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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by zeugma on March 14, 2004, at 13:02:12
Nortriptyline is an effective AD for me. However, I am also taking 80 mg Strattera a day, and that should probably give me enough NE reuptake effect, so that 75 mg nortriptyline is unnecessary. The problem is that I seem to need the combination of 75 mg nortriptyline and 15 mg buspirone at night to fall asleep reliably (and not experience hypnagogic hallucinations). I think the anticholiergic effects of nortriptyline are not that bad, however, the combination of the TCA with Strattera definitely results in more constipation and dry mouth than either would alone. Here are my concerns:
1) Without sedating drugs at night that increase monoaminergic neurotransmission I have insomnia, aggravated by hypnagogic hallucinations which cause sudden (and painful) wakening; less than 75 mg nortriptyline doesn't seem sufficient to block these.
2) I want to simplify my med regime and minimize the side effects. Remeron combines properties of nortriptyline and buspirone (alpha-2 adrenergic antagonism, 5-HT2A antagonism, histamine blockade). So possibly I could exchange the nortriptyline/buspirone combination for a suitable dose of remeron.
I am not concerned about weight gain, in fact it is extremely difficult for me to gain weight and that would be a desired side effect. I am concerned about possible loss of concentration or motivation, but I am hopeful that remeron, if anything, tends to increase motivation.
How realistic does this plan sound?
Thanks in advance.
Posted by King Vultan on March 14, 2004, at 15:50:30
In reply to replacing nortriptyline with remeron?, posted by zeugma on March 14, 2004, at 13:02:12
> Nortriptyline is an effective AD for me. However, I am also taking 80 mg Strattera a day, and that should probably give me enough NE reuptake effect, so that 75 mg nortriptyline is unnecessary. The problem is that I seem to need the combination of 75 mg nortriptyline and 15 mg buspirone at night to fall asleep reliably (and not experience hypnagogic hallucinations). I think the anticholiergic effects of nortriptyline are not that bad, however, the combination of the TCA with Strattera definitely results in more constipation and dry mouth than either would alone. Here are my concerns:
>
> 1) Without sedating drugs at night that increase monoaminergic neurotransmission I have insomnia, aggravated by hypnagogic hallucinations which cause sudden (and painful) wakening; less than 75 mg nortriptyline doesn't seem sufficient to block these.
>
> 2) I want to simplify my med regime and minimize the side effects. Remeron combines properties of nortriptyline and buspirone (alpha-2 adrenergic antagonism, 5-HT2A antagonism, histamine blockade). So possibly I could exchange the nortriptyline/buspirone combination for a suitable dose of remeron.
>
> I am not concerned about weight gain, in fact it is extremely difficult for me to gain weight and that would be a desired side effect. I am concerned about possible loss of concentration or motivation, but I am hopeful that remeron, if anything, tends to increase motivation.
>
> How realistic does this plan sound?
>
> Thanks in advance.
Of the two, I've only tried nortriptyline and not Remeron, but my research seems to indicate that Remeron is much more sedating. I agree that taking both the Strattera and nortriptyline is somewhat redundant, as both are norepinephrine selective reuptake inhibitors. I think substituting the Remeron makes sense, and I think the concomitant administration of the Strattera will tend to minimize excessive weight gain. If the Remeron winds up being too sedating, you might also consider trazodone, which has somewhat similar properties. I am not familiar with hypnagogic hallucinations, but if this is in any way a psychotic effect, might it also not make sense to consider an atypical antipsychotic? These obviously also blockade 5-HT2A receptors and seem to be pretty sedating.Todd
Posted by zeugma on March 14, 2004, at 17:12:47
In reply to Re: replacing nortriptyline with remeron?, posted by King Vultan on March 14, 2004, at 15:50:30
Hypnagogic hallucinations are associated with narcolepsy and not with psychosis. They are effectively treated with TCA's, but buspirone also helps, so I think that they occur due to a deficit in monoaminergic, and reciprocal overactivity of cholinergic, neurotransmission ( while cholinergic enhancers induce them more than any other class of med).
If buspirone works, I don't see why remeron wouldn't. Of course I'm wary of changing ANY element of a med regime that is literally life-changing for me- I was virtually paralyzed by years of severe depression and ADD, anxiety, etc. The dry mouth and constipation are getting difficult to handle though, and I think the Remeron might work as a substitution for buspirone and nortriptyline.
Posted by Sad Panda on March 15, 2004, at 10:09:59
In reply to Re: replacing nortriptyline with remeron? » King Vultan, posted by zeugma on March 14, 2004, at 17:12:47
I take Remeron. It's the most potent H1 blocker available. It's nearly double the strength of Doxepin, 10x the strength of Amitriptyline & 50x stronger than Nortriptyline. 15mg is heaps for sleep, a lot of people get by on just 7.5mg. The amount required just for sleep probably means that it doesn't have much affect on any other receptors. If you are looking for H1 + 5-HT2A for sleep, you may be better off with low dose Trimipramine or Doxepin.
