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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 30. This is the beginning of the thread.
Posted by TriedEveryMedication on June 21, 2018, at 23:47:33
So currently, I'm on 20mg of prozac and 20mg of desipramine. It seems pretty decent. SSRIs alone make me feel dopey out of it. Desipramine alone makes me a raging *ssh*l*. Together I find myself somewhat cheerful and having energy.
I'm having EKGs every couple weeks to check for QTc prolongation and I'm having blood tests done.
(According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.)
supposedly, prozac is a potent blocker of p450 2d6, which supposedly is how desipramine is metabolized. I say "supposedly" because according to the literature, I should have an 800% AUC increase of desipramine in my blood stream.
Yet my blood tests are showing pretty low desipramine levels. Lower than if I were taking the 100mg therapeutic dose alone.
So what gives? Has anyone combined an SSRI and a TCA before?
how about an SSRI and moclobemide?
Posted by SLS on June 22, 2018, at 12:32:59
In reply to Let's talk about combing SSRIs and TCAs, posted by TriedEveryMedication on June 21, 2018, at 23:47:33
> So currently, I'm on 20mg of prozac and 20mg of desipramine. It seems pretty decent. SSRIs alone make me feel dopey out of it. Desipramine alone makes me a raging *ssh*l*. Together I find myself somewhat cheerful and having energy.
Does nortriptyline affect you the same way? I find that desipramine makes me somewhat edgy. Nortriptyline is more calming for me.
> (According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.)I never heard of nortriptyline or desipramine producing serotonin syndrome when combined with a SSRI. Can you provide a link to the webpage?
> supposedly, prozac is a potent blocker of p450 2d6, which supposedly is how desipramine is metabolized. I say "supposedly" because according to the literature, I should have an 800% AUC increase of desipramine in my blood stream.
>
> Yet my blood tests are showing pretty low desipramine levels. Lower than if I were taking the 100mg therapeutic dose alone.
>
> So what gives? Has anyone combined an SSRI and a TCA before?While taking Paxil (paroxetine), another 2D6 inhibitor, I had to cut my dosage of desipramine in half. I took at least 100 mg/day, though. I don't know what my DMI blood levels were, but I did not experience more robust side effects than I did when I took 200 mg/day of desipramine alone. Perhaps you can continue to increase gradually using blood tests as a guide.
What is your rationale for combining Prozac and desipramine?
> how about an SSRI and moclobemide?
I would discourage this. I would expect serotonin syndrome to develop using these two drugs in combination. I don't see how reversibility would prevent this.
- Scott
Posted by rjlockhart37 on June 22, 2018, at 13:14:32
In reply to Let's talk about combing SSRIs and TCAs, posted by TriedEveryMedication on June 21, 2018, at 23:47:33
desipramine yeah is safe because it only affects norepinephrine, prozac works on serotonin, im glad its working for you
moclobemide is not safe with fluoxetine, not advise it at all, it's a MAOI reversible, but combined with fluoxetine that would not a good case, serotonin syndrome and others associated with it
Posted by TriedEveryMedication on June 22, 2018, at 14:41:02
In reply to Re: Let's talk about combing SSRIs and TCAs, posted by SLS on June 22, 2018, at 12:32:59
Hi Scott,
> Does nortriptyline affect you the same way? I find that desipramine makes me somewhat edgy. Nortriptyline is more calming for me.nortrip never did much of anything for me. Perhaps I didn't have a high enough dose or
> > (According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.)
>
> I never heard of nortriptyline or desipramine producing serotonin syndrome when combined with a SSRI. Can you provide a link to the webpage?If you have an account at online.epocrates.com, log in and go to the interaction checker. Or here's screen shot from mine:
https://i.imgur.com/HzMqYAo.png
>
> What is your rationale for combining Prozac and desipramine?desipramine for adhd and motivation, fluoxetine for depression. Desipramine is literally a miracle drug for me when it comes to doing work or solving problems. In college I went from a D student with no direction to a straight A math major on desipramine. desip makes me irritable and angry, prozac makes me lethargic and fatigued. Rationale is trying to nullify the side effects while keeping the beneficial action of the two. I know usually this doesn't always work out. Anyway, seems like SSRIs are good for my anxiety and depression, norepi increasers are usually good for my adhd.
