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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by CaptainAmerica1967 on November 21, 2008, at 21:02:44
Has anyone used mirtazapine with tranylcypromine? I had used phenelzine for refractory depression for about fifteen years and it stopped working in 2003 and have been on Cymbalta since, but I haven't been the same and am going to go on tranylcypromine and maybe a tricylic like amitriptyline with it, but don't want the TCA side effects so I thought about mirtzapine (tetracylic)?
Posted by desolationrower on November 21, 2008, at 23:47:03
In reply to tranylcypromine + mirtazapine?, posted by CaptainAmerica1967 on November 21, 2008, at 21:02:44
I'd be rather worried about blood pressure on this combination, the alpha2 receptor is the feedback mechanism. I have looked and have not seen any documented combinations of MOAI & alpha2 antagonist being used, because i personally benefitted from yohimbe and wanted to try it with an MAOI, but decided it was too risky. Secondary TCAs don't have as bad as side effects as ones like amitriptilyine, if you have taken that before.
-d/r
Posted by jedi on November 22, 2008, at 3:28:27
In reply to tranylcypromine + mirtazapine?, posted by CaptainAmerica1967 on November 21, 2008, at 21:02:44
> Has anyone used mirtazapine with tranylcypromine? I had used phenelzine for refractory depression for about fifteen years and it stopped working in 2003 and have been on Cymbalta since, but I haven't been the same and am going to go on tranylcypromine and maybe a tricylic like amitriptyline with it, but don't want the TCA side effects so I thought about mirtzapine (tetracylic)?
Hi,
I would think that the combination of mirtazapine with a MAOI would have a high risk of serotonin syndrome. Each medication increase serotonin by different mechanisms, thus potentially raising the serotonin to too high a level.I have used nortriptyline with phenelzine in the past. The side effects of nortriptyline seem to be less than amitriptyline, and nortriptyline is the major active metabolite of amitriptyline. The TCAs that have a very small affect on serotonin are relatively safe with the MAOIs.
Be Well,
Jedi
Posted by CaptainAmerica1967 on November 22, 2008, at 10:49:38
In reply to Re: tranylcypromine + mirtazapine?, posted by desolationrower on November 21, 2008, at 23:47:03
> I'd be rather worried about blood pressure on this combination, the alpha2 receptor is the feedback mechanism. I have looked and have not seen any documented combinations of MOAI & alpha2 antagonist being used, because i personally benefitted from yohimbe and wanted to try it with an MAOI, but decided it was too risky. Secondary TCAs don't have as bad as side effects as ones like amitriptilyine, if you have taken that before.
>
> -d/r
You'd be worried about serotonin syndrome? Mirtazpaine is an adrenergic alpha-antagonist so it would theoretically block or lower BP like phentolamine which is used for hypertensive crisis for MAOI's.
Posted by jedi on November 22, 2008, at 12:01:02
In reply to Re: tranylcypromine + mirtazapine?, posted by CaptainAmerica1967 on November 22, 2008, at 10:49:38
> > I'd be rather worried about blood pressure on this combination, the alpha2 receptor is the feedback mechanism. I have looked and have not seen any documented combinations of MOAI & alpha2 antagonist being used, because i personally benefitted from yohimbe and wanted to try it with an MAOI, but decided it was too risky. Secondary TCAs don't have as bad as side effects as ones like amitriptilyine, if you have taken that before.
> >
> > -d/r
>
>
> You'd be worried about serotonin syndrome? Mirtazpaine is an adrenergic alpha-antagonist so it would theoretically block or lower BP like phentolamine which is used for hypertensive crisis for MAOI's.
>
>
>
There are documented, though rare, cases of serotonin syndrome in patients using mirtazapine as monotherapy. These patients probably had reduced, serotonin metabolism. Yes, I would be very careful mixing mirtazapine with a MAOI. JediAnn Pharmacother. 2002 Apr;36(4):641-3.
Severe serotonin syndrome induced by mirtazapine monotherapy.
Hernández JL, Ramos FJ, Infante J, Rebollo M, González-Macías J.
