Posted by zeugma on October 11, 2004, at 11:53:16
In reply to Re: effects, side effects and procrastination » zeugma, posted by karaS on October 10, 2004, at 18:15:34
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.
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.
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.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.
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. I know you tried buspar and it didn't help you. 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.
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.
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?
An advantage to AvPD, too, is a heightened awareness of others' reactions. But the anxiety has to be controlled first.
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.
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.
-z
poster:zeugma
thread:397388
URL: http://www.dr-bob.org/babble/20041007/msgs/401574.html