![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 26 to 50 of 121. Go back in thread:
Posted by desolationrower on January 9, 2009, at 3:06:07
In reply to Re: I want to switch from nortriptyline to desipramine, posted by SLS on January 8, 2009, at 16:04:31
hm, good luck with the change.
i think betahistine would be ideal to counter weight gain, but probably not something you could get a doc to do. modafinil might be helpful in its stead, i sort of remember you saying you didn't take it, but a low dose might not bother you?
not sure what else you take, but at minimum i'd suggest
fish oil
vitamin d3
vitamin k2
magnesium
sounds like you excercise and i assume eat healthy.for weight loss also sesamin would be useful especially for triglycerides too, tho some people find it makes them sluggish or less libido. ashwaghadha is interesting, can't think if its ok with your regimine. green tea extract too. i would give it a try. those numbers are scary.
also, can't you just ask for plasma level of the tca if you think its not high enough?
-d/r
Posted by SLS on January 9, 2009, at 7:36:47
In reply to Re: I want to switch from nortriptyline to desipramine, posted by desolationrower on January 9, 2009, at 3:06:07
> hm, good luck with the change.
>
> i think betahistine would be ideal to counter weight gain, but probably not something you could get a doc to do. modafinil might be helpful in its stead, i sort of remember you saying you didn't take it, but a low dose might not bother you?
>
> not sure what else you take, but at minimum i'd suggest
> fish oil
> vitamin d3
> vitamin k2
> magnesium
> sounds like you excercise and i assume eat healthy.
>
> for weight loss also sesamin would be useful especially for triglycerides too, tho some people find it makes them sluggish or less libido. ashwaghadha is interesting, can't think if its ok with your regimine. green tea extract too. i would give it a try. those numbers are scary.That's a nice list of alternatives, D/R. Thank you. I think I'll try them. My fear is that without knowing it, my consuming any other substances might destabilize me and prevent me from responding to the medication regime. I think I'll wait until I am stable on the desipramine before adding anything.
> also, can't you just ask for plasma level of the tca if you think its not high enough?
If I have to fight my doctor on this one, I will go for blood levels at that point. I have been on desipramine often enough to know where my clinical range lies. One time, I was told to take 450mg of imipramine, and my blood levels still had not exceeded the therapeutic range. As purported in the PDR and other medical literature, most people will need no more than 200mg of desipramine. However, outpatients and people with more severe depressions are encouraged to target 300mg if necessary.
Thanks again.
- Scott
Posted by JadeKelly on January 9, 2009, at 9:40:30
In reply to Re: I want to switch from nortriptyline to desipramine, posted by SLS on January 8, 2009, at 16:04:31
> Woohoo!
>
> My doctor is letting me crossover from nortriptyline to desipramine. He is being rather cautious, but methodical in the way he makes the switch. I told him that, in the past, I needed 300mg of desipramine to get the most out of it. His first reaction was to not go so high in dosage. I explained to him that I am a rapid metabolizer of tricyclics. Seeing that I demonstrated a need to take 150mg of nortriptyline, it makes sense that I would need 300mg of desipramine. It is well known that 1mg nortriptyline = 2mg desipramine in terms of clinical equivalency. I guess I will just have to suffer for awhile. I will be reducing the nortriptyline and increasing the desipramine simultaneously.
>
> I am going to need to be patient to follow my doctor's protocol for making the switch. I am probably going to feel worse for some period of time until I get up to 300mg with the desipramine.
>
> Practicing patience really sucks.
>
> I want to be feeling good yesterday.
>
>
> - Scott
Some smart guy told me once that practicing patience really pays off (even tho it sucks).Good luck, hope you are feeling good soon.
~Jade
>
Posted by SLS on January 9, 2009, at 9:52:15
In reply to Re: I want to switch from nortriptyline to desipramine » SLS, posted by JadeKelly on January 9, 2009, at 9:40:30
> > Practicing patience really sucks.
> >
> > I want to be feeling good yesterday.> Some smart guy told me once that practicing patience really pays off (even tho it sucks).
>
> Good luck, hope you are feeling good soon.I really appreciate your sincere sentiments. I might go through a bad spell. Knowing that people are behind me helps immensely.
Thanks.
Since we are not on the subject, how are you doing?
:-)
If Parnate 60mg doesn't seem to be doing the trick for you, would you increase the dosage of methylphenidate first, or increase the Parnate?
