Pharmacology Help: Is My Sertraline Inhibiting My Oxycodone?

[Rybee]

Hi All,


Pre-note: I have a 'fair' knowledge about the medications I take. Certainly enough to understand what I'm taking and roughly how it might work to produce its' effects, but I am by no means an pharmacological expert and thus my knowledge is somewhat rudimentary. Therefore, anything I say will be to the best of my knowledge, so please do feel to correct me on anything I've stated that isn't quite correct. After all, a little bit of education on this topic is only going to benefit me, so I'd actually appreciate it.


Background Information:
I'm after a bit of pharmacological/biological knowledge/help regarding the possible interaction between Sertraline and Oxycodone. I just went to my local pharmacy to speak to a Pharmacist, but they didn't offer up much help at all. So once again I've turned to you guru's on BL...

Basically, I have a Pars Defect and a Herniated Spinal Disc in the lower of my spine (L2-L3 I think) which results in terrible neuropathic pain shooting down my sciatic nerve; from the top of my bum down to through my thighs, hamstrings, calves and to the heels of my feet. In the past few years I've slowly graduated from taking:

- Dihydrocodeine (IR)
- Tramadol (IR)
- Morphine (IR)
- Buprenorphine (TD patch)
- Morphine (ER)
- Fentanyl (TD patch)
- Tapentadol (ER)
- Oxycodone (IR)

I've been doing okay on the Oxycodone but it's become less and less effective over time and I've had to keep increasing the dose. In January 2015 I went back to my pain management consultant who said he would like us to stop increasing the Oxycodone and instead change me over Methadone. His rationale for doing so was that Methadone is generally better for targeting neuropathic pain than the other opiates I've tried, and that I would also benefit to some degree from some opiate rotation. I'm still waiting for my appointment to initiate this change, which seems to be a bit slow, and I need to chase this up ASAP.

However, ~4 weeks ago I saw a Psychiatrist again for my low mood (MDD) and anxiety (GAD) and I agreed to try a small dose of Sertraline/Zoloft (50mg) to see if that helped. At this point, I had just increased my Oxycodone from 3x10mg to 4x10mg per day (which is down from the 200mg per day of MS Contin/Morphine ER that I was taking previously. We've made such good progress in reducing my opiate load over the last 12 months so I'm very nervous about increasing it again), whilst my Methadone referral was being arranged.

Within a week of taking the Sertraline I noticed that the increase from 3x10mg to 4x10mg of Oxycodone had not only not helped, but the pain had in fact worsened. Yesterday I was in a lot of pain, so I took 1x50mg in the afternoon to help ease the pain before spending a long night out with friends later, but to also catch a little buzz I guess. The pain had me feeling very miserable and fed up all week so I thought a little opiate buzz would help perk me up a bit, ready for the night out. But after an hour I felt nothing. No reduction in pain, and not even a light warm buzz - which is strange because I stopped 'abusing' my opiates a long, long time ago as it was only increasing my tolerance to them and being counterproductive in decreasing my opiate load and providing sufficient pain relief.

So with no other recent changes, I can only think that Sertraline is the culprit and is somewhat interfering with the metabolism/mechanism of the Oxycodone?


My Theory: (please note, as aforementioned, my knowledge is rather rudimentary and based on a self-taught reading of internet articles - so please feel free to correct me)

So from what I can gather from reading into this subject earlier today, this is a very simplified explanation of what I think is happening - and I appreciate that there is in fact a whole lot more going on in these processes.

Sertraline is metabolised by CYP2B6 into Desmethylsertraline (amongst some other things)
This process inhibits: CYP2D6, CYP2B6 and CYP2C9

Oxycodone is metabolised by CYP3A and CYP2D6 into Oxymorphone and Noroxycodone (amongst many other things)
This process inhibits: CYP2C19, CYP2D6 and CYP2C9

Again, I know this is a very basic explanation, and I'm not sure if it's completely accurate, but that's how I understand it right now. So would I be right in saying that because Sertraline inhibits CYP2D6, and because Oxycodone is partly metabolised by CYP2D6, then the Sertraline is stopping the Oxycodone from being fully metabolised and thus not being broken down properly into its' active compounds such as Oxymorphone/Noroxycodone etc.., which is resulting in me experiencing the reduced pain killing effects, as well as the inability to catch a small buzz on a relatively high dose to what I'm currently taking?


What I'm asking:
1) Is what I'm saying correct, or thereabouts? If not, could you please correct me?

