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Dr. Bob is Robert Hsiung, MD,
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Posted by johnj on May 31, 2008, at 20:29:03
In reply to Re: The best Tricyclic for anxiety...., posted by linkadge on May 31, 2008, at 19:45:23
Wow, I think you are on to something with this observation. I tend to agree that ssri's just don't do a long term job as tca's have done. Remeron long term just doesn't seem practical either. It seems with ssri's people have to take a combo to feel well. I know tca's have side effects but like I said before I would rather have constipation or dry mouth instead of insomnia. I can't take a long term med induced insomnia.
Posted by torachan on May 31, 2008, at 22:24:27
In reply to Re: The best Tricyclic for anxiety...., posted by linkadge on May 31, 2008, at 19:45:23
Thank you Linkadge and johnj. Excellent advice. I think I'm on a mission now to "strongly" suggest to my doc to give me a shot with a TCA. In the short time I've known him, he's been very accommodating, more than most docs I've met. It's just when I make suggestions like a TCA--I seem to remember mentioning this, but you know how it is, spit out as many words as you can in 5-10min then it's out the door--and a MAOI or Lithium, stuff like that, but he leans toward the newer drugs, as most do. I think it's primarily because of money and the believe that science is always advancing. But that's not always the case; case in point, BENZOS. They still can't beat the efficacy of those drugs developed in the '60's.
Anyways, I think with enough prodding he'll go for it.
Link, johnj suggested Nortryptyline. How does it fare against Amitryptyline and Doxepin? Also, is Cyproheptadine similar in chemistry and effects to Zoplicone?
Posted by yxibow on June 1, 2008, at 3:37:21
In reply to The best Tricyclic for anxiety...., posted by jms600 on May 27, 2008, at 16:53:33
> Hi everyone
>
> My Generalized Anxiety Disorder is going from bad to worse and I'm desperate to try and find some relief. I'm considering trying a Tricyclic antidepressant as I haven't tried one yet.
>
> Does anyone know which is the best Tricyclic for anxiety?? I also suffer from depression and panic disorder.
>
> I've already tried:
>
> Valium
> Leaxapro
> Seroxat (Paxil)
> Prozac
> Zoloft
> Effexor
> Remeron
> Zyprexa
> Seroquel
> Amisulpride
> Promazine
> Haloperidol
> Stelazine
>
> Any suggestions for a good Tricyclic anti-depressant for anxiety would be grately appreciated.
>
> Thanks!This thread has quite a few posts, so I don't know if it was already mentioned, but as far as tricyclics, I would say Anafranil (Clomipramine). It was the first or one of the first early agents used for OCD when brain mapping was being discovered and can be considered an "SRI", before SSRIs.
It does carry some side effect burdens such as sweating and other things, although not everybody gets the anticholinergic effects of each tricyclic. Most are fairly sedating, although I think Elavil (amitriptyline) is probably the most, although Sinequan (doxepin) can zonk out some initially.
-- tidings
Posted by SLS on June 1, 2008, at 5:28:04
In reply to Re: The best Tricyclic for anxiety...., posted by linkadge on May 31, 2008, at 19:45:23
> The TCA can be more tollerable than the SSRI's for some. Amitrpytaline is still considered a gold standard against which AD efficacy is measured.
>
> The TCA's also have a record of actually getting people *well*.At this point, it seems that Effexor is closest to the TCAs with respect to percentage of responders and quality of response.
Imipramine was considered to be the gold standard and was used as the standard comparator drug in clinical trials. However, amitriptyline is indeed somewhat better with regard to percentage of responders, and clomipramine better yet.
Regarding anxiety, some people experience an improvement with desipramine, especially once they begin to see the depression abate. Perhaps Linkadge knows of a receptor to which it binds other than NE alpha-1. Or perhaps there are NE pathways that are inhibitory upon the anxiogenic serotonergic tracts.
It is hard to say whether the anxiety is constantly in the background like GAD or a psychosocial consequence of being to asked to perform while in the depressed state.