- Scott
Posted by JadeKelly on January 9, 2009, at 11:36:39
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by SLS on January 9, 2009, at 9:52:15
> > > Practicing patience really sucks.
> > >
> > > I want to be feeling good yesterday.
>
> > Some smart guy told me once that practicing patience really pays off (even tho it sucks).
> >
> > Good luck, hope you are feeling good soon.
>
> I really appreciate your sincere sentiments. I might go through a bad spell. Knowing that people are behind me helps immensely.
>
> Thanks.
>
> Since we are not on the subject, how are you doing?
>
> :-)
>
> If Parnate 60mg doesn't seem to be doing the trick for you, would you increase the dosage of methylphenidate first, or increase the Parnate?
>
>
> - Scott
>Ah, you want to know what grasshopper will do when you are the one in need of support? Okay, I'll tell you as a distraction. However, I've been looking at some old posts (really didn't know so much babble ends up on google) and you really should give your brain a rest and get some support for yourself. Are you going to tell us when you switch, and will you stay on the board when you don't feel good? I hope so. I promise not to ask you any questions : )
Okay. For now, I'm remaining a patient patient. I know, you're tearing up. I did add lithium so I'll see what that does, if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer. So...it looks like we will both have to be patient patients! I'm sorry your's may be worse, I hope you'll seek comfort for yourself while you need it.
~Jade
Posted by SLS on January 9, 2009, at 14:04:39
In reply to Re: I want to switch from nortriptyline to desipramine » SLS, posted by JadeKelly on January 9, 2009, at 11:36:39
> Okay. For now, I'm remaining a patient patient.
:-)
I wish I could say the same. I am scheming even as we speak.
> I know, you're tearing up.
Not yet, but I will, I imagine.
1. The pain.
2. The frustration.
3. The unfairness.
> I did add lithium so I'll see what that does,
Good call. I like your decision.
> if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work. Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor will probably allow you to remain on the increased dosage of methylphenidate. However, if you were to ask him to do this after arriving at 80mg, he might be reluctant and say no.
I will try to continue to post, regardless of how bad I feel.
- Scott
Posted by JadeKelly on January 9, 2009, at 16:42:15
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by SLS on January 9, 2009, at 14:04:39
> > Okay. For now, I'm remaining a patient patient.
>
> :-)
>
> I wish I could say the same. I am scheming even as we speak.Well, since yours is a temporary insult to your system, I geuss a little scheming doesn't seem so bad. Just don't risk your health, (and I'll have some of what your having).
>
> > I know, you're tearing up.
>
> Not yet, but I will, I imagine.
>
> 1. The pain. Physical pain? Emotional? Both?
>
> 2. The frustration. This has to be the worst.
>
> 3. The unfairness. Definately.Can you add something for pain during this period?
>
>
>
> > I did add lithium so I'll see what that does,
>
> Good call. I like your decision.
>
> > if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
>
> Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
Patient patient. That was the best advice I've gotten. I can just be. Thanks.
>
>
I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work.After my "temporary remission", whatever one calls that, I increased from 5mg R to 10mg R but nothing. A little more energy as you would expect. So you are saying go to 15mg R or just go to 80mg Parnate since I already tried the Rit increase?
Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor
What doctor would that be? haha My doctor doesnt even know I'm taking ritalin. He said no.
So I'm gonna find one quick, can you see a PDoc putting me on 80mg Parnate? I'll find a way, I always do. I need to call the 2 you gave me and hopefully i'll get somewhere. I'll find one. And I'll use the litmus test!! They HAVE to pass the litmus test if they want to treat me.>
> I will try to continue to post, regardless of how bad I feel.If nothing else it'll be a distraction for you.
How long in between where neither tca is working? Isn't there SOMETHING you can take for the worst part? Schemer? I hope you have family or friends that will help you when its bad. Sounds like this kind of thing is harder than I thought. I feel for ya.
Btw- I am getting small A/D action from Parnate, that scary, panicky feeling is mostly gone. But its just like you guys said, if I don't take it on time and keep a regular sleep schedule I'll feel worse again. I have a long way to go, but I'm optimistic. Just didn't want you to think I wasn't being helped at all.So let us know when. In the mean time, I think you should hop around the board and annoy people....in a civil way, of course. It makes for good entertainment for you and us (well me anyway!) Its a win win!
