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Re: documention of *high dose* Parnate?

Posted by Maxime on May 12, 2005, at 19:10:41

In reply to Re: documention of *high dose* Parnate?, posted by EERRIICC on May 11, 2005, at 21:23:46

Hi, here is some info on using Parnate with Stims, and high doses of Parnate. Also, if you go to Depression Central you will find some stuff there under Treatment Resistant Depression.

Hope this helps.


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,

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 <>
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 <>
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" <>
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 <>
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 <>
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 <>
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: (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" <>
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.

From: (Joel S Hoffman)
Date: Wed, 21 Feb 1996 08:29:48 -0500
Subject: MAOIs with stimulants

By the way, I do not get signed consent. I do not think that that holds up very well anyway. Well documented clear chart notes indicating the clinical rationale and including what is told to the patient should always be standard practice and especially with atypical treatment modalities such as this.




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