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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by torachan on June 3, 2008, at 20:31:11
Yeah, I just got a script for Nortryptiline. I was wondering if this med has strong enough 5HT2 antagonism to counterbalance with the Effexor for anxiety? I know you mentioned Doxepin and amitryptiline, and I mentioned these to the doctor, but he gave me Nortyptiline.
I checked out the Wiki page for this med, and it states it's involved in the uptake inhibition of norepinephrine. Wouldn't this be similar to Remeron? Also, it stated that sleep would be disrupted for a while until improvement appears.
How would you rate this TCA compared to the others as an augmenting agent with Effexor for the contribution of anxiolytic and hypnotic effects?
Thanks
PS. Read your above post in the Best TCA thread. Very thorough. Do you by chance have an advanced degree in neuroscience or do you just simply read a lot on this subject?
Posted by linkadge on June 4, 2008, at 8:37:22
In reply to Linkadge?, posted by torachan on June 3, 2008, at 20:31:11
>Yeah, I just got a script for Nortryptiline. I >was wondering if this med has strong enough 5HT2 >antagonism to counterbalance with the Effexor >for anxiety? I know you mentioned Doxepin and >amitryptiline, and I mentioned these to the >doctor, but he gave me Nortyptiline.
Nortryptaline can be a very effective antidepressant. According to the PDSP website it is actually a SNRI with stronger affinity for the norepinephrine reuptake pump (maybe 2:1 or less).
It does appear to be a fairly potent 5-ht2a/c antagonist but I'd have to look for more data.
>I checked out the Wiki page for this med, and it >states it's involved in the uptake inhibition of >norepinephrine. Wouldn't this be similar to >Remeron? Also, it stated that sleep would be >disrupted for a while until improvement appears.It would be different from Remeron in a few ways. Remeron doesn't affect the reuptake of any monoamines. I personally didn't feel it had the same umph as the TCA's.
Some people find it activating and others find it sedating. This profile may change to a certain degree after a few weeks.
>How would you rate this TCA compared to the >others as an augmenting agent with Effexor for >the contribution of anxiolytic and hypnotic >effects?
It sounds promising. It is an effective AD and there is litureature for its use as an augmenting agent. There are a few questions (you may already have answered in previous posts i'm not sure). If you respond to effexor but only at higher doses (>75mg) then you may be benifitting from the norepinephrine reuptake inhibition. Since effexor has stronger affinity for serotonin, the combination for effexor and nortryptaline may allow you to fine tune an uptake ratio of serotonin/norepinephrine which helps you most. This may mean that lower doses of effexor are effective. For some people the norepinephrine reuptake may initially disrupt sleep but it may also improve sleep. I know a few posters who said the first dose knocked them out.
I think the key here is to take it slowly. You will likely get certain initial side effects that will fade with time. Does it come in 10mg? If so, I'd say start with 5mg on the first night, then slowly go up. You may only need 25mg for a good augmenting effect but play it by ear.
Take all your effexor in the morning if possable and the nortryptaline at night. When I added doxapin to celexa I noticed fairly soon that I needed less celexa. At this point lowering the celexa from 20 to 10mg actually led to clinical improvement. So, keep open to the possability that a lower dose of effexor may be more benificial (especially if the higher doses of the effexor caused apathy). The nortryptaline is *very* unlikely to cause or increase apathy (if this is a problem for you). In many cases it has been used effectively to reduce the apathy caused by SSRI's.
>PS. Read your above post in the Best TCA thread. >Very thorough. Do you by chance have an advanced >degree in neuroscience or do you just simply >read a lot on this subject?
No it's just been a personal interest for a while.
Take care and good luck over the next few days.
Linkadge
Posted by johnj on June 4, 2008, at 10:28:25
In reply to Re: Linkadge?, posted by linkadge on June 4, 2008, at 8:37:22
Good luck John,
I used nort for about 10 years with great luck. I did augment it with lithium too. I don't recall much start up anxiety but at that time I could take a benzo so I might not have noticed. I pray that it will work for you. I had a very bad night last night. I was wound up before bed and I have a very hard time letting things go hence I was up at 12:30. Uggh, today is tough.
