Posted by screwocd on February 26, 2013, at 10:46:24
In reply to Re: 100mg Anafranil + 100mg Luvox too much? » screwocd, posted by Phillipa on February 25, 2013, at 20:37:55
Here are the main sources I looked at to suggest that combining Luvox and Clomipramine may work for treating refractory OCD. The literature suggests that Clomipramine (CMI) at a target concentration of 500ng/mL will be effective for treating refractory OCD and MDD. (1,2)
The reasoning behind the combination is that Luvox is mostly metabolized by the enzyme CYP1A2, which also is one of the primary enzymes that metabolizes CMI into its active metabolite, desmethylclomipramine (DCMI). (3,4) DCMI functions as a strong norepinephrine transporter (NET) inhibitor, having a Ki value of less than 1nM, compared to CMI, which has a Ki value for NET of 54nM.(5) The logic is, if fluvoxamine is added, it will competitively inhibit the metabolism of CMI into DCMI. Inhibiting the CMI to DCMI metabolism will effectively increase the level of CMI, which will promote more serotonergic activity, while decreasing the level of DCMI, which would otherwise promote adregnergic activity. For this reason, it may not be a wiser choice to augment CMI with fluoxetine since fluoxetine is metabolized by CYP2D6, one of the primary enzymes that metabolizes DCMI by hydroxylation (3,6). Therefore, if the goal is to increase serotonergic activity, augmenting CMI with fluvoxamine would be the better choice when compared to fluoxetine. I looked up all of this information and hopefully have compiled it in a logical manner.
(1): http://www.ncbi.nlm.nih.gov/pubmed/8666564
(2): http://neuro.psychiatryonline.org/article.aspx?articleid=99634 (a good case study of a patient with OCD and MDD)
(3) http://www.pharmgkb.org/pathway/PA165960076
(4): http://www.ncbi.nlm.nih.gov/pubmed/8846617
(5): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/
(6): http://www.ncbi.nlm.nih.gov/pubmed/10631623
poster:screwocd
thread:1038782
URL: http://www.dr-bob.org/babble/20130222/msgs/1038888.html