Pdoc wants to increase serotonin in my current cocktail - any suggestions?

[Catnapper]

I'm fighting my way out of a bad bipolar II depressive episode - I was almost finished with the index, or starting, series of ECT, which is the 3 - 4 week period where you get 2 - 3 treatments per week. I have had a great response to ECT, and the plan was for me to continue on with maintenance ECT. The only downside of ECT for me and many others is the high relapse rate, which can often be kept at bay by continuing maintenance ECT treatments and/or medication. ECT has been put on hold due to the coronavirus, so the monthly or so maintenance treatments are not on the calendar at this time, and who knows how long that will last.

Meanwhile, my regular pdoc, who I trust a great deal, has assured me that he won't let me fall all the way down to the bottom of the abyss again if there's anything he can do about it. I have been seeing him for over three years for medication, and for the last year and a half or so for weekly psychotherapy. He also used to work at the hospital where I get my ECT treatments, so all the involved doctors know each other and talk as needed about my case, which is very reassuring to me.

I can feel the depression nipping at my heels again, partly due to external stressors, and since ECT isn't available, my regular pdoc and I have been discussing adding another med to my current cocktail. He wants to use something that increases serotonin, so I wondered if anyone has a similar cocktail and can suggest a med that they are using or have used in the past. He knows I spend time here, and that I also do a lot of reading on PubMed and other places on my own, and he is okay with that. He has suggested Viibryd, but is open to suggestion. I didn't do well with straight SSRIs like Prozac, which turned me into a zombie, but I'm desperate so will try anything at this point. 

My signature below is accurate as of May 16, 2020, and here is my current cocktail:

In the morning:

• 450 mg of generic Wellbutrin XL 

At bedtime:

• 300 mg of Lamictal
• 10 - 20 mg of Ambien

I also take meds for high blood pressure, low thyroid (recent tests show normal range), and overactive bladder. Thanks in advance for your help. 

 

[Iceberg]

25 minutes ago, Catnapper said:

I'm fighting my way out of a bad bipolar II depressive episode - I was almost finished with the index, or starting, series of ECT, which is the 3 - 4 week period where you get 2 - 3 treatments per week. I have had a great response to ECT, and the plan was for me to continue on with maintenance ECT. The only downside of ECT for me and many others is the high relapse rate, which can often be kept at bay by continuing maintenance ECT treatments and/or medication. ECT has been put on hold due to the coronavirus, so the monthly or so maintenance treatments are not on the calendar at this time, and who knows how long that will last.

Meanwhile, my regular pdoc, who I trust a great deal, has assured me that he won't let me fall all the way down to the bottom of the abyss again if there's anything he can do about it. I have been seeing him for over three years for medication, and for the last year and a half or so for weekly psychotherapy. He also used to work at the hospital where I get my ECT treatments, so all the involved doctors know each other and talk as needed about my case, which is very reassuring to me.

I can feel the depression nipping at my heels again, partly due to external stressors, and since ECT isn't available, my regular pdoc and I have been discussing adding another med to my current cocktail. He wants to use something that increases serotonin, so I wondered if anyone has a similar cocktail and can suggest a med that they are using or have used in the past. He knows I spend time here, and that I also do a lot of reading on PubMed and other places on my own, and he is okay with that. He has suggested Viibryd, but is open to suggestion. I didn't do well with straight SSRIs like Prozac, which turned me into a zombie, but I'm desperate so will try anything at this point. 

My signature below is accurate as of May 16, 2020, and here is my current cocktail:

In the morning:

• 450 mg of generic Wellbutrin XL 

At bedtime:

• 300 mg of Lamictal
• 10 - 20 mg of Ambien

I also take meds for high blood pressure, low thyroid (recent tests show normal range), and overactive bladder. Thanks in advance for your help. 

 

I think that viibryd is as good a choice as any for your situation 

[CrazyRedhead]

Another vote for Viibryd...

[mikl_pls]

I did alright with Viibryd and Wellbutrin in combination, as well as Viibryd on its own. For me, it wasn't strong enough at its max dose of 40 mg both with Wellbutrin and on its own. The idea behind Viibryd from what I've read is that the 5-HT1A partial agnonism both reduces side effects of and reduces the need for extra SERT occupation (and thus serotonin reuptake inhibition), so it doesn't have the typical ~80%+ SERT occupation at the target dose that most typical SSRIs have. I think it's closer to ~60-ish% SERT occupation. It didn't ever have the emotional flattening effects that typical SSRIs have.

Personally, I have done exceedingly well with Zoloft for several years now. I know that you have that one as one of your past meds that I'm guessing didn't work out too well for you. For a good few years, I took Zoloft with the secondary amine TCA Norpramin (desipramine), and for a little while Vivactil (protriptyline), but mostly Norpramin. Until recently, that antidepressant combo did pretty well for me, but it turned on me suddenly for some reason when I switched antipsychotics to Caplyta.