- Scott
Posted by torachan on June 1, 2008, at 14:25:30
In reply to Re: The best Tricyclic for anxiety...., posted by SLS on June 1, 2008, at 5:28:04
> > The TCA can be more tollerable than the SSRI's for some. Amitrpytaline is still considered a gold standard against which AD efficacy is measured.
> >
> > The TCA's also have a record of actually getting people *well*.
>
> At this point, it seems that Effexor is closest to the TCAs with respect to percentage of responders and quality of response.
>
> Imipramine was considered to be the gold standard and was used as the standard comparator drug in clinical trials. However, amitriptyline is indeed somewhat better with regard to percentage of responders, and clomipramine better yet.
>
> Regarding anxiety, some people experience an improvement with desipramine, especially once they begin to see the depression abate. Perhaps Linkadge knows of a receptor to which it binds other than NE alpha-1. Or perhaps there are NE pathways that are inhibitory upon the anxiogenic serotonergic tracts.
>
> It is hard to say whether the anxiety is constantly in the background like GAD or a psychosocial consequence of being to asked to perform while in the depressed state.
>
>
> - ScottScott, I still don't understand how SSRI/NRI's can be effective for anxiety as some are indicated for anxiety use when, as you say, serotonergic tracts can be anxiogenic. As I understand these particular drugs, the increase the action of serotonin by blocking reuptake. Why is there this inconsistency between claims made that increased serotonin activity aggravates anxiety and the claim that serotonin activating drugs improve anxiety?
And do the trycyclics work in any significantly different way in this respect to the SSRI/NRI's?
Honestly, in my opinion as I mentioned somewhere else on this board, the medical community has yet to develop drugs effective for anxiety that rival the benzodiazepines, even though long term benzo treatment carries some disadvantages like tolerance and reduced sleep quality. I believe drugs are being primarily developed with depression/bipolar in mind, while largely ignoring Anxiety. Even these SSRI's have relatively low efficacy with depression which they're meant to treat primarily, so how can they be considered effective against anxiety?
Also, do you know of any promising new drugs on the horizon which focuses on anxiety. I looked at Valdoxan, which should help with sleep, but it's still focused on depression.
Posted by SLS on June 1, 2008, at 16:34:56
In reply to Re: The best Tricyclic for anxiety.... » SLS, posted by torachan on June 1, 2008, at 14:25:30
> Scott, I still don't understand how SSRI/NRI's can be effective for anxiety as some are indicated for anxiety use when, as you say, serotonergic tracts can be anxiogenic.
> As I understand these particular drugs, the increase the action of serotonin by blocking reuptake. Why is there this inconsistency between claims made that increased serotonin activity aggravates anxiety and the claim that serotonin activating drugs improve anxiety?
Remember that part of what is going on here is the downregulation of postsynaptic receptors. Sometimes more equals less. During the first 1-2 weeks, these receptors are flooded with neurotransmitter. One might anticipate things getting worse before getting better when it comes to anxiety, especially with serotonin reuptake inhibitors. It isn't until 2-4 weeks that this downregulation takes place and reregulates synaptic dynamics.
It is perhaps no surprise that Lexapro makes anxiety worse (at 2 weeks) before it makes it better.
> And do the trycyclics work in any significantly different way in this respect to the SSRI/NRI's?
This is where things get tricky. There is still no complete understanding of how these drugs work for the various illnesses they have shown efficacy in. To assume that we can predict how a drug will affect any one person requires that we know all the properties these drugs possess. We don't.
> Honestly, in my opinion as I mentioned somewhere else on this board, the medical community has yet to develop drugs effective for anxiety that rival the benzodiazepines,
What type of anxiety do you have?
It would have been interesting to be able to combine an SSRI with gepirone or ritanserin. Unfortunately, gepirone (a 5-HT1a partial agonist) is deemed not-approvable by the FDA, and the patent on ritanserin (5-HT2 antagonist) has run out. I don't know the percentages, but a minority of people have a robust anti-anxiety response to buspirone (DA antagonist / 5-HT1a partial agonist). The one problem with gepirone and buspirone is that their major metabolite, 1-PP, is a potent NE alpha-2 antagonist. Some people can't handle the activation of certain NE pathways. It can make depression worse. I don't know about anxiety, though.
