Posted by zeugma on May 9, 2004, at 5:04:05
In reply to Re: ok, here's what my pdoc said » zeugma, posted by Questionmark on May 9, 2004, at 2:54:12
> > <Hi. Since you seem to have severe anxiety, i would increase the Klonopin dosage regardless of what else you do (as long as you're not tOO afraid of physical dependency, though i think it's worth it anyway).
> > Beyond that, my suggestion would be to add in clomipramine (Anafranil) since you're already on a TCA and the side effects would probably not be as severe (and since you already appear to be able to tolerate TCAs' side effects fairly well). Also, you sound as if pro-NE effects are beneficial to you, which is another reason to go with the clomipramine over the Lexapro. If you find that the clomipramine is not suitable or helpful enough, then you should move to the Lexapro. Furthermore, it would be easier to move from nortriptyline to clomipramine and then Lexapro than from nortriptyline to Lexapro to clomipramine.
> > Good luck. >
> >
> > Thanks, ? (not questioning your sincerity, merely expressing my gratitude)
> >
> > It was my thought exactly that i could substitute 25 mg of clomipramine for 25 mg of nortriptyline, and then later, if the clomipramine worked, deconstruct it into Lexapro. He said that clomipramine had more interactions w/ other meds than lexapro, and that was his main reason for favoring the Lex. Also, he said that clomipramine was much more sedating than nortriptyline, and as my depression currently is marked by prominent vegetative signs (exhaustion, slowed movement and thought, anhedonia) that the lexapro would work better than clomipramine. And theoretically, lex with a diminished dose of nortriptyline plus strattera leaves me with substantial pro-NE effect, simulating an action of clomipramine anyway. But he left the choice up to me. he said switching in 25 mg clomipramine with 25 mg nortriptyline would be feasible.
> >
> > About the klonopin: he wrote me a prescription for double the amount i currently take (ie, for 1.5 mg/day). I had wanted to switch klonopin in for another benzo, because of a possible depressogenic effect (he actually brought this up, but it was in my notes, of course) but, as he put it, he wanted to move one chess piece at a time. but he was clearly indicating that my next move, after lowering the nortriptyline (and giving the dose reduction until Monday or Tuesday to kick in) my next move could be to up the Klonopin. I take his writing the prescription for 1.5 mg as indicating that, if I chose and consulted with him, I could either up the klonopin, add clomipramine (since it isn't a controlled substance, he could call in a script) or open the Lexapro starter pack and cut a pill in half (or quarters, or take the whole pill as the pack directs). Or keep the status quo for a little longer. A lot obviously depends on my mood between now and next week (currently awful, unsurprisingly). But I agree with your reasoning as to how to sequence the changes, while also seeing his point about the Lexapro being less sedating. It's the weekend, so my anxiety is lowered while the fatigue, anhedonia, etc., are more subjectively distressing. If the Klonopin is contributing to these symptoms, which it may well be, it's best to keep it where it is for the moment.
> >
> > As for dependency, that is not a consideration. I have ADD, so i will always need Strattera or a stimulant, and I actually fear dependency from SSRI's as much as dependency on benzos. Besides, my pdoc knows my history of social phobia and he also knows that I have tried MANY, MANY other approaches to resolve it (CBT, Prozac, Zoloft, Buspar, years of conventional therapy), and I think that in his mind it is preferable to give Klonopin a good run for its money before trying a MAOI (I concur with his reasoning here, as I tolerate TCA's pretty well and NE reuptake inhibition is therapeutic for me).
> >
>
>
> Okay, let's see. First of all, i think harryp's idea with the Parnate could be good, except that it's often not very good for anxiety, and can sometimes be downright terrible for it. Maybe Parnate plus Klonopin would be a good combination though (which is something i've always been curious to try, since the Parn would help negate the Klon's negative effects on cognition and mood, and the Klon would counter Parnate's anxiogenic and overemotional effects.) Actually, since you have such anergic, anhedonic depression (suggesting inhibited transmission of NE, DA, or both), then i wonder if your anxiety is related to low catecholamine transmission as well (of course, it's possible they could be low in some areas and high or normal in others-- i have no idea). If this is the case, then maybe something like Parnate WOULD be quite beneficial for you. Just a thought.Since I do have ADD, and a nasty, shape-changing form- extremely hyperactive when a child, becoming more and more inattentive in adolescence until by the time I was an adult I was literally swimming in 'brain fog'- it suggests poor NE and DA neurotransmission (all theorists agree that ADD/ADHD is liked to dopaminergic abnormalities, some pin it on the dopamine transporter's being overexpressed, some on the enzymatic catabolic processes - COMT and MAO-B- some on problems with the DA receptors themselves, etc.) Further evidence is the fact that I have many narcoleptic symptoms- EDS, which I've always had, and a nasty form of sleep paralysis, which i have not seen described in the way that i experience it, anywhere. It's commonly known that sleep paralysis produces hypnagogic hallucinations that tend to be terrifying to the dreamer, but I experience actual pain, shooting through my head, limbs, and feeling like electrical shocks. All the while the dream-content is usually of myself having a seizure- once, I told myself, that I would call 911 when I woke up, because i was having either a stroke or a grand mal seizure in my sleep! On waking, the pain generally subsides, but I usually feel both shaken and have a residual headache, and sometimes I've had whole series of these events- each time i would fall asleep, this thing would happen, each episode lasting at most three minutes after falling asleep (I keep two clocks across from my bed, and have for years, since I've had so much difficulty waking up, and that's been another factor in my checkered job and academic history.)