I would like to find some strong norepinephrine RI that I could combine without my doctor bugging me to get weekly ekgs (I can see why he is cautious because he did almost kill me one time - legit stevens-johnson syndrome - long story).
Maybe MPH/vyvanse/daytrana would be an option to combine? (I've tried adderall + ssri in the past and ended up more lethargic)
> I would discourage this. I would expect serotonin syndrome to develop using these two drugs in combination. I don't see how reversibility would prevent this."This open clinical trial suggests that combined SSRI-moclobemide treatment appears to be safe and well tolerated."
https://www.ncbi.nlm.nih.gov/pubmed/8294388discussion of risk/benefit of moclo and ssri:
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3458.2004.tb00006.x
Thanks again for your insight
Posted by SLS on June 23, 2018, at 0:15:03
In reply to Re: Let's talk about combing SSRIs and TCAs » SLS, posted by TriedEveryMedication on June 22, 2018, at 14:41:02
Many years ago, I researched moclobemide. I read the stuff written by Joffe and Bakish. I ended up taking it, even though I was not impressed with its efficacy as reported by several researchers and the US FDA. I remained in compliance with tyramine food restrictions and avoided mixing it with serotonin reuptake inhibitors. I don't recommend consuming more than 50 mg of tyramine at any one meal while taking moclobemide.
Moclobemide monotherapy is not terribly impressive as an antidepressant. Many people experience a very strong therapeutic effect during the first week at low dosages. Very few side effects are reported. The problem is that depression returns quickly and requires dosage escalations to maintain an antidepressant response. Some doctors will go up to 1200 mg/day without seeing a persistant improvement.The US FDA rejected moclobemide. The US clinical trials failed to demonstrate efficacy. If you are going to add a SSRI to moclobemide, you might consider having cyproheptadine (Periactin) around to mitigate a serotonin syndrome event.
https://psychotropical.info/moclobemide-s-sris/
I am currently mixing nortriptyline with Trintellix (vortioxetine). If that doesn't work, I will combine nortriptyine with Effexor (venlafaxine). I received a partial response from this combination, but at dosages that were too low. I expect that I will need a minimum of 300 mg/day of Effexor with 100 mg/day of nortriptyline. I am also taking lithium, prazosin, and Lamictal now. I wasn't taking these drugs during my previous Effexor/nortriptyline trial. I would consider taking Abilify or Latuda if necessary.
I am open to all suggestions. I could use a few more.
- Scott
Posted by TriedEveryMedication on June 23, 2018, at 0:33:55
In reply to Re: Let's talk about combing SSRIs and TCAs, posted by SLS on June 23, 2018, at 0:15:03
> Moclobemide monotherapy is not terribly impressive as an antidepressant. Many people experience a very strong therapeutic effect during the first week at low dosages. Very few side effects are reported.funny you mention this. I've experienced just that on moclo... I wonder if there's a way to reset that therapeutic action, the way some augmenters can reset ssri poop out.
> I am currently mixing nortriptyline with Trintellix (vortioxetine). If that doesn't work, I will combine nortriptyine with Effexor (venlafaxine). I received a partial response from this combination, but at dosages that were too low. I expect that I will need a minimum of 300 mg/day of Effexor with 100 mg/day of nortriptyline. I am also taking lithium, prazosin, and Lamictal now. I wasn't taking these drugs during my previous Effexor/nortriptyline trial. I would consider taking Abilify or Latuda if necessary.
>
> I am open to all suggestions. I could use a few more.
>
I've tried these: vortioxetine + desipramine. paroxetine + desipramine. effexor + desipramine. prozac + desipramine. I think out of that bunch, prozac + desipramine works the best. I definitely feel better, though I feel like I could feel even better and I've hit a plateau. Only real problem with this combo as I mentioned before is potential QTc prolongation. effexor + desipramine seemed to work, but my mood would crash towards the end of the day.
