Posted by Tomatheus on January 8, 2006, at 20:18:35
In reply to Re: Questions about Wellbutrin, posted by elkat on January 8, 2006, at 13:37:25
Elkat,
See below for my responses...
> Last time I saw doctor I mentioned the dopamine situation. I thought maybe either Provigil, an ADD med like Adderall, or a dopamine drug like Mirapex, but I don't think she agrees with my experimental approach to drug therapy. So she suggests Lithium.
Did she tell you why she suggested lithium?
> She gave me a mood chart to see if I have bipolar. So far it's all on the down side.
With respect to treatment-induced hypomanic symptoms, the current prevailing theory among researchers and psychiatrists is that patients who experience any kind of hypomania from taking any antidepressant have some type of bipolar disorder - usually the prototypical "bipolar III." The implication, of course, is that these patients do not stand to benefit from antidepressant therapy alone, but from either mood stabilizer monotherapy or some combination of mood stabilizers and antidepressants. Even though I do think that *some* patients with treatment-induced (hypo)mania might require a mood stabilizer to control any breakthrough (hypo)manic symptoms that might emerge from antidepressant therapy alone, I don't think that enough is known about the etiologies of mood disorders to justify the position that *all* patients with any kind of treatment-induced (hypo)mania must take a mood stabilizer to achieve the best results. Some patients, for example, may develop (hypo)manic symptoms from taking one antidepressant but may be able to achieve remission from their depressive symptoms without feeling any (hypo)manic symptoms on another antidepressant. And remember that in your case, it took 450 mg of Wellbutrin combined with 45 mg of Remeron and 1.5 mg of Klonopin to trigger manic symptoms - and this didn't even happen until you tried going onto this combination for a second time. There's really no way to say for sure that the med combo that you were taking wouldn't have triggered the same manic symptoms in the typical unipolar patient because no researcher has ever tested your specific combo for its tendency to induce (hypo)mania.
Having said what I've said about bipolarity, I don't think patients should necessarily dismiss the possibility that they might benefit from a mood stabilizer, either. Lamictal, for example, tends to be a better antidepressant agent than it is an antimanic agent, and it's sometimes even prescribed to patients who are completely unipolar. So, I guess what I'm saying is that you should trust your "instincts" (or perhaps more accurately, your knowledge about how you respond to meds based on past experiences) to a certain extent. But at the same time, consider the merits of what your doctor recommends, and do your best to try to understand your doctor's rationale for prescribing you a certain medication or med combo.
> Are the MAOI's good for dopamine?
In short, yes. All of the MAOIs increase the amount of dopamine being released into the synapses by inhibiting MAO-A, MAO-B, or both. MAO-A breaks down serotonin and norepinephrine in their respective neurons by converting the neurotransmitters into inactive metabolites. MAO-B, on the other hand is selective in its metabolism of benzylamine and phenylethylamine (Lotufo-Neto et al., 1999). Both MAO enzymes break down dopamine, so inhibiting either MAO-A or MAO-B (or obviously both) makes more dopamine available to be released from dopaminergic neurons. So, to summarize, the inhibition of MAO-A potentiates the release of serotonin, norepinephrine, and dopamine; the inhibition of MAO-B allows for a greater release of benzylamine, phenylethylamine, and dopamine; and the inhibition of both MAO enzymes makes more serotonin, norepinephrine, benzylamine, phenylethylamine, and dopamine (X2) available to be released from neurons.
In most Western countries, moclobemide is the only commercially available MAO inhibitor that is nearly completely selective in its inhibition of MAO-A. But unlike most commercially available MAOIs, moclobemide is reversible, which means that the drug's inhibition of the MAO enzymes is not permanent. So after a certain amount of time (a few hours, I believe), moclobemide "lets go" of the MAO-A enzyme so it can once again perform its functions. In terms of its ability to allow for more dopamine to be released, moclobemide is believed to be somewhat less potent than the older irreversible inhibitors.
Because Nardil, Parnate, Marplan, and selegiline all inhibit both MAO-A and MAO-B to some extent, they are all relatively potent in their abilities to potentiate dopamine release. Nardil is generally believed to slightly less potent in terms of its effects on dopamine than the other irreversible MAOIs, in part because of its ability to increase GABA levels (which tends to reduce the firing of dopaminergic neurons). I don't really have a whole lot to say about Marplan because I'm not the least bit familiar with its clinical and pharmacokinetic properties. Parnate tends to be more activating (and consequently, more dopaminergic) in most patients than Nardil, which may be at least partially due to Parnate's structural similarity to that of amphetamine. Selegiline, which also possesses strong dopaminergic properties, is highly preferential to MAO-B at low doses (i.e., 5 to 10 mg/day or less) but loses some of this selectivity at higher doses (Thase et al., 1995). Selegiline is currently available in pill form and is expected to become available as a transdermal patch soon (I believe on Feb. 26).
So, that pretty much sums up your MAOI options, assuming that you live in the United States. Considering that you're looking for something relatively dopaminergic, it might be a good idea to try Emsam (the selegiline patch) when it becomes available because it has a much lower tendency to potentiate a hypertensive crisis than Nardil, Parnate, or even oral selegiline. Of course, if you do decide that it might be a good idea to try an MAOI, the biggest challenge that you'll probably have to face will be convincing your doctor that an MAOI is right for you. Most doctors are at least somewhat hesitant to prescribe MAOIs - especially doctors who don't like to take experimental approaches to drug therapy.
Having said that, I do wish you luck in whatever you decide to do.
Tomatheus
==
Lotufo-Neto, F., Trivedi, M., & Thase, M. E. (1999). Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology, 20, 226-47.
Thase, M. E., Trivedi, M. H., & Rush, A. J. (1995). MAOIs in the contemporary treatment of depression. Neuropsychopharmacology, 12, 185-219.
poster:Tomatheus
thread:594725
URL: http://www.dr-bob.org/babble/20060108/msgs/596804.html