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Combining nardil and selegiline

Middleway

Middleway

Ex-Bluelighter
Joined
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I have been on nardil in the past for depression and social phobia but had to stop it because of sexual dysfuntion and postural hypotension. I was wondering if I low dose of selegiline, with a low dose of nardil may have a synergistic effect and minimise the side effects. Selegiline being pro sexual and having a pressor effect from being metabolised into amphetamines I figure could deal with the hypotension.
Is there really a reason why a low dose of both should be that much more risky than a high dose of one?
I have been on almost every medication that exists, I am really looking for answers
 
Short answer is that It would be risky without that much benefit. You are already getting MAO-B inhibition with the Nardil. Nardil's interactions are so many and so potent, that I tell people to take it if its going to be the only agent they are going to need for a considerable block of time, otherwise its to problemsome.
 
Nardil is a non-competetive (ie irreversible) inhibitor of MAO-A, which unlike competetive/reversible inhibitors like moclobemide can very very easily & rapidly progress to a hypertensive crisis in combination with anything that has sympathiomimetic activity. Plenty of people have died from mixing non-competetive MAOIs with other drugs such as amphetamine & when you consider that selegeline is metabolized to methamphetamine/amphetamine, I'd book an ambulance and probably an undertaker if you're going to combine the two...

Do I need to explain any further?
 
Ok, I have no doubts that it is a questionable combination that carries some risk, but Doctors combine dexamphetamine with irriversable maois in some cases of treatment resistant depression, shorely selegiline would be less of a risk.
I am not just throwing idle thoughts around or looking at this combination for some fun, I am about to go back on Nardil, the only thing that has ever worked for me and If there is any way to make it more effective at a lower dose so as to minimize its awful side effects
 
fastandbulbous said:
Nardil is a non-competetive (ie irreversible) inhibitor of MAO-A
Click to expand...

Sorry for going slightly offtopic, but non-competetive is not the same like irreversible. What about allosteric inhibition? It's non-competitive, too, but for sure can it be reversible!

I'm talking strictly about the term, not Nardil or it's action. Could indeed be that Nardil acts irreversibly...
 
Here are a bunch of abstracts on using Nardil with a stimulant.

Maxime

1: J Clin Psychopharmacol. 1991 Apr;11(2):127-32.

CNS stimulant potentiation of monoamine oxidase inhibitors in
treatment-refractory depression.

Fawcett J, Kravitz HM, Zajecka JM, Schaff MR.

Department of Psychiatry, Rush-Presbyterian-St. Luke's Medical Center,
Chicago,
Illinois.

We report on our clinical experience with a combination of a CNS stimulant (either pemoline or dextroamphetamine) and a monoamine oxidase inhibitor (MAOI) for treating 32 depressed patients (mainly outpatients) refractory to standard
antidepressant pharmacotherapy. This combination, though not approved by the FDA, appears to be safe and effective. Twenty-five (78%) of these patients experienced at least 6 months of symptom remission with a stimulant + MAOI combination. Many patients required adjunctive antidepressant treatment, including tricyclics and lithium. Side effects were not excessive, though 6 patients (3 unipolar and 3 bipolar) cycled to mania (N = 1) or hypomania (N = 5). None developed hypertensive crises. With properly motivated and complaint patients and careful clinical monitoring by the prescribing psychiatrist, stimulant potentiation of MAOIs may be a viable option for treatment-resistant depressed patients.

PMID: 2056139 [PubMed - indexed for MEDLINE]


2: J Clin Psychiatry. 1985 Jun;46(6):206-9.

Combined MAOI, TCA, and direct stimulant therapy of treatment-resistant depression.

Feighner JP, Herbstein J, Damlouji N.

Patients with "treatment resistant" depression who do not respond to standard methods or relapse over time have a moral and legitimate right to innovative
therapy. Combined treatment with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and stimulants has been resisted by practitioners because of hypertensive and hyperthermic crises noted in certain cases. This paper reports a case series demonstrating the safety and efficacy of adding a stimulant to an MAOI or to a combination of TCA and MAOI in the treatment of intractable depression.

