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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by TriedEveryMedication on July 1, 2016, at 12:02:37
desipramine really really works for my ADHD-I. Night and day difference, it feels like my IQ goes up 25 pts when I'm on it.
I've developed a reaction to it where it tends to wake me around 2:30am and I feel very wired like I'm on stims until about 4 or 5am.
It wasn't always like this - it used to knock me out (histamine action, I guess) when I took it at night and then I'd wake up fresh and early.
Now it doesn't seem to matter when I take it - the insomnia comes on at the same time every night.
I was kinda fearing it so much that last night I stayed up until 4am just to avoid it. I still woke up at 9, but I guess that's better than getting woken up in the middle of the night.
Any ideas on how I could manage this? (ambien doesn't touch the insomnia and kinda ruins the ADHD-treating effects of desipramine, as do other drugs like trazadone and remeron)
Thank you
Posted by jonhed on July 1, 2016, at 12:50:17
In reply to managing desipramine insomnia - again., posted by TriedEveryMedication on July 1, 2016, at 12:02:37
Nitrazepam!
I promise that will help you if clonazepam 2-4mg doesn't work.Both lasts all night.
Myself sleep better in clonazepam but anyway i sleep through the nitght on nitrazepam cause of it's long half life! :-)
Posted by linkadge on July 1, 2016, at 13:15:25
In reply to Re: managing desipramine insomnia - again., posted by jonhed on July 1, 2016, at 12:50:17
Hmm. Possibly clonidine?
Clonidine alone is useful for ADHD (as well as some use in anxiety and insomnia). It actually lowers norepinephrine (temporarily) by activating norepinephrine feedback autoreceptors.
Because it has a shorter half life, it might be useful in temporarily lowering norepinephrine release during sleep time.
Cyproheptadine might also be worth a try.
Linkadge
Posted by TriedEveryMedication on July 1, 2016, at 14:29:17
In reply to Re: managing desipramine insomnia - again., posted by linkadge on July 1, 2016, at 13:15:25
> Hmm. Possibly clonidine?
>
> Clonidine alone is useful for ADHD (as well as some use in anxiety and insomnia). It actually lowers norepinephrine (temporarily) by activating norepinephrine feedback autoreceptors.
>
> Because it has a shorter half life, it might be useful in temporarily lowering norepinephrine release during sleep time.
>
> Cyproheptadine might also be worth a try.
>
> Linkadge
>
>I really like your Clonidine idea. Does guanfacine have the same effect? Because I think I actually might have some guanfacine somewhere.
Posted by jonhed on July 1, 2016, at 14:33:49
In reply to Re: managing desipramine insomnia - again. » linkadge, posted by TriedEveryMedication on July 1, 2016, at 14:29:17
Oh yeah, i use clonidine sometimes when my adrenaline is too high to sleep, it works for 3 days, then you have to have a break, and so on!
Try guanfacine, it should work :-)
Posted by linkadge on July 2, 2016, at 8:32:56
In reply to Re: managing desipramine insomnia - again. » linkadge, posted by TriedEveryMedication on July 1, 2016, at 14:29:17
Hi,
Yes, guanfacine does have the same effect (alpha-2 agonist) which temporarily supresses norepinephrine release and facilitates cholingeric neurotransmission.
You *may* wish to approach the combination of guanfacine + desipramine with doctor supervision. While there is no direct interaction, there could be BP fluctuations depending on doses & timing.
I know guanfacine has been used successfully in combination with Ritalin and / or straterra. There are case reports of cardiac side effects.
Linkadge
Posted by Horse on July 22, 2016, at 22:34:32
In reply to managing desipramine insomnia - again., posted by TriedEveryMedication on July 1, 2016, at 12:02:37
I think clonidine and guafacine are good suggestions, and maybe while not providing the entire answer, can be a positive addition to treatment. I've used guanfacine at night for the same purpose, and I needed to slowly increase the dose, and then back down when the dose caused side effects (feeling awful the next day). There's also an extended release version, and my doctor said the overall dose and with that benefit can be increased, although I haven't tried this.
I don't know if prazosin is similar and helps with sleep onset, or just decreases arousal during sleep. My science is pretty sketchy.
Posted by TriedEveryMedication on October 18, 2016, at 5:38:31
In reply to Re: managing desipramine insomnia - again., posted by linkadge on July 1, 2016, at 13:15:25
> Hmm. Possibly clonidine?
>
> Clonidine alone is useful for ADHD (as well as some use in anxiety and insomnia). It actually lowers norepinephrine (temporarily) by activating norepinephrine feedback autoreceptors.
>
> Because it has a shorter half life, it might be useful in temporarily lowering norepinephrine release during sleep time.
