Tuesday, March 3, 2009

Moclobemide is a Good Antidepressant

The antidepressant moclobemide is a reversible monoamine oxidase inhibitor. Once again, this is a drug that was frequently prescribed for a time, but has subsequently faded in popularity.

It was released in the late 80's; around 1990 many studies came out, comparing moclobemide with other antidepressants, including tricyclics and fluoxetine, showing that it worked just as well for treating depression. Many of these studies were published in Scandinavia. There have been very few clinical studies since then. Part of the reason may be that moclobemide was never approved in the U.S. (I do not understand why not).

Moclobemide has also been used effectively to treat social phobia.

In my opinion, it is a neglected option in treating depression. Because it has faded in popularity, it is usually tried as a third-line medication. For this reason, it is prescribed to patients who are more likely to have a more refractory depression. For this reason, it is less likely to be seen to help as much; this leads to clinicians pronouncing it ineffective, and not prescribing it. If it was prescribed as a first-line agent, I think we would see that it works pretty much as well as any other antidepressant.

Its advantages relate to the side-effect profile: its side effects in general are probably closest to placebo among all the antidepressants. And there are minimal or no sexual side effects with moclobemide, compared to the SSRI's. Here's a reference:

http://www.ncbi.nlm.nih.gov/pubmed/10974600

Other references:

http://www.ncbi.nlm.nih.gov/pubmed/17168253
{a 2006 meta-analysis showing that moclobemide works as well as SSRI's}

http://www.ncbi.nlm.nih.gov/pubmed/16702988
{a 2006 article from the British Journal of Pharmacology suggesting that moclobemide may have neuroprotective or even neurogenerative effects in the hippocampus}

http://www.ncbi.nlm.nih.gov/pubmed/12595913
{a 2003 review}

Addendum:

There was one case series study published in 2000 by Magder, Aleksic, and SH Kennedy, describing the successful use of very high-dose moclobemide in combination with lithium and/or trazodone for treatment-resistant depressed patients. The doses used were up to 1500-1650 mg/day, which is much higher than the usual maximum of 600 mg. They advocated using an MAOI diet at these doses. Moclobemide was well-tolerated, and the patients appeared to benefit over 1-2 years of follow-up. It's worth looking at this brief article in its entirety, here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/10831036

7 comments:

mysadalterego said...

Does it have all the same MAO restrictions? I have seen lots of patients who, according to old lit, would benefit from a MAOI, but no one seems to use them anymore or even really know how.

GK said...

Taking moclobemide generally does not require dietary restrictions, unless one is using extremely high doses, beyond the usual dose range, or if one is ingesting foods with extremely high amounts of tyramine. According to the drug monograph, at a dose of 600 mg/day moclobemide (this is in the high end of the normal dose range), studies showed that it was safe to ingest 100 mg tyramine, corresponding to 200 grams (7 ounces) of strong cheese.

The old MAO inhibitors can still be very good drugs, I will write a post about them later. But these drugs (phenelzine & tranylcypromine) have much more severe side effects, and require very careful dietary restrictions.

Dr Shock said...

We tried to switch patients only responding to a classic MAO inhibitor (irreversible inhibitor like tranylcipromine)after resistance to a SSRI and TCA. We had to quit the trial since most of them quickly relapsed. The results were published but onbly in a Dutch.
I guess the problem is that for the first line of treatment there are many alternatives read SSRI's studied in many trials. Also the lack of side effects of moclobemide makes you wonder.
Kind regards Dr shock
P.S impressive blog

GK said...

Thanks for the compliment, Dr.Shock--please also see my addendum in my post, regarding the use of high-dose moclobemide.

Anonymous said...

Hi,

I just had a couple of questions about moclobemide.

1)Do you know why it is not approved in the United States?

2)Some of the research done on Moclobemide was based on diagnostic criteria for depression (listed in the DSM III). Was there a significant difference in the criteria in the DSM III compared the the IV-TR?