Department of Internal Medicine, Hospital Marqués de Valdecilla, Santander, Spain. joselhh@teleline.es
OBJECTIVE: To document a case of serotonin syndrome (SS) associated with mirtazapine monotherapy, review the previously reported cases of SS associated with this tetracyclic antidepressant, and discuss the possible pathogenic mechanisms leading to this serious adverse drug reaction. CASE SUMMARY: A 75-year-old man developed agitation, confusion, incoordination, and gait disturbance because of progressive rigidity. Mirtazapine had been started 8 days earlier to control major depression. Physical examination revealed diaphoresis, low-grade fever, hypertension, tachycardia, bilateral cogwheel rigidity, hyperreflexia, tremor, and myoclonus, symptoms and signs that are consistent with severe SS. DISCUSSION: A review of the cases of SS with implication of mirtazapine as the cause was performed. The possible pathogenic mechanisms leading to this adverse reaction in this patient are also discussed, and pathophysiologic hypotheses are formulated. CONCLUSIONS: Although mirtazapine offers clinicians a combination of strong efficacy and good safety, we suggest bearing SS in mind when prescribing this drug, especially in frail, elderly patients with underlying chronic conditions. In these patients, it might be more adequate to start mirtazapine therapy at a lower dose (<15 mg/d).
Publication Types:
* Case Reports
PMID: 11918514 [PubMed - indexed for MEDLINE]Clin Neuropharmacol. 2003 Mar-Apr;26(2):54-7.Click here to read Links
Comment in:
Clin Neuropharmacol. 2003 Nov-Dec;26(6):287-8; author reply 289-90.
Clin Neuropharmacol. 2003 Nov-Dec;26(6):288-9; author reply 289-90.
Mirtazapine-induced serotonin syndrome.
Ubogu EE, Katirji B.Division of Neuromuscular Diseases, Department of Neurology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Hanna House 5th Floor, 11000 Euclid Avenue, Cleveland, OH 44106-5040, USA. eeubogu@excite.com
An 85-year-old woman developed sudden confusion and dysarthria progressing to mutism, orobuccal dyskinesias, generalized tremors worse with activity, ataxia, and rigidity with cog wheeling without high-grade fevers or dysautonomia. These findings were related temporally to the institution of mirtazapine as monotherapy for a major depressive illness with superimposed anxiety disorder. Withdrawal of the agent resulted in early notable clinical resolution with only residual hypertonia after 2 weeks. This is a rare report of serotonin syndrome induced by mirtazapine monotherapy. The hypothesized pathophysiologic mechanism in this case is overstimulation of serotonin (5-hydroxytryptamine or 5-HT) type 1A receptors (5-HT(1A)) in the brainstem and spinal cord in an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism.
PMID: 12671522 [PubMed - indexed for MEDLINE
Posted by desolationrower on November 22, 2008, at 16:00:49
In reply to Re: tranylcypromine + mirtazapine? » CaptainAmerica1967, posted by jedi on November 22, 2008, at 12:01:02
well phentolamine is mostly used because its an alpha1 blocker. alpha 2 blockade increases blood pressuer. alpha2 is the adrenoceptor autoreceptor that controls release.
As for serotonin syndrome, I'm not sure that is a risk. It is a 5ht2 antagonist, which blocks ss. I would try to get my hands on the full text of this review:
Hum Psychopharmacol. 2006 Mar;21(2):117-25.Click here to read Links
A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status.
Gillman PK.A systematic review of published work concerning mirtazapine was undertaken to assess possible evidence of serotonergic effects or serotonin toxicity (ST) in humans, because drug toxicity and interaction data from human over-doses is an useful source of information about the nature and potency of drug effects. There is a paucity of evidence for mirtazapine having effects on any indicator of serotonin elevation, which leads to an emphasis on ST as an important line of evidence. Mirtazapine is compared with its analogue mianserin, and other serotonergic drugs. Although mirtazapine is referred to as a dual-action 'noradrenergic and specific serotonergic drug' (NaSSA) little evidence to support that idea exists, except from initial microdialysis studies in animals showing small effects; those have not subsequently been replicated or substantiated by independent researchers. Also, new data indicate its affinity for Alpha 2 adrenoceptors is not different to mianserin. It appears to exhibit no serotonergic symptoms or toxicity in over-dose by itself, nor is there evidence that it precipitates ST in combination with monoamine oxidase inhibitors, as would be expected if it raises intra-synaptic serotonin levels. Mirtazapine has no demonstrable serotonergic effects in humans and there is insufficient evidence to designate it as a dual-action drug.
-d/r
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