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Some advice and non-serotonergic ideas for you... loolot

Posted by Ame Sans Vie on October 17, 2003, at 3:22:10

In reply to Re: Do wellbutrin etc., inadvertently raise serato Ame Sans Vie, posted by loolot on October 16, 2003, at 11:14:01

> > Actually, I believe Wellbutrin has a direct effect on serotonin... or so I've read.
> Thanks ASV.

Anytime. :-)

> Do you have links to any articles?

I don't have any cut and dry information on this yet, but I'll start doing some research and let you know by tomorrow. I'm rather interested too as I just started taking both Prozac and Wellbutrin XL.

> This is interesting because my Pdoc was suggesting I could try and take a large dose (like 600 mg!) of Wellbutrin because mine is pooping out and nothing else seems to work.

I'm sure there are those who require such a high dose, but *be careful*! I'd guess such a raise in dose could be quite dangerous as bupropion can induce seizures and it appears that seizure risk raises exponentially with every dose increase. All the official literature on the subject I've come across *warns* not to exceed 400mg/day (I mean, it doesn't just list 400mg as the maximum FDA recommended dose -- it considers higher doses to be quite risky territory). I believe the seizure risk is 1/1,000 at 200mg/day and 1/250 at 400mg/day (I may be wrong on the 200mg part, but the rest I'm sure of) -- 600mg could greatly increase your risk of seizure... 1/100? Who knows... I personally wouldn't take those odds, but that's just me. :-)

Be especially careful if you do end up increasing dose to 600mg and you're taking a benzodiazepine. Make sure you never run out of the benzo too early -- as most of us know, there's quite a likelihood of convulsions when benzos are stopped cold turkey. I imagine that the vastly decreased seizure threshold from higher-than-recommended doses of bupropion could be an almost guaranteed seizure should you miss a few doses of a benzo. The same goes for many other CNS depressants (alcohol, barbiturates, Xyrem [sodium oxybate; GHB] and novel agents such as Ambien [zolpidem], Sonata [zaleplon], Placidyl [ethchlorvynol], Doriden [glutethimide], Miltown/Meprospan/Equanil/Neurospan [meprobamate], Soma [carisoprodol] and Noctec [chloral hydrate]).

Oh, and just one last thing which is pretty important... following poop-out, it seems that, more often than not, a dose increase does very little or no good.

> Now I am thinking it isnt good idea,, bc I dont do well on seratonin, I think.

Well, perhaps you can take comfort in knowing that bupropion's serotonergic effect (if it really has one) is very weak at best. I'm practically positive you wouldn't even notice it. After all, it is prescribed as an adjunct to serotonergic antidepressants to combat sexual side effects (as are quite a few other drugs), and it's widely held that bupropion is helpful in this way via its effects on DA and NE. If bupropion truly had a meaningful effect on serotonin, which would most likely be though reuptake inhibition, I doubt it would work as well as it does -- there are even names for combos of SSRIs + bupropion, such as "Cel-Well" -- Celexa taken with Wellbutrin. This is gaining a lot of popularity due to bupropion's obvious success in many cases, so once again, I'd hazard to guess that the serotonergic activity is nothing to concern yourself with.

> Are there any ADS which are not at all seratonergic? Maybe dopamine agonists?

Dopamine agonists (i.e. Symmetrel [amantadine], Mirapex [pramipexole], Dostinex [cabergoline], Parlodel [bromocriptine], Requip [ropinirole]) *usually* tend to be more useful for symptoms *associated* with mood disorders but which aren't always a factor in the depression. It seems that many symptoms relieved fall more under the personality disorder heading (In other words, they're most often not very useful for depression, but -- if motivation, confidence, drive, libido, and anhedonia are all things that could use a boost, I'm most definitely all for DA agonists. So atypical depression of many types may benefit greatly from a DA agonist. I'd probably recommend trying an ergot-derived drug though (i.e. Dostinex, Parlodel) before getting to the others. The reason is simply the dangerous sleep attacks that Mirapex, and fairly often Requip as well, tend to induce. Though they are wonderful, wonderful drugs if you:

