Posted by Elizabeth on May 16, 2001, at 16:54:46
In reply to For Elizabeth » Elizabeth, posted by SalArmy4me on May 12, 2001, at 21:53:43
> I am hopeful that you will still be able to find an effective pharmacological treatment, despite having tried so many of them. I got some nice ideas for you:
>
> 1) Mirapex - proven as effective as imipramine in depression:
>
> Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety. 2000;11(2):58-65.
>
> DeBattista C, Solvason HB, Breen JA, Schatzberg AF. Pramipexole augmentation of a selective serotonin reuptake inhibitor in the treatment of depression. J Clin Psychopharmacol. 2000 Apr;20(2):274-5.That's an interesting idea (although I don't see anything about imipramine in either of your citations, and Medline seems to be down so I can't check right now). I'd forgotten about that one. I'll look into it and mention it to my pdoc. It sounds like there is very little research, but what there is has been consistently positive.
> 2) Pindolol - it once was a wonder drug for me that I took without an antidepressant, (but most people will need one).
Tried that one, at a variety of doses, and with a couple different serotonergic ADs. (Wrote a paper on it while I was using it myself. That was fun. Unfortunately my instructor -- a PhD behavioural pharmacologist who was, at the time, a post-doc at the primate lab doing animal experiments -- didn't share my orientation toward molecular pharmacology, so, while I got a decent grade, I don't think he appreciated my excitement about the subject.)
BTW, the evidence is stronger for pindolol as an AD accelerator than as an augmentor. (Well, it was when I was immersed in the topic, anyhow.) I actually ended up being more impressed with buspirone by the time I finished that paper, believe it or not! I believe the apparent failure of BuSpar as an antidepressant-anxiolytic is due to the use of inadequate doses.)
> 3) Definitely try Tegretol XR if you get a chance.
> Its very tolerable.I know a young woman who takes it for temporal lobe epilepsy and (probably secondary) rapid-cycling/dysphoric bipolar II disorder. It has a very minor place in the treatment of TRD. If I were to try another anticonvulsant, I'd prefer carbamazepine's analog oxcarbazepine, which is safer, more tolerable, and less likely to interact with other drugs.
Incidentally, my neuro consult confirmed what I already expected: that there's no evidence that what I experienced was the result of any type of seizure. (I *still* haven't gotten the report on the SPECT scan, though!)
> 4) Ludiomil (MAPROTILINE) - that's a good one that few have heard about since it came out around the time Prozac came out and was overshadowed by Prozac.
Maprotiline, despite a novel variation in the middle ring, turned out to be basically just another tricyclic -- it has similar biochemical properties and works for roughly the same patient population as the rest of the TCAs. Its side chain -- the part of TCAs that is most associated with structure-activity relationships -- has a secondary amine structure which results in NE-selectivity comparable to protriptyline's (but not increased potency). The term "tetracyclic" is really kind of misleading, IMO; it's basically a tricyclic with a novel center ring (this is also what distinguishes imipramine, amitriptyline, and doxepin (and the secondary amine forms of IMI and AMI -- DMI and NOR). The middle ring has an ethylene-type bridge connecting opposite carbons. Such a bridge increases the rigidity of a molecule's structure and may contribute to maprotiline's relatively long elimination half-life (which is not even close to protriptyline's but is on the high end for TCAs).
My pdoc actually considers it *less* effective than his preferred TCAs (nortriptyline, clomipramine, desipramine, imipramine, amoxapine) in TCA-responsive patients. It has the same type of side effects that I find so hard to tolerate in TCAs, as well as a greater propensity than other TCAs for lowering the seizure threshold.
If I want to give another shot at that class of drugs, it would be desipramine, Like maprotiline, DMI is extremely NE-selective and lacks those pesky sexual side effects. Unlike maprotiline, DMI has little affinity for muscarinic or H1 receptors, and was considered one of the preferred TCAs for epileptics before the much safer SSRIs showed up on the scene.
My family history of "V-type" atypical depression (as described in the Columbia Atypical Depression Study) makes tricyclics a dubious choice for me, anyway, despite my dx of melancholia. (I'm sure you know how tricky such diagnostic subtleties can be!)
> 5) Geodon (ziprasidone) - works on serotonin and norepinephrine with little weight gain or sedation.