> Also, do you know of any promising new drugs on the horizon which focuses on anxiety. I looked at Valdoxan, which should help with sleep, but it's still focused on depression.
Drugs don't "focus". Only people focus. The drug is what it is. One of the properties of agomelatine is that it selectively antagonizes 5-HT2c receptors. This might decrease anxiety more than it does depression.
- Scott
Posted by johnj on June 1, 2008, at 18:53:55
In reply to Re: The best Tricyclic for anxiety.... » torachan, posted by SLS on June 1, 2008, at 16:34:56
"It would have been interesting to be able to combine an SSRI with gepirone or ritanserin. Unfortunately, gepirone (a 5-HT1a partial agonist) is deemed not-approvable by the FDA, and the patent on ritanserin (5-HT2 antagonist) has run out. I don't know the percentages, but a minority of people have a robust anti-anxiety response to buspirone (DA antagonist / 5-HT1a partial agonist). The one problem with gepirone and buspirone is that their major metabolite, 1-PP, is a potent NE alpha-2 antagonist. Some people can't handle the activation of certain NE pathways. It can make depression worse. I don't know about anxiety, though."
I always wondered why some people say buspar increased their depression, thank you. I would love to try it but I definatley don't need the anxiety gone and a worse depression. Drugs can be so frustrating.
Do you know if the NE pathway for buspar is the same as NE drugs like some of the tcas? So, for anxiety some drugs like nortryptiline, desipramine which increase NE actually flood the pathway like srri's do with serotonin and this takes time to down regulate? Is it possible it never down regulates?
The hardest thing for me was the anxiety increasing aspect of ssri's as benzo's do not work well for me anymore and it was too much to handle. Luvox never lost it's physical anxiety even after a month on only 12.5-mg. I know it is a very, very small dose but when I raised it to 25 I basically stopped sleeping. I actually felt kind of giddy on 25 mg of luvox. I am afraid to try another one even though celexa or lexapro intrigue me.
regards
johnj
Posted by Phillipa on June 1, 2008, at 19:37:11
In reply to Re: The best Tricyclic for anxiety.... » SLS, posted by johnj on June 1, 2008, at 18:53:55
Wierd as luvox is the only SSRI I can tolerate. No side effects ever even the first time when I got to 250mg. Now I stay on 50mg doesn't do much but brain addicted to it I guess. Love Phillipa ps that is what the ER doc said when a pdoc took me off it and I didn't sleep for two weeks and that pdoc had put me on incredibly high doses of benzos. Went back to 50 of luvox and 20mg of valium and at least I function.
Posted by linkadge on June 3, 2008, at 17:26:57
In reply to Re: The best Tricyclic for anxiety)Link/johnj, posted by torachan on May 31, 2008, at 22:24:27
>Link, johnj suggested Nortryptyline. How does it >fare against Amitryptyline and Doxepin? Also, is >Cyproheptadine similar in chemistry and effects >to Zoplicone?
As a class of drugs, the TCA's have a diverse range of monoamine uptake site affinities. Nortryptaline and desipramine have the most effect on norepinephrine and the least on serotonin. Clomipramine has the most effect on serotonin and least on norepinephrine. One of the TCA's 'surmontil' or 'trimipramine' actually has no effect on monoamine uptake at all. Some of the TCA's are serotonin antagonists and others are not. Some respond to certain TCA's and not others. Interestingly, all of the TCA's produce the same long term adaptive changes regardless of monoamine uptake affinity. They all appear to increase the responsivness of d2/d3 receptors in certain limbic regions implicated in depression. So, the adaptive changes may be due to some yet unidentified mechanism of the TCA's. All of the TCA appear to have a final dopaminergic or opioid related activity.
Its hard to say which one may affect you most positively. Nortryptaline and desipramine can cause tachycardia in some patients. I would avoid desipramine unless depression is very anergic. Nortyrptaline has mixed stimulant/sedative effects. For some people it causes sedation and others it causes activation.