>
> Cyproheptadine might also be worth a try.
>
> Linkadge
>
>So I finally got around to trying this. Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
Sure enough it works magic on the desipramine-induced insomnia. Haven't taken it long enough to see if it will interfere with the benefits of the desipramine during the day - hopefully not.
Thanks for a great idea.
Posted by SLS on October 18, 2016, at 7:16:21
In reply to Re: managing desipramine insomnia - again. » linkadge, posted by TriedEveryMedication on October 18, 2016, at 5:38:31
> Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
I am going to assume that you already tried nortriptyline.
- Scott
Posted by cakethread on October 22, 2016, at 0:27:03
In reply to Re: managing desipramine insomnia - again. » TriedEveryMedication, posted by SLS on October 18, 2016, at 7:16:21
> > Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
>
> Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
>
> I am going to assume that you already tried nortriptyline.
>
>
> - ScottHey,
I'm curious how this works. Isn't the primary mechanism of action of desipramine as a norepinephrine re-uptake inhibitor? In that case, wouldn't blocking alpha receptor subtypes have a cancellative effect?
Posted by SLS on October 22, 2016, at 7:39:33
In reply to Re: managing desipramine insomnia - again., posted by cakethread on October 22, 2016, at 0:27:03
> > > Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
> >
> > Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
> >
> > I am going to assume that you already tried nortriptyline.
> >
> >
> > - Scott
>
> Hey,
>
> I'm curious how this works. Isn't the primary mechanism of action of desipramine as a norepinephrine re-uptake inhibitor? In that case, wouldn't blocking alpha receptor subtypes have a cancellative effect?That's a great question. I could only guess what's going on pharmacologically. So, instead of guessing at this point, I can offer you empirical observations of what I have experienced. While taking prazosin, I have taken nortriptyline and desipramine. Desipramine feels the same to me with or without prazosin. It's antidepressant effect was not affected negatively. The same is true for nortriptyline. If I discontinue either of these two drugs while taking prazosin, I relapse into depression.
As for guessing, it is important to recognize that:
1. Not all NE receptors are alpha receptors.
2. There are postsynaptic NE beta receptors in the brain.
3. It is the beta receptors that becomes downregulated by desipramine.
4. There are NE alpha heteroreceptors that function on neurons that use other transmitters to communicate. For examaple, there are might be NE alpha receptors located on the membrane of serotonin neurons.
Posted by SLS on October 22, 2016, at 8:17:34
In reply to Re: managing desipramine insomnia - again., posted by SLS on October 22, 2016, at 7:39:33
*** Sorry. I submitted my post accidentally before I had a chance to finish it.
__________________________________________
> > > > Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.> > >
> > > Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
> > >
> > > I am going to assume that you already tried nortriptyline.> > I'm curious how this works. Isn't the primary mechanism of action of desipramine as a norepinephrine re-uptake inhibitor? In that case, wouldn't blocking alpha receptor subtypes have a cancellative effect?
That's a great question. I could only guess what's going on pharmacologically. So, instead of guessing at this point, I can offer you empirical observations of what I have experienced. While taking prazosin 30 mg/day, I have taken nortriptyline and desipramine. Desipramine feels the same to me with or without prazosin. Its antidepressant effect was not affected negatively. The same is true for nortriptyline. If I discontinue either of these two drugs while taking prazosin, I relapse into depression.
You have given me a lot to think about. As for guessing, it is important to recognize that:1. Not all NE receptors are alpha receptors.
2. There are postsynaptic NE beta receptors in the brain.
3. It is the beta receptors that become downregulated by desipramine.
4. There are NE alpha heteroreceptors that function on neurons that use other transmitters to communicate. For examaple, there are NE alpha-1 receptors located on the membrane of serotonin neurons.
5. NE alpha heteroreceptors can act as inhibitors of serotonin neurons. Blocking them with prazosin might disinhibit (stimulate) serotonin or dopamine neurons.
6. Prazosin blocks only NE alpha-1 receptors (alpha-1a/b/d), and not beta receptors.
7. It is the NE alpha-2 receptor that acts as an autoreceptor on NE neurons, and not alpha-1 receptors.
I'm not sure prazosin will help with most cases of insomnia. It does, however, inhibit the experience of nightmares associated with PTSD without affecting the time spent dreaming. This effect occurs at very low doses of prazosin - as little as 1-3 mg taken at night.
Please post what you come up with regarding the pharmacology of prazosin. I am missing something. It is my hypothesis that it is the NE alpha-1d receptor that is involved in the anti-PTSD and anti-depressant properties of prazosin.
