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Re: NRIs w/o antichol fx? desipramine high dose vs low

Posted by zeugma on April 12, 2005, at 17:15:44

In reply to NRIs w/o antichol fx? desipramine high dose vs low, posted by iforgotmypassword on April 12, 2005, at 11:34:27

Hi, I have this abstract lying around, for just this occasion:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15385827

Ther Drug Monit. 2004 Oct;26(5):468-73.


Excess fatality from desipramine and dosage recommendations.

Amitai Y, Frischer H.

Department of Mother, Child and Adolescent Health, Ministry of Health, Jerusalem, Israel. yona.amitai@moh.health.gov.il

Higher case fatality rates (CFR) were previously reported from desipramine than for 3 other tricyclic antidepressants (TCAs): amitriptyline, nortriptyline, and imipramine. The database of the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) for the 20 years 1983-2002 was used to evaluate the CFR of desipramine and the other TCAs. The CFR of desipramine was 2.25-, 2.31-, and 2.62-fold the CFR for amitriptyline, nortriptyline, and imipramine, respectively (P < 0.001). Mechanisms of desipramine toxicity and its dosage recommendations are discussed. Desipramine and nortriptyline have higher distribution volumes and erythrocyte/plasma ratios than their parent compounds imipramine and amitriptyline. This implies lower therapeutic plasma levels and reduced doses for desipramine and nortriptyline compared with their parent compounds. Such adjustments have been done for nortriptyline, but not for desipramine. The authors suggest that the high CFR of desipramine might be reduced by lowering its dose, therapeutic plasma level, and maximal pill content.


I don't know what to make of this, honestly. The therapeuric range for desipramine, according to some official source or other, is 116 ng/mL and up. Nortriptyline's is roughly 50-150 ng/mL. Why desipramine would have an open-ended plasma range, while nortriptyline would have a curvilinear one, escapes me completely. Desipramine is approximately four times more potent at its presumed site of action, the NE transporter, which is the same as nortriptyline's, so why nortriptyline would be effective at lower concentrations than desipamine is obscure.

I asked my pdoc about desipramine vs. nortriptyline once, and he told me that in his clinical judgement, the two drugs were virtually identical except that nortriptyline was effective at lower doses.

As for other NRI's, there is Strattera, which has no anticholinergic activity. It worked really well for me for a while, but eventually either pooped out or actively caused me to become depressed. I favor the latter hypothesis because each time I retried it my depression worsened. There's also reboxetine, available in the UK, but supposedly its reputation is so low that side-effect-ridden TCA's like amitriptyline are prescribed far more often.

-z


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