Here is a challenge for you - Phenelzine and weight gain and treatment options

[zendog78]

Hi

This is my first post here. I am a registered Nurse and I take Phenelzine as a last resort for a rather crippling panic disorder
I have been taking this medication for around 8 months and after butting on around 12 KG in the first 2 months, my body has defied every effort to lose weight.
Intense resistence and cardiovascular exercise and calorie control stop me from gaining more weight but according to my most concervative estimates I am eating minimum 4000kj a day less than what it would take to maintrain homeostasis.

There are several studies on treatment of medication induced weight gain

Effectiveness of medications used to attenuate ant... [Neuropsychopharmacology. 2010] - PubMed result

Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis.
Maayan L, Vakhrusheva J, Correll CU.

Child Study Center, New York University School of Medicine, New York, NY, USA.

Abstract
Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of Science, PsycNET, and EMBASE for randomized, open and double-blind, placebo-controlled trials of medications targeting antipsychotic-induced weight gain was performed. Primary outcome measures were change and endpoint values in body weight and body mass index (BMI). Secondary outcomes included >or=7% weight gain, all-cause discontinuation, change in waist circumference, glucose and lipid metabolism parameters, and psychiatric symptoms. Sensitivity analyses were conducted to explain heterogeneity of the results. Across 32 studies including 1482 subjects, 15 different medications were tested: amantadine, dextroamphetamine, d-fenfluramine, famotidine, fluoxetine, fluvoxamine, metformin, nizatidine, orlistat, phenylpropanolamine, reboxetine, rosiglitazone, sibutramine, topiramate, and metformin+sibutramine. Compared with placebo, metformin had the greatest weight loss (N=7, n=334, -2.94 kg (confidence interval (CI:-4.89,-0.99)), followed by d-fenfluramine (N=1, n=16, -2.60 kg (CI:-5.14,-0.06)), sibutramine (N=2, n=55, -2.56 kg (CI:-3.91,-1.22)), topiramate (N=2, n=133, -2.52 kg (CI:-4.87,-0.16)), and reboxetine (N=2, n=79, -1.90 kg (CI:-3.07,-0.72)). Weight loss remained significant with metformin initiation after weight gain had occurred, but not when started concomitantly with antipsychotics. Nausea rates were not higher with any treatment compared with placebo. In all, 5 of 15 psychopharmacologic interventions aimed at ameliorating antipsychotic-induced weight gain outperformed placebo. Results were most robust for metformin, although these were modest and heterogeneous. Only one (negative) combination treatment study was available and head-to-head studies are absent. None of the agents were able to entirely reverse weight gain because of antipsychotics. At present, no treatment has sufficient evidence to recommend broad clinical usage. Antipsychotics with no or minimal cardiometabolic liability, as well as interventions that prevent or normalize adverse antipsychotic cardiometabolic effects are needed.

Efficacy of metformin and topiramate in prevention... [Ann Pharmacother. 2010] - PubMed result

Efficacy of metformin and topiramate in prevention and treatment of second-generation antipsychotic-induced weight gain.
Ellinger LK, Ipema HJ, Stachnik JM.

University of Illinois at Chicago College of Pharmacy, 60612, USA.

Comment in:

Ann Pharmacother. 2010 Jul;44(7):1349-50; author reply 1350-1.

Abstract
OBJECTIVE: To review the literature describing the efficacy of metformin and topiramate for the treatment of second-generation antipsychotic-induced weight gain. DATA SOURCES: Articles were identified by searching the MEDLINE database (from 1949 through January 2010) using the key words metformin, topiramate, antipsychotic, weight, weight gain, and obesity. STUDY SELECTION AND DATA EXTRACTION: All randomized, placebo-controlled trials of metformin and topiramate were selected for review. DATA SYNTHESIS: Weight gain due to second-generation antipsychotic use is a concern due to the risk of long-term metabolic and cardiovascular effects with these agents. These effects include obesity, hyperglycemia, and insulin resistance, all of which may contribute to diabetes and cardiovascular disease. Second-generation antipsychotics vary in the degree to which they cause weight gain, and dietary and lifestyle changes may not be feasible or sufficient in counter-acting this weight gain. Although other pharmacologic agents may be beneficial to prevent and treat antipsychotic-induced weight gain, metformin and topiramate have been the most extensively studied in this setting. Metformin acts peripherally to cause weight loss, while topiramate acts centrally. Review of 11 randomized, controlled trials demonstrates beneficial effects of metformin and topiramate in prevention and treatment of weight gain. Metformin is generally well tolerated and has been studied in pediatric patients, while topiramate is associated with more drug interactions and may possibly interfere with control of schizophrenia. CONCLUSIONS: Data for the use of metformin and topiramate in the treatment and prevention of second-generation antipsychotic-induced weight gain are limited. Both may be effective in helping patients lose weight via mechanisms that have yet to be clearly defined. The use of metformin results in greater weight loss than topiramate, and topiramate is associated with more risks and may compromise the treatment of schizophrenia. Treatment of antipsychotic-induced weight gain with metformin may be an option after lifestyle and dietary changes have failed.

This is a study particular to phenelzine and weight loss, its findings on the whole seem rather paradoxical, it seems to inhibit trigliseride storage and formation of preadiposites.
It couldnt come up with any clear findings but from what I could understand from the study with my own limited knowlage is that it seems to prevent lipid mobilization from fat cells... would someone mind reading the discussion at the end of the article and tell me if that is correct?

