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Re: Bupropion + modafinil alternatives Tony P

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


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 = dopamine

The 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.

Some see things as they are and ask why.
I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.




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