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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by Adam on December 9, 1999, at 1:09:25
As some of you may have read in my prior posts, I have contended with
with severe depression and comorbid OCD. I have tried a number of
serotinergic drugs (Anafranil, Zoloft, Effexor, Serzone, Celexa).
Anafranil was intolerable to me. Zoloft, Effexor, and Celexa all
seemed to help with obsessions somewhat, but did little or nothing
for depression and caused serious sexual dysfunction. While on serzone
I experienced a dramatic worsening of my condition and wound up in
the hospital. I'm not certain of the connection, but obviously
wasn't getting me what I wanted (I've wondered about it's
properties as a 5-HT2 antagonist related to this problem).My only relief from depression has been selegiline, which has been a
lifesaver. Unfortunately, my OCD symptoms have been flaring up, and
this seems to be worsening. Behavioral therapy is helping, but an
effective way to augment selegiline with another drug would be nice.
Unfortunately, options appear to be few. While selegiline at low doses
is most-likely safe with SSRIs, I am taking it at a nonselective dose
for MAO, increasing the risk of serotonin syndrome with SSRI
coadministration, and likely ruling out such an approach. Other
drugs known to affect the serotonin system (litium, pindolol, bupirone)
that might be safely combined with selegiline have shown little or
no efficacy for OCD, either alone or in combination with other drugs.An as-of-yet still mysterious connection between serotonin siganalling
and OCD had been clearly demonstrated. Recent work with agonistic
compounds specific for certain serotonin receptor subtypes have implicated
the 5-HT2C receptor in mediating the anti-obsessional effects of
increased serotonergic stimulation. Interestingly, 5-HTC receptors
specifically activate a distinct signal transduction pathway involving
phospholipase C (PLC). 5-HT2C activation leads to production of cyclic
GMP,a so-called "second messenger" molecule that activates PLC, which
in turn metabolises phosphotidyl inositol, a rare phospholipid in the
cell membrane. This releases inositol triphosphate, which in turn
mediates signalling via release of intracellular calcium stores.It was also noted that administration of exogenous inositol (a sugar much
like glucose) leads to activation of PLC and intracellular signalling.
Recent studies have indicated that inositol is efficacious for some
psychiatric disorders, including OCD. Its efficacy in OCD is thought to
be related to its ability to trigger downstream events in the 5-HTC-
mediated signal-transduction cascade. This study (by Fux, et al., Am
J Psychiatry, 153:1219-1221, 1996) showed efficacy of inositol similar
to SSRIs, even in some patients who did not respond to SSRI or
Anafranil treatment.
Posted by Adam on December 9, 1999, at 1:20:33
In reply to Inositol, posted by Adam on December 9, 1999, at 1:09:25
Inositol is supposedly very well tolerated, and may have a
wide range of applications, due to the variety of neurotransmitter systems
shown to involve phosphatidyl-inositol signalling.So, obviously, I'm interested in trying inositol, gathering information about it,
and also relaying whatever information I have learned about the use of inositol
in psychiatric illnesses. I probably won't be able to use inositol until I am
finished with with the selegiline study I am currently enrolled in, as it does not
allow augmentation.In the mean time, has anybody here tried inositol as a treatment, for OCD or other
problems? Was it helpful? Did you experience any adverse effects? Has anyone
tried to combine it with a non-selective MAOI?
Posted by jamie on December 9, 1999, at 3:43:31
In reply to Inositol, Part II, posted by Adam on December 9, 1999, at 1:20:33
If I remember correctly, doses needed are about 12g a day. Since the pills are 500mg, that's 24 pills a day! That's a lot of pills to carry around. But if it works I guess it's worth it. I think inositol is also available as a powder for larger dosing. I tried it once, but found taking in 12g a day to be an incredible chore.
There is a theory that excess inositol is implicated in mania. And that one way lithium works in mania is by inhibiting inositol. By the way, inositol is a lot like a sugar. I found I could mix it in coffee just like sugar and it tasted the same. I don't think inositol would be dangerous with maois, though it would be wise probably to try one 500mg pill, then two, then three, etc...feel it out carefully. It's not heavily studied, so I doubt anyone knows for sure about inositol in general or in combination with maois. I just suspect its indirect nutritive action would have no compatability problems with maois. After all, it's basically just a version of sugar.