I am not sure if nort comes in 5 mg. I had capsules so I used 10 mg. At those low doses you should have very little side effects and if you do it should dissipate rather quick.
Regards
johnj
Posted by linkadge on June 4, 2008, at 13:18:00
In reply to Re: Linkadge? » linkadge, posted by johnj on June 4, 2008, at 10:28:25
It may not come in 5mg but some people open up 10mg caps.
Theres no reason you couldn't start at 10mg. I know with doxapin even 10mg can pretty strong at the start.
Yes the combination of nortryptaline and lithium is particularly effective in treatment resistant depression. It is apparently effective in preventing ECT relapse.
Linkadge
Posted by torachan on June 4, 2008, at 13:30:22
In reply to Re: Linkadge? » johnj, posted by linkadge on June 4, 2008, at 13:18:00
I started with 25 mgs on doctors orders. I initially noticed some unpleasant side effects, like some gastrointestinal discomfort, a little abnormality in my heart rhythm, though I'm always oversensitive to this effect. It did not knock me out like my first dose of Remeron did at 15mgs, but this may be due to the fact I've been on Rem for awhile and am discontinuing the dose abruptly, though I must confess, I did take about 7.5mgs last night with the Nor. Also, the Remeron may have desensitized me to antihistaminic effects.
Despite this, I did "feel" like I would sleep well, despite getting about 4 hours or so. I take comfort in the fact knowing the Nor typically does disrupt sleep initially till the sleep promoting effect takes hold.
But you know what is encouraging to a great extent. Despite not sleeping all that great, I feel fine; more than fine perhaps. Whereas before with the Remeron if I didn't sleep well I'd feel miserable and have the hangover effect and "foggy" head. My mind is clear now.
Anyways, I may heed your advice Link, and keep my Effexor dose around 37.5 and go up slowly on the Nor to maybe 75mgs in the future to see if this drug will be my mainstay rather than Effexor. We'll see.
Johnj, sorry to hear about your troubles. Are you taking the Nor now, and do you feel the effects have worn off? If so, get your blood levels checked, because I read for TCA's this is crucial to maintain the proper serum levels for therapeutic effect.
Regards, John
Posted by linkadge on June 4, 2008, at 18:12:46
In reply to Re: Linkadge? » linkadge, posted by torachan on June 4, 2008, at 13:30:22
>But you know what is encouraging to a great >extent. Despite not sleeping all that great, I >feel fine; more than fine perhaps. Whereas >before with the Remeron if I didn't sleep well >I'd feel miserable and have the hangover effect >and "foggy" head. My mind is clear now.
I think that is a good sign. Non depressed people experience insomnia too but when you're depressed though insomnia is hell. I found it was a good sign when the nights of less sleep didn't whipe me over.
The remeron may amplify certain effects/side effects of the nortryptaline (notably cardiac side effects) since remeron stronly affects norpeinephrine release and nortrpytaline affects the reuptake.
(I am currently prescribed remeron and strattera) which would be similar to remeron and nortryptaline. I usually only take remeron as needed for sleep but I do notice that it increases certain cardiac side effects of strattera when I take the two together.
>Anyways, I may heed your advice Link, and keep >my Effexor dose around 37.5 and go up slowly on >the Nor to maybe 75mgs in the future to see if >this drug will be my mainstay rather than >Effexor. We'll see.
That sounds like a good plan. Some people do well on TCA's alone, some people find that a combination of TCA and SSRI/SNRI allows doses of either that are low enough that side effects are not pronounced. Remember though, if you do tollerate the nortryptaline in lower but not higher doses, don't throw in the towel alltogether.
Linakdge
Posted by johnj on June 4, 2008, at 18:45:08
In reply to Re: Linkadge? » linkadge, posted by torachan on June 4, 2008, at 13:30:22
Tora-chan
Are you more anxious or depressed or a combo? You may not need to go as high as 75. At one point I tried to raise my dose from 50 and it did not work well for me. For anxiety you may only need a low dose as the blood levels are more for depression improvement. I would see what a low dose does for anxiety and then go from there.
Since you seem to tolerate it at 25 that is very encouraging. Yes, for me too it took a while to help with sleep. I am happy you feel better. Go slow on the remeron wean. I was on it and it took quite some time to come off of it. It was harder than a benzo to come off of in the sleep department. I did take nor with remeron too.