Side effects weren't the main issue for me with the atypical antipsychotics. It was lack of efficacy. I'm aware of some of the novel effects of ziprasidone at 5-HT and NE transporters, but I'd prefer something that isn't a dopamine antagonist (*clearly* not an appropriate choice for me) if I want to go that route again!
> 6) BuSpar - only effective in depression at higher doses according to the last study done on it and depression.
Yes, I mentioned this one. I found it innocuous when I took it (up to I think 45mg, with several different ADs), although it had no beneficial effects. (My above-mentioned paper focused on buspirone and pindolol as prototypes of antidepressants acting specifically at the 5-HT1a receptor, so I'm reasonably well-versed.)
> 7) Serzone - I was on it for a month with no side-effects.
Tried it. Twice, in fact (both were adequate trials).
> Thyroid Hormones T3 + T4 - pioneered by Dr. Whybrow at UCLA.
I've considered this. I'm not sure that they are such a great choice for someone with panic disorder, though.
> Foreign drugs:
Before going any further, I'd like to point out that I already said I'm not willing to do this. Doing it the legit way takes too much red tape and time, and I'm not going to go shopping on internet "pharmacies" (i.e., drug dealers!). Among other things, I can't afford these (mostly quite expensive) drugs, which would not be covered by my insurance because they are not FDA-approved.
> *Reboxetine,
Not worth the hassle. I'm not concerned about SSRI/SNRI sexual side effects. I'd just as soon try Meridia, which I can get here and which my prescription plan will cover. (Effexor is something I need to avoid due to a very bad toxic reaction I had in 1998. I think that there were probably other, unknowable contributing factors, but all the doctors I've consulted with consider it too risky to repeat the experiment, particularly since I had milder toxic syndromes the two times I tried immediate-release Effexor.)
> *Moclobemide (I can prove that it is effective, albeit not more than irreversible MAOI's)
I think I've mentioned why I don't consider this a worthwhile pursuit. In countries where it is marketed, moclobemide is a good first-line drug (rather than a drug for people who've already tried everything else) due to its safety profile. It's not a good choice when irreversible MAOIs are tolerated but are not sufficient to do away with the depression.
> *Mianserin,
I believe its metabolite, mirtazapine (you know -- Remeron???) is responsible for most of its antidepressant activity. Thus, I don't consider it worthwhile trying the very similar (and less safe, and more expensive) mianserin after having tried Remeron.
Something that does interest me is a combination approach utilising Meridia and Remeron (with the option of adding Buspar, Provigil, high-dose alprazolam, and others).
> *Tianeptine,
This one does interest me, one of the few foreign drugs that do.
> *Modafanil,
That's Provigil -- not a foreign drug.
> Brofaromine,
More promising than moclobemide, probably due to a dual RIMA/reuptake inhibitor action. But still not worth the hassle.
> *Amisulpride,
Again, of interest.
> *Adrafanil.
Might be worthwhile for augmentation, but I'm not clear that it's better than Provigil.
> Others: Bromocriptine, Ropinirole (another dopamine agonist),Direct dopamine agonists are overrated, I think. Anyone want to weigh in (who's gotten this far < g >)?
> Norvasc(?),
Ca++ blocker. Good for refractory bipolar disorder but might actually exacerbate depression.
> Pemoline(?) (a stimulant),
Cylert. I used it for a few months in college. It helped somewhat.
> *Seroquel,
Tried it. (I mentioned low-dose atypical neuroleptics (and moderate-dose Zyprexa), didn't I? The only exception is Clozaril (too risky).
> Tamoxifen(?),
Cancer drugs? Jeez. You know that depression is a known side effect of this drug, right???
(Don't suggest estrogens either...I have a history of depressive relapse and exacerbation on hormonal contraceptives. This is why I now use only "natural birth control" -- condoms, that is. < g >)
> Doxepin,
Just Another Tricyclic, with a side effect profile comparable to imipramine or amitriptyline. (In particular, doxepin is *very* sedating, probably because it's such a strong antihistamine -- there's even a topical version marketed for pruritis.)
> Yohimbine,
Anxiogenic.
> the new Depakote _ER_,
Depakote had no beneficial effect for me. I'm not interested in other preparations of valproate.
> Nomifensine.
Now that's an interesting one. But I thought it had been removed from the market worldwide. Do you happen to know where it might be available?
Thanks for your ideas. Always interested in new thoughts.
-elizabeth
poster:Elizabeth
thread:61760
URL: http://www.dr-bob.org/babble/20010515/msgs/63255.html