Okay-keep in touch, feel free to babblemail if you're having a rough time. Whenever.
~Jade
>
> - Scott
Posted by Sissy35 on January 11, 2009, at 17:18:11
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by SLS on January 9, 2009, at 14:04:39
The two drugs are very simulair so I hope you don't experience too many side effects. One good thing desipramine kicks in faster for depression. but abit more stimulating. But I am sure you know all this already.
I just wanted to wish you luck and hope you don't lose your sense of humor or I will start a pettition to get you on drugs that make you who you are again.
All the best MR S, or is it DR.S now?
sissy35
Posted by bulldog2 on January 13, 2009, at 10:20:23
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by SLS on January 9, 2009, at 14:04:39
> > Okay. For now, I'm remaining a patient patient.
>
> :-)
>
> I wish I could say the same. I am scheming even as we speak.
>
> > I know, you're tearing up.
>
> Not yet, but I will, I imagine.
>
> 1. The pain.
>
> 2. The frustration.
>
> 3. The unfairness.
>
>
>
> > I did add lithium so I'll see what that does,
>
> Good call. I like your decision.
>
> > if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
>
> Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
>
> I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work. Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor will probably allow you to remain on the increased dosage of methylphenidate. However, if you were to ask him to do this after arriving at 80mg, he might be reluctant and say no.
>
> I will try to continue to post, regardless of how bad I feel.
>
>
> - ScottYou also might find you need less thann you needed previously.
Posted by JadeKelly on January 13, 2009, at 12:26:50
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by SLS on January 9, 2009, at 14:04:39
> > Okay. For now, I'm remaining a patient patient.
>
> :-)
>
> I wish I could say the same. I am scheming even as we speak.
>
> > I know, you're tearing up.
>
> Not yet, but I will, I imagine.
>
> 1. The pain.
>
> 2. The frustration.
>
> 3. The unfairness.
>
>
>
> > I did add lithium so I'll see what that does,
>
> Good call. I like your decision.
>
> > if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
>
> Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
>
> I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work. Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor will probably allow you to remain on the increased dosage of methylphenidate. However, if you were to ask him to do this after arriving at 80mg, he might be reluctant and say no.
>
> I will try to continue to post, regardless of how bad I feel.
>
>
> - ScottMaybe
haha
I went up to 70mg. Until I find new Doc I don't want to run risk of running out. Maybe I will stay at current dose of Ritalin, seems like getting the Parnate at therapeutic range is most important. Darn, had a dream last night. Stubborn brain.
Hope you are doing/feeling well : )
~Jade
Posted by JadeKelly on January 13, 2009, at 12:49:21
In reply to Re: I want to switch from nortriptyline to desipramine, posted by bulldog2 on January 13, 2009, at 10:20:23
> > > Okay. For now, I'm remaining a patient patient.
> >
> > :-)
> >
> > I wish I could say the same. I am scheming even as we speak.
> >
> > > I know, you're tearing up.
> >
> > Not yet, but I will, I imagine.
> >
> > 1. The pain.
> >
> > 2. The frustration.
> >
> > 3. The unfairness.
> >
> >
> >
> > > I did add lithium so I'll see what that does,
> >
> > Good call. I like your decision.
> >
> > > if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
> >
> > Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
> >
> > I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work. Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor will probably allow you to remain on the increased dosage of methylphenidate. However, if you were to ask him to do this after arriving at 80mg, he might be reluctant and say no.
> >
> > I will try to continue to post, regardless of how bad I feel.
> >
> >
> > - Scott
>
> You also might find you need less thann you needed previously.Oh,
Sorry BullDog,
You might not have understood my response, I thought it was Scott, so what were you referring to, the Parnate or the Ritalin. Are you taking Parnate? How much-or somthing else?
~Jade
Posted by JadeKelly on January 13, 2009, at 13:20:15
In reply to Re: I want to switch from nortriptyline to desipramine » SLS, posted by JadeKelly on January 13, 2009, at 12:26:50
Oops!
Message was from BullDog
Diregard!
~Jade
;-)
Posted by bulldog2 on January 13, 2009, at 13:41:13
In reply to Re: I want to switch from nortriptyline to desipramine, posted by JadeKelly on January 13, 2009, at 12:49:21
> > > > Okay. For now, I'm remaining a patient patient.
> > >
> > > :-)
> > >
> > > I wish I could say the same. I am scheming even as we speak.