Zoloft is pretty unique in that it is also a moderately potent dopamine reuptake inhibitor in addition to being an SSRI. Depending on the source of your data, Zoloft is actually almost as, if not, more, potent of a dopamine reuptake inhibitor than Wellbutrin, and a more potent norepinephrine reuptake inhibitor than Wellbutrin. I tried looking up the IC50 (the half maximal inhibitory concentration—a quantitative measure that indicates how much of a particular inhibitory substance is needed to inhibit, in vitro, a given biological process or biological component by 50%) of bupropion at the NET and DAT to compare it to the IC50 of Zoloft at the NET and DAT (in relevance to the IC50 at the SERT for Zoloft), and while I got one set of numbers for Zoloft, I got different numbers for Wellbutrin.

• Wellbutrin IC50 NET = 3400 nM, 3715 nM
• Wellbutrin IC50 DAT = 6500 nM, 443 nM, 305 nM
• Zoloft IC50 SERT = 2.8 nM
• Zoloft IC50 NET = 925 nM
• Zoloft IC50 DAT = 315 nM

The lower the number, the more potent it is at inhibiting that transporter. Obviously Zoloft is very potent at the SERT as it is an SSRI. It's surprising though that its potency at inhibiting the DAT approaches one IC50 number I found for Wellbutrin and exceeds the potency of the other two numbers, as well as exceeding (by quite a lot) the potency at inhibiting the NET.

Viibryd's IC50 (inhibition potency) for its target transporters/receptors are as follows:

• Viibryd IC50 SERT = 1.6 nM
• Viibryd IC50 NET = ? nM (prescribing information only gives Ki, which is binding affinity)
• Viibryd IC50 DAT = ? nM (prescribing information only gives Ki, which is binding affinity)
• Viibryd IC50 5-HT1A = 2.1 nM (~60-70% intrinsic activity)

So I'm not sure how to compare it with Wellbutrin in those regards, unfortunately. This is a very unpopular opinion in psychiatry, especially if there is the possibility of the presence of bipolar of any kind, but some may benefit better from a more traditional stimulant than from Wellbutrin. I see Adderall is in your past meds though. What about that experience didn't go well for you if you can remember? Have you tried any other amphetamine-based stimulants (i.e., Vyvanse, Dexedrine, Evekeo)? Have you tried any Ritalin-based stimulants (i.e., Ritalin of course, Metadate CD/Ritalin LA, Concerta, Daytrana, Focalin, etc.)? Some do better with the Ritalin-based ones if they don't do well with amphetamine-based ones. For me, Wellbutrin actually does cause seizures (at any dose), where as even max doses of amphetamine-based stimulants do not cause seizures at all for me. Also, I'm far more relaxed with amphetamines than I ever was with Wellbutrin, actually more relaxed with amphetamines than I am without them (on account of.my ADHD). Wellbutrin makes me extremely high strung and very jittery. Not to mention that the traditional stimulants are far more potent at increasing dopamine and norepinephrine than Wellbutrin is.

Compare Ritalin's and Foalin's IC50's at the NET and DAT to Wellbutrin's:

• Ritalin IC50 NET = 51 nM, IC50 DAT = 20 nM
• Focalin IC50 NET = 39 nM, IC50 DAT = 23 nM

Amphetamines, while they also work as inhibitors of monoamine transporters, work primarily via inducing release of neurotransmitters through other various mechanisms of action, so their potencies can't be compared this way.

Here's basically the TL;DR of what I'm writing a wall of text about:

1. Try the Viibryd (or perhaps even something like Zoloft) along with the Wellbutrin and see how the combo works for you.
2. If you don't get any benefits from the combination, seeing as you're on the max dose of Wellbutrin, discuss with your doctor the possibility of switching the Wellbutrin to an amphetamine-based or Ritalin-based "classical" stimulant on the basis that it would be more potent at increasing dopamine and norepinephrine release. I would opt to start with a lower dose than is typically used to start with for ADHD.

[Catnapper]

Thanks, all, for your replies. Viibryd it is, and I took my first 10 mg pill earlier today.

I woke up in the middle of the night Thursday/early Friday morning, and would have offed myself if I could have summoned the energy to get out of bed. I called my pdoc and left a message Friday morning, the last word of which was, "Help." He's great about calling back so I talked to him that afternoon and started on Viibryd today.

I'm not suicidal anymore, at least at this moment, and I hope the Viibryd works. My pdoc also does therapy, so it is a relief to know that I will talk to him again on Wednesday afternoon. (It's Sunday night right now.) 

[echolocation]

hey cat, i don't have any wise words about viibryd, but i hope it helps you. i'm sorry to hear you're feeling so low again. depression is such a heavy burden. i hope you see some lighter days soon.