Bupropion - Immediate vs delayed effect

[Sync]

Recently started bupropion hcl. A few days in I felt GREAT, suddenly had motivation (honestly a foreign feeling), energy, was able to enjoy things and etc. Didn't realize this was a temporary start-up effect. It went away and I asked my pdoc about it, she says it has a temporary immediate effect and a delayed effect and to wait for the delayed effect to kick in before deciding if we need to increase dose. I'm supposed to check in with her in another few weeks. 

Question: Anyone with experience here know if the delayed effect would be likely to be the same as the immediate effect once it does kick in? Feeling like a normal person for the first time ever for a few days and then losing that is making my depression much much harder to tolerate  

Edited July 8, 2018 by Sync

[Velvet Elvis]

It's the same but a lot milder, if that makes any sense.

[Sync]

It does, thanks. 

Kinda what I was afraid of, since that's mostly how I'm feeling now. Will probably have to bug my pdoc in a few weeks for a higher dose if this maintains.

[argh]

There’s generally a bit of a honeymoon period with bupropion. Xl, Sr or Ir?

had maybe a week or two at week 6 on 300mg xl. I’d echo @Velvet Elvis take on it.

about the same, just quite a bit more milder. Over time I’d say that bupropion is definitely a subtle drug, I can tell it’s still working but it’s not in your face. Least for me. Hope it didn’t poop out and that’s not what it’s supposed to be like.

[Sync]

Thanks, Argh.

It just says bupropion hcl, I think that's immediate release? Insert says not to take more than 150mg at once.

Do you think an increased dose (dr is looking at 200mg as the increase when I'm currently at 100mg) would be likely to have a similar effect as the lower dose startup effect long-term? I'm going absolutely barmy now that I know what not feeling awful all the time is like. I wish pdoc had warned me that the startup is temporary.

[Velvet Elvis]

300mg is the most common theraputic dose.

[Sync]

Yeah, she's probably starting me on such a low dose because I tend to react to lower doses of meds. Wish she wouldn't make me wait so long to increase though. At least I know I have a lot of room to go up.

[argh]

How many times per day are you taking it? If you can’t tell if you have ir or sr, I believe ir is 3x day, sr is 2x and xl is 1x.

To be honest, it’s definitely a stick with it and see what happens sort of deal. Never had the honeymoon on 150xl myself but I’d imagine that as the dose gets higher it would get closer to any honeymoon on 100.

good luck

[Sync]

She has me taking it once in the morning. I don't notice any particular difference in effects based on the time of day or anything. I can look at the packaging again and see if it says specific info about release type.

Thanks! My pdoc is great and has good judgement, so I just keep trying to remind myself she knows what she's doing. I do wish this sort of thing were easier to sort out or more of an exact science so I could at least have something I could confidently look forward to while twiddling my thumbs.

Thanks again for the info.

[Sync]

I wasn't able to find any specific references to how it's released, but I managed to find a label that says "three times a day after titration," so it looks like it is IR.

[Iceberg]

3 hours ago, Sync said:

I do wish this sort of thing were easier to sort out or more of an exact science so I could at least have something I could confidently look forward to while twiddling my thumbs.

Don't we all!! Yeah it sounds like IR so you might gradually talent more often 

[mikl_pls]

I actually didn't have an immediate effect from Wellbutrin at all. I had a period of about two weeks where I had extreme brain fog, memory loss, and decreased coordination from Wellbutrin SR 150 mg, but yet I was remembering things that I hadn't thought about since childhood to early adolescence. It was very strange. My stomach also hurt very badly and couldn't eat at all, and would up losing 12 lb during that two week period. But afterwards, my mood did lift quite a bit for the first time in quite a long time, but it didn't last for very long, and I think it's because I was just taking the SR version once a day. My doctor didn't understand that it had to be raised to being taken twice a day... When I went back and asked about it being raised in dosage, he ABSOLUTELY REFUSED to raise the dose every time for like half a year, until I saw a different doctor at that practice, who raised me to Wellbutrin XL 300 mg, which was a miracle medicine for about a month or two, but also eventually fizzled out for me.

[Sync]

Is SR or XL much better than IR? Looks like with IR I'll need to do a bunch of pills a day which might lead to problems with forgetting (morning pills are easy but afternoon pills I suck at). Beyond that, are the effects much different?

[Iceberg]

I think that theoretically it should be similar but I kno my doc only does the XR and many do SR but I feel like the IR is not as common. Of course that's anecdotal I may be wrong but if you forget easily it might be worth a conversation about it with your doc

[Sync]

Huh, ok. I'll ask her about it then. She's usually really good about listening and explaining her reasoning for things like this.

Thanks!

[argh]

older article..but probably somewhat helpful.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163271/

the seizure risk appears to be lower with SR vs IR. No data on XL but I believe i've seen it somewhere as lower than SR.

Also of note the plasma concentrations definitely follow a different curve between the 3, with allegedly less insomnia with XL

Can't quite comment if there's a 1:1 relationship between plasma concentration and mood/effect, but I would imagine if there was, the IR/SR would feel a bit different throughout the day.