A.) are lucky enough to not experience the narcoleptomimetic effects of the drugs, or...
B.) take a good stimulant along with the drug to ward off these side effects... Wellbutrin alone can be enough of a stimulant to get this job done, though Provigil (modafinil) seems quite promising as well (in theory), as do amphetamines (Adderall, Dexedrine, DextroStat, Desoxyn, amphetamine sulfate), methylphenidate (Ritalin, Concerta, Metadate-CR et al.), magnesium pemoline (Cylert... not recommended -- serious liver complications with long-term use), adrafanil (less safe than Provigil, though similar in effect, and you have to order it from overseas -- whole hell of a lot cheaper though), Strattera ('atomoxetine' or 'tomoxetine'), Edronax (reboxetine)... or perhaps even mildly stimulating OTC remedies (though some find these to be much more than mildly stimulating, so be careful)... such as NADH (nicotinamide adenine dinucleotide -- expensive, but quite worth it for many!), DL-phenylalanine, L-tyrosine, pregnenolone, TMG (trimethylglycine), DMG (dimethylglycine), ALA (alpha-lipoic acid), DMAE (dimethyl amino ethanol), CoQ10 (coenzyme Q10, CDP-choline(cytidine 5-diphosphocholine), higher doses of picamilon, acetyl-L-carnitine, B-complex vitamins (in doses five-to ten times the RDA), pantothenic acid, Oriental ginseng... hell, even cinnamon, betel nut and cayenne pepper, lol. I feel obligated to add that although not generally stimulating, fish oil and other sources of essential fatty acids should really be taken by every adult (IMHO). That's all I can think of off the top of my head at the moment, lol.

Just a quick endorsement though <g> -- I brought DA agonists to my pdoc's attention months ago when I decided I wanted to ask him for Mirapex. During our 45-minute appointment the other day (45 minutes!?! I love my doctor! xD ), he mentioned that, thanks to my bringing the psychotherapeutic potential of DA agonists to his attention, he's thusfar been able to successfully treat two other treatment-resistant melancholic patients with them (both of whom he had pretty much given up on since both refused ECT or MAOIs). In these patients he tried an SSRI + DA agonist + benzo approach. They were never able to tolerate SSRIs before, but with the DA agonists were happy as clams, according to the doctor. So now he likes to do this regularly -- prescribe a bit of one of these medications along with sexually detrimental antidepressants, even in patients who are trying ADs for the first time. He says he's had less than half the complaints of sexual dysfunction from SSRIs (particularly Paxil, Celexa, and Prozac) he used to since he started making this combo pretty much standard practice. He also noted that, though it isn't obvious to some of the patients right away, he has been able to detect a much greater air of confidence and assertiveness around those treated this way after just 2-4 weeks of treatment at most.

His patients have had too much difficulty with sleepiness on Mirapex and Requip though (like me... grrr...), and he says Dostinex and Parlodel (both quite similar; ergot-derived) exert the best effect in most patients he's treating this way, though a few patients find Symmetrel more helpful. Since Dostinex and Parlodel help to normalize androgen levels, it could be that they're most helpful in those whose hormones are out of whack in some way.

Of course there's also Eldepryl/selegiline/deprenyl/whatever-you-want-to-call-it which is the MAO inhibitor that raises levels of dopamine at doses of 5-10mg without affecting serotonin or norepinephrine. No dietary restrictions at standard doses as with Nardil and Parnate.

I've also heard of Sinemet-CR (carbidopa/levodopa) being used successfully as an adjunct in treating mood abnormalities. This is also primarily a drug for Parkinson's disease which is the immediate precursor to dopamine. Of course, by becoming dopamine within the brain, levels are increased. L-dopa (short for levodopa) can also be purchased at most health food stores, and of course a prescription isn't needed -- this form of l-dopa is plant derived (from Mucuna pruriens I believe... someone correct me if I'm wrong). You'd need to take high doses to notice any true effect though, most likely -- without the carbidopa that's in Sinemet, much of the l-dopa bcomes dopamine before it attempts to enter the brain. Dopamine can't pass the blood-brain barrier. Carbidopa helps to prevent the early transformation from occurring and so I suggest the prescription form.

Of course I also mentioned Edronax (not available in the U.S.) and Strattera above. They don't affect serotonin or dopamine, at least to any appreciable degree. Their actions are to inhibit reuptake of norepinephrine, thus increasing its levels in the brain. Some find these drugs make wonderful antidepressants. And naturally there are the classical stimulants I also mentioned above (amphetamines, methylphenidate).

If you're interested in what *I* would do if I were you... hmmm.... well, I'd remain at the current dose of bupropion (unless your returning depression is bordering on suicidal ideation, of course... then I most certainly would seek help at an institution) and ask the doc about adding on Dostinex, Parlodel, Symmetrel, Sinemet-CR, Edronax, Strattera, high-dose Provigil (400-800mg daily?), amphetamines, and/or methylphenidate. I'd also begin taking:

*Fish Oil: If you don't already take it that is... it's really a necessity; usually about 2-6 grams daily, with food, and label should indicate a 3:2 ratio of EPA to DHA in the oil -- the more it contains, the better, and a common amount of EPA to DHA is 360mg/240mg per gram of oil; only purchase from a reputable health food store where they keep their fish oil refrigerated. When you buy it off a shelf you never know if it's lost potency, but refrigeration helps preserve it.