> > >
> > > > I know, you're tearing up.
> > >
> > > Not yet, but I will, I imagine.
> > >
> > > 1. The pain.
> > >
> > > 2. The frustration.
> > >
> > > 3. The unfairness.
> > >
> > >
> > >
> > > > I did add lithium so I'll see what that does,
> > >
> > > Good call. I like your decision.
> > >
> > > > if nothing within 2nd week, I'll switch to lamictal, and I was told that will take longer.
> > >
> > > Just to get to 100mg will take 5 weeks. You might not realize an optimal response until you get to 200mg.
> > >
> > > I was thinking that while you are still taking 60mg of Parnate, you might want to increase the dosage of the methylphenidate. It might work. Then, if it doesn't, you can then proceed to 80mg of Parnate. Your doctor will probably allow you to remain on the increased dosage of methylphenidate. However, if you were to ask him to do this after arriving at 80mg, he might be reluctant and say no.
> > >
> > > I will try to continue to post, regardless of how bad I feel.
> > >
> > >
> > > - Scott
> >
> > You also might find you need less thann you needed previously.
>
> Oh,
>
> Sorry BullDog,
>
> You might not have understood my response, I thought it was Scott, so what were you referring to, the Parnate or the Ritalin. Are you taking Parnate? How much-or somthing else?
>
> ~Jade
>
>Hi jade
You thought I was to old for an maoi so I ditched the idea.(i'm 61). Currently on low dose nortriptyline but not sure if that's the med for me. Won't address issues of social phobia or anxiety that the maois address. tend to be reclusive. Any ideas.
Still using the neurontin several days a week and that helps but can't use it every day as that builds tolerance rapidly.
I was telling Scott if he's lucky he may not have to go up to 300 mg of desipramine and it may work this time at a lower dose.
Posted by JadeKelly on January 13, 2009, at 14:53:04
In reply to Re: I want to switch from nortriptyline to desipramine, posted by bulldog2 on January 13, 2009, at 13:41:13
> > >
> > > You also might find you need less thann you needed previously.
> >
> > Oh,
> >
> > Sorry BullDog,
> >
> > You might not have understood my response, I thought it was Scott, so what were you referring to, the Parnate or the Ritalin. Are you taking Parnate? How much-or somthing else?
> >
> > ~Jade
> >
> >
>
> Hi jade
>
> You thought I was to old for an maoi so I ditched the idea.(i'm 61). Currently on low dose nortriptyline but not sure if that's the med for me. Won't address issues of social phobia or anxiety that the maois address. tend to be reclusive. Any ideas.
> Still using the neurontin several days a week and that helps but can't use it every day as that builds tolerance rapidly.
> I was telling Scott if he's lucky he may not have to go up to 300 mg of desipramine and it may work this time at a lower dose.Hi BullDog,
Please consider the source of that information.
Sorry for the misunderstanding, of which I think there have been many. So my idea is that you turn on your babble mail. Just a thought. Unless you have any heart problems, I don't know why you couldn't try MAOI if you wanted to. I think you were on the fence about it. I saw where it was posted that "someone said anyone over 60" should not be on MAOI. I did mention seeing an old article to someone, but when I saw it posted, I posted my opinion on the subject as well. Which is, as I said, I see NO reason why a healthy person in their sixties shouldn't try an MAOI if thats what they decide with their Doctor. I would!As far as sticking to your current plan, seems like their ought to be several other things you could alternate, aren't there? I don't think you should have to suffer 3 days so you can have 4 good ones! How long on the Nort? What about trying the one Scott's trying Des? What about (and I'm just listing some things I've heard others talk about) Lyrica, Bup-sp?, Ritalin,
benzo, (Ritalin and Klonopin worked for many years for me. ADD & Nerve Pain but I think they may offer a/d response too) Ah, I'm just repeating at this point what I've seen on the board. What is it you are looking for and what are you considering?~Jade
Posted by sissy35 on January 13, 2009, at 16:03:12
In reply to Re: I want to switch from nortriptyline to desipramine, posted by bulldog2 on January 13, 2009, at 13:41:13
Hi bulldog2
I was on nardil for over 20yrs and I am an old duck. No one ever said I shouldn't take it. Nardil is excellent for social phobia or anxiety of which I had both. Never left the house for 2yrs.