Cheers,
Panda.
Posted by zeugma on March 15, 2004, at 17:14:44
In reply to Re: replacing nortriptyline with remeron? » zeugma, posted by Sad Panda on March 15, 2004, at 10:09:59
> I take Remeron. It's the most potent H1 blocker available. It's nearly double the strength of Doxepin, 10x the strength of Amitriptyline & 50x stronger than Nortriptyline. 15mg is heaps for sleep, a lot of people get by on just 7.5mg. The amount required just for sleep probably means that it doesn't have much affect on any other receptors. If you are looking for H1 + 5-HT2A for sleep, you may be better off with low dose Trimipramine or Doxepin.
>
> Cheers,
> Panda.Panda,
yes, I was thinking along those lines when I saw how powerfully antihistaminic Remeron is, and how steep its side effect profile appears (not much of an improvement on the tertiary amine TCA's). Plus, remeron seems to have a tendency to elevate levels of cholesterol, and even though I am extremely underweight (so much so that i have been pulled off every stimulant I have ever tried within two weeks because of rapid and dangerous weight loss) my cholesterol levels have always been high.
Low dose trimipramine or doxepin are intriguing choices, especially given my favorable response to nortriptyline. trimipramine has weak D2 blocking effects also, mimicking one of buspirone's effects. It is the only TCA devoid of reuptake blocking effects, and might be a good way to go.
>
Posted by zeugma on March 15, 2004, at 19:44:54
In reply to Re: replacing nortriptyline with remeron? » zeugma, posted by Sad Panda on March 15, 2004, at 10:09:59
Trimipramine seemed like a great idea, but then I came across this study that compared its effects on sleep to that of impramine:
Depression. 1996;4(1):1-13. Related Articles, Links
Trimipramine and imipramine exert different effects on the sleep EEG and on nocturnal hormone secretion during treatment of major depression.Sonntag A, Rothe B, Guldner J, Yassouridis A, Holsboer F, Steiger A.
Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Germany.
In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.
Publication Types:
Clinical Trial
Randomized Controlled TrialPMID: 9160649 [PubMed - indexed for MEDLINE]
This suggests that trimipramine would not be a suitable treatment for narcolepsy-related problems, as the symptoms I have are related to sleep-onset REM periods (SOREMPs) and so I need powerful REM suppressants in order to get past the hypnagogic sleep-paralysis phenomena that inevitably disrupt my sleep within minutes of falling asleep. Imipramine is the TCA classically used, but nortriptyline works too, and the mechanism responsible is the amine reuptake blockade. Any of the TCA's should work, given high enough doses- I'll ask my pdoc at my next appointment what he thinks. But it looks like trimipramine is out.
There IS some significant research out now suggesting that trimipramine may be a good treatment for primary insomnia:
1: Pharmacopsychiatry. 2002 Sep;35(5):165-74. Related Articles, Links
Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Ruther E, Wiegand MH, Laakmann G, Baghai T, Fischer W, Hoffmann M, Hohagen F, Mayer G, Berger M.
Department of Psychiatry and Psychotherapy, University of Freiburg, Germany. dieter_riemann@psyallg.ukl.uni-freiburg.de
In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.
Publication Types:
Clinical Trial
Controlled Clinical TrialPMID: 12237787 [PubMed - indexed for MEDLINE]
Posted by Sad Panda on March 15, 2004, at 20:37:07
In reply to esoterica- sleep and trimipramine related, posted by zeugma on March 15, 2004, at 19:44:54
> Trimipramine seemed like a great idea, but then I came across this study that compared its effects on sleep to that of impramine:
>
> Depression. 1996;4(1):1-13. Related Articles, Links
>
>
> Trimipramine and imipramine exert different effects on the sleep EEG and on nocturnal hormone secretion during treatment of major depression.
>
> Sonntag A, Rothe B, Guldner J, Yassouridis A, Holsboer F, Steiger A.
>
> Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Germany.
>
> In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.
>
> Publication Types:
> Clinical Trial
> Randomized Controlled Trial
>
> PMID: 9160649 [PubMed - indexed for MEDLINE]
>
> This suggests that trimipramine would not be a suitable treatment for narcolepsy-related problems, as the symptoms I have are related to sleep-onset REM periods (SOREMPs) and so I need powerful REM suppressants in order to get past the hypnagogic sleep-paralysis phenomena that inevitably disrupt my sleep within minutes of falling asleep. Imipramine is the TCA classically used, but nortriptyline works too, and the mechanism responsible is the amine reuptake blockade. Any of the TCA's should work, given high enough doses- I'll ask my pdoc at my next appointment what he thinks. But it looks like trimipramine is out.
