Posted by Robert_Burton_1621 on March 2, 2015, at 21:24:00
In reply to Re: Has anyone tried Strattera?, posted by ed_uk2010 on March 1, 2015, at 14:30:53
> >I am thinking about whether it would make sense to add a SSRI because I also have depression.
>
> Strattera interacts with certain SSRIs, but it should be possible to combine it with sertraline (Zoloft). In spite of some dubious information online, sertraline does not appear to prolong the QT interval.
>Ed and fido, I understand that nearly all studies of straterra state that it has negligible effect on transporters other than NET. However, I've just come across the below 2014 paper which concludes that it occupies SERT, too. I am not competent to understand critically the methods or results of this paper, but might it have a bearing on the question whether a suitable SSRI can be combined with straterra?
Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD.
Authors
Ding YS1, Naganawa M2, Gallezot JD2, Nabulsi N2, Lin SF2, Ropchan J2, Weinzimmer D2, McCarthy TJ3, Carson RE2, Huang Y2, Laruelle M4.
Author information
Journal
Neuroimage. 2014 Feb 1;86:164-71. doi: 10.1016/j.neuroimage.2013.08.001. Epub 2013 Aug 9.
Abstract
BACKGROUND: Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [(11)C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [(11)C]MRB (a NET ligand) and [(11)C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys.METHODS: Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01-0.12mg/kg/h and 0.045-1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated.
RESULTS: ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0-1.8mg/kg, approx. 300-600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates.
CONCLUSION: Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.
© 2013.
PMID 23933039 [PubMed - indexed for MEDLINE]
Elsevier Science: Full text
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