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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by Tony P on April 4, 2024, at 5:24:23
I have been taking bupropion and modafinil for about two years, for MDD and severe daytime sleepiness. Now, for a couple of reasons, I am having to drop the bupropion, and revisit my use of modafinil.
Last year, I went on tamoxifen (breast cancer followup) and the oncologist was very insistent I drop bupropion, as it strongly interacts with tamoxifen (inhibits via CYP enzymes). I negotiated a compromise to reduce my dose by 1/2. Ironically, I was just about to ask my GP about _increasing_ my dose, as I had developed tolerance to the low dose I was on (100 mg/day) and wasn't getting the same benefit as originally. So now I'm looking for a substitute that doesn't interact with tamoxifen, an NDRI or similar. I've done fairly well on Cymbalta in the past (it's only a moderate inhibitor of tamoxifen), but it's not covered by my insurance and I only tolerated it in combination with clonazepam; having spent over a year withdrawing from benzos, I'd be very reluctant to go back on them, even if I could persuade a Dr to prescribe one in the present disfavoring climate. In any case, Cymbalta is only an SNRI, and I really need the dopamine, not so much for pleasure, but for decisiveness and coping skills.
I've also developed tolerance to the modafinil, in retrospect I probably shouldn't have been on it for so long. AFAIK there's no substitute for its unique "wakefulness" effect, so I may have to go off it for a while -- I've been tapering a bit in anticipation. I am continuing to have problems with compulsive daytime sleepiness, verging on narcolepsy, often falling asleep at my desk and (nearly) falling -- a few times I _have_ fallen, luckily no serious injury, but at my age (77) falls are a real concern. We haven't completely diagnosed the cause of my dropping off, it's partly just irregular sleep habits and DSPD, but we haven't ruled out sleep apnea. I'm seriously overweight, which is a risk factor for that, so an NDRI might help with losing weight too.
I've tried occasional doses of Ritalin, but I don't want to make my stimulant tolerance even worse! I came across a reference to an NDRI rejoicing in the name of Atomoxetine (Strattera), which sounds like a nuclear fission moderator, but my GP (who's uncomfortable prescribing anything that says "stimulant" in the monograph) declined the suggestion. I do take kava-kava regularly, quite a large dose (4-8g per day of standardized 30%), and it helps my mood considerably (it's a mild MAOI as well its better-known sedative properties), but it's more of a pleasant intoxicant than an activator. I've been on low-dose selegeline in the past with some success, and I've considered stronger MAOI's, but I'd have trouble with the dietary restrictions. First generation TCAs are a possibility, but besides their unpleasant S/E, I came across a disturbing comment on trimipramine: that it (and possibly other TCAs) have been implicated in causing breast cancer after 11-15 years -- an aha! moment, I was taking it exactly 11 years before I developed breast cancer myself, which is the main reason I'm looking for a new A/D!
BTW, I was also getting considerable benefit from testosterone injections -- I was diagnosed years ago with serious hypogonadism -- but the oncologist vetoed that too! So I've been off that, as well, for 6 months. I really miss it; besides the expected mood benefits, I was somewhat surprised to find it helped my age-related stiffness.
In my own consultations with the oncologist, he has said it's my choice to decide how to balance the expected five-year survival benefit of tamoxifen, dropping any meds which interact (& the testosterone), against the benefits of the latter. However my GP says he can't go against the advice of the oncologist, which sounds like it was much more peremptory and categorical as communicated to him. Professional ethics, I guess.
My GP has referred me to a geriatric psychiatrist, whom I saw a couple of times two years ago -- he prescribed the modafinil. I have an appointment in about 3 weeks, but I always like to come to a session prepared. So I'm looking for suggestions, especially to replace the bupropion.
Posted by SLS on April 4, 2024, at 16:42:13
In reply to Bupropion + modafinil alternatives, posted by Tony P on April 4, 2024, at 5:24:23
Hi.
The first two drugs that come to mind are tricyclics and venlafaxine (Effexor). It's too bad that buproprion is off your list. Combining bupropion with venlafaxine is a potent treatment. MAOIs should be a consideration. Tranylcypromine (Parnate) might be a good choice because of its stimulant properties. However, my belief is that phenelzine will get more people well than any other "standard" antidepressant. I used the word "standard" because it refers to drugs that have had a FDA indication for depression, most of which act at synapses that use biogenic amines as neurotransmitters. Perhaps "modulator" is the best way to look at them:
NE = norepinephrine
5-HT = serotonin
DA = dopamineThe thought is that these neurtransmitters act to modulate the neural activity of the two major neurotransmitters in the brain:
The major excitatory neurotransmitter is glutamate.
