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Absorption Of Cymbalta


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#1 fishinghat

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Posted 13 October 2019 - 05:19 PM

The bottom line on this article is that despite being given a set dose of 60 mg/day to each of 66 depression patients, the serum levels varied from 30-120 ng/mL after 3 months. That means that the person with the highest level in their blood had 4 times as much in their system than the person with the lowest level. Of course the higher the blood serum level the better it controlled depression.

 

https://www.ncbi.nlm...pubmed/30611837
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:127-132. doi: 10.1016/j.pnpbp.2019.01.001. Epub 2019 Jan 3.
Duloxetine plasma level and antidepressant response.
Abstract
BACKGROUND:
Major Depressive Disorder (MDD) is associated with a high rate of inadequate treatment response, which is mainly due to the large inter-individual genetic variability in pharmacokinetic and pharmacodynamic targets of antidepressant drugs. Little is still known about the exact association between plasma level of first-line antidepressants and clinical response. This is particularly true for duloxetine, a dual serotonin and norepinephrine reuptake inhibitor recommended as first-line treatment for MDD. The aim of this study was to investigate the association between serum concentration of duloxetine (SCD) and antidepressant response (AR).

 

METHODS:
66 MDD patients treated with duloxetine 60 mg/day monotherapy were recruited in an outpatient setting and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, at month 1, and at month 3 to assess AR. SCD was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCD and AR.

 

RESULTS:
SCD showed a high inter-individual variability in our sample, despite the duloxetine fixed oral dosage. We found a strong association between SCD and AR following a bell-shaped function at month 1 and at month 3. Nonetheless, within the recommended SCD range of 30-120 ng/mL a more linear correlation between SCD and AR was observed.

 

DISCUSSION:
Our results suggest that for duloxetine the association between SCD and AR likely follows a bell-shaped quadratic function with poor AR at subtherapeutic SCD and progressive decrease of AR at higher SCD. The maximum antidepressant efficacy seems to require SCD values next to the highest recommended SCD (30-120 ng/mL), probably because of the optimal saturation of both serotonin and norepinephrine transporters. Thus, taking into account the observed high interindividual variability of SCD, our findings suggest that for MDD patients treated with duloxetine, SCD could be a useful tool to guide the treatment by optimizing the oral dosage in order to increase the AR rate.


#2 invalidusername

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Posted 13 October 2019 - 05:31 PM

Interesting find there Hat. You would have thought that these types of tests should be carried out as part of the screening process. Understanding that subjectivity is playing a very large part in all this, but if the chemical compounds being used in the drug are such that variability exceeds that by comparison to other such drugs that it should be revised given that the highest dose given to patients could still only be getting such a small percentage of the "benefit" assuming there would be one, whereas the truth of the matter is that they could be far better off with another drug that wouldn't cause them to suffer the same loss of benefit.

 

Ideally what this needs is the same patients experiencing the lower levels to see if they find the same conclusions on other monotherapy - not that this would happen. But rather than augmenting the therapy with other drugs and of course, adding to the complications of withdrawal and side effects, they might consider alternative routes of medicinal therapy.

 

Still so much to learn, yet they dish this out like candy.... *sigh*

 

Again, cracking find - thanks for sharing. I'll have a proper read tomorrow.


#3 fishinghat

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Posted 14 October 2019 - 08:13 AM

"...but if the chemical compounds being used in the drug are such that variability exceeds that by comparison to other such drugs that it should be revised"

Exactly what I thought. Your comment about it being subjective is also right on. What else was the patients on? Any ppis or other meds that would effect absorption? Did they have underling But again most drs don't consider these items either. lol

#4 invalidusername

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Posted 14 October 2019 - 04:19 PM

Absolutely. This is why such clinical conditions are so difficult to represent. Doing my own research you realise just how many factors are involved in getting accuracy. Granted I am dealing with emotion rather than medicine, but the subjectivity issues are still there all the same...





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