![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 32. This is the beginning of the thread.
Posted by SLS on May 1, 2009, at 18:01:39
While eating my Raisin Bran earlier, it occurred to me that in OCD there is probably something out of whack in the balance between the locus coeruleus and raphe nuclei - the regional source of norepinephrine (NE) and serotonin (5-HT) respectively. Perhaps this is why clomipramine works so well. It might help to reregulate both pathways simultaneously.
Why not combine Prozac, an atypical SSRI with anti-OCD properties, with either desipramine or nortriptyline to treat OCD and avoid the anticholinergic side effects of clomipramine?
Just a thought.
- Scott
Posted by yxibow on May 1, 2009, at 18:15:59
In reply to OCD - Just a thought., posted by SLS on May 1, 2009, at 18:01:39
> While eating my Raisin Bran earlier, it occurred to me that in OCD there is probably something out of whack in the balance between the locus coeruleus and raphe nuclei - the regional source of norepinephrine (NE) and serotonin (5-HT) respectively. Perhaps this is why clomipramine works so well. It might help to reregulate both pathways simultaneously.
>
> Why not combine Prozac, an atypical SSRI with anti-OCD properties, with either desipramine or nortriptyline to treat OCD and avoid the anticholinergic side effects of clomipramine?
>
> Just a thought.
>
>
> - ScottWell there was a small study which you may not be able to access
http://ajp.psychiatryonline.org/cgi/content/abstract/154/9/1293
I suppose its sufficiently old that I can post it
"Am J Psychiatry 1997; 154:1293-1295
Copyright © 1997 by American Psychiatric Association
Addition of desipramine to serotonin reuptake inhibitors in treatment- resistant obsessive-compulsive disorderLC Barr, WK Goodman, A Anand, CJ McDougle and LH Price
Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, USA.OBJECTIVE: The purpose of this study was to determine whether combined treatment with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30 patients with obsessive-compulsive disorder whose symptoms were refractory to SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There were no significant differences between the adjunctive desipramine and placebo groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine"
The OCD foundation at the time, btw, was in New Haven CT. Their address now reflects Boston.
Which basically means that at least in this small study your idea, while an interesting posture, showed an insignificant difference with Anafranil.
Personally, though, NE now raises my anxiety level (eventually converted to adrenaline) and so I cant take a higher dose of Anafranil than I already am.But others may react differently
-- Jay
Posted by SLS on May 1, 2009, at 18:36:04
In reply to Re: OCD - Just a thought. » SLS, posted by yxibow on May 1, 2009, at 18:15:59
CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine"
Oh, well. I guess I'll just finish my Raisin Bran and think about nothing.
:-)
- Scott
Posted by Phillipa on May 1, 2009, at 20:57:08
In reply to Re: OCD - Just a thought. » yxibow, posted by SLS on May 1, 2009, at 18:36:04
Seriously I suggests you both read the newest on ad's I just posted in relation of what will be coverered for those with mediciare and medicaid in disabilities. Disturbing to say the least. Love Phillipa
Posted by johnj1 on May 1, 2009, at 22:15:57
In reply to OCD - Just a thought., posted by SLS on May 1, 2009, at 18:01:39
I don't know if you addressed this thread to me at all but you did have me thinking about it. The only problem is the anxiety that ssri's cause. I haven't been able to do well because they disrupt my sleep and make me more anxious. Med sensitive I guess. I am having some trouble with even a small dose of 10 mg of nortyp. I have reduced some anxiey but have a lot of side effects and kind of a different type of anxiety. Some benefit for sure but not sure what to do as anafranil seems to have much worse side effects.
Posted by greywolf on May 2, 2009, at 5:23:30
In reply to OCD - Just a thought., posted by SLS on May 1, 2009, at 18:01:39
Clomipramine has always puzzled me. I've got quite a variety of OCD behaviors (it took 10 single-spaced pages to describe them to my therapist), so every pdoc has prescribed Clomipramine and every other med that has anti-OCD properties. None of them had any--not even the slightest--effect on my OCD. It's been really disappointing, especially repeatedly hearing how a particular med's the answer and then it turns out to be completely ineffectual.
Greywolf
Posted by SLS on May 2, 2009, at 7:20:18
In reply to Re: OCD - Just a thought. » SLS, posted by yxibow on May 1, 2009, at 18:15:59
Recent research seems to be focusing on the evolution of hyperactive dopaminergic circuitry loops in the basal ganglia (cortico-striato-thalamic) that are allowed to occur due to a deficit of serotonergic modulation afferent from the raphe nuclei. There appears to be no interest in the locus coeruleus or noradrenergic pathways.