2) Would I benefit from supplementing my Oxycodone with another opiate that is not metabolised by the enzymes inhibited by Sertraline (CYP2D6, CYP2B6 and CYP2C9) until I swap over from Oxycodone to Methadone? If yes, what are my choices? From a quick Google, I think:

Buprenorphine - which is metabolised by CYP3A4 and CYP2C8
Morphine - which is metabolised by UGT2B7 and UGT1A1
Fentanyl - which is metabolised by CYP3A4

3) Would I benefit from changing from Sertraline to another SSRI that does not inhibit CYP3A and CYP2D6 which metabolise Oxycodone? I looked this up quickly, but couldn't find any/many that don't inhibit CYP3A or CYP2D6 that are used to metabolise Oxycodone?

Fluoxetine/Prozac - which strongly inhibits CYP2D6 and mildly inhibits CYP1A2, CYP2B6, CYP2C9/2C19, and CYP3A4
Fluvoxamine/Luvox - which is a potent CYP1A2 inhibitor and a mild inhibitor of CYP2C19, CYP3A4, and to some extent CYP2C9
Paroxetine/Paxil - potent inhibitor of CYP2D6 and CYP2B6 and a weak inhibitor for CYP3A4, CYP1A2, CYP2C9, and CYP2C19
Citalopram/Celexa - which is a weak CYP2D6 inhibitor and has weak or no effects on CYP1A2, CYP2C19, and CYP3A4

So I don't think that any of them SSRIs will really seem to help me? Perhaps Citalopram/Celexa being the best of a bad bunch of choices?

4) I also read that Sertraline can increase the levels of Methadone in the body by up to 40%, which is something I have to consider when I begin to initiate titrating my dose of Methadone from Oxycodone, if I am still taking Sertraline at this point?


Summary:
I quite like Sertraline as I've had no bad side effects and actually find it mildly stimulating, as opposed to when I tried taking Fluoxetine/Prozac and Citalopram/Celexa, as well as all of the Tricyclics which I found to make me feel absolutely awful and very drowsy. So I'd quite like to stay on that if possible.

So if all I have said is correct (or to some degree at least) my best choice would be to temporarily supplement my Oxycodone with Buprenorphine/Morphine/Fentanyl/Other-Opiate until I can switch over to Methadone?

Again, I'm so sorry if I've really missed the mark here and am completely off-course with my knowledge of Pharmacology or have provided inaccurate information?

I guess all I'm asking is:


a) Is it possible that Sertraline is responsible for me feeling less effect from the Oxycodone, which has resulted in me experiencing more pain?
b) What would be the best opiates I could used to supplement my Oxycodone until I switch over to Methadone?
c) Would I be okay on Methadone whilst taking Sertraline?
d) Any other comments?


Any help/information would be greatly appreciated. I've only recently started a new job and the pain is really interfering with my performance/happiness and I don't want to be taking time off already and be seen as an early health-liability whilst I'm still on my probation period

Cheers BL, I'd appreciate any kind of response from anyone. And as said, please do feel to tell me if I'm barking up the wrong tree?

Rybee x

 

[sekio]

Oxycodone is active without metabolism to oxymorphone and any metabolism is rather minor in its effects. So I doubt adding sertraline would block the effects to the extent you're seeing. It's entirely possible that it is, but you'd need to switch off it to be sure, and that's not really an easily achieved task.

If you're already increasing your oxycodone dose and have taken opioids for a while I'd suspect opioid hyperalgesia. It's probably the beginning of the end of your career of opioid usage. You can try other opioids that are available to you, but don't expect miracles.

 

[Erikmen]

I see this happening when one is above its Fentanyl dosage, 24/7 and using hard core opiates for breaking through severe pains.
That's when 1 g of heroin is hardly noticed.

 

[serotonin2A]

Seiko is correct that the analgesia produced by oxycodone is not due to a metabolite:

http://www.ncbi.nlm.nih.gov/pubmed/16678548

Oxycodone is metabolized to oxymorphone, a stronger opiate, but apparently that doesn't make a contribution to the effects of oxycodone. It looks like only about 10% of the oxycodone is converted to oxymorphone.

 

[Rybee]

Hey guys - thanks for taking the time out to reply, I really appreciate that.

That's actually very interesting about Oxycodone being active in its own right, as I had formed the impression from the articles that I was reading that it had to be metabolised into Oxymorphone before it had any painkilling effect.

Sekio - I had opiate hyperalgesia in the back of my mind but I just thought the introduction of Sertraline and the seemingly new 'immunity' to Oxycodone was too coincidental, though maybe it is that and I'm just adding two and two together to make things add up.

I think I am going to rotate off of Oxycodone and try another opiate. I found a few old 30mg MS Contin tablets at the weekend and just two of them hit way harder than I could have expected, considering they were continuous release and not instant, too. I got surprisingly very warm and fuzzy from that, it almost caught me off guard.

I'm due to see my pain doctor on Thursday so I'll have a chat about maybe changing to MS Contin whilst my Methadone referral is still being processed.

Really appreciate the replies though guys. I don't often get involved into the mechanics of opiates, but that's definitely helped me understand it better.