Nicotine induced inhibition of desvenlafaxine? Urgent!

[DexyDevil]

I have been taking 50mg of desvenlafaxine (Pristiq) for two weeks. I smoke about a pack of cigarettes a day. The desvenlafaxine seemed very effective initially... now I'm not so sure.

This study (http://www.ncbi.nlm.nih.gov/pubmed/22426847) claims...

In smokers, mean serum levels of ODVEN were 21% lower than in non-smokers.

What are the chances that smoking causes a clinically significant decrease in the efficacy of desvenlafaxine? Here on crazy meds (http://www.crazymeds.us/pmwiki/pmwiki.php/Meds/Pristiq) it is claimed that nicotine interacts with desvenlafaxine but not venlafaxine (Effexor), yet desvenlafaxine is an active metabolite of venlafaxine and is widely regarded to be the primary reason for venlafaxine's therapeutic efficacy. Why would nicotine reduce the effectiveness of one and not the other?

Studies have indicated that desvenlafaxine shows no increase in efficacy at doses higher than 50mg. Should I ask for a dose increase from 50mg to 100mg (the only other available dose) to account for the 21% decrease in mean serum levels? Am I overthinking this?

I really, really need this medication to be effective as I have attempted suicide several times in the last year due to depression.

Incidentally, I also take 20mg of mixed amphetamine salts IR 2x daily, 150mg of pregabalin 3x daily, and 30mg of mirtazapine and 200mg of quetiapine in the evening. The previously mentioned study also states...

Co-medication with other psychotropic drugs was associated with a decreasing ODVEN/VEN ratio indicating a reduced metabolism in patients receiving polypharmacy.

I do not have access to the actual study as I don't pay the PubMed fee, but I'm really worried that my smoking and/or use of other psychotropic meds will prevent me from fully recovering from depression and remaining in remission. Can anyone ease my mind, offer advice or answer my questions?

Thank you so much in advance!

 

[sekio]

PubMed is free, they don't charge, it's companies like Elsevier that do.

You're overthinking this - the study is talking about levels of desvenlafaxine in people who are administered venlafaxine only. The ODV in that case would be all made from hepatic metabolism of VEN. That explains why e.g. smoking alters the amount of ODV in that situation - smoking is known to effect liver enzymes.

In your case, you are taking ODV straight up, and no liver metabolism is involved in its production, so you don't have to worry.
Context is important when you read these studies

 

[DexyDevil]

PubMed is free, they don't charge, it's companies like Elsevier that do.

You're overthinking this - the study is talking about levels of desvenlafaxine in people who are administered venlafaxine only. The ODV in that case would be all made from hepatic metabolism of VEN. That explains why e.g. smoking alters the amount of ODV in that situation - smoking is known to effect liver enzymes.

In your case, you are taking ODV straight up, and no liver metabolism is involved in its production, so you don't have to worry.
Context is important when you read these studies

Wow! Thank you for getting back to me so quickly. I feel so much better! Your explanation makes perfect sense, especially considering how illogical it seemed that smoking would effect one and not the other. I may just send an email to that CrazyMeds administrator and let him know. After all, if I got so worked up about it then it stands to reason that someone else would too.

I guess I'll need to give it the standard 6-8 weeks to fully take effect. Thanks again!!

 

[DexyDevil]

I think I was misled by the information on CrazyMeds. Interestingly enough, I now realize that the opposite is true; nicotine wouldn't interfere with desvenlafaxine it would interefere with Venlafaxine. I really do need to send the CrazyMeds administrator an email.