The major inhibitory neurotransmitter is GABA gamma amino butyric acid (GABA)For each of these, there are multiple receptor subtypes.
I guess you can include as non-standard antidepressants NMDA receptor blockers, glutamate agonists and antagonists, and psychedelic substances like psilocybin.
Have you ever tried venlafaxine? Its efficacy is similar to that of TCAs, although each is presumably targets different depressive diatheses (subtypes). Low-dosage lithium (300 - 600 mg/day) is effective in depression. However, where mania is part of the presentation, standard dosages lie between 900 mg/day and 1500 mg/day. Perhaps using venlafaxine alone or combination with adjuncts is an avenue worth exploring. Adjuncts would include nortriptyline, lithium, lamotrigine, stimulants, and perhaps an antipsychotic with antidepressant properties.
I'd be curious to know which drugs have had the most positive effects on you.
- Scott> I have been taking bupropion and modafinil for about two years, for MDD and severe daytime sleepiness. Now, for a couple of reasons, I am having to drop the bupropion, and revisit my use of modafinil.
>
> Last year, I went on tamoxifen (breast cancer followup) and the oncologist was very insistent I drop bupropion, as it strongly interacts with tamoxifen (inhibits via CYP enzymes). I negotiated a compromise to reduce my dose by 1/2. Ironically, I was just about to ask my GP about _increasing_ my dose, as I had developed tolerance to the low dose I was on (100 mg/day) and wasn't getting the same benefit as originally. So now I'm looking for a substitute that doesn't interact with tamoxifen, an NDRI or similar. I've done fairly well on Cymbalta in the past (it's only a moderate inhibitor of tamoxifen), but it's not covered by my insurance and I only tolerated it in combination with clonazepam; having spent over a year withdrawing from benzos, I'd be very reluctant to go back on them, even if I could persuade a Dr to prescribe one in the present disfavoring climate. In any case, Cymbalta is only an SNRI, and I really need the dopamine, not so much for pleasure, but for decisiveness and coping skills.
>
> I've also developed tolerance to the modafinil, in retrospect I probably shouldn't have been on it for so long. AFAIK there's no substitute for its unique "wakefulness" effect, so I may have to go off it for a while -- I've been tapering a bit in anticipation. I am continuing to have problems with compulsive daytime sleepiness, verging on narcolepsy, often falling asleep at my desk and (nearly) falling -- a few times I _have_ fallen, luckily no serious injury, but at my age (77) falls are a real concern. We haven't completely diagnosed the cause of my dropping off, it's partly just irregular sleep habits and DSPD, but we haven't ruled out sleep apnea. I'm seriously overweight, which is a risk factor for that, so an NDRI might help with losing weight too.
>
> I've tried occasional doses of Ritalin, but I don't want to make my stimulant tolerance even worse! I came across a reference to an NDRI rejoicing in the name of Atomoxetine (Strattera), which sounds like a nuclear fission moderator, but my GP (who's uncomfortable prescribing anything that says "stimulant" in the monograph) declined the suggestion. I do take kava-kava regularly, quite a large dose (4-8g per day of standardized 30%), and it helps my mood considerably (it's a mild MAOI as well its better-known sedative properties), but it's more of a pleasant intoxicant than an activator. I've been on low-dose selegeline in the past with some success, and I've considered stronger MAOI's, but I'd have trouble with the dietary restrictions. First generation TCAs are a possibility, but besides their unpleasant S/E, I came across a disturbing comment on trimipramine: that it (and possibly other TCAs) have been implicated in causing breast cancer after 11-15 years -- an aha! moment, I was taking it exactly 11 years before I developed breast cancer myself, which is the main reason I'm looking for a new A/D!
>
> BTW, I was also getting considerable benefit from testosterone injections -- I was diagnosed years ago with serious hypogonadism -- but the oncologist vetoed that too! So I've been off that, as well, for 6 months. I really miss it; besides the expected mood benefits, I was somewhat surprised to find it helped my age-related stiffness.
