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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by tom2228 on March 17, 2014, at 19:24:38
Seeing new doc in a week and hoping to add a TCA to Marplan, or if she's not cool with that swap Marplan and try the TCA alone.
I was thinking of desipramine because of its least side effects in general, particularly the sedation -- and protriptyline in that sense.
My depression is severe and I'm nervous that if she won't go for the combo that the TCA alone won't be enough, so I was wondering about nortriptyline. What steers me away from its purported effectiveness is the sedation. But I do get pretty agitated when depressed, so it could be somewhat of a good thing if not for the anergia and fatigue I already have from the depression.
That being said, is the nortripyline sedation more calming, or is it more of the heavy, tiring, sleepy, mind-blocking type? Does the energizing aspect of the med overcome the functional-impairing aspect of sedation? Is nortrip, desipramine, or protrip good for anergic bipolar depression?
I find Abilify, which I'm on now, to be particularly bad in causing somnolence and am thinking of asking to decrease or switch to Invega as it's said to be the least sedating AAP. But I wouldn't call Abilify sedating.. just very tiring and making me want to sleep.
The only thing I have to compare as far as sedation is Saphris -- for anyone who's taken both, how does nortrip's compare to Saprhis in this respect. SLS I included you in the subject as I know you've trialed both meds.
^That and Benadryl. A work on google books ranked nortrip as having 4 times the affinity for H1 than diphenhydramine, but that doesn't translate to an overall comparison of how sedating the two meds are.
I know it's all trial and error but I don't want to waste anymore time.
Posted by phidippus on March 17, 2014, at 21:56:58
In reply to TCAs calming vs. sedating/ nortrip vs. Saphris SLS, posted by tom2228 on March 17, 2014, at 19:24:38
> I was thinking of desipramine because of its least side effects in general
It has the same anticholergenic side effects the rest of the TCAs have.
> My depression is severe and I'm nervous that if she won't go for the combo that the TCA alone won't be enoughDesipramine alone will not be anywhere near as effective as Marplan. Your best bet would be to add the drug.
, so I was wondering about nortriptyline.
It is a straight up NRI (norepenephrine reuptake inhibitor) and unlike Desipramine has little or no effect on serotonin.
> That being said, is the nortripyline sedation more calming, or is it more of the heavy, tiring, sleepy, mind-blocking type?It was more calming for me.
Is nortrip, desipramine, or protrip good for anergic bipolar depression?
yes
>am thinking of asking to decrease or switch to Invega as it's said to be the least sedating AAP.I had trouble sleeping on Invega. It is very energizing in some ways.
>how does nortrip's compare to Saprhis in this respect.
I would say Saphris is a lot more sedating than Nortryptaline
My recommendation is to request to add Nortryptaline to your Marplan and switch to Invega, but be aware you may lose some antidepressant benefits when you go off the Abilify. Maybe Latuda would be a better switch.
Eric
Posted by tom2228 on March 17, 2014, at 22:17:15
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » tom2228, posted by phidippus on March 17, 2014, at 21:56:58
> > I was thinking of desipramine because of its least side effects in general
>
> It has the same anticholergenic side effects the rest of the TCAs have.
>
but the least anticholinergic among the TCAs? -- according to the table on the wiki article for tricyclic AD , despiramine has Kd of 232.6 nm at mAChR (average?) -- at least compared less to nortrip (94 nm) and much less than protrip (25 nm)?> > My depression is severe and I'm nervous that if she won't go for the combo that the TCA alone won't be enough
>
> Desipramine alone will not be anywhere near as effective as Marplan. Your best bet would be to add the drug.What would you recommend if she says no to the MAOI + TCA combo?
>
> , so I was wondering about nortriptyline.
>
> It is a straight up NRI (norepenephrine reuptake inhibitor) and unlike Desipramine has little or no effect on serotonin.Are you sure or am I reading this wrong?
according to the table, despiramine has (Kd) 179nm for SERT and 2.27 for NET, while for nortrip the numbers are 16.5 for SERT and 1.65 for NET, and for protrip 19.6 nm (SERT) and 1.41 nm (NET)
>
> > That being said, is the nortripyline sedation more calming, or is it more of the heavy, tiring, sleepy, mind-blocking type?
>
> It was more calming for me.
>
> Is nortrip, desipramine, or protrip good for anergic bipolar depression?