Posted by SLS on June 23, 2018, at 1:16:41
In reply to Re: Let's talk about combing SSRIs and TCAs » SLS, posted by TriedEveryMedication on June 23, 2018, at 0:33:55
> I've tried these: vortioxetine + desipramine. paroxetine + desipramine. effexor + desipramine. prozac + desipramine. I think out of that bunch, prozac + desipramine works the best. I definitely feel better, though I feel like I could feel even better and I've hit a plateau. Only real problem with this combo as I mentioned before is potential QTc prolongation. effexor + desipramine seemed to work, but my mood would crash towards the end of the day.Effexor + desipramine:
What dosages of each?
How did you divide your dosages.I experience a deterioration in mood at the end of the dosing period when I take Effexor XR only once a day. I take both drugs in divided doses. My mood is more consistent when I do this.
How did you react to the combination of vortioxetine + desipramine? I started vortioxetine 5 mg/day today in combination with drugs that will hopefully work synergistically to effect a robust improvement in my bipolar depression.
Currently:
Trintellix (vortioxetine) 5 mg/day
nortriptyline 100 mg/day
Lamictal 300 mg/day
lithium 300 mg/day
prazosin 30 mg/dayI recently discontined Abilify for increase body weight and high triglycerides.
I discontined Panate because the partial improvement I experienced early in treatment slowly disappeared and represented a dead end. At higher dosages, Parnate actually made me feel lazy (reduced interest and little motivation), and got nothing done.
- Scott
Posted by sigismund on June 23, 2018, at 1:26:21
In reply to Re: Let's talk about combing SSRIs and TCAs, posted by SLS on June 23, 2018, at 1:16:41
I recall Maxime saying, 'I have to accept that the Parnate is no longer helping'.
Posted by ed_uk2010 on June 23, 2018, at 3:57:12
In reply to Let's talk about combing SSRIs and TCAs, posted by TriedEveryMedication on June 21, 2018, at 23:47:33
>According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.
Electronic interaction checkers (and some textbooks) often treat all TCAs as if they were the same. You therefore get shown side effects which are not relevant to all medications in the group eg. serotonin syndrome when adding the non-serotonergic desipramine.
Posted by ed_uk2010 on June 23, 2018, at 5:15:38
In reply to Let's talk about combing SSRIs and TCAs, posted by TriedEveryMedication on June 21, 2018, at 23:47:33
>How about an SSRI and moclobemide?
This combination has been tried. Unlike SSRI + phenelzine or tranylcypromine, it does not routinely cause life threatening serotonin toxicity.
What this combination does cause, however, is a very high incidence of adverse effects, mostly serotonergic, and agitation.
Posted by SLS on June 23, 2018, at 8:19:05
In reply to Re: Let's talk about combing SSRIs and TCAs » SLS, posted by sigismund on June 23, 2018, at 1:26:21
> I recall Maxime saying, 'I have to accept that the Parnate is no longer helping'.
Your point is well-taken, Sigi. Right now, my depression has stabilized such that it is no worse now than it was on Parnate 80 mg/day. Reducing anxiety with Ativan has helped a great deal at turning off the catastrophic and suicidal thinking. I definitely experienced an increase in the severity of depression immediately after discontinuing Parnate, but I recovered. Perhaps it was a rebound withdrawal effect. In retrospect, I would have taken 3 weeks to taper and use Ativan for anxiety.
I began taking Trintellix (vortioxetine) yesterday.
- Scott
Posted by ed_uk2010 on June 23, 2018, at 10:34:49
In reply to Re: Let's talk about combing SSRIs and TCAs » sigismund, posted by SLS on June 23, 2018, at 8:19:05
Hi Scott,
>I began taking Trintellix (vortioxetine) yesterday.
Excellent. Any initial side effects? How do you plan to titrate up on it?