Do neuroleptics help at all?
- Scott
Posted by greywolf on May 2, 2009, at 7:42:16
In reply to Re: OCD - Just a thought. » yxibow, posted by SLS on May 2, 2009, at 7:20:18
Scott, I think I'm fairly smart, but I don't understand half of what you wrote. The breadth of your knowledge is pretty impressive.
Greywolf
> Recent research seems to be focusing on the evolution of hyperactive dopaminergic circuitry loops in the basal ganglia (cortico-striato-thalamic) that are allowed to occur due to a deficit of serotonergic modulation afferent from the raphe nuclei. There appears to be no interest in the locus coeruleus or noradrenergic pathways.
>
> Do neuroleptics help at all?
>
>
> - Scott
Posted by SLS on May 2, 2009, at 8:01:36
In reply to Re: OCD - Just a thought. » yxibow, posted by SLS on May 2, 2009, at 7:20:18
> Recent research seems to be focusing on the evolution of hyperactive dopaminergic circuitry loops in the basal ganglia (cortico-striato-thalamic) that are allowed to occur due to a deficit of serotonergic modulation afferent from the raphe nuclei. There appears to be no interest in the locus coeruleus or noradrenergic pathways.
>
> Do neuroleptics help at all?
>
>
> - Scott
Recent research seems to be focusing on the formation of circular loops that run on and on and on. These loops use dopamine as their primary neurotransmitter. These brain circuits are located in an area of the brain called the basal ganglia. More specifically, imaging techniques have isolated these looping circuits to comprise areas of the brain known as the cerebral cortex, striatum, and thalamus. Normally, the level of activity in these areas are regulated by serotonin coming from another structure of the brain known as the raphe nuclei. Without enough serotoninergic control to suppress the dopamine neurons, they are allowed to become hyperactive and form endless loops.Do antipsychotics that block dopamine receptors help at all?
Better?
:-)
- Scott
Posted by greywolf on May 2, 2009, at 8:15:14
In reply to Re: OCD - Just a thought., posted by SLS on May 2, 2009, at 8:01:36
Yeah, that helps a lot.
I've been on atypicals like Seroquel, Zyprexa, and Abilify, but not a straight antipsychotic. Would that make a difference?
Greywolf
Posted by johnj1 on May 2, 2009, at 8:25:38
In reply to Re: OCD - Just a thought. » yxibow, posted by SLS on May 2, 2009, at 7:20:18
Wouldn't serotonin meds work then because they would cut off the dopamine circuit? If you use a dopamine med wouldn't that leave you with less dopamine and serotonin then? How do you think they would target this?
Posted by SLS on May 2, 2009, at 8:35:47
In reply to Re: OCD - Just a thought., posted by greywolf on May 2, 2009, at 8:15:14
> Yeah, that helps a lot.
>
> I've been on atypicals like Seroquel, Zyprexa, and Abilify, but not a straight antipsychotic. Would that make a difference?I don't know. I had the atypicals in mind - risperidone in particular.
- Scott
*****************************************************
1: J Am Acad Nurse Pract. 2009 Apr;21(4):207-13.Click here to read Links
Efficacy of treatments for patients with obsessive-compulsive disorder: a systematic review.
Choi YJ.Red Cross College of Nursing, 98 Saemoonan-Gil,Jongno-Gu, Seoul 110-102, Korea. [email protected]
PURPOSE: This systematic review examines the efficacy of pharmacological therapy for obsessive-compulsive disorder (OCD), addressing two major issues: which treatment is most effective in treating the patient's symptoms and which is beneficial for maintaining remission. DATA SOURCES: Seven databases were used to acquire articles. The key words used to search for the relative topics published from 1996 to 2007 were "obsessive-compulsive disorder" and "Yale-Brown obsession-compulsion scale." Based on the inclusion and exclusion criteria, 25 studies were selected from 57 potentially relevant studies. CONCLUSIONS: The effects of treatment with clomipramine and selective serotonin reuptake inhibitors (SSRIs: fluvoxamine, sertraline, fluoxetine, citalopram, and escitalopram) proved to be similar, except for the lower adherence rate in case of clomipramine because of its side effects. An adequate drug trial involves administering an effective daily dose for a minimum of 8 weeks. An augmentation strategy proven effective for individuals refractory to monotherapy with SSRI treatment alone is the use of atypical antipsychotics (risperidone, olanzapine, and quetiapine). IMPLICATIONS FOR PRACTICE: Administration of fluvoxamine or sertraline to patients for an adequate duration is recommended as the first-line prescription for OCD, and augmentation therapy with risperidone, olanzapine, or quetiapine is recommended for refractory OCD.