>
> yes
>
> >am thinking of asking to decrease or switch to Invega as it's said to be the least sedating AAP.
>
> I had trouble sleeping on Invega. It is very energizing in some ways.Was Invega at all calming for you? How about for agitation?
>
> >how does nortrip's compare to Saprhis in this respect.
>
> I would say Saphris is a lot more sedating than Nortryptaline
>
> My recommendation is to request to add Nortryptaline to your Marplan and switch to Invega, but be aware you may lose some antidepressant benefits when you go off the Abilify. Maybe Latuda would be a better switch.
>Tried Latuda. It's funny, most meds I try have benefits I like and aspects that make my issues worse. Like Abilify -- brighter on my mood, helps with the obsessive nature of my thoughts/ tendency to ruminate, and can be calming -- but is activating in an annoying way, yet makes me very sleepy, and sucks up my interest in life
> Eric
Thanks for your reply Eric.
Posted by SLS on March 18, 2014, at 1:34:36
In reply to TCAs calming vs. sedating/ nortrip vs. Saphris SLS, posted by tom2228 on March 17, 2014, at 19:24:38
Hi.
I prefer nortriptyline to desipramine. I find that nortriptyline is less apt to cause "anticholinergic" side effects. Desipramine increases sympathetic tone more potently than nortriptyline due to its being a more potent NRI. This causes desipramine to produce side effects that appear much like anticholinergic effects. These include dry mouth, constipation, blurred vision, tachycardia, delayed micturition, urinary retention, nasal stuffiness, etc. For me, NOR is milder than DMI. However, NOR made me very sleepy for the first two days. I began treatment at 25 mg/day. I probably should have started at 10 mg/day. Thereafter, I found NOR to be free of somnolence and sedation. It is actually a pretty clean drug. Some people will respond to NOR and not to DMI. The reverse is also true.
DMI and NOR are good choices to add to Marplan. They are safe, and even have a protective effect against a tyramine pressor reaction. Hypotension with dizziness can be a problem, as the TCA will block NE alpha-1a receptors peripherally. This usually is limited to orthostatic challenge, though. Although trimipramine should be safe to add to MAOI, I have never heard of it being done. Clomipramine is prohibited, and I would avoid imipramine as well. Both of these drugs are too serotonergic and can produce serotonin syndrome. I would also add that Wellbutrin is safe to take with MAOI.
- Scott
Posted by tom2228 on March 18, 2014, at 10:33:43
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » tom2228, posted by SLS on March 18, 2014, at 1:34:36
> Hi.
>
> I prefer nortriptyline to desipramine. I find that nortriptyline is less apt to cause "anticholinergic" side effects. Desipramine increases sympathetic tone more potently than nortriptyline due to its being a more potent NRI. This causes desipramine to produce side effects that appear much like anticholinergic effects. These include dry mouth, constipation, blurred vision, tachycardia, delayed micturition, urinary retention, nasal stuffiness, etc. For me, NOR is milder than DMI. However, NOR made me very sleepy for the first two days. I began treatment at 25 mg/day. I probably should have started at 10 mg/day. Thereafter, I found NOR to be free of somnolence and sedation. It is actually a pretty clean drug. Some people will respond to NOR and not to DMI. The reverse is also true.
>
> DMI and NOR are good choices to add to Marplan. They are safe, and even have a protective effect against a tyramine pressor reaction. Hypotension with dizziness can be a problem, as the TCA will block NE alpha-1a receptors peripherally. This usually is limited to orthostatic challenge, though. Although trimipramine should be safe to add to MAOI, I have never heard of it being done. Clomipramine is prohibited, and I would avoid imipramine as well. Both of these drugs are too serotonergic and can produce serotonin syndrome. I would also add that Wellbutrin is safe to take with MAOI.
>
>
> - ScottThanks for your reply.
Can alpha-1 antagonism also be a source of sedation? and If so, the NET action would likely override that, is that right?
Here's a link referring to a trial of trimipramine + MAOIs.
http://www.ncbi.nlm.nih.gov/pubmed/6355073
Supposedly that combo is one of the only if not the only controlled trial of the TCA + MAOI combo, as of 1983. Trimipramine monotherapy was found to be superior to the combination and MAOI monotherapy.If I have to ditch the MAOI -- is imipramine less sedating that nortrip, as per the binding table? (24 nm vs. 8.2 for H1, respectively)?