Posted by SLS on June 23, 2018, at 13:50:53
In reply to Re: Let's talk about combing SSRIs and TCAs » SLS, posted by ed_uk2010 on June 23, 2018, at 10:34:49
> Hi Scott,
>
> >I began taking Trintellix (vortioxetine) yesterday.
>
> Excellent. Any initial side effects? How do you plan to titrate up on it?
>
>I think I feel a bit numb and slowed-down. It is hard to tell. It is nothing that I am concerned about at this juncture.
I think Ill stay at 5 mg/day for a week and then go up to 10 mg/day. Slow. I guess the target is 20 mg/day. Do you have any recommendations?
- Scott
Posted by Lamdage22 on June 24, 2018, at 7:19:58
In reply to Re: Let's talk about combing SSRIs and TCAs » sigismund, posted by SLS on June 23, 2018, at 8:19:05
Good luck, Scott. Its good to see you up and running again. I didnt realize that Parnate was doing so little to help you.
Posted by Lamdage22 on June 24, 2018, at 7:20:34
In reply to Re: Let's talk about combing SSRIs and TCAs, posted by Lamdage22 on June 24, 2018, at 7:19:58
TCA and SSRI sounds like the ultimate sex killer to me
Posted by linkadge on June 24, 2018, at 13:12:15
In reply to Let's talk about combing SSRIs and TCAs, posted by TriedEveryMedication on June 21, 2018, at 23:47:33
I combined amitriptyline and escitalopram before with good success.
Yes, go for the regular checkups, but drugs like notriptyline or desipramine are somewhat common adjuncts.
Linkadge
Posted by TriedEveryMedication on June 24, 2018, at 14:36:22
In reply to Re: Let's talk about combing SSRIs and TCAs, posted by linkadge on June 24, 2018, at 13:12:15
> I combined amitriptyline and escitalopram before with good success.
>
> Yes, go for the regular checkups, but drugs like notriptyline or desipramine are somewhat common adjuncts.
>
> Linkadge
>Thanks. I notice on epocrates it is kinda inconsistent which SSRIs get QTc warnings.
amitriptyline + lexapro = no QTc warning.
amitriptyline + fluoxetine = QTc warning
desipramine + lexapro = QTc warning.
desipramine + fluoxetine = QTc warning.
My doctor is being strict about me getting testing after my Stevens-Johnson incident, so it would be nice to come up with a combo that doesn't have the cardiac warnings. I'll have a look at lexapro + amitriptyline.Thanks.
Posted by TriedEveryMedication on June 24, 2018, at 14:39:30
In reply to Re: Let's talk about combing SSRIs and TCAs » TriedEveryMedication, posted by ed_uk2010 on June 23, 2018, at 3:57:12
> >According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.
>
> Electronic interaction checkers (and some textbooks) often treat all TCAs as if they were the same. You therefore get shown side effects which are not relevant to all medications in the group eg. serotonin syndrome when adding the non-serotonergic desipramine.Thanks, Ed.
so how to know for sure? my doctor relies heavily on epocrates... I guess I could trawl through studies, etc. but some of those papers seem very low quality.
Posted by linkadge on June 24, 2018, at 15:43:14
In reply to Re: Let's talk about combing SSRIs and TCAs » linkadge, posted by TriedEveryMedication on June 24, 2018, at 14:36:22
Lexapro itself can cause QTc issues (especially in doses above 10mg). I was only taking 5-10mg of Lexapro with 25mg of amitriptyline.
SSRI + TCA can be very effective for some people.
Linkadge
Posted by linkadge on June 24, 2018, at 15:46:42
In reply to Re: Let's talk about combing SSRIs and TCAs » ed_uk2010, posted by TriedEveryMedication on June 24, 2018, at 14:39:30
I would think any risk of serotonin syndrome would present itself quickly (if it does), upon introduction or dose escalation.
Desipramine does have a metabolite which is more serotonergic. That being said, the combination of 2 reuptake inhibitors is usually safe. Like you say, desipramine mostly affects the norepineprine transporter.