PMID: 3997787 [PubMed - indexed for MEDLINE]


MAOIs in high doses and with stimulants

Date: Sat, 1 Apr 1995 13:33:03 -0800 (PST)
From: Ivan Goldberg <[email protected]>
Subject: Non-response to tranylcypromine

The commonest reason people do not respond to tranylcypromine (Parnate) is an inadequate dose. When using an MAOI I follow platelet MAO levels and keep increasing the dose is sufficient to reduce those levels almost to zero. This often takes > 60 mg/day of tranylcypromine.

If a month or so on 80 mg/day or so does not lead to a significant improvement, the next thing I usually do is to add a psychostimulant such as methylphenidate or dextroamphetamine to the cocktail. Starting with small doses, the dose is gradually increased until the patient is taking about 30 mg/day of dextroamphetamine, or twice as much methylphenidate.

Date: Fri, 14 Apr 1995 15:06:15 -0700 (PDT)
From: Ivan Goldberg <[email protected]>
Subject: MAOIs in high doses and with stimulants

There are recently been a number of warnings posted there that MAOIs should not be prescribed together with psychostimulants. While that is the conventional wisdom, if universally implemented, it would deprive many severely and intractably depressed people from relief.

In the olden days, the early 1960s, we used to treat some patients with resistant depressions with up to 200 mg/day of tranylcypromine and if that was not effective potentiate it with dextroamphetamine, starting with 2.5 mg once a day and gradually increasing to 15 or 20 mg/day.

Until it was recently withdrawn, a 60ish year old patient of mine was only able to continue in his professional work by taking 170 mg/day of isocarboxazid + 5 mg of dextroamphetamine t.i.d. Since the isocarboxazid became unavailable, he has been doing almost as well on phenelzine 135 mg/day + the dextroamphetamine.

When treating patients with unusually hard to treat syndromes it is often necessary to use combinations [and doses] of medication that are conventionally considered to be contraindicated.

From: "Steven L. Dubovsky" <[email protected]>
Date: 15 Apr 95 08:47:17 MST-0700
Subject: MAOIs in high doses and with stimulants

It is common practice where I come from to combine MAOIs and stimulants for MAOI-induced hypotension and treatment resistance. This is also mentioned in Jan Fawcett's book of a number of years ago. Also, remember Feighner's report of MAOI + TCA + stimulant in ECT-resistant depression. I have tried this a number of times and found it helpful. Since half the caucasian population are (is?) rapid acetylators, higher doses of Parnate are frequently necessary. Other patients are rapid metabolizers of hydrazide MAOIs and need high doses of those. The PDR is a legal, not a medical, document, so I don't think their doses are always reliable.

From: Donald Franklin Klein <[email protected]>
Date: Sun, 16 Apr 1995 23:44:11 -0400
Subject: MAOIs with stimulants

MAOIs plus methylphenidate (Ritalin) has not been a problem in my hands although theoretical risk requires discussion with patient, consent, and available nifedipine . Very useful for orthostatic hypotension.

Date: 06 Sep 95 11:38:03 EDT
From: Troy Caldwell <[email protected]>
Subject: MAOIs with stimulants

None other than my teacher, John Rush, some years ago referred just such a refractory person to me specifically to try adding a stimulant to her MAOI. This was in the days when doctors could still hospitalize and had authority to do things. Apparently, we private practitioners had a bit more autonomy than the university MDs at that time, so I got the referral.

Social commentary aside, I put the pt in the ICU and added very slowly Dexedrine or Desoxyn to the patient's regimen. It was wonderful -- a grand remission occurred -- and complications were zero. I've tried it since a few times, starting a low doses and titrating gradually upward, and each time no complications arose. Like all treatment efforts, it has been variably effective, but definitely worth trying. Of course, give them nifedipine as an antidote to carry.

