Posted by karaS on October 16, 2004, at 17:17:37
In reply to Re: effects, side effects (long) » karaS, posted by zeugma on October 11, 2004, at 11:53:16
z,
Thanks for posting the message asking where I've been. It was so nice to feel missed. I finally have the time to tackle this post so here goes.
> hi kara,
>
> you raised a number of interesting points, and also noted my tendency to glaringly omit certain details :) anyway, here goes:
>
> I don't know much about getting a pharmacy to compound a patch. I imagine it would be very expensive. A Strattera patch might be interesting, but it would still intensify the fatigue as a delayed reaction (Strattera is a very difficult drug to pin down- its metabolite interacts with the opioid system in a complex way, which could be both beneficial and hurtful, and also disceprepancies have been noted between its plasma half-life and clinical effect.). But it is something to think about. I am not going to throw my Strattera out. But its peculiar combination of alerting and fatiguing makes it only a short-term solution, as far as I can see.
If it weren't for the fatiguing effect that Stratter has on you, I'd say try to get your insurance to cover the cost of a patch. (Maybe if your doctor claimed that it was imperative for your functioning that you could get it covered - but it's a moot point because of the other side effect.)
> I repeatedly asked my pdoc about desipramine last year. In his estimation nortriptyline and desipramine produce similar clinical effects. Now nortrip is definitely more sedating for most. So for me, if i take nortriptyline at 7 pm, I can expect to be asleep by 10:30. I don't think desipramine would have this effect. It's a moot point though, as I can't afford to stay up late anymore with any frequency anyway. The narcolepsy worsens with any degree of sleep deprivation, and I can't do the 'all-nighters' I used to that got me through college and most of the way through grad school. Another point to consider is pharmacokinetic. Nortriptyline has a longer average half-life than desipramine. That would mean that I would probably have to take larger amounts of DMI to make up for its shorter half-life, say at 6 am and 7 pm, and the dosing guidelines for DMI are higher than for NOR. As it is, there is a 'trough period' with NOR where I am vulnerable to cataplexy. Plus, NOR is more anticholinergic than DMI, and this is believe it or not probably a point in NOR's favor. Pro-cholinergic drugs intensify cataplexy. Anti-cholinergic drugs reduce it.It's definitely a dificult choice to replace the nort. because it fits in so well with your routine. You'd have to switch a lot of things around to make "room" for something else - all the while risking some dysfunction. OTOH, what choice do you have if the current combination isn't taking care of all of your needs?
Anticholinergics also have benefit for me in that they mask my cholinergic urticaria. OTOH, the anti choline effect is not great for optimal brain function. It so often comes down to a balancing act, doesn't it?
> Protriptyline: now that one is interesting. It is like Prozac in its snail-like pharmacokinetics. It also is the most stimulating of the TCA's. So one benefit would be that I would avoid the 'trough period' that NOR leaves open for cataplexy. It also might stimulate me a little, and it is anti-cholinergic to boot. To see clearly the relationship between TCA's, as well as other AD's, (unfortunately Cymbalta was left offf this list), see http://www.primarypsychiatry.com/pdf/art_453.pdf
> and scroll down to the end where you will see a chart outlining receptor affinities of these various drugs. As King Vultan said a long time ago (sorry, I have a hyper-cholinergic memory for certain things, though unmedicated I forget my keys when i go to the laundry room) protriptyline is almost exactly between nortriptyline and desipramine in its pharmacodynamic profile. It is interesting nonetheless, because of its slow clearance. In clinical trials with narcoleptics, however, it did not have impressive results as a stimulant and so is used mostly as an anti-cataplectic agent. But it is a valid suggestion, and I am going to do some more research on this one.I wonder why it wouldn't be good as a stimulant but clinical trials are probably better predictors than theory. Let me know what your research shows on this one. (BTW, I believe that SLS's chart shows receptor affinities for Cymbalta.)
> My parents do not have narcolepsy. They do both have 'shadow syndromes' for ADHD and social anxiety, and if you combine their traits and intensify them I will result (I did!). My brother is free of these disorders. My sister has some of my own symptoms: panic disorder, and a propensity for sleep paralysis. She takes Prozac for panic with lorazepam for situational anxiety. She gets sleep paralysis about once a month. But she does not get the painful maifestations that I do (I got them last night too- ouch!) and does not have full-blown narcolepsy. She is in her late 20's and generally narcolepsy manifests in the late teens to early 20's. There is clearly genetic input, plus it is believed there is some kind of autoimmune reaction that impairs orexigenic transmission that combines with the inborn propensity to produce the full disorder. Provigil acts on this obscure transmitter, hence its special value for narcolepsy.
I think you're amazing in terms of not feeling sorry for yourself - or at least not showing it. I would have written a comparable response about my sister getting all of the good mental health genes and I would surely have added a "lucky me" in there somewhere.
I forgot - what was the side effect that keeps you from taking Provigil?
> Buspirone is a strange drug that, like the TCA's, has multiple mechanisms of action. It is a partial agonist at 5-HT 1A receptors, and a weak blocker of D2 receptors. Now I may be wrong, but aren't presynaptic D2 receptors the analogues of 5HT1A presynaptic receptors and alpha-2 noradrenergic receptors, ie inhibitory autoreceptors? If dopamine autoreceptor hypersensitivity is part of your problem, then presynaptic D2 blockade should help it.