Linkadge
Posted by rjlockhart37 on June 24, 2018, at 22:46:09
In reply to Re: Let's talk about combing SSRIs and TCAs » SLS, posted by sigismund on June 23, 2018, at 1:26:21
she did say that, i remember reading her posts about 10-12 years ago about her struggles with severe depression.....it sad she could not make it through to today, i always will remember her
Posted by ed_uk2010 on June 25, 2018, at 13:49:37
In reply to Re: Let's talk about combing SSRIs and TCAs » ed_uk2010, posted by TriedEveryMedication on June 24, 2018, at 14:39:30
> > >According to epocrates, this should kill me, either with serotonin syndrome or prolonged heart QT intervals or whatever.
Serotonin syndrome can occur when adding a strongly serotonin-elavating drug to an SSRI eg. an MAOI.
Desipramine is mainly a noradrenergic antidepressant, although one of its metabolites might act as an SRI like Link pointed out. Even so, severe cases of serotonin syndrome (rather than just serotonergic side effects) only occur due to combining two or more drugs which elevate sertonin by different mechanisms. That is why MAOI plus SSRI is such an issue. Even combining two potent SSRIs would generally only cause side effects, rather than a major case of serotonin syndrome. There is only so much you can elevate serotonin just via reuptake inhibition...
>heart QT intervals
This depends on...
a) does the two antidepressants elevate each other's blood levels through a metabolic interaction. For example, fluoxetine can increase desipramine levels, and desipramine prolongs the QTc interval.
b) do the individual drugs both affect the QTc interval? Most tricyclic antidepressants can increase the QTc interval if the blood level is high. Among the SSRIs, citalopram (Celexa) and escitalopram (Lexapro) are the ones which directly increase the QTc interval.
The main issue with your fluoxetine + desipramine combination is that fluoxetine can alter the metabolism of desipramine. Cautious desipramine dose increases are therefore important to avoid the risk of unexpectedly high desipramine levels - which could lead to cardiac effects. It sounds like you've had a blood level to check this. You can also do an ECG (EKG).
I am not aware of any cases of serotonin syndrome with your combination, and it would not be expected.
Posted by TriedEveryMedication on June 25, 2018, at 14:46:19
In reply to Re: Let's talk about combing SSRIs and TCAs » TriedEveryMedication, posted by ed_uk2010 on June 25, 2018, at 13:49:37
> The main issue with your fluoxetine + desipramine combination is that fluoxetine can alter the metabolism of desipramine. Cautious desipramine dose increases are therefore important to avoid the risk of unexpectedly high desipramine levels - which could lead to cardiac effects. It sounds like you've had a blood level to check this. You can also do an ECG (EKG).
>my blood levels of desipramine have been very low. my doc is kinda baffled by this because fluoxetine is supposedly such a strong 2D6 inhibitor.
Posted by sigismund on June 26, 2018, at 1:54:43
In reply to Re: Let's talk about combing SSRIs and TCAs » sigismund, posted by SLS on June 23, 2018, at 8:19:05
>Ativan has helped a great deal at turning off the catastrophic and suicidal thinking.
And goodness me, where you draw the line? Because things are not, and perhaps never have been, OK. But in my lifetime never as bad as now.
>I began taking Trintellix (vortioxetine) yesterday.
I'm interested in the mind clearing effects (if any).
I actually had a better than usual day on ashwaganda and rhodiola. With other herbals to minimise benzo need.
Posted by ed_uk2010 on June 26, 2018, at 18:37:16
In reply to Re: Let's talk about combing SSRIs and TCAs » ed_uk2010, posted by TriedEveryMedication on June 25, 2018, at 14:46:19
Hi,
>my blood levels of desipramine have been very low.
In that case, if you need to increase desipramine to help relieve depression, be guided by:
1. Typical desipramine adverse effects such as elevated heart rate (can easily monitor this), very excessive sweating etc. If these appear, consider reducing desipramine again.
2. Your ECG/EKG. Consider checking after dose increases. Can measure the QTc interval and other cardiac indices.
Increasing the dose in small steps is advisable.
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