TCA + Wellbutrin - Greenlight?

[Blitz2006]

Just wondering your thoughts on:

1. TCA (Depression dose) + Wellbutrin

2. TCA (Neuropathic Pain Dose) + Wellbutrin

3. I presume it is safer obviously to proceed with secondary TCA (vs. Tertiary) when combining with Wellbutrin, or does it not make a difference?

Thanks!

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[splik]

There are some studies from the 90s supporting using antidepressant doses of TCA combined with Wellbutrin and I consider it an option for patients needing augmentation of a TCA. The other options are lithium, T3, methylphenidate or an MAOI.

 

[adiradirim]

Wellbutrin is a strong inhibitor of CYP2D6 which can lead to increased TCA levels.

 

[Stagg737]

There are some studies from the 90s supporting using antidepressant doses of TCA combined with Wellbutrin and I consider it an option for patients needing augmentation of a TCA. The other options are lithium, T3, methylphenidate or an MAOI.

Are you saying TCA + other option or instead of the TCA?

 

[Old&InTheWay]

Is the main concern related to both meds lowering the seizure threshold?

 

[clausewitz2]

Are you saying TCA + other option or instead of the TCA?

Plus, those are all augmentation strategies. As long as it is not clomipramine or imipramine TCA+MAOI is a venerable and time-tested combo for TRD.

 

[Stagg737]

Plus, those are all augmentation strategies. As long as it is not clomipramine or imipramine TCA+MAOI is a venerable and time-tested combo for TRD.

Sure, guess I was just questioning the TCA + stimulant more. I don't have a ton of experience with TCAs outside of 3-4 of them and would probably be pretty hesitant to try that d/t lack of experience. I also haven't really encountered this other than patients who are on low doses of TCAs for sleep.

 

[clausewitz2]

Sure, guess I was just questioning the TCA + stimulant more. I don't have a ton of experience with TCAs outside of 3-4 of them and would probably be pretty hesitant to try that d/t lack of experience. I also haven't really encountered this other than patients who are on low doses of TCAs for sleep.

If you want to really go for it and have the stomach for it, Parnate + Ritalin

 

[Blitz2006]

Thanks for responses.

Maybe I should try TCA + abilify for depression?

What about TCA pain dose (like 50 mg pamelor) and then add on 15 mg abilify. Reasonable for depression?

 

[splik]

Thanks for responses.

Maybe I should try TCA + abilify for depression?

What about TCA pain dose (like 50 mg pamelor) and then add on 15 mg abilify. Reasonable for depression?

There is no evidence really for TCAs augmented with atypical antipsychotics. In this case I would optimize the TCA to an antidepressant dose (ie 75mg nortriptyline at least) and only augment if needed.

 

[clausewitz2]

Don’t be shy about using TCAs.

If people take one thing away from this thread, please take away this. There are so many people I work with who were on the endless SSRI/SNRI carousel without ever having any clear benefit who I put on a TCA and then stop being meaningfully depressed. The Dutch psychopharmacology guidelines are very pointed about saying there's not great evidence for switching from an SSRI that doesn't work to a second SSRI in terms of actual improvement and come out against it. I don't necessarily go that far with everyone but if there's actually been an adequate SSRI trial in the past, going to a different class is way more likely to lead to improvement.

 

[Old&InTheWay]

If people take one thing away from this thread, please take away this. There are so many people I work with who were on the endless SSRI/SNRI carousel without ever having any clear benefit who I put on a TCA and then stop being meaningfully depressed. The Dutch psychopharmacology guidelines are very pointed about saying there's not great evidence for switching from an SSRI that doesn't work to a second SSRI in terms of actual improvement and come out against it. I don't necessarily go that far with everyone but if there's actually been an adequate SSRI trial in the past, going to a different class is way more likely to lead to improvement.

Do you know if the Dutch guidelines you mention above are available in English? I couldn't find anything with a quick google search, but my partner tells me I'm very good at not seeing things that are right in front of me. Would be interested to learn more.

 

[clausewitz2]

Do you know if the Dutch guidelines you mention above are available in English? I couldn't find anything with a quick google search, but my partner tells me I'm very good at not seeing things that are right in front of me. Would be interested to learn more.

Here is an article laying out the old guidelines in English, it looks like they were updated in 2019 but am having a hard time getting my hands on them.


https://doi.org/10.1111/j.1600-0447.2009.01492.x

I remembered them slightly incorrectly; they definitely don't seem to recommend switching to second SSRI but this author spends more time on criticizing prolonged trials of high doses of SSRIs for depression.