It does have a lot of hypotension in the beginning but is not as touchy as parnate it is a bit more forgiving. Never had high bp like with parnate. I woild still be on it if it still was working. 20yrs was a good run so I can't complain. It diffently is worth a try.
Sissy35
sorry jade don't hurt me!!!
Posted by bulldog2 on January 13, 2009, at 16:40:10
In reply to Re: I want to switch from nortriptyline » bulldog2, posted by sissy35 on January 13, 2009, at 16:03:12
> Hi bulldog2
> I was on nardil for over 20yrs and I am an old duck. No one ever said I shouldn't take it. Nardil is excellent for social phobia or anxiety of which I had both. Never left the house for 2yrs.
> It does have a lot of hypotension in the beginning but is not as touchy as parnate it is a bit more forgiving. Never had high bp like with parnate. I woild still be on it if it still was working. 20yrs was a good run so I can't complain. It diffently is worth a try.
> Sissy35
> sorry jade don't hurt me!!!Shame nardil changed to formula and now people need higher doses of it to obtain the same effect.
Posted by SLS on January 15, 2009, at 7:28:03
In reply to Re: I want to switch from nortriptyline to desipramine » bulldog2, posted by JadeKelly on January 13, 2009, at 14:53:04
Hi.
I'm starting to lose it. Depression is re-ermerging. Some derealization, too. I am still only taking 50% of the dosage of desipramine that I think I'll need. I'm not terribly scared, but I wish I could treat myself with this one. I do respect my doctor's wishing to be cautious and do no harm. I just wish that these were better days. I feel like they are being wasted.
Feeling lonely and old...
- Scott
Posted by JadeKelly on January 15, 2009, at 9:17:24
In reply to Re: I want to switch from nortriptyline to desipramine, posted by SLS on January 15, 2009, at 7:28:03
> Hi.
>
> I'm starting to lose it. Depression is re-ermerging. Some derealization, too. I am still only taking 50% of the dosage of desipramine that I think I'll need. I'm not terribly scared, but I wish I could treat myself with this one. I do respect my doctor's wishing to be cautious and do no harm. I just wish that these were better days. I feel like they are being wasted.
>
> Feeling lonely and old...
>
>
> - ScottHi Scott,
I wish there were something I could do. Depression Sucks. Just remember it will end. How long until you get to 100% desipramine dosage? I haven't taken it so I don't know how long it takes to work. I'm sorry you're lonely but we're here...and I've heard you're not old, so. I hope this goes quickly for you and take good care of yourself. You're a good guy and you deserve to be well. Better days are coming.
;-)
Patient patient, Jade
Posted by JadeKelly on January 15, 2009, at 12:27:28
In reply to Re: I want to switch from nortriptyline to desipramine » SLS, posted by JadeKelly on January 15, 2009, at 9:17:24
Hi Scott,
Hope you're feeling even a little better would be nice, heh? Anyway, I'm looking for a new Doc and came across something interesting. Don't know if you're feeling like lookin at this kinda stuff right now or not but here it is:
My current PDoc lectures at Sheppard Pratt in Baltimore, and this PDoc was giving a lecture there as well, Dr. David Goodman. This was 10 years ago which was interesting to me. You may have already seen it. PDoc Goodman worked (works? I hope) at the Green Spring Station Johns Hopkins out patient Clinic, Psych Dept. I couldn't get the link to email so here it is:
http://www.mdpsych.org./SP99dGoodman.htm.
This was Spring 1999; Vol.No.1.
If you haven't seen this, read to the bottom. I think you'll find it interesting. Let me know if you want more of the lecture, etc.
I'll be calling over there anyway to get an appt with Goodman or his protege I hope.
Maybe you're watching a comedy and having an awesome lunch. I hope so.
~Jade
Posted by JadeKelly on January 15, 2009, at 12:43:16
In reply to Re: I want to switch from nortriptyline to desipramine » JadeKelly, posted by JadeKelly on January 15, 2009, at 12:27:28
Diagnosis and Treatment of Refractory Depression
Sheppard Pratt Psychiatric Lecture Series, February 1999
by Dr. David Goodman[Spring 1999; Vol.26 No. 1]
I had the honor of being invited to present an update on pharmacologic treatment of refractory depression. For this presentation, refractory depression was defined as a patient who has been on adequate dosing trials of at least 6 to 8 antidepressant combinations and failed to adequately respond. For the purpose of diagnosis, it is important to remember that a patient uses the term "depressed" or "anxious" as a descriptor of mood, and not a diagnosis. It is the clinician who needs to enumerate the patient's symptoms in order to substantiate a clinical psychiatric diagnosis. Although we may speak about depression as a clinical diagnosis, in fact, depression is a mood phase which can be seen in major recurrent depression or bipolar disorder. Diagnostic accuracy is essential in determining effective treatment. Many unsuccessful treatments have been started prematurely without an accurate assessment of symptoms and conclusive diagnosis.