Doxapin, amitryptaline, surmontil and amoxapine are probably the best choice for mixed depressive/anxiety and insomnia issues. They can be helpful adjunctives for depression which is partially responsive to SSRI's or they can be used to relive certain side effects of SSRI's.
Some people use a combination of TCA's, i.e. doxapin in the evening + desipramine in the morning.
I did well on a combination of 10mg of doxapin + 10mg of celexa. Even though this is a low dose of a TCA it made some major impact on my depresion. Sleep improved, anxiety improved, and SSRI anhednoia improved quite significantly.
Cyproheptadine is an antihistamine with high affinity for the 5-ht2a/c receptors as an antagonist. It is not an anticonvulsant tranquilizer but it can act as a sedative.
Linkadge
Posted by linkadge on June 3, 2008, at 17:30:10
In reply to Re: The best Tricyclic for anxiety.... » jms600, posted by yxibow on June 1, 2008, at 3:37:21
I tried clomipramine too and it is a powerful mood elevator. I felt like I was on ecstacy or something, although I have never done ecstacy.
The only thing I think was problematic was that it wasn't as good for insomnia as other TCA's. Some people don't have that problem with it though. I am guessing cause it was such a strong serotonin uptake inhibitor.
Linkadge
Posted by linkadge on June 3, 2008, at 17:36:18
In reply to Re: The best Tricyclic for anxiety...., posted by SLS on June 1, 2008, at 5:28:04
>It is hard to say whether the anxiety is >constantly in the background like GAD or a >psychosocial consequence of being to asked to >perform while in the depressed state.
Wow. That is a good way to put it. I have though the same thing but not in so few words.
I personally didn't find antidepressants all that good for generalized anxiety in a nondepressed state, (benzo's worked much better for that). When I am depressed though they did help anxiety (but a different form of anxiety), which like you said was probably created by the lack of ability to perform task which one is normally able to perform. I.e. even the simplest tasks can be daunting when depressed.
Linkadge
Posted by linkadge on June 3, 2008, at 18:02:26
In reply to Re: The best Tricyclic for anxiety.... » johnj, posted by Phillipa on June 1, 2008, at 19:37:11
>Scott, I still don't understand how SSRI/NRI's >can be effective for anxiety as some are >indicated for anxiety use when, as you say, >serotonergic tracts can be anxiogenic. As I >understand these particular drugs, the increase >the action of serotonin by blocking reuptake. >Why is there this inconsistency between claims >made that increased serotonin activity >aggravates anxiety and the claim that serotonin >activating drugs improve anxiety?
I think SLS answered that well. I just wanted to add a few things. Both serotonin and norepinephrine can be highly anxiety provoking when released in certain areas of the brain.
Like SLS said, one theory suggests that it is the downregulation of serotonin and norepinephrine receptors that produces the clinical changes. Ie after prolonged administration certain circuts actually become less responsive to the neurotransmitter and in doing so less responsive to stress induced neurotransmitter release.
This theory does't answer many things though. For instance, if certain areas of the brain become less responsive to the neurotransmitter then doesn't the antidepressant effect stop (ie doesn't the AD effect depend on the neurotrophic actions of serotonin?)
There are other theories. There is the allopregnanalone theory. All of the SSRI's actually have a recently detected common mechanism. The appear to directly increase the synthesis of a powerful gabaergic neurosteroid called allopregnanalone. This effect is independant of their effect on serotonin uptake inhibition. It is not an effect shared by the TCA's.
It may infact be that the serotonin uptake effect is anxiogenic and the allopregnanalone effect is what is reducing anxiety.
A more comprehensive effect looks at the brain region that the drugs work at. Increasing serotonin in the hippocampus may confer the antianxiety effect and the antidepressant effect. Stimulation of 5-ht1a receptors in the hippocampus appears to reduce anxiety and depression. SSRI's however are not that selective. They increase serotonin transmission at every single site in the body and brain. increasing serotonin in the dorsal raphai neucleus can be very anxiety provoking. Certain agents actually reduce serotonin release there to reduce anxiety. Buspar and nicotine inhibit serotonin firing in the dorsal raphai neucleus to reduce anxiety. Serotonin release in the amygdala is also highly anxiogenic.