Date: Fri, 09 Feb 1996 10:57:43 -0600
From: Kevin Miller <[email protected]>
Subject: MAOIs with stimulants

Hypotension is a frequent side-effect of MAOIs. If hypotension limits appropriate dosage increases, either based on clinical response, or on not reaching the target dose of about 1 mg/kg in the case of phenelzine (Robinson and Nies), the slow and careful addition of stimulants while monitoring BP makes wonderful sense. The hypotension is treated, the antidepressant effect is augmented, and, if methylphenidate is used, there may be pharmacokinetic effects as well. This is riskier with tranylcypromine given that spontaneous elevations of BP have been noted with this MAOI despite strict dietary adherence. It's also easier to do safely on an inpatient basis.

From: [email protected] (Joel S Hoffman)
Date: Sun, 18 Feb 1996 21:43:52 -0500
Subject: MAOIs with stimulants

There is fortunately a small literature on combining MAOI and stimulant medication: Fawcett, J Clin Psychopharm 1991, 127-132; Feighner, J Clin Psych 1985, 206-209. Also, Clary, J Clin Psych 1990, 226-231, reported in a survey of prescribing habits of Pennsylvania psychiatrists that among those who prescribed MAOIs, use of high doses and combined use of MAOIs with stimulant meds were not unusual.

I have used this combination for the treatment of refractory depression and have at times have found it a great help and at other times useless. I do not remember it being helpful when a patient was not at least partially responsive to either the stimulant or the MAOI alone. However if there is a partial response to one of those meds, then when the two are combined, there can be either an additive or synergistic effect.

I have never had a problem with elevated BP, however I most often add the MAOI to the stimulant rather than the reverse... If I do add a stimulant to an MAOI, I start with 1.25 mg d-amphetamine or equivalent, the idea being that it probably takes at least 5 mg tyramine to precipitate a hypertensive crisis, and since the molecular weights are about the same 1.25 mg amphetamine would be sub-threshold. Starting at that level has not caused any reactions, but I still prefer to start with the stimulant and add the MAOI later.

I find that with time, as more treatment options are available, I use this combination less but there are still some patients for whom nothing else seems to work. The side effects that do cause problems include activation sometimes resembling or identical to dysphoric mania. Stereotypy and choreiform movements including bucco-facial dyskinesia can also occur. These side effects have to watched for closely. If it is essential to continue the regimen, pimozide can usually alleviate the movement disorder.

From: "David A. Kahn" <[email protected]>
Date: Wed, 21 Feb 1996 10:31:11 EDT
Subject: MAOIs with stimulants

I'm always in the position of trying to augment an existing MAOI regimen, so it's never seemed feasible to stop the MAOI, start the stimulant, and then restart the MAOI. I just add the stimulant. The only adverse reaction I've encountered is an odd lability of blood pressure on two occasions, where supine blood pressure was somewhat elevated on a tonic basis, together with a worsening of orthostatic hypotension. The supine elevation made it impossible to think of Florinef, etc., so we had to stop the combination. Interestingly, both of these individuals had prior histories of intermittent bordereline essential hypertension which had resolved on the MAOI alone.
 
Ok maybe I should have left the first line not in bold to highlight that it was different from the rest which was a cut and paste. EXuuuuse me
 
bold is difficult to read, see that quote thing? that's what it's used for.

don't be a jackass just because you can't admit making a mistake.
 
No dude, I admit that the quote feature would have been more appropriate, but the fact of the matter is that I really dont give a shit and it suprises me that there are people who have so little to do than to come into this thread and contribute nothing to the topic at hand, instead, Murphycox twice in this (short) thread contributes nothing but criticism on peoples posts. So I dont give a shit ok. And If you want to get picky, captitalisation is usually used at the start of each sentence. It makes sentences easier to read, thats what they were invented for.
Can we get over this now?
I would still like some more info on mixing MAOIS, if not selegiline and nardil then maybe nardil and parnate to get a better side effect profile. Of course these drugs carry more risks than a SSRI but you can tell me that there is no way to experiment combining them. Such as taking a tiny sliver of the medication you want to augment with and gradually increase it over a few days while watching for side effects.
Nardil was a wonder drug for me, the only that ever worked, but the side effects were a nightmare. I really want to recapture that effects somehow without the side effects.
Thanks
 
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my shift key and my down key are both missing, so until the new keyboard for this laptop arrives, you'll have to bear with me.

it's not really true that capitalization was invented to make sentences easier to read. or at least, if it is, it's been lost to time and there's no way to prove that.