Posted by SLS on May 2, 2009, at 8:47:55
In reply to Re: OCD - Just a thought. » SLS, posted by johnj1 on May 2, 2009, at 8:25:38
> Wouldn't serotonin meds work then because they would cut off the dopamine circuit?
I am guessing that those are thoughts that occurred to the investigators.
> If you use a dopamine med wouldn't that leave you with less dopamine and serotonin then?
You probably know more than me about this stuff. How does a atypical neuroleptic (antipsychotic) reduce serotonin activity? I know that they block 5-HT2a receptors, but that is not the same as producing a global reduction in serotoninergic tone. The downregulation of somato-dendritic 5-HT1a autoreceptors is probably important to increase tone. You would need an SRI antidepressant for that to occur. I think it is the combination of drugs that is necessary to produce a synergistic effect that might help people with treatment-resistant OCD.
Maybe Prozac + Risperdal?
- Scott
Posted by linkadge on May 2, 2009, at 15:12:32
In reply to Re: OCD - Just a thought., posted by SLS on May 2, 2009, at 8:01:36
There is little evidence that OCD is a biochemical disorder as research has not conclusively shown the existence of biochemical abnormalities.
There is some evidence that there is a deficit of grey matter within the OCD circuit (orbitofrontal cortex, the caudate nucleus, and the thalamus). This may be what is resulting in the relative inability to properly process and filter anxiety.
The SSRI's kind of put the breaks on this circuit perhaps by altering the ballance of monoamines in this region.
Another thing to keep in mind is that clomipramine has some dopamine and acetylcholine antagonism which may also reduce glutamatergic function in the frontal cortex.
Shame about its carcinogenic potential. It was a darn good psychotropic.
Linkadge
Posted by linkadge on May 2, 2009, at 15:15:13
In reply to Re: OCD - Just a thought. » johnj1, posted by SLS on May 2, 2009, at 8:47:55
I wouldn't personally use risperidal for OCD. Infact OCD can be a side effect of risperidal.
My mother developed an intense OCD like reaction to risperidal usage.
There are some studies suggesting seroquel can augment SSRI's for OCD. Perhaps norquetiapine has some efficacy here.
Linakdge
Posted by SLS on May 2, 2009, at 15:28:35
In reply to Re: OCD - Just a thought., posted by linkadge on May 2, 2009, at 15:15:13
> I wouldn't personally use risperidal for OCD. Infact OCD can be a side effect of risperidal.
>
> My mother developed an intense OCD like reaction to risperidal usage.
>
> There are some studies suggesting seroquel can augment SSRI's for OCD. Perhaps norquetiapine has some efficacy here.
You could be right about risperidone. Perhaps it is not the ideal choice as an augmenter. I had thought that its stronger binding to DA receptors would be useful. I am not very knowledgeable in this area - or perhaps any area.
- Scott
***********************************************
1: Eur Neuropsychopharmacol. 2008 May;18(5):364-72. Epub 2008 Feb 15.Click here to read Links
8-week, single-blind, randomized trial comparing risperidone versus olanzapine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder.
Maina G, Pessina E, Albert U, Bogetto F.Department of Neurosciences, Mood and Anxiety Disorders Unit, University of Turin, Italy. [email protected]
The aim of the present pilot study was to investigate in a single-blind manner, over a period of 8 weeks, the comparative efficacy and tolerability of risperidone versus olanzapine addition in the treatment of OCD patients who did not show a >or=35% decrease in the YBOCS score after 16-week SRI treatment (defined as resistant). The study consisted of two different phases: a 16-week open-label prospective phase to ascertain resistance to SRI treatment and an 8-week single-blind addition phase for resistant subjects only. Ninety-six subjects with DSM-IV OCD (YBOCS>or=16) entered the open-label prospective phase; at the end of the 16-week period, 50 (52%) were judged to be resistant and were randomized to receive risperidone (1 to 3 mg/d) or olanzapine (2.5 to 10 mg/d) addition for 8 weeks. Overall, patients in both groups responded significantly, without differences between the two treatment groups; although no differences emerged for the proportion of patients reporting at least an adverse event, the profiles of adverse experiences differed significantly, being risperidone associated with amenorrhoea and olanzapine with weight gain.