I am not taking it right now. After 10 years it didn't seem to work anymore. However, that was after an illness and my doc wonders if it was because I became very sensitive to meds and all we should have done was lower doses :(
I think you feel better because of the lower remeron dose. It gave me "sponge brain" and going off felt very good. Fogginess was always a problem along with irritablity and anxiety on remeron. Good luck and keep us posted.
johnj
Posted by johnj on June 4, 2008, at 18:47:40
In reply to Re: Linkadge?, posted by linkadge on June 4, 2008, at 18:12:46
"The remeron may amplify certain effects/side effects of the nortryptaline (notably cardiac side effects) since remeron stronly affects norpeinephrine release and nortrpytaline affects the reuptake."
Wow, that could explain why I slept ok on remeron but when on both of those my physical anxiety was terrible. Chest and stomach were always tight.
Posted by johnj on June 4, 2008, at 18:53:57
In reply to Re: Linkadge? » johnj, posted by linkadge on June 4, 2008, at 13:18:00
I did well on the combo for 10 years then an illness and all hell broke lose. I have been struggling for 7 years now. 3 lost years of that on remeron. I hate what it did to me head.
Anyway, I may try nort again. My biggest problem right now is my inability to shake stuff off like an argument with my wife I dwell on and become overly negative. Same with anything stressful at work. I get "stuck" on stuff and have a hard time getting off of that. I even wake up and start thinking again. When I have a lack of sleep it is even worse. I don't really know what direction to go. The remeron experience made me so leary. I have tried ssri's and benzo to no avail, they made me worse. I know I have anxiety/ocd type stuff and even some depression now but it is all mixed up and I am getting confused. Maybe I was just meant to suffer and this is my cross.
Posted by linkadge on June 4, 2008, at 21:08:45
In reply to Re: Linkadge? » linkadge, posted by johnj on June 4, 2008, at 18:53:57
I know what you are talking about since I have had the same side effects on remeron.
Depression with obsessive tendancies or rumination can be hard to treat especially if the depression has hints of anhedonia. On the one hand you want you may want to increase activity in the frontal cortex to improve motivation and vigilance, but if the activity here gets to be too much it can be hard to stop or let go, thoughts can go over and over again.
The 5-ht2a/c receptors put the breaks on activity in the frontal cortex. When you block them with remeron you decrease the ability of gaba to inhibit the frontal cortex. SSRI's work in part for OCD by increasing 5-ht2a/c agonism in the frontal cortex and incresing inhibition there which reduces repetitive types of thoughts.
You might give clomipramine a try. Remeron is not very good for obsessive type of thinking.
Somtimes a combination of low dose SSRI plus nortrpytaline can allow individuals to fine tune the ratio of certain chemicals. If you find your thoughts are too repetitive you can take more SSRI, but if you become too apathetic you can lower the SSRI in relation to nortryptaline.
Linkadge
Posted by torachan on June 4, 2008, at 21:26:28
In reply to Re: Linkadge? » linkadge, posted by johnj on June 4, 2008, at 18:53:57
We're all meant to suffer to some degree, johnj. Some more so than others. I get what you say about dwelling on negative incidents like with your wife. I have the same problem, at times. I suppose we can't merely lay all the blame at the feet of chemical imbalances, though. A little positive thinking can go along way. It's tough to get in the habit of thinking positively, but I find it to be a "very" gradual process.
It's too bad you're exercise intolerant. Exercise does wonders for me in many ways. I wasn't even aware exercise intolerance existed. Does your heart rate get out of control? Do you become easily fatigued? Try long walks, if that's your style.
John
Posted by linkadge on June 5, 2008, at 8:30:56
In reply to Re: Linkadge? » johnj, posted by torachan on June 4, 2008, at 21:26:28
I do agree. At some point you need to accept or reject medications and hopefully adapt to which side effects they have.