You might be on the IR right now at once a day to titrate. Do you feel it all day or does it peak and then taper off?

[Sync]

Thanks for the article!

I feel it all day. I actually have been paying very close attention to how I feel at different times of day since I started it, and there really seems to be just no difference at all.

If the xl formulation has less insomnia that might be a plus. I have problems with insomnia that were worse during the honeymoon period.

[argh]

something to note if you do try XL. There was an issue with one generic manufacturer a few years back where their XL wasn't bio-equivalent and didn't quite work well..to the point it got recalled. If that happens to you on XL, you might want to switch generic mfgs or try the brand-name stuff if you can get it.

There's also bupripion hydrobromide, Aplenzin, which some members here have found a bit more effective than bupropion HCL. Always an option if the HCL stuff doesn't agree with you.

[Sync]

Yeah, Teva right? I have a different manufacturer, something with an S. And my insurance does also cover brand-name if that ends up being necessary. I'll keep all that in mind, I remember hearing good things here about aplenzin.

[Sync]

So my pdoc knows what she's doing with the low doses apparently, lol. I went up to 200 IR and it made me crazy, thoughts racing, talking fast, can't sit still, OCD and anxiety sx through the roof, insane temper, eventually asked my pdoc about it when I started doing ill-advised impulsive shit at work. She's switched me to 150 XL as of a couple days ago, for the next few weeks until our next appt. I do feel like I've fallen into a hole. Would that make sense as just a difference in metabolism between XL and IR? Would I maybe just need a while to adjust to the XL? Seems weird since I'm going down in dose yknow? 

Can't ask pdoc about it until next appt. I hate feeling this way.

[argh]

The SEs that you described..was that under the IR dosing or was that even after the 150 XL switch? Is the magnitude in SEs at least different between the 200 IR and 150 XL?

Was this 200 IR split into twice a day or 200 IR at once?

If this crazy is under IR, I'd say give it a few more days to see if you end up calming down on the XL. 

Bupropion, in general, is also known to acerbate anxiety in some people.

I'll be honest in that I'm not 100% sure of how genes fully work with inhibition, however my best laymens guess is that there may also be an interaction between your two medications.

Setraline is a CYB2P6 inhibitor. Bupropion relies on CYB2P6 for metabolism. Meaning that Setraline is increasing the actual concentrations of bupropion in your body, by inhibiting the metabolism of the bupropion, despite the lower dose. I could be misinterpreting that however. Maybe @browri can confirm?

[Sync]

Oh yeah, the crazy side effects dropped immediately on switching from 200 IR to 150 XL. Like halfway through the day the first day I took it it was like a wave of relief. I guess IR has a really short half-life?

It was 2x a day, but my pdoc said it was fine to take all at once if I needed to. Just that I would probably have more side effects, so I set an alarm and did a split.

Now I'm just like, tired and depressed? But maybe I just need to adjust to the new dose. I imagine a sudden drop in noradrenaline levels can cause some fatigue. Funnily enough, the 100 IR and the 150XL both seem to decrease my anxiety. But the 200 was absolute hell on it.

Would make sense if the sert means I need a lower dose, my pdoc was big on not going up very quickly. 

[argh]

That sounds about right based on the plasma concentration charts in one the links above.

To be fair, both 150mg and 300mg XL both decreased my anxiety too. Never went to 450mg nor had been on anything but XL, so I couldn't tell you if I personally hit a point where the anxiety shot up.

I can't quite recall how long you've been on bupropion as a whole, but the drop in norepinephrine, may make you crash somewhat hard.

I stepped down from 300mg XL to 150mg XL after about 9 months. The combination of sleeping less in the summer along with sleeping significantly less, period due to the bupropion, was getting somewhat problematic. I pretty much had been sleeping about 4.5 hrs to 5.5 hrs, of broken sleep, consistently since early summer. The first day on 150mg XL wasn't bad. The 2nd day i had to call in sick as I couldn't think, felt awful/ill, and ended up sleeping about 16 hrs. After about two days of being tired, it seems to have evened out. My mood never did drop, however, as the gabapentin that I take seems to act as an anti-depressant for me (despite not being one at all).

The depression-like feeling that you have right now might be perfectly normal with this shift as you're also lessening the dopamine reuptake inhibition as well.

 

[Sync]

Yeah, it's only been a couple days on 150xl. Saturday was day 2 and I almost fell asleep in the middle of the day. I do really hope the depression and tiredness lets up, I am feeling a bit shit atm. I was on 100IR for about a month and 200IR for about three weeks IIRC.

BUT pre-buproprion I was extremely depressed and barely functional to the point where I couldn't feed myself and was having constant suicidal thoughts, so on the whole I'm still very much improved.

[argh]

well hey, take those improvements where we can get them. might not be a full panacea, but one step closer.

good luck.