That's music to my ears. It's a mystery to me why Dr. Jay Goldstein and my own pdoc have said that we don't have medication for this condition yet. I'll have to do some serious research on this one. Todd (King Vultan) has suggested (if I’m understanding him correctly) that we should be able to downregulate the dopamine autoreceptors in the same way that the SSRIs do for serotonin autoreceptors. Any thoughts on this?
>I know you tried buspar and it didn't help you.
I don't know that it wouldn't have helped me had I been able to tolerate it. It made me very nauseous and that side effect didn't go away.
>The only other drugs I know of that block D2 autoreceptors would be amisulpiride ( not available in the US) and possibly Abilify. Abilify might be worth a shot. Unlike other atypical AP's it only produces a partial agonism of D2 receptors. Also Seroquel might be worth a shot.
Amisulpride has been on my list to explore for a while now because of the success of many on this board who are TRDs with dopamine inadequacies. I'm sure I could find it (and hopefully I could convince my doctor to write a script). My pdoc also recently suggested I try Abilify - but for other reasons. He thought it might help me because of my possible "soft bi-polar" tendencies. I'm still afraid of APs though. I know that the newer ones are more safe but I still worry about movement disorders.
> I agree, and disagree, with your point about modern trials being more selective. If depression were a nice homogeneous disorder, then yes, I would say don't include those with comorbidities in trials. This may well actually be good for the vast majority who take Lexapro and don't hang out at Psycho-Babble for long periods. So you may be right overall. Still, most of us here at PB have comorbidities and require multiple psych meds, and I also think there is something to the idea of slowly seeing a pattern emerge from trying out the drug on a heterogeneous group, rather than a priori projecting an 'antidepressant' effect and then looking for separation from placebo in a specially selected group. But no drug company can afford to be so profligate with their resources as the early companies were, who had no idea what imipramine was for ( they wrongly guessed it to be an AP), given the enormous costs of drug development. So I'll concede half your point, and I'll wish we lived in a different world.Speaking as a TRD who hangs out at Psycho-Babble, I see both sides as well.
> Do you have AvPD? So do I. There are advantages to this condition you know. Circumspection and evading the point(not that I'm accusing you of this, it is me with my endless parentheses that evade the point!) can be great assets in certain professions, such as diplomacy. They also result in fewer PBC's and bans on this carefully civil site. :)Do you take/have you taken Klonopin? To my knowledge, Klonopin and Nardil are best for AvPD. Marplan and Parnate might work too, but they've been less studied. Then there's the new pregabalin. have you tried its older analogue, Neurontin?I've never been diagnosed with AvPD. I just assumed I have it based on the fact that I endlessly procrastinate. I am in such serious financial trouble and yet I haven't been able to push myself to job hunt. Maybe that's just depression and not actually AvPD though. I don't know. I would make a good diplomat however. After getting addicted to Ativan over very little usage, I've stayed away from benzos. I never would have guessed that one of them would be good for AvPD. Neurontin made me very sick. I have yet to try an MAOI but they are a good next choice for me for many reasons. I'd prefer to start wtih Marplan and then Parnate though. I don't want to take anything that could make me more tired or lethargic.
> An advantage to AvPD, too, is a heightened awareness of others' reactions. But the anxiety has to be controlled first.
I do have a heightened awareness of others' feelings as well as their reactions to me. Rejection sensitivity is probably an adequate description of the latter. I used to have problems with GAD but don't seem to have that problem now. Even though i went off of all meds recently, I still am not having that constant knot in my stomach or the panic attacks. Maybe years of SSRI usage has numbed me out for life.
> I realize I have not responded to your point about narcolepsy not being fully treatable. People with narcolepsy need to be extremely up on their sleep hygiene, ie they cannot miss any sleep without repurcussions later, regardless of meds. I have had two cataplectic attacks in the last week that are due to staying up later than planned due to work obligations. I am currently considering leaving my job for one less taxing on my time for this reason. But this would not be something I would want to do (I like my job a lot). Hence my increased anxiety level, and more desperate search for a solution.That would be too bad if you had to quit a job that you really like. Would it be possible for you to get something in your field that you would like as much that isn't as demanding of your energy and time? What field are you in? I'm very curious after reading your posts. (You don't have to answer that in this forum if you aren't comfortable with it. You could BabbleMail me or just not answer.)
I have an MBA though I haven't really had any jobs that required it. It's amazing to me that I was able to get it (it was a grueling program too) considering my lack of drive.> Have you told your dr. about your suspicion of AvPD? This could be important to the outcome of your treatment. Obviously you can't take Nardil concurrently with Cymbalta. Med anxiety kept me away from meds for many years. Desperation sent me back.
Yes, that desperation can be quite powerful, can't it? I saw another post of yours regarding Cymbalta. You said it was just an updated version of imipramine. Why? It has an SSRI added in, it doesn't seem to produce the tachycardia that many TCAs do and it doesn't seem to have the anticholinergic effects either. Maybe they have affinities for the same receptor sites, but it still seems like there are significant differences (improvements?) to me.
No, I haven't told my doctor yet about my AvPD suspicions. I'll have to bring it up with him next time I can afford to see him. I've seen him a number of times though and he knows my situation so I would think this might have crossed his mind once or twice.
Hope you're doing ok. Talk to you later,
K
poster:karaS
thread:397388
URL: http://www.dr-bob.org/babble/20041012/msgs/403923.html