Symptoms of clinical depression are well-known amongst physicians and mental health professionals. However, diagnostic confusion arises when patients present with depressed mood accompanied by anxiety and/or agitation. There seems to be increased focus on the treatment of depression with anxiety, as many pharmaceutical companies attempt to establish their antidepressant in this area. However, anxiety with depression is distinctly different from depression with agitation. Anxiety is accompanied by worry, a sense of impending doom, general fearfulness and usually no significant insomnia. In contrast, agitation is characterized by physical restlessness, irritability, an internal sense that the "motor is revved," and significantly decreased sleep. It is important to make this distinction because agitation occurring with depression may reflect an underlying bipolar diathesis. This diagnostic distinction becomes important because bipolar patients in depressed phases are typically less responsive to antidepresants without a mood stabilizing agent when compared to the antidepressant response of major depressed patients.
In a study of 50 inpatients by Ghaemi, et al, it was found that bipolar disorder was severely under-diagnosed. Forty-two percent of the bipolar patients had carried other diagnoses. Of the 42%, 90% of them carried a diagnosis of unipolar depression. Therefore, that which we call refractory depression may in fact be a patient with a bipolar disorder who is only partially responsive to any antidepressants they have been on.
Since mental health professionals are probably most familiar with the selective serotonin re-uptake inhibitors, the five U.S. SSRIs were reviewed. The kinetics and active metabolites of fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine were discussed. Linear kinetics applies only to sertraline and citalopram. The presence of food seems to have no clinical effect on SSRI absorption. The only two SSRIs with clinically active metabolites are fluoxetine and sertraline. Citalopram is the latest SSRI in the U.S. market. Specific kinetic and clinical features were reviewed. Citalopram seems to have the lowest inhibitory effect on the P450 system in in-vitro studies. This has lead clinicians to believe that it probably has fewer possible drug-drug kinetic interactions. In addition, it is the most highly selective serotoninergic antidepressant as judged by the ratio of dopamine re-uptake affinity to serotonin re-uptake receptor affinity.
There are five key clinically relevant psychopharmacologic concepts that are important in the poly psychopharmacologic treatment of refractory patients.
1. Drug-drug interactions: Pharmacokinetics (changes in drug absorption, distribution, metabolism, and excretion) versus pharmacodynamics (when two drugs act at the same or interrelated receptor site). A clinician must decide in which of these two categories a patient's side effects occur because this will determine how drug doses are modified.
2. Genetic polymorphism: There are five isoenzymes which are particularly relevant in psychiatry. Two of these isoenzymes 1A2 and 3A4 have no genetic polymorphism, that is, there is not much variation from 1 patient to another in the metabolism of substrates through these isoenzymes. This is in contrast to 2C19 and 2D6, for which the slow versus fast metabolizers exist. There are ethnic and racial differences. Approximately 20% of the Japanese and 4% of Caucasians are slow metabolizers for 2C19 substrates. Approximately 7% of Caucasians, but only 2% of Asians are slow metabolizers for 2D6 substrates.
3. The clinical onset of drug-drug interactions: The inhibition of drug metabolism and decrease in drug clearance causes an elevation in serum levels. The clinical effect of this elevation is usually seen in 2-5 half-lives of the drug whose metabolism is inhibited. However, when a drug's metabolism is induced and serum levels fall, the clinical effect is not seen for several weeks. Therefore, if you know the temporal relationship between a drug and the onset of side effects, you might be able to deduce whether metabolic inhibition or induction has taken place.
4. The clinical relevance and differences between in-vitro versus in-vivo study results: Isoenzyme inhibition, seen in-vitro, takes into account only a parent drug. The in-vivo studies will take into account inhibitory effects of any metabolites. This was seen when comparing three SSRIs with desipramine blood levels. So although we may be able to extrapolate clinical information from in-vitro data, it should not be presumed as conclusive.