I was thinking, if she doesn't go for the combo, I do have 3 refills of Marplan left (as long as it's not imipramine or clomi).. and I'd tell her in a few months or so. Although that's probably enough for a new doctor to drop you. Ugh it's enough trying to hide the meth history until she trusts me w/ Desoxyn.
Posted by tom2228 on March 18, 2014, at 10:55:15
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » SLS, posted by tom2228 on March 18, 2014, at 10:33:43
Aside from TCAs' propensity to cause mania/ accelerate cycling, could the blockade of sodium channels offer some mood stabilization? Or is this property of TCAs different from the sodium channel blockade of anticonvulsants?
Posted by phidippus on March 18, 2014, at 18:01:42
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS, posted by tom2228 on March 17, 2014, at 22:17:15
> but the least anticholinergic among the TCAs?
You're still going to get anticholergenic effects.
> What would you recommend if she says no to the MAOI + TCA combo?
If she says no, try a TCA alone. I would recommend Clomipramine-especially since you suffer from obsessive ruminations.
>for nortrip the numbers are 16.5 for SERT and 1.65 for NET
Keep in mind nortryptaline:
- Boosts neurotransmitter norepinephrine/noradrenaline
- Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission
-Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, nortriptyline can increase dopamine neurotransmission in this part of the brain
-A more potent inhibitor of norepinephrine reuptake pump than serotonin reuptake pump (serotonin transporter)
-At high doses may also boost neurotransmitter serotonin and presumably increase serotonergic neurotransmission> Was Invega at all calming for you? How about for agitation?
Perfect for agitation and very calming.
Eric
Posted by SLS on March 18, 2014, at 19:42:19
In reply to TCAs, sodium channel blocking, posted by tom2228 on March 18, 2014, at 10:55:15
You have a large amount of knowledge, and you use it well to come up with theories. I really don't know if there is anything I can contribute other than to say that we still don't know everything that these drugs do and how they might work to improve a condition that we know too little about.
I am not telling you to throw your hands up in the air and enter a blind trial-and-error approach. I am saying that I would not overlook or exclude a drug from consideration without some compelling clinical findings. For example, I would not eliminate desipramine from your list of things to try if you failed to respond to nortriptyline. I really don't care to propose a pharmacological explanation for this right now. I just know that the doctors that I have seen over the years have described this phenomenon as being their clinical experience with these two drugs when treating real people.
TCAs are L-type calcium channel blockers. Nimodipine and verapamil have been studied as mood stabilizers and antidepressant augmenters. Reports of success using these drugs are sparse. The NIMH really, really wanted nimodipine to work. It didn't. Perhaps it helps for depression caused by cerebral vascular insufficiency. I don't know to what extent CCB contributes to the therapeutic activity of TCA. I would doubt that it does at all, but I can't be certain.
- Scott
Posted by tom2228 on March 18, 2014, at 21:29:46
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » tom2228, posted by phidippus on March 18, 2014, at 18:01:42
> > but the least anticholinergic among the TCAs?
>
> You're still going to get anticholergenic effects.
>
If you or anyone has taken Zyprexa, how does the anticholinergic effects of TCAs compare? Olanzapine is pretty potent at the mAChRs and H1. I'm not really anxious about the anticholinergic effects, more so the sedation.The sedation could be good though. I decided to take a Zyprexa 2.5mg tonight b/c I'm counting the days to the appointment on Monday.. it's just calming.. every time I take it it reminds me of how much better life can be without anxiety and maybe without all this dopamine I'm taking in with Marplan and Mirapex.
> > What would you recommend if she says no to the MAOI + TCA combo?
>
> If she says no, try a TCA alone. I would recommend Clomipramine-especially since you suffer from obsessive ruminations.
>
> >for nortrip the numbers are 16.5 for SERT and 1.65 for NET
>
> Keep in mind nortryptaline:
> - Boosts neurotransmitter norepinephrine/noradrenaline
> - Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission
> -Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, nortriptyline can increase dopamine neurotransmission in this part of the brain
> -A more potent inhibitor of norepinephrine reuptake pump than serotonin reuptake pump (serotonin transporter)
> -At high doses may also boost neurotransmitter serotonin and presumably increase serotonergic neurotransmission
>
> > Was Invega at all calming for you? How about for agitation?