3)Pertaining to the meta-analysis of moclobemide; (your second link)

Although the evidence and data presented is visually pleasant...it states on page 785 that "all 12
studies (included) were sponsored by Roche, the maker of moclobemide."
--This makes me question the data and the selection criteria for the inclusion of the specific studies investigated.

Also the limitations stated on page 788 that there were no control/placebo groups? Is this normal? How can there be statistical significance if there is no comparison?

Perhaps I just missed something in the article.

I any case-- would you be able to post some extra links to meta analysis/review articles that you find in support of your position?

Cheers!

GK said...

Thanks for the comment.

I can't find an exact description of DSM-III vs. DSM-IV criteria right now, but in general DSM-III might include less severely symptomatic individuals in diagnostic categories. If this is the case, there could be some bias.

Your point about the 12 studies all being sponsored by Roche is very important. This certainly weakens the conclusions. I missed that point before; perhaps also the whole issue of biases in industry-sponsored research was something I learned about only after I published this post originally.

I don't have a big objection to a study design which compared a new treatment with another established treatment. In fact, I find this a much stronger study than one which only compares with placebo. The strongest study of all would have three wings: a new treatment, an established treatment, AND a placebo (perhaps an "active placebo" which has some benign side effects). Yet, to do 3 wings you would need more subjects, and if you have only a fixed number of subjects 3 separate wings would cause the power of the study to diminish. So all these things have to be balanced.

I don't know why moclobemide isn't approved in the U.S. Maybe they didn't feel there was enough evidence about effectiveness.

In conclusion, I guess I have to say the evidence isn't quite as strong as I initially portrayed in my post. I guess I have to demote moclobemide a bit, yet I do affirm that it is an antidepressant that is available in Canada, has quite a benign side-effect profile, and has been subjectively effective for some people.

There should be some more research studies including this drug.

In my opinion it remains a reasonable alternative to an SSRI.

Anonymous said...

Moclobemide has been extensively evaluated in the treatment of depressive disorders. See e.g. http://www.biopsychiatry.com/moclobemide.html

About the 'not approved in the US'. " "Sadly, the role of MAO in deaminating tyramine (from the Greek word tyros, meaning cheese) wasn't at first understood. Certain MAOI-treated patients suffered hypertensive crises after eating varying amounts of tyramine-rich aged cheese; and several died. It is now recognised that the use of any MAOI which is both irreversible and unselective must be accompanied by dietary restrictions. But the adverse publicity of the initial inexplicable fatalities, combined with the introduction of a succession of dirty but sometimes tolerably effective tricyclic compounds, sent the use and reputation of MAOIs into a precipitous decline from which they still haven't fully recovered. The older non-selective and (more-or-less) irreversible inhibitors tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan) are nonetheless valuable antidepressants. Outside America, the the selective and reversible MAOI moclobemide. is used too. Of greater interest still are central-nervous-system-selective compounds, notably the neuroprotective antidepressant and anti-Alzheimer's drug TV3326 (ladostigil). MAOIs that lack the peripheral effects of currently explored drugs herald an exciting new window of therapeutic opportunity."

If you investigate the latest ideas about Moclobemide in the US - moclobemide is more common in Europe - then this drug has a kind of revival. You can easily find information about this on the internet or see e.g. psychiatrist.com. For your information: more independent research is done in The Netherlands, where I live, the last years and the results are rather good.

But ofcourse, combining this drug with other drugs like SSRI or recreational, is not a good idea. So if you don't trust the person who's gonna use it, he or she doesn't get it. Maybe this could also be a reason why it's not very popular in the US. In the US big money lawsuites are never far away when something goes wrong.

Moclobemide has also positive results for sexual dysfunction in healthy subjects. I can imagine that there are some pharmaceutical politics at work here.

And you are sure right sir! Most research is (a little) adjusted for better results.