The differences in responce to SSRI's for anxiety may have a lot to do with which SERT gene you have. Individuals with the SS gene for the serotonin transporter have a lower uptake of serotonin and individuals with the LL gene have a higher uptake level. Indivdiuals with the SS gene do not seem to respond well to SSRI's, probably because their serotonin transporter levels are already low. LL individuals respond better and have fewer side effects.
So it could be that all the people who get super agitated and anxious on SSRI's nomatter how long they take them have the SS varient of the gene and that the SSRI is raising their serotonin levels even higher in anxiety provoking brain regions.
5-ht2 blockers can reduce the effect of serotonin acting on the amygdala. This may conver antianxiety effects and even antischizophrenic effects. It can also improve sleep by altering the serotonin/melatonin ratio in the penal gland.
My personal theory is that for SSRI's, the serotonin upake inhibition is not really critical. I personally think the alloprenanalone boost is what reduces dysphoria and anxiety. Individuals with the LL varient probably tollerate the serotonin uptake inhibition better than do indivudals with the LL varient.
I think there is a dysregulation of serotonin in depression but it has absolutely nothing to do with serotonin uptake or monoamine oxidase.
I think its got to do with the sensitivity of the presynaptic 5-ht1b serotonin autopreceptors. These receptors selectively control serotonin release in the hippocampus and do not affect serotonin release in the dorsal raphai neucleus or amygdala. Long term lithium, exercise, shock, rTMS or antidepressant seem to favorably alter the level of this autoreceptor. Even antidepressant drugs that do not directly affect serotonin neurotransmission alter the level of this autoreceptor. The expression of this autoreceptor is highly sensitive to stress hormones.
Drugs that selectivly desensitize or funcitonally inhibit the activity of the 5-ht1b autoreceptor would be able to rapidly increase serotonin neuotransmission in brain regions implicated in depression without causing distressing physical or emotional side effects.
Linkadge
Posted by johnj on June 3, 2008, at 18:47:36
In reply to Re: The best Tricyclic for anxiety...., posted by linkadge on June 3, 2008, at 18:02:26
Thanks for the response, good stuff even though I don't understand it all, it just shows that A LOT is going on with these meds.
johnj
Posted by SLS on June 3, 2008, at 19:27:39
In reply to Re: The best Tricyclic for anxiety...., posted by linkadge on June 3, 2008, at 18:02:26
Nice post!
- Scott
Posted by KarenRB53 on October 12, 2008, at 18:31:35
In reply to Re: The best Tricyclic for anxiety.... » johnj, posted by linkadge on May 30, 2008, at 16:42:59
What tricyclic is best for depression? I do have anxiety as well but have been diagnosed with Major Depression. Prozac worked for a long time but pooped out. My pdoc has suggested Imipramine. Any suggestions appreciated.
Thanks
Posted by X-ray on October 13, 2008, at 7:51:57
In reply to Re: The best Tricyclic for anxiety...., posted by KarenRB53 on October 12, 2008, at 18:31:35
Hello Karen,
I think that Elavil is number one among the tricyclic drugs.
I have been on this drug for 35 years, so I know everything about it.
If you take 30-50 mg two hours before bedtime, you will get a good night's sleep.But I think that Remeron might be a better choice for you.
It's a benign drug that has few side effects.Best regards,
X-ray
Posted by KarenRB53 on October 13, 2008, at 10:53:34
In reply to Re: The best Tricyclic for anxiety...., posted by X-ray on October 13, 2008, at 7:51:57
> Hello Karen,
>
> I think that Elavil is number one among the tricyclic drugs.
> I have been on this drug for 35 years, so I know everything about it.
> If you take 30-50 mg two hours before bedtime, you will get a good night's sleep.
>
> But I think that Remeron might be a better choice for you.
> It's a benign drug that has few side effects.
>
> Best regards,
> X-rayThanks so much for responding. Can you tell me why you think Remeron would be better for me? Other than the fact that it has few side effects. Just curious.
