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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Iansf on August 29, 2006, at 0:09:03
From Synergy Times
CELECOXIB ENHANCES THE ANTIDEPRESSANT RESPONSE TO REBOXETINE
Elevations in indices of inflammation, such as increased levels
of pro-inflammatory cytokines and prostaglandin E2 (PGE2), have
been described in patients with major depression. Cyclooxygenase-
2 (COX-2) inhibitors inhibit the production of pro-inflammatory
cytokines and PGE2. Therefore, might COX-2 inhibitors attenuate
symptoms of depression? This unusual question was examined by
Muller et al (2006) in a 6-week, double-blind, placebo-controlled
trial of celecoxib add-on therapy in reboxetine-treated patients.
The study was partly supported by the pharmaceutical industry.The sample comprised 40 subjects, almost all inpatients,
diagnosed with a DSM-IV (nonpsychotic) major depressive episode.
The age of the patients ranged from 23 to 63 years. The sample
was 50% female. These patients were randomized to receive either
celecoxib (400 mg/day) or placebo; all patients also received
reboxetine (4-10 mg/day). Lorazepam was the only other
psychotropic medication permitted during the study, prescribed on
an as-needed basis for acute anxiety or agitation.The drop out rate was high: 50% with celecoxib and 60% with
placebo. However, only 5 of 10 patients dropped out of celecoxib
treatment because of inefficacy in contrast with 9 of 12 placebo
patients; and, whereas the celecoxib patients dropped out after
an average of 4 weeks, the placebo patients dropped out after an
average of about 3 weeks.Response was defined as at least 30% attenuation of HAM-D scores.
Remission was defined as an endpoint HAM-D score of 7 or less.IMPORTANT FINDINGS WERE:
1. There was significantly greater attenuation of HAM-D scores in
the celecoxib group as compared with the placebo group (55% vs
33%, respectively). Response was recorded in near-significantly
more celecoxib than placebo patients (75% vs 45%, respectively;
P=0.053). Remission was also observed in near-significantly more
celecoxib patients (45% vs 20%, respectively; P=0.09).2. Adverse events accounted for 4 drop outs with celecoxib and 3
with placebo. Almost all adverse events could be attributed to
reboxetine. No cardiovascular adverse events were observed either
clinically or in the ECG in celecoxib-treated patients.3. Lorazepam use and plasma levels of reboxetine did not differ
between the two groups; therefore, neither confounded the
results.CONCLUSIONS
Across a 6-week period, celecoxib (400 mg/day) significantly
improves the response to reboxetine (4-10 mg/day) in inpatients
experiencing a nonpsychotic major depressive episode.COMMENTS
1. Response is usually defined as an improvement of 50% or more;
using a 30% cut-off unwarrantedly inflated the response rates.
Furthermore, the use of one-tailed tests in the response and
remission analysis unwarrantedly favored celecoxib.2. In their review of literature, Muller et al (2006) observed
that, in animal models of depression, pro-inflammatory cytokines
induce symptoms such as lack of drive, lack of appetite, loss of
weight, and fatigue. In humans, depressed patients have elevated
levels of pro-inflammatory cytokines and PGE-2. Conventional
antidepressant drugs attenuate PGE-2 synthesis, perhaps through
an inhibition of pro-inflammatory cytokines. These data, along
with the findings of the present study, suggest that inflammatory
mechanisms may contribute to the clinical features of depression.