5. Drugs can be metabolized through multiple isoenzymes: It is important to be apprised of the substrate's major pathway when looking at spreadsheets of substrates and isoenzymes. Both imipramine and propranolol run through four isoenzymes. Clozapine runs through three isoenzymes. If you are not familiar with the major metabolic pathway, you may presume clinically relevant drug interactions where none exist and thereby avoid potentially useful drug combinations.
As had been mentioned earlier, diagnostic accuracy is essential in treating depressed patients. Patients who are depressed and bipolar should avoid tricyclic antidepressants because of a tendency to increased cycling frequency and worsen the pharmacologic response of the illness.
With the drive to identify depression in primary care, the issue of diagnostic accuracy in the consideration for bipolar disorder seems to have been lost. Although we might say that SSRIs do not increase cycling frequency, it took 25 years before we determined that tricyclic antidepressants increase cycling frequency. Who is to say what we will decide 20 years from now. Therefore, the prescription of these medications should be used judiciously and with diagnostic accuracy.
Pharmacologic algorithms have suggested that clinicians change from one class of antidepressant to another class of antidepressant if a patient fails to respond. Although this makes sense at face value, it wasn't until recently that we had research in this area. The response rate if you switch from a TCA to a TCA is approximately 22%. Switching from a TCA to an SSRI produces a 45% response rate. Switching from an SSRI to a TCA produces a 62% response rate. However, the question to be answered is, what is the response rate when you switch from one SSRI to another SSRI. Keep in mind that the SSRI structures are completely different. I have often said that what we know about these drugs we can stuff in a thimble and what we don't know about these drugs can fill a library. There is one study by Jaffe, et al, which took a look at response rates when switching from one SSRI to another. In general, he found a 50% response rate when changing from one SSRI to another. Therefore, it is important not to discard the whole class of SSRIs simply because the patient failed to respond to one. It is also well established that patients developing side effects on one SSRI may very well tolerate an alternative SSRI.
I reviewed the typical adjunctive agents used in refractory depression. In Pharmacotherapy, 4th Generation of Progress, there are reviews of response rates for adjunctive agents. Twelve studies of lithium augmentation to TCAs produced a response rate of 56%. Twelve reported T3 potentiation to TCAs showed a response rate of 40%. The addition of fluoxetine to TCAs in two studies showed a response rate of 47%. The addition of MAOIs to TCAs in ten studies produced a response rate of 54%. As you read this, you may notice a very untraditional drug combination, that is MAOIs with TCAs. Yes, there are several papers supporting the use of these agents without severe drug reactions.
Historically, the use of MAOIs has been infrequent, despite the fact that overwhelming research supports their benefit. Years ago, the dietary restrictions seemed to be so severe that clinicians worried that the patient would inadvertantly eat a restricted food, have a severe hypertensive reaction and suffer a stroke or heart attack. However, as the years have gone on, experts have revised and simplified the MAOI dietary restrictions. The current restrictions are very workable for most patients. Many patients who are judged to be refractory have never been on MAOIs. Clinicians who fail to use MAOIs eliminate a very effective class of agents.
To further complicate the treatment, MAOIs can be used with stimulants and TCAs. Although there are severe warnings and contraindications, there is a body of literature supporting their combined use. My clinical experience in about 8 patients, has been fairly rewarding. I stress that no physician should consider these drug combinations before the patient has been tried on the typical and traditional drug combinations. The MAOI combinations should be used by a clinician familiar with the literature and in patients who are trustworthy. It is important that patients monitor blood pressure and pulse as dosages of MAOIs and stimulants or tricyclics change. For those clinicians wishing to gain more experience in this area, I recommend Clinical Advances in Monoamine Oxidase Therapies, edited by Sidney Kennedy, MD, published by American Psychiatric Press, Inc. In this book, there is a report of nine trials with over 1,000 patients on MAOIs-TCA combinations, with no death or severe toxic events. Three open trials and 3 chart reviews showed treatment responses between 65-80%. These are remarkable response rates given the fact that patients have been severely refractory to other agents.
When using MAOIs, it is important to know the recommended wash-out period from other drugs. In general, when going from an MAOI to an SSRI, 4-5 weeks needs to be allotted.
