Posted by SLS on May 19, 2000, at 12:25:17
In reply to Reboxetine + ?, posted by ghb on May 18, 2000, at 17:42:38
> Thanks for the response. I thought Wellbutrin was a dopamine active med. Which ones are dopamin active meds. I'm sure I've tried some. I've tried all of them in the last 15 years. I'm just beginning to understand how they all work since I've had access to the internet in the last year.
I would just like to second Andrew's thoughts regarding experimentation with dopaminergic drugs. He probably has the best insight as to how to go about it. That you responded so well to nomifensine may support this idea. Nomifensine inhibits the reuptake of both dopamine and norepinephrine. It might also promote the release of norepinephrine, but my memory is vague on this. Unfortunately, as you probably know, nomifensine was pulled off the market worldwide when reports of fatal hemolytic anemia surfaced.The only way I can think of to obtain nomifensine would be to steal it off of a university laboratory shelf. If you can't find it on the shelf, you may want to consider stealing the rats and performing hundreds of blood transfusions. You can then return them back to their cages so that they can receive subsequent injections.
Sorry - a bit of self-amusement that is probably not amusing to anyone else.
* The rest of this post is unnecessary.
If one were to look at things superficially (which doesn't always work), you could say that reboxetine hit one of the two targets that nomifensine hits - norepinephrine reuptake inhibition.Which dopaminergic drugs have you tried, and how did you respond to each of them?
- Dexedrine
- Adderal
- Desoxyn (ouch)
- Ritalin
- Cylert
- Parlodel
- Permax
- Mirapex
- Symmetrel
I myself experienced quite a robust response to nomifensine, but it lasted for only a few days. This has also been my experience with amphetamine and Parlodel. I think I may suffer from some sort of deficit in dopaminergic neurotransmission somewhere along the line. Unfortunately, only two antidepressants (amineptine and nomifensine) ever fit the bill as dopamine reuptake inhibitors. Both drugs are no longer marketed.Wellbutrin (bupropion) is a drug for which the mechanisms of action are poorly understood. I believe most of the current thought involves norepinephrine, although it certainly has been shown to inhibit the reuptake of dopamine. However, the degree to which it does so is considered small when used at therapeutic dosages. Does this mild dopaminergic effect contribute to its success as an antidepressant? Some researchers tentatively say that it is. Wellbutrin made me feel worse, but so did reboxetine. Perhaps this observation gives credence to the notion that Wellbutrin potentiates noradrenergic activity.
I haven't seen the combination of Wellbutrin and reboxetine used (yet). It might work despite any attempts to determine its usefulness based on theory. It may be worth a try if there are no contradictions otherwise. I don't know of any, but if there are, I'm sure either Cam W. or PeterJ would be able to tell you.
I can't comment on Serzone, as I don't have much of a feel for this drug. It may be the one serotonergic drug that yields an immediate increase in dopaminergic neurotransmission by acting as a 5-HT2 antagonist. 5-HT2 antagonists seem to promote an increase in the activity (dopamine release) within the prefrontal cortex, a region considered important for the perception of mood and motivation. Disturbances in this area often produces apathy. The atypical neuroleptics also potently block 5-HT2 receptors, and this action is thought to be responsible for their ability to improve the negative vegetative symptoms (depression-like) of schizophrenia.
* For anyone: Is the prefrontal cortex involved in SSRI-induced apathy?
If you have not yet tried adding drugs like Mirapex, Permax, or Parlodel to reboxetine, it may be useful to see how you respond to them. Even if you respond to them only transiently, it will provide information, and demonstrate that dopaminergic drugs may help. If a positive response to these drugs doesn't stick, you can employ another angle of attack - low doses of neuroleptics. Many people here have used amisulpride (Solian) with success. This would be my first choice. Amisulpride is not sold in the U.S., but it is not difficult to get. There are plenty of threads regarding foreign sources of amisulpride. AndrewB and JohnL know of some. The drug sulpiride, a relative of amisulpride, works similarly, but has more side effects and does not seem to be prescribed as often for depression or dysthymia.Other low-dose neuroleptic choices would include Zyprexa, Seroquel, and Risperdal. Of these, Risperdal has the lowest risk of weight gain. In addition to acting as dopamine receptor antagonists, these drugs are also potent antagonists of 5-HT2 receptors. This is the same action elicited by nefazodone. Risperdal is quite potent in this respect.
I always seem to make a mess of things. Unfortunately, trial and error is still a necessity. If your doctor insists on trying Wellbutrin or Nefazodone, I don't see that it can hurt. You may be wonderfully surprised. My guess is that nefazodone would be a better choice, as it might offer greater complementarity to reboxetine, and not potentiate some of the anxiety and agitation produced by reboxetine.
Have you ever tried Wellbutrin without reboxetine?
Dopaminergic alternatives:Based on AndrewB's experience with amisulpride in combination with reboxetine, you may want to consider this first. If not, using one of the dopamine receptor agonists (Mirapex, Permax, or Parlodel) would be a good idea to see if dopamine potentiation helps. It wouldn't take long to see a response - probably a matter of hours or days.
As far as using U.S. approved low-dose neuroleptic treatment for depression (augmentation of reboxetine), You will probably find Risperdal more attractive because it tends to produce less weight-gain. Zyprexa can definitely produce antidepressant effects and may be the best at doing so, but it is notorious for increasing appetite along with producing metabolic changes that increase body weight. Andrew often suggests Stelazine. I don't know anything about its efficacy in treating depression, but it often produces weight loss.
And then there are the MAO-inhibitors...
Sorry. I don't have the energy to go back and correct for redundancy.
- Scott
poster:SLS
thread:33935
URL: http://www.dr-bob.org/babble/20000517/msgs/34009.html