 

[clausewitz2]

Okay, here are the current Dutch guidelines:

Eerste keuze-middelen bij depressie - Richtlijn - Richtlijnendatabase

richtlijnendatabase.nl

Obviously not in English. Quick sanity check with Google Translate compared to how I would translate it suggests it can cope with this text pretty well, so worth taking a look at even for non-Dutch speakers.

These are if anything even more favorable towards TCAs in recommendations.

 

[splik]

If people take one thing away from this thread, please take away this. There are so many people I work with who were on the endless SSRI/SNRI carousel without ever having any clear benefit who I put on a TCA and then stop being meaningfully depressed. The Dutch psychopharmacology guidelines are very pointed about saying there's not great evidence for switching from an SSRI that doesn't work to a second SSRI in terms of actual improvement and come out against it. I don't necessarily go that far with everyone but if there's actually been an adequate SSRI trial in the past, going to a different class is way more likely to lead to improvement.

Also many patients who don't tolerate SSRIs tolerate TCAs well. The idea they are poorly tolerated is not quite true. they have different adverse effect profiles and some patients don't tolerate them but many do. My patient population skews heavy to neurologically/medically complex and also lots of somatization/functional symptoms and often these patients can do well on TCAs including for some physical symptoms like pain, tinnitus, GI symptoms. If they have significant depression you need to use antidepressant doses though, not piddly doses.

Finally, desipramine is an under-utilized non-stimulant option for patients with ADHD.

 

[Stagg737]

If you want to really go for it and have the stomach for it, Parnate + Ritalin

I'm not that brave. I don't have great exposure to MAOIs, but something I've been wanting to try especially because we have some excellent older psychiatrists supervising our outpatient clinic who are very familiar with them.

I have a pt with a neurodegenerative disease and depression doing great on 200mg amitriptyline with Ritalin for depression. Also has pseudobulbar affect. This combination has been great. Couldn’t tolerate SSRIs or Wellbutrin interestingly. Don’t be shy about using TCAs. They can be safely combined with stimulants too as can MAOIs.

Interesting case. I'm not really shy with TCAs. I use them fairly frequently at lower doses for insomnia with the plan to potentially increase to antidepressant doses if other meds aren't working. I'm pretty comfortable with Am/Nortriptyline, Doxepin, and clomipramine to a lesser extent. I'd like to get more comfortable with imipramine and desipramine as well.

If people take one thing away from this thread, please take away this. There are so many people I work with who were on the endless SSRI/SNRI carousel without ever having any clear benefit who I put on a TCA and then stop being meaningfully depressed. The Dutch psychopharmacology guidelines are very pointed about saying there's not great evidence for switching from an SSRI that doesn't work to a second SSRI in terms of actual improvement and come out against it. I don't necessarily go that far with everyone but if there's actually been an adequate SSRI trial in the past, going to a different class is way more likely to lead to improvement.

I don't know that I agree with that recommendation. I'll commonly start with Zoloft or Lexapro and switch to Prozac for quite a few people if not contraindicated because it's a bit more activating and does have some NMDA activity. I'm don't do it out of caution for starting other meds, I just think that for some there is a big enough difference in SSRI effect that switching classes or augmenting isn't necessary for second-line therapy.

 

[clausewitz2]

Also many patients who don't tolerate SSRIs tolerate TCAs well. The idea they are poorly tolerated is not quite true. they have different adverse effect profiles and some patients don't tolerate them but many do. My patient population skews heavy to neurologically/medically complex and also lots of somatization/functional symptoms and often these patients can do well on TCAs including for some physical symptoms like pain, tinnitus, GI symptoms. If they have significant depression you need to use antidepressant doses though, not piddly doses.

Very much this. Many people would rather deal with dry mouth and constipation if it means they don't end up feeling apathetic and uninterested in sex. My experience to date has been that if I tell people very specifically about the likely side effects of TCAs, they don't end up being an issue; it's a problem when they have these weird symptoms and have no idea why and freak out a bit. If they know it's coming and why it's happening I rarely hear complaints, especially once they take my advice and stock up on sugar-free hard candies from the diabetic aisle at Walgreen's or whatever.

It's also great when my patients who also have untreated migraines suddenly don't have headaches anymore for the first time in forever, another moment where I get to look like a wizard.

Finally, desipramine is an under-utilized non-stimulant option for patients with ADHD.