>
> In my own consultations with the oncologist, he has said it's my choice to decide how to balance the expected five-year survival benefit of tamoxifen, dropping any meds which interact (& the testosterone), against the benefits of the latter. However my GP says he can't go against the advice of the oncologist, which sounds like it was much more peremptory and categorical as communicated to him. Professional ethics, I guess.
>
> My GP has referred me to a geriatric psychiatrist, whom I saw a couple of times two years ago -- he prescribed the modafinil. I have an appointment in about 3 weeks, but I always like to come to a session prepared. So I'm looking for suggestions, especially to replace the bupropion.
>
Posted by Tony P on April 6, 2024, at 0:31:54
In reply to Re: Bupropion + modafinil alternatives » Tony P, posted by SLS on April 4, 2024, at 16:42:13
Hi Scott,
Good to hear from you. I always value your experience and your helpful suggestions.
I've tried Effexor and for me it's a washout, I get intolerable anxiety. Cymbalta, which gives a different ratio of NE & 5HT iirc, is much better, but not ideal, for reasons I think I mentioned in my original post. I've come to believe that my 5HT levels are likely adequate; just about any A/D that targets 5HT makes me unpleasantly anxious, even lamotrigine did. In fact, years ago I had the unpleasant experience of serotonin syndrome from an unexpected interaction between Serzone and Wellbutrin (I posted screeds of nonsense on this very board all night just to keep sane, until someone else signed on and "talked" me down). So I've concluded it's DA that I lack, and probably NE.
One idea I was reminded of earlier tonight by a video that YouTube helpfully algorithmically served up to me is that DA can be boosted by some activities. I don't have much capacity for exercise these days, as I have peripheral arterial disease and can't even walk far without pain. But I _can_ walk, and I can start progressively doing more, also getting back to a set of exercises a physio recommended to me -- if I can break my lifelong sedentary habit and resistance to most exercise.
Another physical DA booster I've heard suggested a couple of times is a cold shower (just 1-2 minutes). I'm a bit shower-shy lately, partly because I don't have an en suite shower, but really it's just a matter of making my mind up to it. I have a health worker coming once a week who will help me shower if I just ask him!
As you can see, I'm posting at length to try and talk myself into doing some of these things. I'm a lifelong pill popper, though, so I really want an NDRI to give me a chemical kick-in-the-pants to get going!
Thank you for the MAOI suggestion. The last time I saw the pdoc I'm going to in a couple of weeks, he mentioned them, but I demurred on account of my favourite lunch or snack is often salami or aged cheese.
As a last resort ;-) to overcome my inertia, I may try self-hypnosis. I've been amusing myself recently with some of the many recorded hypnosis sessions on the web, and one of the practitioners I like has one to encourage exercise that I haven't tried yet. Well, maybe tomorrow....
Thanks once again for responding, Scott. I hope you are well. I will post again when I know what I'm doing!
--Tony
Posted by SLS on April 12, 2024, at 11:56:38
In reply to Re: Bupropion + modafinil alternatives » SLS, posted by Tony P on April 6, 2024, at 0:31:54
Hi, Tony.
I went back and reread your previous posts.
If you live in the U.S.
https://www.singlecare.com/blog/cymbalta-generic/
"Is there a Generic for Cymbalta?"
"Yes, a generic version of Cymbalta is available. The patent for brand-name Cymbalta expired in 2013, allowing other companies to produce and market duloxetine, the Cymbalta generic name. Various manufacturers, including Sun Pharma, Teva, Lupin, and Aurobindo, began to produce the generic version after the original patent expired. The introduction of duloxetine as a generic has provided more options for patients needing this type of medication".
If you don't live in the U.S., you can import it with a regular doctor's prescription. Better yet, use Google to find generic duloxetine in your country.
> I've tried Effexor and for me it's a washout, I get intolerable anxiety. Cymbalta, which gives a different ratio of NE & 5HT iirc, is much better, but not ideal, for reasons I think I mentioned in my original post. I've come to believe that my 5HT levels are likely adequate; just about any A/D that targets 5HT makes me unpleasantly anxious
That's the type of information that will lead you to success.
I think you are right in looking towards dopamine, especially if there is a lack of energy, motivation, and anhedonia as prominent symptoms.