>
> Perfect for agitation and very calming.Great. I need that calm, which I realize after having taken the Zyprexa tonight. hopefully Invega and/ or nortrip can do that for me without massive sedation or massive weight gain.
Thinking of trying nortrip at this point with or without the Marplan. Despiramine seems to have comparatively smaller AD effects among TCAs from what I'm reading.. but these are just studies; the med with the smallest AD effects could wind up "curing" me just as the MAOIs may not be the best for me.
The Zyprexa is telling me as I type, "I can't wait til this gets sorted out, you stop thinking about these things so much, and just chill."
>
> Eric
Posted by phidippus on March 19, 2014, at 11:14:00
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » phidippus, posted by tom2228 on March 18, 2014, at 21:29:46
What did you think of the idea of Clomipramine?
Eric
Posted by tom2228 on March 19, 2014, at 12:05:21
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » tom2228, posted by phidippus on March 19, 2014, at 11:14:00
> What did you think of the idea of Clomipramine?
>
> EricI am concerned about how potently serotonergic it is and that it might feel like an SSRI and have the related side effects like apathy, sexual dysfunction
Regarding the "obsessive ruminations"/ GAD there is a part of this aspect of me that is ego-syntonic; I am a very cognitive person and hate the mind-numbing apathy "blah" feeling that I associate with SSRIs and that isn't there with the MAOI.
I realize that I'm generalizing and that the feeling of these drugs often doesn't match up with what we expect based on our perception and interpretation of binding affinities, etc.
Otherwise it does seem relatively kind regarding sedation compared to other TCAs.. well, with respect to H1; it's the least kind at a1. On that note, I'm not quite sure about trying nortrip first anymore.. Having taken Zyprexa last night I am reminded about how much I hate sedation. According to Stahl sedation and cognitive functions are mediated by the same histaminergic, alpha-adrenergic, and anticholinergic (when combined with anitihistaminergic effects). I'd rather have the calming aspects mediated through something other than H1 which brings us back to clomipramine. This is driving me crazy! As if.
Also it would take a 2-week washout to try clomi and I seriously cannot take that. The safety of starting desip/ protrip/ nortrip with less of a washout will be part of my argument of just adding the TCA to the MAOi.
That and if the new pdoc is not cool with the combo, I would ask if the MAOI could be added back slowly if a TCA alone failed -- this would not be possible with clomi.Have you tried clomipramine? If so, how was it with the "SSRI" side effects I talked about above?
Posted by tom2228 on March 19, 2014, at 12:12:34
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » phidippus, posted by tom2228 on March 19, 2014, at 12:05:21
I should note the obsessive thoughts I have are just anxiety/ GAD , ruminations, and neuroticism. I don't have OCD.
But I do need to do something about this that isn't a benzo. I am leery of Lyrica for its similarity and don't want to add too many more meds (at 7 now).
Posted by phidippus on March 19, 2014, at 12:35:33
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » phidippus, posted by tom2228 on March 19, 2014, at 12:05:21
>The safety of starting desip/ protrip/ nortrip with less of a washout will be part of my argument of just adding the TCA to the MAOi.
Then you could add Clomipramine to the Nortryptaline which I hear is an excellent combo.
>Have you tried clomipramine? If so, how was it with the "SSRI" side effects I talked about above?
I was on Clomipramine for about a year and experienced only one side effect - anorgasmia. Drove me nuts.
Eric
Posted by tom2228 on March 19, 2014, at 12:45:33
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS, posted by phidippus on March 19, 2014, at 12:35:33
Posted by SLS on March 21, 2014, at 8:39:21
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS, posted by phidippus on March 19, 2014, at 12:35:33
> Then you could add Clomipramine to the Nortryptaline which I hear is an excellent combo.
Interesting. Is it effective for any particular symptom profile?
- Scott
Posted by phidippus on March 21, 2014, at 14:34:56
In reply to Re: TCAs calming vs. sedating/ nortrip vs. Saphris SLS » phidippus, posted by SLS on March 21, 2014, at 8:39:21
I was on the combo for about 8 months a couple years back. The clomipramine targeted my OCD symptoms whilee the Nortryptaline targeted depressive symptoms.
Eric
This is the end of the thread.
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