Posted by Adam on December 9, 1999, at 12:27:41
In reply to Re: Inositol, Part II, posted by jamie on December 9, 1999, at 3:43:31
Hey, Jamie,
I read about the effects of lithium on phoshphatidylinositol turnover, and how that might
be one explanation for its "paradoxical effects" on serotoninergic signalling. It's very
interesting. I'm hoping mania isn't a problem. Selegiline can make me kind of hyper,
but that's probably it.The OCD study I cited used 18(!)g/day of inositol, dissolved in juice. One thing nice about
the study is the subjects couldn't distinguish it from the glucose control. To think, a
sugar that isn't the placebo.That's definitely good advice about ramping the dose, though my guess also is there should
be no problems in conjunction with an MAOI. Where did you get the 500mg pills? Did you
need a prescription? Was it expensive? And lastly, did it do anything for you besided be
inconvenient :)? Thank you!> If I remember correctly, doses needed are about 12g a day. Since the pills are 500mg, that's 24 pills a day! That's a lot of pills to carry around. But if it works I guess it's worth it. I think inositol is also available as a powder for larger dosing. I tried it once, but found taking in 12g a day to be an incredible chore.
>
> There is a theory that excess inositol is implicated in mania. And that one way lithium works in mania is by inhibiting inositol. By the way, inositol is a lot like a sugar. I found I could mix it in coffee just like sugar and it tasted the same. I don't think inositol would be dangerous with maois, though it would be wise probably to try one 500mg pill, then two, then three, etc...feel it out carefully. It's not heavily studied, so I doubt anyone knows for sure about inositol in general or in combination with maois. I just suspect its indirect nutritive action would have no compatability problems with maois. After all, it's basically just a version of sugar.
Posted by Noa on December 9, 1999, at 19:13:53
In reply to Re: Inositol, Part II, posted by jamie on December 9, 1999, at 3:43:31
I had to take a deep breath and read through your post slowly, Adam, because I find the scientific terms very intimidating. I can't say I follow the science exactly, but I get the gist of a cascade of reactions affecting various receptors, etc.
This sounds like an interesting path to pursue, given that it sounds like it shifts the serotonin target just enough to possibly help people for whom the ssris just don't do it.
What kind of substance is this sugar, inositol? Is it a supplement, a drug? Where would one get it? Could it be used to boost the effects of ADs in refractory depression? Could it be used with lithium? Are there pdocs using it with patients now?
Posted by Adam on December 9, 1999, at 23:02:56
In reply to Re: Inositol, Part II, posted by Noa on December 9, 1999, at 19:13:53
Hey, Noa,
The substance in question is actually referred to as myo-inositol, which is one of a few possible isomers of inositol that
exist. It's chemical formula (C6H12O6) is the same as that of glucose and many other monosaccharides, though it has some
important structural differences. I guess a lot of myo-inositol is found in the heart (hence the name). Another name is
vitamin B8.I've known about the use of inositol in OCD and other disorders for only a few days, so I'll post more info. as I dig it up.
I came across it as I was learning about the importance of the 5-HT2C receptor and OCD. What is really kind of cool (for
me) is I used to work a little with inositol! I've done experiments with it to study intracellular free calcium and its
role in the growth and differentiation of skin cells. A modified form of it belongs to a group of molecules referred to as
"second messengers", which help carry chemical signals (like serotonin) from the outside of a cell to other receptors on the
inside of a cell. For some reason, addition of plain old myo-inositol triggers some of the events that occur downstream
of the initial signal. I think its lack of adverse effects vs. some antidepressants may be related to the fact that
its action is relatively targeted. Or, perhaps, because exogenous inositol just doesn't do all that much. I hope it's the
former and not the latter.
Here is a review of inositol in some psychiatric disorders...
Eur Neuropsychopharmacol 1997 May;7(2):147-55Controlled trials of inositol in psychiatry.