What sort of dosing do you use for this? It is my go-to for people who have trouble with anticholinergic sx with other TCAs but I've not used it for ADHD. What benefits seem to be consistent with it versus, say, Vyvanse?

 

[clausewitz2]

I don't know that I agree with that recommendation. I'll commonly start with Zoloft or Lexapro and switch to Prozac for quite a few people if not contraindicated because it's a bit more activating and does have some NMDA activity. I'm don't do it out of caution for starting other meds, I just think that for some there is a big enough difference in SSRI effect that switching classes or augmenting isn't necessary for second-line therapy.

That's not unreasonable, and if it's an issue of side effects that is causing someone not to want to be on a full dose SSRI then switching within class makes sense to me. I would switch to another SSRI any day over augmenting with neuroleptics for the vast majority of people. I would also do that if I was somewhat suspicious of possible bipolar diathesis but hadn't been able to definitively figure it out, since SSRIs don't consistently do worse than placebo in inducing mania but TCAs sure as heck do.

 

[FlowRate]

While we're on the topic of antidepressant algorithms, I came across an interesting article yesterday about partial response at X time and likelihood of response at 8 weeks which, TL;DR recommended trying something different if no response at all by 4 weeks because at that point the likelihood of responding at 8 weeks is like <20%. I don't remember the exact stats and the abstract words it funny, but here's a link.

 

[hebel]

While we're on the topic of antidepressant algorithms, I came across an interesting article yesterday about partial response at X time and likelihood of response at 8 weeks which, TL;DR recommended trying something different if no response at all by 4 weeks because at that point the likelihood of responding at 8 weeks is like <20%. I don't remember the exact stats and the abstract words it funny, but here's a link.

Maudsley says something similar (I think they actually said 2 weeks).

To me, it depends on the med. Something like Effexor could have different effects before and after around the 150mg range.

 

[FlowRate]

Maudsley says something similar (I think they actually said 2 weeks).

To me, it depends on the med. Something like Effexor could have different effects before and after around the 150mg range.

Agreed--in such a case I think "something different" could well be a dose increase.

 

[Stagg737]

While we're on the topic of antidepressant algorithms, I came across an interesting article yesterday about partial response at X time and likelihood of response at 8 weeks which, TL;DR recommended trying something different if no response at all by 4 weeks because at that point the likelihood of responding at 8 weeks is like <20%. I don't remember the exact stats and the abstract words it funny, but here's a link.

Maudsley says something similar (I think they actually said 2 weeks).

To me, it depends on the med. Something like Effexor could have different effects before and after around the 150mg range.

There's a study that showed no response to Prozac within first week predicts therapeutic failure fairly well. It wouldn't surprise me at all to see larger data sets showing that no response at 4 weeks generally equates to therapeutic failure. This is basically how I practice, and if there's not response by week 4 we're either increasing dose (if on lower dose) or changing meds if at a solid dose. I also tend to be a bit more aggressive on titrating up as outpatient than some though, so usually by the first follow-up I've got a solid idea if I'm changing meds or not.

 

[NickNaylor]

While we're on the topic of antidepressant algorithms, I came across an interesting article yesterday about partial response at X time and likelihood of response at 8 weeks which, TL;DR recommended trying something different if no response at all by 4 weeks because at that point the likelihood of responding at 8 weeks is like <20%. I don't remember the exact stats and the abstract words it funny, but here's a link.

Maudsley says something similar (I think they actually said 2 weeks).

To me, it depends on the med. Something like Effexor could have different effects before and after around the 150mg range.

I would just add that the antidepressant should obviously be at a therapeutic dose for an adequate period of time before declaring treatment failure. This seems obvious to me but apparently isn't given the number of patients that I see in our TRD clinic that have been tried on many antidepressants that haven't been titrated beyond an initial starting dose.

I agree with @splik with respect to trying the older antidepressants even in patients that are unable to tolerate the newer antidepressants that supposedly have a smaller side effect burden. While this is generally true, I've frequently come across patients that have trouble tolerating SSRIs and SNRIs but have no trouble tolerating TCAs or even MAOIs. The side effect profiles are different, and while the latter are generally thought of as causing all kinds of troublesome side effects, many patients tend to tolerate them better than the predominantly serotonergic side effects of the newer antidepressants.

 

[FlowRate]

I would just add that the antidepressant should obviously be at a therapeutic dose for an adequate period of time before declaring treatment failure.

How are you defining that? The point of posting that article was that maybe the traditional length of time (6/8 weeks, some people define as like 10/12!) is an unnecessary delay if there's been no response at all.