I think its important to know however, which drugs may be contributing to which types of moods or behaviors. Remeron can increase irritability, there is even a phrase for the pheonomina..."rem rage"
Linkadge
Posted by johnj on June 5, 2008, at 8:58:21
In reply to Re: Linkadge? » johnj, posted by torachan on June 4, 2008, at 21:26:28
Yes, I know what you mean about suffering. It is part of who we are as humans. When I have a bad day positive thinking is really hard. Last night I slept for close to 5 hours and then woke up and had anxiety for about 30 minutes and fell back to sleep for almost 3 hours. Go figure.
I don't feel bad when exercising but it messes up my sleep really bad. It takes a day or so to improve. I am going to try and start again and see if I can go ever so slowly and build up. I had some immune system problems after my pneumonia and the doc thinks they are related but doesn't know how or what to do with it.
How is the nort?
Posted by johnj on June 5, 2008, at 9:06:45
In reply to Re: Linkadge?, posted by linkadge on June 5, 2008, at 8:30:56
I definately had rem rage and started to hit the wall and things. It seem to amplify a natural short fuse I have made me start to act out. I feel so bad that I did things like that. I hated what it did to me. The only thing it did was let me sleep. I got to the point where I started avoiding people and just wanted to go away. That is why I would take constipation and dry mouth of tca's over those type of side effects any day. You are right as we have to decide what side effects we will live with.
Link, you mentioned meds that affect the frontal cortex. I need something that slows is down. Do you know of any meds that help besides ssri's? They are just way too activating for me. Thank you.
johnj
Posted by linkadge on June 5, 2008, at 9:30:45
In reply to Re: Linkadge? » linkadge, posted by johnj on June 5, 2008, at 9:06:45
Not sure. I'd have to look in to it. Taurine may help. Ginger root perhaps.
Linkadge
Posted by johnj on June 5, 2008, at 12:21:52
In reply to Re: Linkadge?, posted by linkadge on June 5, 2008, at 9:30:45
Do any tca's help slow the frontal cortex down? Where did you hear about ginger root?
Posted by linkadge on June 5, 2008, at 19:00:02
In reply to Re: Linkadge? » linkadge, posted by johnj on June 5, 2008, at 12:21:52
This study seems to suggest that both mirapex and venlafaxine have some ability to increase gaba levels in the prefronal cortex.
http://cat.inist.fr/?aModele=afficheN&cpsidt=17217135
Here's some study of the effect of hallucinogenic 5-ht2a/c agonists on the prefrontal levels of gaba.
http://www.nature.com/npp/journal/v20/n1/abs/1395229a.html
There is some evidence that anticholinergic substances can reduce the release of glutamate in the prefrontal cortex. In some models of depression, acetylcholine levels are elevated in the prefrontal cortex leading to prefrontal hyperactivity. In these cases anitcholinergic drugs may reduce activity (ie benadryl, scopolamine etc).
Taurine increases the levels of GAD (which increases GABA synthesis). It also interacts directly with gaba receptors to produce inhibition.
As far as the ginger root goes, it has a nonsedating gabergic effect. It is also a mild MAOI which may decrease prefrontal hyperativity.
Linkadge
Posted by torachan on June 5, 2008, at 23:33:22
In reply to Re: Linkadge? » torachan, posted by johnj on June 5, 2008, at 8:58:21
The Nortryptiline is coming along nicely. I'm not sleeping as well as I was when using Remeron, but that may be due to the fact I've almost dropped the Remeron, hence some withdrawal reaction.
I'm not sure also if I can attribute the positive effects I'm feeling lately to the discontinuation of Rem or the effects of the Nor. Maybe a bit of both. I'll continue with the Nor for at least a month or more to gain a full judgment as to its benefits for me.
John
Posted by linkadge on June 6, 2008, at 11:21:25
In reply to Re: Linkadge?, posted by torachan on June 5, 2008, at 23:33:22
Good to hear,
take care
Linkadge
Posted by johnj on June 6, 2008, at 12:19:47
In reply to Re: Linkadge?, posted by torachan on June 5, 2008, at 23:33:22
Yes, dropping the REM and adding nort might make it hard to tell what is causing what. REM cessation does have some sleep issue problems. I would stay on the nort for longer as you will probably get better results as time goes by.
Posted by johnj on June 16, 2008, at 14:18:18
In reply to Linkadge?, posted by torachan on June 3, 2008, at 20:31:11
How is the nort trial going?
This is the end of the thread.
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