Levine J
Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Inositol is a simple polyol precursor in a second messenger system important in the brain. Cerebrospinal fluid inositol has been reported as decreased in
depression. A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed. Significant overall benefit for inositol
compared to placebo was found at week 4 on the Hamilton Depression Scale. No changes were noted in hematology, kidney or liver function. Since many
antidepressants are effective in panic disorder, twenty-one patients with panic disorder with or without agoraphobia completed a double-blind,
placebo-controlled, four week, random-assignment crossover treatment trial of inositol 12 g per day. Frequency and severity of panic attacks and severity of
agoraphobia declined significantly with inositol compared to placebo. Side-effects were minimal. Since serotonin re-uptake inhibitors benefit obsessive compulsive
disorder (OCD) and inositol is reported to reverse desensitization of serotonin receptors, thirteen patients with OCD completed a double-blind controlled
crossover trial of 18 g inositol or placebo for six weeks each. Inositol significantly reduced scores of OCD symptoms compared with placebo. A controlled
double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients, did not show any beneficial effects. A double-blind
controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients, with on clearly significant therapeutic
effects. Antidepressant drugs have been reported to improve attention deficit disorder (ADDH) with hyperactivity symptomatology. We studied oral inositol in
children with ADDH in a double-blind, crossover, placebo-controlled manner. Eleven children, mean age 8.9 +/- 3.6 years were enrolled in an eight week trial of
inositol or placebo at a dose of 200 mg/kg body weight. Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo. Recent
studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism. However a controlled double-blind crossover trial of inositol
200 mg/kg per day showed no benefit in nine children with autism. Cholinergic agonists have been reported to ameliorate electroconvulsive therapy
(ECT)-induced memory impairment. Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors. Inositol 6 g daily
was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients, without effect. These results suggest that
inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors, including depression, panic and OCD, and is not
beneficial in schizophrenia, Alzheimer's ADDH, autism or ECT-induced cognitive impairment.
I imagine none of this stuff is new to some here.I hope inositol is as effective as some suggest. It seems to be one of my only options at this point.
Posted by Adam on December 9, 1999, at 23:31:50
In reply to Re: Inositol, Part II, posted by Adam on December 9, 1999, at 23:02:56
I guess I should include this link:
http://web.raex.com/~greggay/inositol/index.htm
I actually spoke to Dr. Jenike, someone mentioned on this web site,
briefly when I was in the hospital (Mass General). I really don't
remember it all that well. Anyway, if he feels inositol is worthy
of a place in his book, that gives me some reassurance.
Posted by jamie on December 10, 1999, at 1:41:24
In reply to Re: Inositol, Part II, posted by Adam on December 9, 1999, at 23:31:50
Adam, the 500mg capsules are available at most healthfood stores. I think the powder in juice method sounds more realistic though. I've seen the powder at healthfood stores too. I only tried it for a few days, so I cannot report much on it. It did boost energy a lot and cut my appetite. You have me re-interested though, maybe I'll go buy some more. It's cheap.
Posted by dove on December 10, 1999, at 9:05:06
In reply to Re: Inositol, Part II, posted by jamie on December 10, 1999, at 1:41:24
I actually tried inositol more than once to combat my depression and before I had sought professional help. I tried low dosage for 6 weeks or there abouts, and no results other than episodes of angry tears. Tried high dosage, very short lived maybe 3 weeks at the most due to extreme aggravation/depression/anger, really went nutso to say the least.
The interesting part is the study Adam quoted, I am ADHD (along w/bipolar,Anxiety-panic, and OCD), and I didn't respond to prozac properly (according to my doc) either. So, maybe these things all correlate, maybe serotonin is not good for people with ADHD, or some other reason connected to what the SSRI's do? Ideas anyone?
dove
Posted by Adam on December 10, 1999, at 12:33:02
In reply to Re: Inositol, Part II, posted by jamie on December 10, 1999, at 1:41:24
Cool. Thanks, jamie. I read a somewhat discouraging message from a doctor posted in Dr. Bob's tips, where he said he
tried inositol on a number of patients and got no results. I also saw a paper where inositol was used as an augmentation
of SSRI treatment in refractory OCD, and again there were no significant benefits. I left a message with my most recent
pdoc (not the one I am seeing for the study, but an OCD specialist at Mass General) to ask for his opinion, and to see if
he has tried it. I don't want to get my hopes up too much, but if it's cheap, easy, and safe, what have I got to lose?> Adam, the 500mg capsules are available at most healthfood stores. I think the powder in juice method sounds more realistic though. I've seen the powder at healthfood stores too. I only tried it for a few days, so I cannot report much on it. It did boost energy a lot and cut my appetite. You have me re-interested though, maybe I'll go buy some more. It's cheap.