Doctors I talk to dont really seem to know anything about these kinds of nonconventional
treatments and furthermore are resistant to considering them even when I present the studies to them, I would really appreciate some advice on a possibble solution given the results of the study below.
Many thanks


Antidepressant Phenelzine Alters Differentiation of Cultured Human and Mouse Preadipocytes

Antidepressant Phenelzine Alters Differentiation of Cultured Human and Mouse Preadipocytes

[sol_adore]

whoa, that's a case study and a half I reckon. Any mental health MI pharmacists out there?

I would first question whether any consideration has been given to changing drugs. I guessing no since phenelzine is like 5th line and as you say it is a 'last resort'.

Metformin is often prescribed off-label for weight-loss, orlistat is licensed for this sort of thing, and would be useful is much of your calorific intake is through fats. Both of these drugs act peripherally, so any interference with phebelzine is unlikely (although this may be incorrect, I'm using NO reference sources here so check everything out yourself - these are merely suggestions).

With regard to influencing docs with your own research, you need to make sure that what you present is from good quality clinical medical studies, no pharmacological experiments in mice etc..

[DavidS]

Also the best way of influencing our medical colleagues* is to present the research in a five star hotel overseas, to ensure they are receptive to the message.


(*I'm only jealous - and I don't think it happens too often now in this country.)

[bobbin]

This is my first post here. I am a registered Nurse and I take Phenelzine as a last resort for a rather crippling panic disorder

How is phenelzine working for your anxiety?

Phenelzine is an effective medication which is almost certainly underused in the UK. Many doctors prefer to continue prescribing newer medications to patients who clearly derive no benefit from them, despite taking high doses for prolonged periods of time (totally pointless). MAOIs work in a very different way to any other type of antidepressant or anti-anxiety medication. Because of this, they can help people who have not been helped by any other treatment.

You will find that most doctors and pharmacists know almost nothing about MAOIs, except having some vague idea that they are 'dangerous'. This is unfortunate because MAOIs sometimes work very well, especially for severe depressive illness and certain types of anxiety. MAOIs are not easy medications to prescribe. Prescribing these drugs safely and effectively requires a lot of knowledge and considerable patient education, which obviously takes a lot of time. The BNF offers very little help here; the information provided is rather out of date. In particular, the dosage recommendations are not in line with modern practice.

Unfortunately, phenelzine causes side effects very frequently. The weight gain is often difficult to deal with, as are the sleep disturbances. I would not generally recommend topiramate (Topamax) for weight loss. It can cause a lot of problems, including psychiatric reactions. Orlistat (Xenical) might help to some extent. Orlistat is a relatively safe drug but it does cause diarrhoea, especially if you eat too much fatty food. Orlistat does not interact with MAOIs.

Have you considered switching to a different MAOI? Tranylcypromine (Parnate) generally causes less weight gain than phenelzine. Occasionally, it even causes weight loss, but the response is of course variable. Tranylcypromine appears to be effective for panic disorder, but it hasn't been studied to the same extent as phenelzine in any anxiety disorder. 30mg to 60mg per day of tranylcypromine should prevent most panic attacks. You have to have been off phenelzine for two weeks before starting tranylcypromine. The initial dose is 10mg once or twice a day, which is increased gradually up to a therapeutic dose. 30mg per day (in divided doses) is likely to be sufficient for panic disorder. Much higher doses are sometimes needed for severe depression.

In the United States, tranylcypromine is used considerably more frequently than phenelzine (although both drugs are only used by specialists). Tranylcypromine causes fewer adverse effects overall, but it is really quite different to phenelzine, and so some patients will have a strong preference for one drug over the other. The BNF provides no useful information about tranylcypromine, except to say that it is 'stimulant' and dangerous. These stupid and unhelpful remarks ought to be removed. I suspect that they were written by someone who has never prescribed it. Anyone who is familiar with MAOIs knows than tranylcypromine is generally better tolerated than phenelzine. As is the case with all MAOIs, tranylcypromine should only be used by psychiatrists who are knowledgable and experienced with their use. The dietary issues and drug interactions require explanation.

Moclobemide (Manerix) is a newer type of MAOI called a RIMA. It is a very weak antidepressant. It is certainly no substitute for the original MAOIs. It does not cause weight gain, but I'm not sure that it would treat your panic disorder either!

[crit care]

underused probably ecause it is an old drug with the well known effect of the "cheese" reaction, so i guess many avoid it and go for the newer drugs

[bobbin]

underused probably because it is an old drug with the well known effect of the "cheese" reaction, so i guess many avoid it and go for the newer drugs

Right, so what about when the newer treatments don't help (which they frequently don't)? The fact that phenelzine is old is not relevent. The dietary restrictions prevent MAOIs from being used as a 1st or 2nd line treatment. Most patients who take MAOIs have already tried many other medications, CBT and other psychological approaches etc.

[johnep]

I remember when Nardil was the hottest thing since sliced bread. The interesting thing to me was that the MAOIs arose from the observation that tuberculosis patients became more cheerful when treated with Rimifon (Isoniazide).
johnep

[crit care]

the fact it is old, probably means that doctors don't use it first line, and its not as marketed as heavily as the newer drugs and but as you rightly point out it is still used in those resistant to the newer drugs.

[bobbin]

I remember when Nardil was the hottest thing since sliced bread. The interesting thing to me was that the MAOIs arose from the observation that tuberculosis patients became more cheerful when treated with Rimifon (Isoniazide).
johnep

I believe that it was iproniazid which cause the depressed TB patients to feel more cheerful. Isoniazid is related but it isn't an antidepressant. Only isoniazid is still used for TB.

[bobbin]

the fact it is old, probably means that doctors don't use it first line, and its not as marketed as heavily as the newer drugs

Absolutely, MAOIs aren't marketed or advertised at all. The patents expired many many years ago.