When changing from a TCA, buproprion, SSRI to MAOI, a 2-week wash-out period is recommended. Keep in mind, that if you change from one MAOI to a second MAOI, there is also a 2-week wash-out recommendation. These recommendations are conservative and experienced clinicians have published reports of drug switches with shorter periods of wash-out.
Perhaps the most critical factor in the treatment of depressed patients is the provision of hope. It is important for the clinician to be diagnostically committed and hopeful that a successful treatment alternative will be identified. As noted, there are a number of pharmacologic alternatives beyond traditional recommendations. Those clinicians treating refractory depression should become familiar with the breadth of pharmacologic options. When patients believe that there is something else to be tried, it allows them to better tolerate their depression, demoralization and frustration.
Dr. David Goodman, is an Assistant Professor of Psychiatry at The Johns Hopkins University, School of Medicine, and is in private practice at Greenspring Station in Baltimore County.
Posted by Phillipa on January 15, 2009, at 20:35:25
In reply to Re: I want to switch from nortriptyline to desipramine, posted by SLS on January 15, 2009, at 7:28:03
Scott so sorry. What's next? Love Phillipa
Posted by sandy404 on January 16, 2009, at 6:17:04
In reply to I want to switch from nortriptyline to desipramine, posted by SLS on January 3, 2009, at 16:30:10
When I was on nortriptyline, I gained 70 pounds. I went from a size 10 to a size 1X. But it was the only med. that worked. I had tried them all. After about 7 years, I went on Zoloft, but the weight didn't fall off. I had to work at it. But it came off.I was pretty good for about 6 years. Now, I don't know what to do. I am so depressed that most days I don't get out of bed, except to check my computer. I'm wondering if I need to go back on nortriptyline.
Posted by SLS on January 16, 2009, at 7:45:20
In reply to Re: I want to switch from nortriptyline to desipramine, posted by sandy404 on January 16, 2009, at 6:17:04
> When I was on nortriptyline, I gained 70 pounds. I went from a size 10 to a size 1X. But it was the only med. that worked. I had tried them all. After about 7 years, I went on Zoloft, but the weight didn't fall off. I had to work at it. But it came off.I was pretty good for about 6 years. Now, I don't know what to do. I am so depressed that most days I don't get out of bed, except to check my computer. I'm wondering if I need to go back on nortriptyline.
It is a hell of a thing to have to choose between obesity and depression. I guess you've already tried desipramine. How did you react to it? Some investigative psychiatrists are now using desipramine to combine with SRI drugs like Zoloft and Effexor.
Parnate, and MAOI, is weight-neutral. Some people even lose weight while taking it.
I'm currently taking:
Parnate 80mg
desipramine 150mg
Lamictal 200mg
Abilify 20mg
I am probably going to need desipramine 300mg to feel really well. I see my doctor today. I am forced to increase the dosage at his cautious and methodical pace rather than the pace I have historically been able to tolerate. It is very frustrating.
- Scott
Posted by SLS on January 16, 2009, at 13:44:56
In reply to Re: I want to switch from nortriptyline to desipramine » sandy404, posted by SLS on January 16, 2009, at 7:45:20
> I'm currently taking:
>
> Parnate 80mg
> desipramine 150mg
> Lamictal 200mg
> Abilify 20mg
>
>
> I am probably going to need desipramine 300mg to feel really well. I see my doctor today. I am forced to increase the dosage at his cautious and methodical pace rather than the pace I have historically been able to tolerate. It is very frustrating.It's official. My doctor will allow me to go up to 200mg of desipramine. But I must stay there for 3 weeks. I would be much better at 300mg for 2 weeks, but I couldn't sell the idea to him. That's ok, I guess. I'm not suffering terribly. If I were in his position, I would be doing exactly the same thing. I can't fault him. He has never seen me on 300mg of desipramine or imipramine, two drugs that I have already demonstrated I need 300mg of.
Oh, well. After two weeks at 200mg, he wants me to get a blood level. This is another smart thing to do, but I know it is unnecessary. Man, this is going to take some self-discipline on my part. I start school next week, and I would have like to have been mentally sharper and have more energy. It will be a push. Dammit. Just like always.
I feel crappy but happy.
- Scott
Posted by Phillipa on January 16, 2009, at 19:36:51
In reply to Re: I want to switch from nortriptyline to desipramine, posted by SLS on January 16, 2009, at 13:44:56
Scott that's funny crappy and happy. Love Phillipa
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