[browri]

@argh you are correct. Sertraline is a moderate inhibitor of CYP2B6, which metabolizes bupropion. Therefore, sertraline would increase bupropion's blood levels. However, there is a bit more to it. Sertraline also inhibits CYP2D6, which is responsible for sertraline's metabolism. So in fact, sertraline actually inhibits its own metabolism similarly to fluoxetine and paroxetine. Taking it even a step further, bupropion ALSO inhibits CYP2D6. So sertraline increases its own blood levels as well as bupropion's, and bupropion increases sertraline's levels, which would theoretically increase bupropion's levels even further, because typically the impact on metabolic enzymes is dose dependent or falls in line with increasing blood levels, simply meaning that as you go to higher doses or reach higher blood levels, the metabolic inhibition increases. Therefore, it may not be the best idea in a pdoc's toolbox to do like 200mg of sertraline and 300mg of bupropion, just as an example. Typically, you would see a combo like this of 50mg sertraline and 150mg bupropion XL, because taking them together makes the lower doses go much further.

One thing I cannot stress more is to not freak out and think its a major interaction or that you're experiencing overdose symptoms. Combining SSRIs with bupropion is a strategy that has been in use for quite some time now. Pretty much all of the SSRIs and many of the tricyclic antidepressants are metabolized by CYP2D6, so the impact that bupropion has on that enzyme is actually a positive treatment mechanism to be explored as long as it's done carefully. A more heroic example would be combining clomipramine and fluvoxamine for treatment-resistant OCD. It has to be dosed VERY carefully because fluvoxamine very dramatically inhibits clomipramine's metabolism, but in low doses of each, the summation is generally greater than its parts.

[argh]

Awesome. Always appreciate the in depth explanations, @browri

[Sync]

That's absolutely fascinating @browri, thank you! I wonder if that explains why the bupropion has improved my anxiety and OCD sx at the lower doses? Sertraline has been a miracle drug for both, so if bupropion is increasing levels of that it would make some sense. 

[browri]

2 hours ago, Sync said:

That's absolutely fascinating @browri, thank you! I wonder if that explains why the bupropion has improved my anxiety and OCD sx at the lower doses? Sertraline has been a miracle drug for both, so if bupropion is increasing levels of that it would make some sense. 

@Sync actually your combo is all the more intriguing. Sertraline at doses 150-200mg actually inhibits dopamine reuptake along with serotonin. Bupropion is stronger at inhibiting norepinephrine reuptake than dopamine reuptake (doesn't touch serotonin at all). Sertraline (as a so-called SSRI) is obviously far more potent at inhibiting serotonin reuptake than dopamine reuptake. However, the two of them together, while modest inhibitors of dopamine reuptake on their own could theoretically be quite synergistic when combined. If you combine two strong reuptake inhibitors and max out the transporter that performs reuptake, there isn't much added benefit.

Imagine thousands of people all trying to carry rocks from one little pile to another little pile. No matter how many people you have to carry those rocks, only so many people can clamor around a small pile to get a rock and then only so many of those people can get close enough to the second pile to drop off the rock. Yeah that rock pile is going to still get moved pretty quickly, but more doesn't always mean you'll get more in the nervous system. Imagine instead that just 1 or 2 people are moving the rocks from one pile to another. If 1-3 more come, then that will certainly pick up the pace, but there comes a point when adding people doesn't actually make it any faster.

I know it's kind of a rough analogy so I welcome criticism, but that's just how it made sense in my brain.

EDIT: Will add that I only understand this to be the case for reuptake inhibitors but I can imagine the concept can be applied, at least in part, to other neurological functions.

Edited August 7, 2018 by browri

[Sync]

I think I'm tracking what you're saying. So you're saying that two modest dopamine reuptake inhibitors would theoretically be a bigger rock pile while a strong dopamine reuptake inhibitor would be more people crowding around the rock?  This is great and fascinating info, thanks for sharing it. 

I've also noticed the bupropion seems to have slaughtered the sexual side effects I've always had from sertraline. IIRC those were meant to be caused by decreased dopamine levels in response to increased serotonin, so to my relatively uneducated self, it all seems to make sense.

On a side note, the XL seems to have kicked in in some way today. I feel actually fantastic.

[browri]

13 hours ago, Sync said:

I think I'm tracking what you're saying. So you're saying that two modest dopamine reuptake inhibitors would theoretically be a bigger rock pile while a strong dopamine reuptake inhibitor would be more people crowding around the rock?  This is great and fascinating info, thanks for sharing it. 

I've also noticed the bupropion seems to have slaughtered the sexual side effects I've always had from sertraline. IIRC those were meant to be caused by decreased dopamine levels in response to increased serotonin, so to my relatively uneducated self, it all seems to make sense.

On a side note, the XL seems to have kicked in in some way today. I feel actually fantastic.

Another good way of looking at it is just in percents to make it clearer. Usually SSRIs need to be dosed to a point where they inhibit the serotonin transporter 60-85%. So let's say Drug A inhibits the transporter to 65% at 50mg and Drug B inhibits 60% at 25mg. If you take those two medications together at those doses, it doesn't equate to 125% inhibition, it might just come out to 75%. Just random numbers I'm throwing out, but it shows that taking two medications of the same class MIGHT be synergistic but not enough to make the side effects worthwhile. Risks outweigh the benefits.