*NADH: 5mg daily; increase dose until adequate

*DL-phenylalanine: Terrific supplement -- absolutely worth a one-month trial at about 500-1,000mg three times daily... after that it's fairly likely you'll want to continue it. It should be taken on a completely empty stomach, along with vitamins C and B6 (though the vitamins should be taken with food) -- these vitamins are essential to the conversion of phenylalanine to dopamine, norepinephrine, epinephrine, and phenylethylamine (the brain's "love chemical" [phenylethylamine is abundant in the brains of those who are in or falling in love]; the "chocolate amphetamine" [it's found in chocolate, which more than likely is a prime reason that chocolate and romance are so closely intertwined]); the L-phenylalanine is more stimulating, while the D-phenylalanine, according to several (many?) studies is especially great at increasing activity of your body's "natural morphine", and I can attest to this wonderful effect

*A very good whole-food multi-nutrient supplement if you can afford the $30 or more per month -- I prefer Super Earth Formula manufactured by Bluebonnet which is the most complete supplement I've seen to date, though several companies make a product called Green Source which is less expensive and still pretty good. I highly recommend spending the money on the ultra-high quality supplements, though Centrum or something similar will be helpful too, to a lesser extent unfortunately. Don't but store-brand multivitamins though! Very often these copycats are of ghastly inferior quality. I might suggest -- they carry some very inexpensive, complete multinutrient supplements there.

*Liquid B-vitamin complex: pills are okay, but liquid B's absorb much more efficiently it seems; this should be taken three or four times daily at least, depending on the quantity of each vitamin in the product -- just try not to take more than 200mg vitamin B6 daily (keeping in mind the supplementary B6 taken with the phenylalanine should you decide to try it) as it could be dangerous. This stuff can be found in most Walmarts, though their brand doesn't contain as much of the vitamins as some more expensive ones... it's cheap though, and so I use it and just take 8ml four times daily instead of the recommended 1ml one to three times daily.

*Ginsengs and "Ginseng": Oriental ginseng is arguably the more stimulating of the two common ginsengs. The other ginseng is American ginseng. I put the second "Ginseng" up there in quotes because it is actually the herb eleuthero root, which used to be called Siberian ginseng (it's not actually a form of ginseng at all, though it acts somewhat like it -- more stress relieving for most than Oriental and American ginseng). It's less energizing but is a very good adaptogen (though if I were to recommend an adaptogen, it'd surely be ashwagandha or reishi mushroom which are superb stress-relievers). If it's a Wellbutrin boost you're after, I'd go for the Oriental ginseng. Failing that, I'd try the other stuff I listed above (especially betel nut, TMG/DMG, ALA, acetyl-L-carnitine, CoQ10, CPD-choline, and DMAE, in that order) which may also prove very useful.

Of course this is just where I'd start personally, but it sounds like a pretty decent plan of attack to me. :-)

Okay, I'll stop rambling on, I'm sorry, lol. I'm just feeling truly awesome (mentally anyway... I start OxyContin and naltrexone on Monday when I return to my pain specialist) for the first time in a pretty good while and felt like writing a bit in-depth on this subject. Plus I went to the State Fair today and still have some excess adrenaline from those crazy rides they have (hmm... could that, two funnel cakes, and three Cokes have contributed to the fact that I'm still awake at 3:15AM? lol). I haven't been to the fair in two years due to the housebound agoraphobia. It was really great being there and running into old friends without all the agoraphobic/avoidant thoughts, worries of panic attacks, and depressive irritability. One very good old friend from high school that I ran into is about to become a daddy this month and then is getting married... pretty amazing how fast time is going now. High school was just two and a half years ago and he's starting a family... wow. I realize that most people more aged than me (<~~~ note tactful avoidance of phrase "older than me", lol) don't get wowed by this stuff quite so easily, but... wow. He's only 20 like me and bought a house, is about to have a kid and is getting married. This is one way I can tell I'm doing so much better, though... under normal circumstances, I'd probably be throwing a fit about my basically wasted life thusfar and wondering why it couldn't be me with all the good fortune, but all I feel is happy for him.

Okay, rambling again -- so sorry, lol. Well, I really hope something in here is helpful, and of course I'm always around and more than willing to help when I can so feel free to ask me whatever's on your mind whenever you want. Oh, and I didn't proofread this so I only hope it's not overly confusing -- let me know if you need anything cleared up. :-)




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