- Scott
Posted by TriedEveryMedication on October 22, 2016, at 15:37:37
In reply to Re: managing desipramine insomnia - again., posted by cakethread on October 22, 2016, at 0:27:03
> > > Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
> >
> > Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
> >
> > I am going to assume that you already tried nortriptyline.
> >
> >
> > - Scott
>
> Hey,
>
> I'm curious how this works. Isn't the primary mechanism of action of desipramine as a norepinephrine re-uptake inhibitor? In that case, wouldn't blocking alpha receptor subtypes have a cancellative effect?
>
>
Prazosin has a short halflife, like 3 hours. I take it before bed so it is only blocking NE receptors while I sleep.At least that's how I understand it.
I don't know anything about the selectivity of desipramine or prazosin.
Posted by TriedEveryMedication on October 22, 2016, at 15:40:09
In reply to Re: managing desipramine insomnia - again. - Oops, posted by SLS on October 22, 2016, at 8:17:34
So would clonidine be better for insomnia than prazosin?
Posted by SLS on October 22, 2016, at 16:19:05
In reply to Re: managing desipramine insomnia - again. - Oops » SLS, posted by TriedEveryMedication on October 22, 2016, at 15:40:09
> So would clonidine be better for insomnia than prazosin?
I don't think prazosin helps with insomnia, except, perhaps, for those people who are afraid to sleep for fear of having a nightmare due to PTSD.
Some people report using clonidine for insomnia. I don't know anyone who has, though. Unfortunately, clonidine tends to be depressogenic, even in people who have never been depressed before. Pharmacologically, it does the opposite of Remeron (mirtazapine) on NE alpha-2 receptors.
- Scott
Posted by TriedEveryMedication on October 22, 2016, at 17:39:22
In reply to Re: managing desipramine insomnia - again. - Oops, posted by SLS on October 22, 2016, at 16:19:05
> > So would clonidine be better for insomnia than prazosin?
>
> I don't think prazosin helps with insomnia, except, perhaps, for those people who are afraid to sleep for fear of having a nightmare due to PTSD.
>
> Some people report using clonidine for insomnia. I don't know anyone who has, though. Unfortunately, clonidine tends to be depressogenic, even in people who have never been depressed before. Pharmacologically, it does the opposite of Remeron (mirtazapine) on NE alpha-2 receptors.
>
>
> - ScottWell, anecdotally for me if I take desipramine alone at bedtime, I wake up at 2:30am consistently and can't go back to sleep until 5 or 6am. Even at low doses of desipramine (10mg)
If I take a 1mg prazosin with the desipramine, I sleep through the night.
Posted by SLS on October 23, 2016, at 2:47:22
In reply to Re: managing desipramine insomnia - again. - Oops » SLS, posted by TriedEveryMedication on October 22, 2016, at 17:39:22
> Well, anecdotally for me if I take desipramine alone at bedtime, I wake up at 2:30am consistently and can't go back to sleep until 5 or 6am. Even at low doses of desipramine (10mg)
>
> If I take a 1mg prazosin with the desipramine, I sleep through the night.That's a pretty neat trick. I wish that would work for me. Perhaps it is the low dosage that is important. I need to take a full 30 mg/day in order to feel less depressed, though.
- Scott
Posted by porkpiehat on November 2, 2016, at 8:58:30
In reply to Re: managing desipramine insomnia - again. - Oops » SLS, posted by TriedEveryMedication on October 22, 2016, at 17:39:22
Effexor gives me pretty bad insomnia, even at 37.5...And I take prazosin (1 mg) at night for night terrors and that doesn't seem to make a difference.
I'm assuming that it's the NE activity OR that it is constantly releasing into my system because it is XR. Nothing but nyquil seems to cut through it...with ativan and melatonin, but that seems to be waning also.
What was the origninal suggestion again and was anyone having luck with it?
Posted by TriedEveryMedication on November 2, 2016, at 9:06:06
In reply to Re: managing desipramine insomnia - again. - Oops, posted by porkpiehat on November 2, 2016, at 8:58:30
> Effexor gives me pretty bad insomnia, even at 37.5...And I take prazosin (1 mg) at night for night terrors and that doesn't seem to make a difference.
>
> I'm assuming that it's the NE activity OR that it is constantly releasing into my system because it is XR. Nothing but nyquil seems to cut through it...with ativan and melatonin, but that seems to be waning also.
>
> What was the origninal suggestion again and was anyone having luck with it?The original suggestion was clonidine. I didn't have any but used guanfacine instead, which worked for me, too.
Note that at 37.5mg, the NE effects of effexor should be pretty minimal. So maybe it is something else about the effexor that keeps you awake.
This is the end of the thread.
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