> Even lamotrigine did.That is certainly not a common complaint, but I don't doubt that it is possible. Lamotrigine can be energizing. What dosage did you work up to? How quickly did you increase the dosage? Lamotrigine seems to be better for people with bipolar depression than it is for unipolar depression. Did you ever have a hypomanic /manic reaction to a drug? Family history?
Using lithium at low dosages (150-450 mg/day) can work for both unipolar and bipolar depression.
> In fact, years ago I had the unpleasant experience of serotonin syndrome from an unexpected interaction between Serzone and Wellbutrin.
That's worth thinking about. As I'm sure you know, nefazodone is both a serotonin reuptaker and 5-HT2a antagonist. The latter mechanism can increase serotonin release. One must always take into consideration that there might be more mechanisms to yet be discovered.
>One idea I was reminded of earlier tonight by a video that YouTube helpfully algorithmically served up to me is that DA can be boosted by some activities.A long time ago, I found a study that reported that when one "acts" manic, dopamine metabolites found in the blood-stream or urine were increased. I actually used this as a strategy to mitigate my depression. In fact, I used it when I was in the waiting room for my NIH screening. Things were so bad at first, that I wanted to turn around and go home. I couldn't let this happen, so I decided to try it. It worked, and I was able to complete the screening process. I was amused when the NIH doctor called my parents to be sure that I wasn't manic. I tend to engage with people, and this animates me. After two weeks after intake, my depression settled back to my baseline severity. At this point, they saw how severe my depression was. The invesitator later said that my staying alive was nothing short of "heroic". Similarly, at the end of my first visit with a doctor at NYU (New York University), he called my depression "horrendous". After he said that, I cried. I felt that this doctor understood. I felt vindicated.
I don't have much capacity for exercise these days, as I have peripheral arterial disease and can't even walk far without pain. But I _can_ walk, and I can start progressively doing more, also getting back to a set of exercises a physio recommended to me -- if I can break my lifelong sedentary habit and resistance to most exercise.Were you more active as a child before your depression began? Your lack of motivation and energy are classic symptoms of an anergic depression. A handful of years ago, triple reuptake inhibitors were in the antidepressant pipeline. These drugs inhibit all three amine neurotransmitters (actually, they act more like modulators). DA + 5-HT + NE. I would like to have seen how you reacted to nomifensine (Merital). It is a potent DA reuptake inhibitor. It was sold around the world. However, there were reports of hemolytic anemia coming out of the Europe. The drug company voluntarily withdrew worldwide. It was FDA approved in 1984 and recalled in 1986. This is one of the few drugs that I had a great response to, but for less than a week. My doctor at the time (Baron Shopsin) said that he had never seen me so well. This is the same pattern of response I had to every other antipressants. It was only when I combined a MAOI + TCA + lamotrigine that I found success with.
For what it's worth, in 1983, after performing some research in a medical school library, that dopamine might be a crucial contributor in *my* case. I was laughed at by my research clinician at Columbia Presbyterian / New York Psychiatric. When I asked for bupropion - not available at the time - on a compassionate use basis, they said "no". I left and found someone who was working with it open-label. It made me moderately worse. Previously, in a phone call to Donald Sweeny, MD, he told me that bupropion didn't work the way I thought it did. It was not a potent DA reuptake inhibitor. He said that no one knows how bupropion works. It was true then. It is true now.
I still think that dopamine hypoactivity is involved in my case. This is probably most true for bipolar disorder.
> Another physical DA booster I've heard suggested a couple of times is a cold shower (just 1-2 minutes). I'm a bit shower-shy lately, partly because I don't have an en suite shower, but really it's just a matter of making my mind up to it. I have a health worker coming once a week who will help me shower if I just ask him!
>
> As you can see, I'm posting at length to try and talk myself into doing some of these things. I'm a lifelong pill popper, though, so I really want an NDRI to give me a chemical kick-in-the-pants to get going!
>
> Thank you for the MAOI suggestion. The last time I saw the pdoc I'm going to in a couple of weeks, he mentioned them, but I demurred on account of my favourite lunch or snack is often salami or aged cheese.Priorities. I am sure that if Nardil or Parnate brings you to remission (or something close), you will be very happy to give those foods up.
I wouldn't overlook playing with a DA receptor agonist. Pramepixole (Mirapex) would be my first choice, but only as an augmenter. I have only rarely see it work, thought.
I guess that's it for now.
Praying for your health...
Sincerely,
Scott
This is the end of the thread.
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