Posted by johnj1 on May 2, 2009, at 16:29:29
In reply to Re: OCD - Just a thought., posted by linkadge on May 2, 2009, at 15:12:32
Thank you for the response. If it would work for me I would take anafranil even with the risk. I wouild rather have 20 good ones that 30 bad years. I used NAC which helped but the headaches sucked.
I may have to ask for namenda or rizhuole. Nortrptline is not helping my anxiety much the side effects are bothersome at 10 mg and I am having a hard time deciding on dosage time. Morning I am anxious for a few hours with side effects but dulled out. Not sure what to do about the night dose as then I can't sleep. It sucks to be me.
Posted by linkadge on May 2, 2009, at 18:49:28
In reply to Re: OCD - Just a thought., posted by SLS on May 2, 2009, at 15:28:35
I'm not necessarily saying it shouldn't be used for OCD, but I know it has been associated with worsening of OCD in some patients.
Linakdge
Posted by linkadge on May 2, 2009, at 18:50:48
In reply to Re: OCD - Just a thought. » linkadge, posted by johnj1 on May 2, 2009, at 16:29:29
>I wouild rather have 20 good ones that 30 bad >years
Thats easy to say before you get cancer.
Linkadge
Posted by yxibow on May 3, 2009, at 0:37:34
In reply to Re: OCD - Just a thought., posted by linkadge on May 2, 2009, at 15:12:32
> There is little evidence that OCD is a biochemical disorder as research has not conclusively shown the existence of biochemical abnormalities.
>
> There is some evidence that there is a deficit of grey matter within the OCD circuit (orbitofrontal cortex, the caudate nucleus, and the thalamus). This may be what is resulting in the relative inability to properly process and filter anxiety.
>
> The SSRI's kind of put the breaks on this circuit perhaps by altering the ballance of monoamines in this region.
>
> Another thing to keep in mind is that clomipramine has some dopamine and acetylcholine antagonism which may also reduce glutamatergic function in the frontal cortex.
>
> Shame about its carcinogenic potential. It was a darn good psychotropic.
Oh.... sigh.... you're entitled to your own opinion but having lived with it for -life- I know it is a biochemical disorder.Its first manifestation is most often triggered by a large psychological event.
In my case that was a double event, discovering that those things below my waist had another function, i.e. puberty, and shortly later finding out that I was gay.
Anyway, shuttle about 6 years later, hoarding, magical thoughts, washing up to the point of 7 hour showers even though I fainted during them and having my hands turn bone white, an anticlimactic graduation from high school, two and a half months of hospitalisation after I had nothing left to do but my OCD, recovering in a program....
And finally working for someone I can't disclose but produced definitive PET scans of people with OCD, treated with CBT, treated with medication, both, etc, yes, large evidence in the caudate, I'm fully convinced that it is biological.
And its not over. Because it never is over. Its dormant, as many OCD patients know -- but CBT helps a lot especially when it is first caught, to minimize events later in life by remembering the steps to take to help you help yourself on your own.But on the bright side it may be dormant or nearly dormant for the remainder of our wondrous existence here. The biochemistry of it may be similar, but it obviously varies slightly from patient to patient.
While I do not know the etiology or even all the parts of what has really taken a swing at my life over the past seven years, what I do know is there is an OC component to it, one that at times can be very obvious.
I haven't had "pure O" ... which technically is a grinding thought that seemingly doesnt stop, so I can't call it that, its many thoughts and scenarios that play out and sit in my head for weeks and change around, but they resemble the general spectrum of OC.And it sucks me into depression and its distracting.
And as for TCAs and genotoxicity, we are talking largely about rat studies. Who knows what any medication that we are taking will affect our lifespan ?
I can tell you that people with serious depression have something else much more tangible to keep in check than a nth degree increase in cancer 50 years down the road and that is death from suicide.
Its your very own choice not to take medications because of cancer studies, but there are more obvious risks of cancer out there, smoking, breast cancer in the family, and just standing outside in the sun all day unprotected for 60 years.