Posted by Adam on December 10, 1999, at 12:36:54
In reply to Re: Inositol, Part II, posted by dove on December 10, 1999, at 9:05:06
What dosage did you try, dove? Did you feel there was a definite corrolation to your change in mood and the use of
inositol? Did the mood shift resemble what you went through with Prozac?Sorry for the barrage of questions, and thank you in advance for any info. you can give! :)
> I actually tried inositol more than once to combat my depression and before I had sought professional help. I tried low dosage for 6 weeks or there abouts, and no results other than episodes of angry tears. Tried high dosage, very short lived maybe 3 weeks at the most due to extreme aggravation/depression/anger, really went nutso to say the least.
>
> The interesting part is the study Adam quoted, I am ADHD (along w/bipolar,Anxiety-panic, and OCD), and I didn't respond to prozac properly (according to my doc) either. So, maybe these things all correlate, maybe serotonin is not good for people with ADHD, or some other reason connected to what the SSRI's do? Ideas anyone?
>
> dove
Posted by dove on December 10, 1999, at 12:58:28
In reply to Re: Inositol, Part II, posted by Adam on December 10, 1999, at 12:36:54
I started taking 500mgs per day, that was the low end, felt the effects within an hour or two during the first week. The effects were agitation, anger, ect..
Higher dosage, 500mgs. five times a day, again I felt the effects within a couple hours and was so agitated I actually thought I needed to be locked up. The mood shift was exactly like the Prozac except I had more energy with the inositol.
I felt the inositol very quickly, not like the TCA's and others. I also felt the Prozac within hours of taking it. I just went through a fairly horrible prozac 6-week trial. 4-6 hours after my last prozac and I felt like a different person. I questioned my doc about this and he didn't give me any real concrete answers other than I may metabolize the meds too quickly. So, this could add to the fact that I seem to feel the effects of psychotropic meds early on.
The price I paid for a bottle of 100 (500mgs) Inositol tablets was $11.99, buying two bottles at once (same amount) cost me $17. I also crushed the tablets and put them in juice, I don't recall (it was at least a year ago) if the effects were different.
dove
Posted by Adam on December 10, 1999, at 15:08:16
In reply to Re: Inositol, Part II, posted by dove on December 10, 1999, at 12:58:28
Dove,
Thank you very much for the info. I am really sorry to hear you had such a bad reaction to inositol and Prozac. That must have
been awful. I hope things get better in the future. I've seen from other posts that you are struggling, and I appreciate your
help during a difficult time.
> I started taking 500mgs per day, that was the low end, felt the effects within an hour or two during the first week. The effects were agitation, anger, ect..
>
> Higher dosage, 500mgs. five times a day, again I felt the effects within a couple hours and was so agitated I actually thought I needed to be locked up. The mood shift was exactly like the Prozac except I had more energy with the inositol.
>
> I felt the inositol very quickly, not like the TCA's and others. I also felt the Prozac within hours of taking it. I just went through a fairly horrible prozac 6-week trial. 4-6 hours after my last prozac and I felt like a different person. I questioned my doc about this and he didn't give me any real concrete answers other than I may metabolize the meds too quickly. So, this could add to the fact that I seem to feel the effects of psychotropic meds early on.
>
> The price I paid for a bottle of 100 (500mgs) Inositol tablets was $11.99, buying two bottles at once (same amount) cost me $17. I also crushed the tablets and put them in juice, I don't recall (it was at least a year ago) if the effects were different.
>
> dove
Posted by Zeke on December 13, 1999, at 9:49:10
In reply to Inositol, Part II, posted by Adam on December 9, 1999, at 1:20:33
Adam --
Several ideas/questions.
The one obvious thing to me is that you're in a study and your OCD is flaring up. Is this a drug study? If so, its likely double-blind and you don't know if you're on the active drug or not. If you are blindly in the placebo phase, it should not be surprising that symptoms would recur.
I think that even if you're on a high dose of selegiline and thus non-selective MAO inhibition, that augmenting other 5-HT active meds should be a RELATIVE contraindication, not an absolute one. Cautious addition of such a drug should at least be considered.
