opioid receptors it appears that mirtazapine has some prominent action on delta and kappa opioid receptors.
I didn't know that. In what ways does it interact?
> I tried a bit of Namenda 20mg BID last week for a few days,
That's twice the recommended dosage. My doctor gave me a starter kit.
week 1: 5mg
week 2: 10mg
week 3: 15mg
week 4: 20mg> and I experienced a tightness in my chest and shortness of breath.
Hmm. Try going to http://www.rxmed.com and check out the side effect profile. I really don't know whether or not it is listed.
What condition are you trying to treat? I have bipolar depression. I've tried just about everything. The NIMH is also looking at riluzole (Rilutek), a drug approved for ALS. Like memantine, it has anti-glutamatergic properties.
Good luck.
- Scott
Posted by SLS on May 4, 2004, at 15:47:58
In reply to Re: Namenda and Remeron, posted by SLS on May 4, 2004, at 15:42:08
Sorry.
http://www.rxlist.com/cgi/generic3/namenda.htm
- Scott
Posted by Jackd on May 4, 2004, at 15:51:44
In reply to Re: Namenda and Remeron, posted by SLS on May 4, 2004, at 15:42:08
Oops, I meant 10mg BID. I decided to try it to treat my *very* resistant bipolar depression. Remeron worked wonders for me but pooped out, and I noticed that certain drugs that are supposed to cause anticociception didn't work, so I suspected a build up of tolerance to opiates. Here's some abstracts I found:
Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?
Schreiber S, Bleich A, Pick CG.
Department of Psychiatry, Tel Aviv Sourasky Medical Center, Tel-Aviv University Sackler School of Medicine, Israel.
The efficacy of each antidepressant available has been found equal to that of amitriptyline in double-blind studies as far as mild to moderate depression is involved. However, it seems that some antidepressants are more effective than others in the treatment of severe types of depression (i.e., delusional depression and refractory depression). Following studies regarding the antinociceptive mechanisms of various antidepressants, we speculate that the involvement of the opioid system in the antidepressants' mechanism of action may be necessary, in order to prove effective in the treatment of severe depression. Among the antidepressants of the newer generations, that involvement occurs only with venlafaxine (a presynaptic drug which blocks the synaptosomal uptake of noradrenaline and serotonin and, to a lesser degree, of dopamine) and with mirtazapine (a postsynaptic drug which enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission via antagonism of central alpha-auto- and hetero-adrenoreceptors). When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid, noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) combined with the alpha2-adrenergic receptor, whereas the antinociceptive effect of mirtazapine mainly involves mu- and kappa3-opioid mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity.
PMID: 11931344 [PubMed - indexed for MEDLINE]
The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms.Schreiber S, Rigai T, Katz Y, Pick CG.
Department of Psychiatry, Tel-Aviv Sourasky Medical Center, Tel-Aviv University Sackler School of Medicine, Tel-Aviv, Israel.
The antinociceptive effects of the noradrenergic and specific serotonergic antidepressant (NaSSA) drug mirtazapine and its interaction with various opioid receptor subtypes were evaluated in mice with a hotplate analgesicmeter. Mirtazapine elicited an antinociceptive effect in a dose-dependent manner following doses from 1 to 7.5mg/kg. As the mirtazapine dose increased beyond 10mg/kg latencies returned to baseline, yielding a biphasic dose-response curve. The effect of opioid, adrenergic, and serotonergic receptor antagonists was examined as to their ability to block mirtazapine antinociception. Mirtazapine (at 10mg/kg)-induced antinociception was significantly inhibited by naloxone, nor-BNI, and naltrindole, but neither by beta-FNA nor by naloxonazine, implying the involvement of kappa(1)- and delta-opioid mechanisms. When adrenergic and serotonergic antagonists were used, both metergoline and yohimbine, decreased antinociception elicited by mirtazapine, implying a combined serotonergic and noradrenergic mechanism of antinociception. When mirtazapine was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated only by kappa(3)-opioid receptor subtypes. Summing up these results we conclude that the antinociceptive effect of mirtazapine is mainly influenced by the kappa(3)-opioid receptor subtype combined with both serotonergic and noradrenergic receptors. These results suggest a potential use of mirtazapine in the management of some pain syndromes, and raise questions regarding a possible indirect opioid-dependence induced by mirtazapine. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mirtazapine when prescribed for pain.
PMID: 12372565 [PubMed - indexed for MEDLINE]
The use of NMDA-receptor antagonists in the treatment of chronic pain.
Hewitt DJ.
Department of Neurology, Emory University Medical Center, Atlanta, Georgia, USA. David_Hewitt@emory.org
Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids.
Publication Types:
Review
Review LiteraturePMID: 10870744 [PubMed - indexed for MEDLINE]
Morphine tolerance and dependence in mice with history of repeated exposures to NMDA receptor channel blockers.
Dravolina OA, Belozertseva IV, Sukhotina IA, Bespalov AY.
Department of Psychopharmacology, Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
Mice were subjected to two successive treatment protocols: first with NMDA receptor channel blockers (14 days, once a day) and second with morphine (5 mg/kg, 8 days, once a day). Treatment with the higher doses of dizocilpine (1 mg/kg), memantine (30 mg/kg), and MRZ 2/576 (30 mg/kg) upon discontinuation revealed only minor behavioral abnormalities attributable to the state of withdrawal. Following repeated administration of low-dose morphine, tolerance to morphine analgesia developed in mice preexposed to dizocilpine (1 mg/kg but not 0.3 mg/kg) but not memantine (10 and 30 mg/kg), MRZ 2/579 (10 and 30 mg/kg), or saline. There were no signs of morphine dependence in any treatment group. Overall, the present study found only minor effects of the subchronic administration of high doses of NMDA receptor channel blockers, suggesting that clinical use of NMDA receptor channel blockers such as memantine will not be accompanied by increased propensity to induction of morphine tolerance and dependence.
PMID: 10462190 [PubMed - indexed for MEDLINE]
Posted by SLS on May 4, 2004, at 20:52:21
In reply to Re: Namenda and Remeron, posted by Jackd on May 4, 2004, at 15:51:44
> Oops, I meant 10mg BID. I decided to try it to treat my *very* resistant bipolar depression. Remeron worked wonders for me but pooped out, and I noticed that certain drugs that are supposed to cause anticociception didn't work, so I suspected a build up of tolerance to opiates. Here's some abstracts I found:
Thanks. I'm not sure what to make of them just yet.
You know, it's interesting. I tried Vicodin twice to see how I would react. Hydrocodone, I think. Anyway, it had absolutely no effect on my cognition or mood. It was like I was taking sugar pills. Of course, I declined to drop a bowling ball on my foot to test its antinociceptive effect.
- Scott
Posted by Jackd on May 5, 2004, at 14:57:32
In reply to Re: Namenda and Remeron - Thanks for the citations, posted by SLS on May 4, 2004, at 20:52:21
Posted by SLS on May 5, 2004, at 15:19:18
In reply to (NM) No Problem, I'll fill you in if this works, posted by Jackd on May 5, 2004, at 14:57:32
I wish you the best of luck with Namenda. Are you taking any other medications?I really thought Namenda was going to be the one. I felt substantially improved up until a week ago. I haven't seen anything since that I could call a true antidepressant response. However, for the moment, I can't say that it is working, but I can't say that it is not working. The damned drug is playing hide-and-go-seek with me.
- Scott
This is the end of the thread.
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