-- Jay
Posted by yxibow on May 3, 2009, at 0:46:08
In reply to Re: OCD - Just a thought., posted by linkadge on May 2, 2009, at 18:50:48
> >I wouild rather have 20 good ones that 30 bad >years
>
> Thats easy to say before you get cancer.
>
> LinkadgeI've perhaps barraged a bit because you often mention this, but is there a streak of cancer in your family that makes you worried about medication?
This is not an accusation, this is an honest question. Its also not my business, you don't have to answer.
I lost a neighbor to cancer, but you know, this man was up on the roof up until he was 80, putting fresh shingles on the house. He had a long and good life, and it was really sad to see him suffer, but even during that period there was a sense of humor nearly up until the end, when he went in the night.Sorry, I'm verklempt. It was over labor day and it was at a point when my depression and aspects of what I was dealing with was particularly acute.
-- Jay
Posted by yxibow on May 3, 2009, at 0:54:35
In reply to Re: OCD - Just a thought. » yxibow, posted by SLS on May 2, 2009, at 7:20:18
> Recent research seems to be focusing on the evolution of hyperactive dopaminergic circuitry loops in the basal ganglia (cortico-striato-thalamic) that are allowed to occur due to a deficit of serotonergic modulation afferent from the raphe nuclei. There appears to be no interest in the locus coeruleus or noradrenergic pathways.
>
> Do neuroleptics help at all?
>
>
> - Scott
I don't know if Seroquel is only offlabel helping the dopamine imbalance which has no etiology and is one of the main sources of something I've never encountered before.From evidence based psychiatry (what seems to have worked), the theory that D2 or even other things have been dampened is particularly obvious.
I think it has been obvious in two particular forms of OCD -- one, the less than 1% where the patient with OCD is not aware at all that their compulsions are out of balance and there is a psychosis component to it, and two, treatment resistant OCD, especially things like "Pure O" which remain a very hard thing to fight.
So yes, judicious and sparing augmentation with low potency neuroleptics have helped people in these situations -- and the MED (minimum effective dose) should definitely be followed because people with affective disorders have higher sequelae to neuroleptics than people with pure psychotic disorders.
I'm not sure that I would use Risperdal, it has basically been one of the only atypicals that has a known record of TD, but on the other hand there are some people who respond best to it.More likely I would wee a scenario with less "jumpy" SSRIS than Prozac and a combination with say Seroquel, Zyprexa, Abilify, even Clozaril although I would imagine that would be extremely exotic.
-- Jay
Posted by linkadge on May 3, 2009, at 8:47:12
In reply to Re: OCD - Just a thought. » linkadge, posted by yxibow on May 3, 2009, at 0:37:34
Just as a side note I know how being gay can be extrordinarily difficult. I am gay and still havn't worked up the courage to come out of the closet - it is really not an option in my hometown - that is if I want to remain a member of society.
Anyhow, life events can produce structural brain changes as well as biochemical ones. Remember, there are all sorts of structural brain changes that occur during puberty. As a side note, if the SSRI's ever worked for me it was when they erradicated by sexual desire. Thats the only way I didn't feel the pain of my sexual orientation.
I am not saying that OCD isn't a bichemical disorder, I am only saying there is no research that has identified any brain chemical that appears responsible for OCD.
Linkadge
Posted by johnj1 on May 3, 2009, at 9:53:13
In reply to Re: OCD - Just a thought., posted by linkadge on May 2, 2009, at 18:50:48
Link,
I appreciate your knowledge very much. But, I can say with certainty that if someone offered me a pill that cured me for 20 years but we give me cancer and cut my life short I would take it in a heartbeat. That said, we don't know anafranil would do that so if it cured me I would risk it for sure.
Posted by johnj1 on May 3, 2009, at 9:58:12
In reply to Re: OCD - Just a thought. » SLS, posted by yxibow on May 3, 2009, at 0:54:35
I had akathisia on seroquel and it really disturbed my sleep. I slept ok at first but would wake up every hour after that. Does this mean that I am likely to get akathisia from all anit-psychotics? I was very jumpy on ssri's too. Although I only tried luvox and paxil. Paxil just made me so spaced out like I was in another universe and that made me freak out.
I am pure O. I stopped the nortryptline as it hurting more than helping. You are right though certain things trigger ocd and then there are days I just laugh at what I thought the day before. I do much better if I just let the thought go but I have a hard time doing that, I like to be in control.
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.