Murphy has more knowledge in his little toe than you, man, so if you want really good answers, why be a dick about it? if you want full copies of those articles or any others, he's the one to be nice to.
 
Nardil was a wonder drug for me, the only that ever worked, but the side effects were a nightmare. I really want to recapture that effects somehow without the side effects.
Click to expand...

ok ..

The side effects, indeed extensive, tend to get a little easier after a long time, from the anecdotes I've read.

I think that Nardil's antidepressant efficacy has a lot to do with:

1) metabolism into phenethylamine (whose metabolism by MAO-B is interrupted)
2) actions at GABA transaminase

and (purely my personal supposition) 3) some weird roundabout NMDA antagonism. Anyway, these actions I think are why, after reaching 1mg/kg, lowering to a "maintenance dose" for MAO inhibition, does NOT work for most people. They also betoken additional problems with combining the MAOIs as you've suggested ... besides that it's quite dangerous (both selegiline and parnate have an adrenergic effect independent of MAO inhibition) and dose control goes out the window, you'll also be trading out some of Nardil's special properties.

The guy* who I talked to who eventually had a lot of success** with a combination of Nardil and dextroamphetamine*** shared the rough side effects that it seems everyone who is prescribed Nardil has to suffer through. For weight gain, which he suspected to be largely water retention, I think he used a low dose of hydrochlorothiazide. For insomnia (this got better after a year) he needed a GABAergic sleep aid, like zopiclone. For some drowsiness/thinking problems (also got better), he suspected central anticholinergic activity, and the symptoms responded quite well to galantamine.

* (his tag on another forum was Chairman MAO, if anyone here knows of him, really brilliant fella)
** (last I checked he's still doing great, his anhedonic depression, ADD, & social phobia, which ruined his life for years, now in remission)
***(60mg/day split into 4 doses, this dose was, with the help of his doctor, extremely carefully titrated upwards from 0 at like 1.25 mg at a time, nifedipine on hand at all times if things got nasty.)
 
Thanks for your extreamely helpful and informative post Grue.
I have just started Parnate today, definetly feel stimulated but its nothing like the "everything is perfect" feeling of nardil I got from the first dose. What killed Nardil for me was the urinary retention, I almost took myself to the hospital to be catheterised a couple of times and every time going to the toilet was a 15 or 20 minute ordeal. Couldn't cum the whole time I was on it and almost fainted in the street many times as well. Damn it that a drug that works so well should have so many side effects.
If Parnate doesnt work out thenI thinkI will be looking at Nardil and Dexamphetamine combo as I have read other people talking highly of this combo
 
But the Dex won't reduce Nardils side-effects...
Click to expand...

Briefly: properly, carefully introduced and titrated, it can help a lot especially with hypotension, and the anecdotal account I have suggested it helped with sexual side effects. And I would expect some help (again, if the dosing is just right, this needs to be done with a really awesome & attentive doctor) with cognitive issues if one is encountering them. I'll write a more detailed post of the little I know about general Nardil issues in a couple days ... I've got an assload of work to do and should institute a moratorium on my forum-browsing :P
 
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I am very sorry that my statements were considered as useless criticism. But I have to insist, that especially my first post was not criticism but rather the attempt to correct a statement by FnB. I continued the communication with him via PM as I did not intend to lead the thread too far offtopic; we cleared the issue. I just don't like to see wrong statements as the one above, therefore my correction.

This said, I have to emphasise that FnB posted everything important and necessary with his first post here (#3 of the thread!!!). In short terms: bad idea!

Peace! Murphy
 
Yeah, all is cool. Live n let live. :)
I would appreciate any info you may have to impart Grue, and anybody else. I am really motivated to find a solution to my....condition after 10+ years of alot of suffering and hardship. If Dexamphetamine let me get away with a lower dose of Nardil and (hopefully) less side effects I would seriously consider starting it again.
 
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