Anyway, this is a lot more than anyone would want to know about my sleep paralysis (which, incidentally, began at 23- typical age of onset for narcoleptic symptoms). Now, Hobson attributes both sleep paralysis, and narcolepsy in general, to cholinergic (I assume he means muscarinic) overactivity and corresponding weakness of the aminergic systems which hold REM in check, particicularly norepinephrine. He cites the example of a female patient of his, who suffered hypnagogic (hallucinations upon falling asleep) and hypnopompic (hallucinations that persist on waking) disruptions when she lowered her dose of amitriptyline, which is strongly anti-muscarinic as well as being pro-NE.
Hobson says that much less is known about the role of DA in REM. But if we put the severe ADD (associated with abnormalities of DA transmission) next to the tendency to go into REM on sleeping (associated with poor NE transmission combined, or caused by, a hyper-cholinergic state) then you could see why melancholic depression, anhedonia, and a vegetative state would eventually result! And theoretically, of course, Hobson's patient would have done just as well if not better on Parnate than amitriptyline.
>
> Good points about the depressiogenic effects of Klonopin and the greater sedative effects of clomipramine (compared to nortriptyline). i'm guessing that the clomip. and the nortrip. are relatively similar in regards to anticholinergic potency. And the clomip. is more sedative due to its H1 antagonistic (or antihistaminic) effects. So if you don't already know, find out how you react and deal with antihistamine effects (maybe buy some benadryl/diphenhydramine?) Some people like it; some people can't stand it (anti-H1 effects that is). That should help you decide about the clomipramine. Also take note that (though you're probably already aware) clomipramine is extremely serotonergic (very potent 5-ht reuptake inhibitor). As far as adverse reactions with other drugs go, just try to find out the liver enzymes affected by any drugs you think you may take in the near future and compare this with those inhibited by clomipramine. If none of the enzymes are the same (or none are strongly inhibited), then you should have nothing to worry about. One thing you should realize though is that i think if you smoke this will significantly increase the concentrations of either clomipramine or its metabolite imipramine, or both (can't remember-- i think will just up the clomipramine).I don't smoke. I find H-1 antagonism to be good for sleep, but at the same time I've been fatigued, and now that I've taken down the nortriptyline I'm not sleeping at all. Even drugs that aren't directly anticholinergic (like MAOI's and Strattera) have anticholinergic-like s/e due to NE potentiation. (Reminds me- I've got to put my sugarless sucking candy in my mouth that my dentist urged me to buy after discovering the cavity-filled desert that orifice has become. I am having emergency root canal next week so- anyway, I suspect I will have "anti-cholinergic" effects from Strattera even if I come off the TCA's entirely.)
> Lexapro might be quite good for your anxiety but it probably won't be good at all for the type of depression you have (just my guess). But maybe with a noradrenergic drug like nortriptyline or Strattera it would be useful. It also should have less side effects than clomipramine would. Oh, and as harryp also mentioned, desipramine might really be worth looking into. For some reason i see desipramine as being better than Strattera, though similar. i'm not sure why, i just have a poor image of Strattera (mostly from alot of anecdotes i think), though maybe it's inaccurate. Alot depends on how much serotonin stimulation you think you need, among other things of course. If little to none, then clomipramine and Lexapro are not even worth considering.
> Yeah, i think you should find the right, good, effective antidepressant drug or combination, and then when you have satisfactorily established that, then gradually add in Klonopin until your anxiety is under control as well.
> Sounds promising. Good luck.I don't know about serotonin. I agree that lexapro would be useless in this kind of vegetative depression by itself, but like you say, combined with TCA or Strattera might be a different story. I've never had a satisfactory trial with an SE drug. That isn't necessarily conclusive evidence that Lex wouldn't help, because in the past I was trying monotherapy with SSRI's. My great fear was that Lexapro would worsen the insomnia that could result from lowering the TCA. Already, down from 75 to 50 mg of nortrip, I'm having that 'early-morning awakening' that could get really tedious after a while. That could be the depression, of course, although I was sleeping ok until this weekend.
I think, since I'm on so much right now, and also I think the time to do a total drug washout will be when the school year ends (I'm a teacher) I'm going to slowly move the pieces around that are already on the board, as my pdoc wants to do. I'm calling him on Monday or Tuesday to report on the effects of the lowered nortrip. I have Klonopin on hand, and a fresh script, so if my anxiety skyrockets when the weekend's over- I'll try 1 mg (the stuff is very sedating, so I don't want to knock myself out more than necessary, and I would prefer using Benadryl for sleep than Klonopin). I prefer clomipramine to Lexapro, but that shouldn't be a problem in terms of calling in a script.
I appreciate both of your insights, you have given me a lot to think about.
poster:zeugma
thread:343353
URL: http://www.dr-bob.org/babble/20040505/msgs/345006.html