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Re: The Forbidden Combination-Squiggles

Posted by ed_uk on November 8, 2004, at 13:38:40

In reply to Re: The Forbidden Combination-Squiggles, posted by jasmineneroli on November 8, 2004, at 13:15:41

Thank you Jas :-)
I thought my post was clear, I really hope it was.
Sadly, at the moment, there isn't any known way of predicting who will experience serious symptoms of the SS when an SRI is combined with an MAOI. If there was a reliable method available, the combination might possibly be helpful for the treatment of people with serious mental health problems which haven't responded to anything else. This is why I was interested.

In particular, I was wondering whether the combination might ever be beneficial in the treatment of conditions like OCD which involve the serotonin pathways in the brain.

There has been a little bit of research into the combination of moclobemide (Manerix- a reversible inhibitor of MAO-A) and an SSRI.

Psychopharmacology (Berl). 1995 Jun;119(3):342-4. Related Articles, Links


Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy.

Ebert D, Albert R, May A, Stosiek I, Kaschka W.

Department of Psychiatry, University of Erlangen, Germany.

Eighteen patients with refractory depression (dysthymia with superimposed major depression) were treated with a combination of fluvoxamine(Luvox/Faverin) and moclobemide for 6 weeks and compared with 18 patients treated with fluvoxamine only. Both groups had improved only slightly after 8 weeks of TCA treatment and 6 weeks of SSRI treatment. Two main observations can be made concerning safety and efficacy. Firstly, side effects in the SSRI-RIMA group were minimal. Secondly, the SSRI-RIMA combination treatment significantly improved depression in refractory depressed patients, with a decrease in depression of about 40%. The SSRI monotherapy group also significantly improved, though only by about 20%, indicating that positive effects of SSRI treatment may still develop even after 12 weeks of treatment. In conclusion, the study gives further support to the hypothesis that SSRI-RIMA combinations may be safe and well tolerated. This treatment may also offer some therapeutic advantages in at least some patients who have not responded to conventional pharmacological treatment.

Here is a summary of another little study...

J Clin Psychiatry. 1994 Jan;55(1):24-5. Related Articles, Links


Combined SSRI-moclobemide treatment of psychiatric illness.

Joffe RT, Bakish D.

Mood Disorders Program, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.

BACKGROUND: To determine the efficacy and safety of a serotonin selective reuptake inhibitor (SSRI) combined with moclobemide in the treatment of 11 patients with various DSM-III-R diagnoses. METHOD: Subjects received moclobemide in doses of 150 to 800 mg/day together with sertraline (N = 5) in doses of 25 to 200 mg/day or fluvoxamine (N = 6) in doses of 50 to 200 mg/day. Patients were carefully monitored for side effects and for clinical response at the end of the trial, which lasted a minimum of 5 weeks. RESULTS: The combination was tolerated extremely well. Insomnia was the most common side effect, occurring in 5 of 11 subjects. A marked or complete therapeutic response was noted in 8 of 11 subjects. CONCLUSION: This open clinical trial suggests that combined SSRI-moclobemide treatment appears to be safe and well tolerated. It may also have therapeutic effects in treatment-refractory patients.

Sadly, the SS may also occur with SSRI+Moclobemide.......

J Anal Toxicol. 2001 Mar;25(2):147-51. Related Articles, Links


Comment in:
J Anal Toxicol. 2001 Nov-Dec;25(8):716-7.

A fatal case of serotonin syndrome after combined moclobemide-citalopram intoxication.

Dams R, Benijts TH, Lambert WE, Van Bocxlaer JF, Van Varenbergh D, Van Peteghem C, De Leenheer AP.

Laboratorium voor Toxicologie, Universiteit Gent, Belgium.

We present a case involving a fatality due to the combined ingestion of two different types of antidepressants. A 41-year-old Caucasian male, with a history of depression and suicide attempts, was found deceased at home. Multiple containers of medication, the MAO-inhibitor moclobemide (Aurorix), the SSRI citalopram (Cipramil), and the benzodiazepine lormetazepam (Noctamid) as active substance, as well as a bottle of whiskey were present at the scene. The autopsy findings were unremarkable, but systematic toxicological analysis (EMIT, radioimmunoassay, high-performance liquid chromatography-diode-array detection [HPLC-DAD], gas chromatography-nitrogen-phosphorus detection, and gas chromatography-mass spectrometry) revealed the following: ethanol (0.23 g/L blood, 0.67 g/L urine), lormetazepam (1.65 microg/mL urine), cotinine (0.63 microg/mL blood, 5.08 microg/mL urine), caffeine (1.20 microg/mL urine), moclobemide (and metabolites), and citalopram (and metabolite). There upon, we developed a new liquid chromatographic separation with optimized DAD, preceded by an automated solid-phase extraction, for the quantitation of the previously mentioned antidepressive drugs. The results obtained for blood and urine, respectively, were as follows: Ro 12-5637 (moclobemide N'-oxide) not detected and 424 microg/mL; Ro 12-8095 (3-keto-moclobemide) 2.26 microg/mL and 49.7 microg/mL; moclobemide 5.62 microg/mL and 204 microg/mL; desmethylcitalopram 0.42 microg/mL and 1.22 microg/mL; and citalopram 4.47 microg/mL and 19.7 microg/mL. The cause of death was attributed to the synergistic toxicity of moclobemide and citalopram, both antidepressants, which, by intentional or accidental combined ingestion, can produce a potentially lethal hyperserotoninergic state. Based on the history of the case and pharmacology of the drugs involved, the forensic pathologists ruled that the cause of death was multiple drug intoxication, resulting in a fatal "serotonin syndrome," and that the manner of death was suicide.

Overall, severe symptoms of the SS seem to occur occasionally when an SSRI is given with moclobemide.....

An open 6-week study in 50 patients with major depression on fluoxetine (or paroxetine) 20 mg daily to which was added up to 600 mg moclobemide daily, indicated that the combination was **possibly effective.** However *one patient developed symptoms suggesting the toxic serotonin syndrome.* Other adverse effects occurred in other patients, the clearest one being insomnia, with dizziness, nausea and headache also occurring frequently. *The high rate of adverse events suggests that there may be a clinically significant interaction.*

I hope this information is of interest...
Ed


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