Karen
Posted by X-ray on October 13, 2008, at 11:31:44
In reply to Re: The best Tricyclic for anxiety...., posted by KarenRB53 on October 13, 2008, at 10:53:34
Hi,
Elavil is a "dirty drug" that has bad side effects, while Remeron is a modern drug.
I would like to switch to Remeron myself, but Elavil gives me better quality of sleep and more sedation.
I did try Remeron for six months last year, but I decided to return to Elavil.Desyrel (trazodone) could be an option for me, and I will probably try this medicine in the future.
If you will try Elavil, I would like to point out one thing:
This drug should be taken in the evening.Best of luck,
X-ray
Posted by KarenRB53 on October 13, 2008, at 11:37:27
In reply to Re: The best Tricyclic for anxiety...., posted by X-ray on October 13, 2008, at 11:31:44
> Hi,
>
> Elavil is a "dirty drug" that has bad side effects, while Remeron is a modern drug.
> I would like to switch to Remeron myself, but Elavil gives me better quality of sleep and more sedation.
> I did try Remeron for six months last year, but I decided to return to Elavil.
>
> Desyrel (trazodone) could be an option for me, and I will probably try this medicine in the future.
>
> If you will try Elavil, I would like to point out one thing:
> This drug should be taken in the evening.
>
> Best of luck,
> X-ray
>
>The TCA my pdoc wants me to try is Imipramine (Tofranil), not sure why. I think Trazodone has been mentioned also.
Karen
Posted by X-ray on October 13, 2008, at 14:52:44
In reply to Re: The best Tricyclic for anxiety...., posted by KarenRB53 on October 12, 2008, at 18:31:35
Hello Karen,
Quote from crazymeds.org about TCAs:
For those of you with Major Depressive Disorder we feel that these are the official antidepressants of last resort.
If you have mild to moderate unipolar depression or various other types of depression other than Major Depressive Disorder, the TCAs in low dosages are fine first-line meds.Do you suffer from a Major Depressive Disorder?
If you do, drugs like Remeron, Desyrel, Effexor or Wellbutrin might be better options.
Now I'm going to get a good night's sleep.
Best regards,
X-ray
Posted by theo on October 13, 2008, at 21:09:53
In reply to Re: The best Tricyclic for anxiety...., posted by KarenRB53 on October 12, 2008, at 18:31:35
A small dose of Trazadone. I can get releif from 12.5mg-25mg. It's not a true tricyclic and much safer.
Posted by KarenRB53 on October 14, 2008, at 8:16:55
In reply to Re: The best Tricyclic for anxiety.... » KarenRB53, posted by theo on October 13, 2008, at 21:09:53
> A small dose of Trazadone. I can get releif from 12.5mg-25mg. It's not a true tricyclic and much safer.
Hi:
Do you use it for anxiety or depression?
Posted by Negcreep on October 15, 2008, at 6:05:21
In reply to Re: The best Tricyclic for anxiety...., posted by KarenRB53 on October 14, 2008, at 8:16:55
Hi I also have GAD, and I cant take SSRI's anymore due to the fact they now give me painfull gastritis. I've recently switched over to the tricyclic Dosulepin (used to be called Dothiapin). Its actually pretty good, am able to cope on a low dose of 50mg. Might go up to 75mg in the future tho, will see how I go.
Side effects, the usual suspects: Weight gain, morning drowsiness, sexual problems (tho not as bad as SSRIs in my opinion).Neg
Posted by theo on October 19, 2008, at 20:44:12
In reply to Re: The best Tricyclic for anxiety...., posted by X-ray on October 13, 2008, at 11:31:44
Why did you stop Remeron? Can it make you sick (lower immune system) by reducing white blood count?
> I did try Remeron for six months last year, but I decided to return to Elavil.
Posted by X-ray on October 20, 2008, at 4:18:33
In reply to Re: The best Tricyclic for anxiety.... » X-ray, posted by theo on October 19, 2008, at 20:44:12
Hello Theo,
I had a very bad day on Elavil last week.
So I'm back on Remeron.Now I hope to be able to stay on this drug.
But I am considering Desyrel as a reserve option.I have only one problem with Remeron.
I just barely get enough sleep.Best regards,
X-ray
This is the end of the thread.
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