>
> There IS some significant research out now suggesting that trimipramine may be a good treatment for primary insomnia:
>
> 1: Pharmacopsychiatry. 2002 Sep;35(5):165-74. Related Articles, Links
>
>
> Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.
>
> Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Ruther E, Wiegand MH, Laakmann G, Baghai T, Fischer W, Hoffmann M, Hohagen F, Mayer G, Berger M.
>
> Department of Psychiatry and Psychotherapy, University of Freiburg, Germany. dieter_riemann@psyallg.ukl.uni-freiburg.de
>
> In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.
>
> Publication Types:
> Clinical Trial
> Controlled Clinical Trial
>
> PMID: 12237787 [PubMed - indexed for MEDLINE]
>
>
>
>
>Hi Zeugma,
Trimipramine is a potent H1 & 5-HT2A blocker. It's not as potent as Doxepin at H1 blockade but I believe it's is the most potent of TCA's at 5-HT2A blocking. Imipramine is very weak H1 & 5-HT2a blocker. This probably explains the difference in that sleep study.
Cheers,
Panda.
Posted by zeugma on March 16, 2004, at 16:42:04
In reply to Re: replacing nortriptyline with remeron? » zeugma, posted by Sad Panda on March 15, 2004, at 10:09:59
> I take Remeron. It's the most potent H1 blocker available. It's nearly double the strength of Doxepin, 10x the strength of Amitriptyline & 50x stronger than Nortriptyline. 15mg is heaps for sleep, a lot of people get by on just 7.5mg. The amount required just for sleep probably means that it doesn't have much affect on any other receptors. If you are looking for H1 + 5-HT2A for sleep, you may be better off with low dose Trimipramine or Doxepin.
>
> Cheers,
> Panda.The potency of Remeron for H1 is staggering (literally!). 75 mg nortriptyline = 15 mg amitriptyline = 1.5 mg Remeron. I already am fighting constant fatigue, feel a lot of weakness, have residual ADD symptoms, etc., and nortiptyline is practically a stimulant compared to Remeron.
since remeron is only slightly more potent than nortriptyline for the 5HT-2A receptor, and I can certainly tolerate a much higher dosage of nortriptyline than Remeron, I might stick with my favorite secondary amine TCA for the time being. I can't deal with a higher level of sedation than I already have, and I feel that my brain chemistry is precariously balanced as regards the sleep/arousal continuum. Remeron, or even amitriptyline, might tip it too far in the direction of somnolence.
Posted by Sad Panda on March 16, 2004, at 17:18:52
In reply to Re: replacing nortriptyline with remeron? » Sad Panda, posted by zeugma on March 16, 2004, at 16:42:04
> > I take Remeron. It's the most potent H1 blocker available. It's nearly double the strength of Doxepin, 10x the strength of Amitriptyline & 50x stronger than Nortriptyline. 15mg is heaps for sleep, a lot of people get by on just 7.5mg. The amount required just for sleep probably means that it doesn't have much affect on any other receptors. If you are looking for H1 + 5-HT2A for sleep, you may be better off with low dose Trimipramine or Doxepin.
> >
> > Cheers,
> > Panda.
>
> The potency of Remeron for H1 is staggering (literally!). 75 mg nortriptyline = 15 mg amitriptyline = 1.5 mg Remeron. I already am fighting constant fatigue, feel a lot of weakness, have residual ADD symptoms, etc., and nortiptyline is practically a stimulant compared to Remeron.
>
> since remeron is only slightly more potent than nortriptyline for the 5HT-2A receptor, and I can certainly tolerate a much higher dosage of nortriptyline than Remeron, I might stick with my favorite secondary amine TCA for the time being. I can't deal with a higher level of sedation than I already have, and I feel that my brain chemistry is precariously balanced as regards the sleep/arousal continuum. Remeron, or even amitriptyline, might tip it too far in the direction of somnolence.
>
>
>After a couple of months of Remeron it doesn't make me dopey anymore, but when I lay down, I go directly to sleep & wake up refreshed. It still makes a nice change after 30+ years of endless tossing & turning. 15mg makes me sleep for 8 hours & I awake refreshed. 30mg takes me up to 9 hours of sleep & I awake refreshed. It truely has been a miracle drug for me.
OTOH, I still have this constant idea of doing the opposite of you, switch Remeron for Nortriptyline, so I can get a big boost of NE in the morning. Things that stop me from trying this is Remeron blocks 5-HT3, which fixes the nausea that Effexor gives me & I'd hate to give up Remeron & then go back to it & find out that it doesn't work for me anymore.
Cheers,
Panda.
This is the end of the thread.
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