On the other hand, there's another path that will likewise drive your psychiatrists nuts. In place of Eldepryl, tramadol(Ultram) might be considered as it has efficacy in OCD and possibly affective disorders. The catch is that it acts on the mu-opioid system as well as 5HT. It is a analgesic by indication but isn't a controlled substance. You might look over at Dr. Bob's psychopharm tips for more about it. One issue is that it may (or may not) produce tolerance in re OCD. To move further down this path, if Eldepryl helps but you face these roadblocks, what about an amphetamine? This should improve mood and possibly OCD symptoms, and would be reasonable if Eldepryl -- an amphetamine congener -- helped.
I'm not well versed on the inositol issue. However, if it precipitates insulin release, that's a good reason to suppose it will increase central 5HT by virtue of increased tryptophan levels in the brain. That by virtue of decreasing competing amino acids for entry.
Posted by Adam on December 13, 1999, at 13:09:51
In reply to Thoughts, posted by Zeke on December 13, 1999, at 9:49:10
Hey, Zeke,
>
> The one obvious thing to me is that you're in a study and your OCD is flaring up. Is this a drug study?I am in a drug study for transdermal selegiline. There was a double-blind portion of the study, followed by an open-label portion
with all subjects getting the active agent. I am currently in that phase of the study, and have been for about 2 1/2 months.
> I think that even if you're on a high dose of selegiline and thus non-selective MAO inhibition, that augmenting other 5-HT active meds should be a RELATIVE contraindication, not an absolute one. Cautious addition of such a drug should at least be considered.
That may be true, and what I have read in the literature indicates actual cases of serotonin syndrome from such a combo. are quite
rare. However, I'm not sure if my doctors would suggest it, and though I would be willing to try it under close supervision, I'm
sure all parties would be happier with a safer solution.> On the other hand, there's another path that will likewise drive your psychiatrists nuts. In place of Eldepryl, tramadol(Ultram) might be considered as it has efficacy in OCD and possibly affective disorders. The catch is that it acts on the mu-opioid system as well as 5HT. It is a analgesic by indication but isn't a controlled substance. You might look over at Dr. Bob's psychopharm tips for more about it. One issue is that it may (or may not) produce tolerance in re OCD. To move further down this path, if Eldepryl helps but you face these roadblocks, what about an amphetamine? This should improve mood and possibly OCD symptoms, and would be reasonable if Eldepryl -- an amphetamine congener -- helped.
I have read about tramadol and its effects on the serotonin system. It seems it is an SRI, though many publications also refer to its
ability to induce 5-HT release. It apparently can cause rapid remission of OCD. I've thought about it, but I've done so well on
selegiline as an antidepressant I'm reluctant to switch, or at least, I'm reluctant to give up on an MAOI. As for amphetamines, the
role of dopamine in OCD is obviously complex. There is mounting evidence that genetic polymorphisms of the dopamine D4 receptor are
associated with risk of OCD in individuals with tics, though I've not seen any functional explanations. There is also evidence that
dopamine receptor antagonists are helpful to those with OCD and tics or a family history of tics. There is one paper I am aware of
showing efficacy of d-amphetamine for OCD. However, it generally appears that pscychostimulants and dopamine receptor agonists can
aggravate OCD or induce OCD-like symptoms in animal models. This is of obvious concern to me. The major metabolite of l-deprenyl is
l-methamphetamine, which is in turn metabolised to l-amphetamine. These weakly induce dopamine release, and there is additional
evidence that selegiline (or a metabolite) has other effects on dopamine not related to MAO-inhibition, perhaps as a dopamine re-uptake
blocker. My guess is that while these properties make selegiline a great antidepressant and contribure to its lack of adverse
sexual effects, it might not be the greatest drug for OCD. I have to weigh that against the profound effects it has had on depression
for me.> I'm not well versed on the inositol issue. However, if it precipitates insulin release, that's a good reason to suppose it will increase central 5HT by virtue of increased tryptophan levels in the brain. That by virtue of decreasing competing amino acids for entry.
I hadn't heard that inositol precipitates insulin release, but rather was involved with mediating insulin-receptor-driven metabolic
processes, in much the same way it mediates signalling from other receptors (ultimate production of the second messenger inositol-
triphosphate). I also was unaware of this insulin-tryptophan connection. Whatever the means inositol might potentiate insulin
signalling, I suppose this could be another beneficial property. I'll read up on that. Maybe this has something to do with the
carbohydrate/serotonin connection I keep hearing about (where hyperphagia and carbo. cravings as a symptom of depression are tantamount
to seeking a serotonin fix).Thanks!
t
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