Muller et al, however, acknowledged that other mechanisms may
also be involved because COX-2 inhibitors also normalize the
hypothalamic-pituitary-adrenal axis, enhance glucocorticoid
receptors in the hippocampus, and increase serotonergic and
noradrenergic neurotransmission.3. In an earlier, 5-week placebo-controlled study, Muller et al
(2002) showed that celecoxib enhanced the antipsychotic response
to risperidone in patients (n=50) with schizophrenia. Celecoxib
has also been suggested to improve cognition in schizophrenia
(Muller et al, 2004).4. Celecoxib also modulates glutamatergic neurotransmission
through actions on NMDA and kainate receptors; these actions may
also contribute to or explain the effects of the drug in
depression and schizophrenia.5. In addition to the therapeutic effects referenced above for
patients with depression and schizophrenia, NSAIDs have been
suggested to lower the risk of neuropsychiatric syndromes ranging
from Alzheimer's disease (Etminan et al, 2003) and Parkinson's
disease (Chen et al, 2003) to ECT-induced amnesia (Rao et al,
2002; Andrade et al, 2005). The limited data available from
controlled clinical trials, however, are discouraging. Therefore,
at present, the use of NSAIDs in neuropsychiatry remains
experimental.6. As a concluding note: chronic treatment with COX-2 inhibitors
may increase the risk of adverse cardiovascular events; however,
whereas this is true of rofecoxib, it may not be a class effect
across the group of COX-2 inhibitor drugs (Sooriakumaran, 2006).REFERENCES
Andrade C, Thyagarajan S, Nandakumar N, Rao NSK, Singh NM, Bhakta
SG, Chandra JS. Brief treatment with celecoxib but not
indomethacin attenuates retrograde amnesia induced by
electroconvulsive shocks in rats. 23rd Annual Meeting of the
Indian Academy of Neurosciences, Dec 11-14, 2005, BangaloreChen H, Zhang SM, Hernan MA, Schwarzchild MA, Willet WC, Colditz
GA et al. Nonsteroidal anti-inflammatory drugs and the risk of
Parkinson Disease. Arch Neurol 2003; 60: 1059-1064.Etminan M, Gill S, Samii A. Effect of non-steroidal anti-
inflammatory drugs on risk of Alzheimer's disease: systematic
review and meta-analysis of observational studies. BMJ 2003; 327:
128.Muller N, Riedel M, Scheppach C, Brandstdtter B, Sokkullu S,
Krampe K et al. Beneficial antipsychotic effects of celecoxib
add-on therapy compared to risperidone alone in schizophrenia. Am
J Psychiatry 2002; 159: 1029-1034.Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of
COX-2 inhibitors on cognition in schizophrenia. Eur Arch
Psychiatry Clin Neurosci 2004; 254: 149-151.Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-
Muller B et al. The cyclooxygenase-2 inhibitor celecoxib has
therapeutic effects in major depression: results of a double-
blind, randomized, placebo controlled, add-on pilot study to
reboxetine. Mol Psychiatry 2006; 11: 680-684.Rao NSK, Andrade C, Reddy KP, Madappa KN, Thyagarajan S, Chandra
JS. Memory protective effect of indomethacin against
electroconvulsive shocks induced by retrograde amnesia in rats.
Biol Psychiatry 2002; 51: 770-773.Sooriakumaran P. COX-2 inhibitors and the heart: are all coxibs
the same? Postgrad Med J 2006; 82: 242-245.
Posted by Declan on August 29, 2006, at 5:13:56
In reply to Cox-II inhibitors for depression, posted by Iansf on August 29, 2006, at 0:09:03
Tangeritin and nobelitin are COX2 inhibitors, perhaps? From citrus peels?
Posted by Iansf on August 29, 2006, at 10:56:12
In reply to Re: Cox-II inhibitors for depression, posted by Declan on August 29, 2006, at 5:13:56
> Tangeritin and nobelitin are COX2 inhibitors, perhaps? From citrus peels?
I have not heard of these compounds before, though I have a bottle of modified citrus pectin tablets and I notice it lists citrus bioflavinoids as one of the ingredients. I supposed tangeritin and nobiletin are among those. But as for their being COX2 inhibitors, I certainly have no idea. Have you read somewhere that they are?
Posted by linkadge on August 29, 2006, at 18:54:40
In reply to Re: Cox-II inhibitors for depression » Declan, posted by Iansf on August 29, 2006, at 10:56:12
Thats why Turmeric is such a good antidepressant. It is both a COX-2 inhibitor and a monamine oxidase inhibitor.
This study found it more potent that prozac in mice. Though you won't hear much about that.
http://www.moodfoods.com/turmeric.html
Linkadge
Posted by Iansf on August 29, 2006, at 22:00:39
In reply to Re: Cox-II inhibitors for depression, posted by linkadge on August 29, 2006, at 18:54:40
The study says they gave the mice 140mg or more per kg of weight - that's a lot of turmeric! I would need to eat 25gm of turmeric per day to match that, and 100gm a day to match the amount used to inhibit MAO-B. I have turmeric capsules measuring 720mg. It would take 34 of them to reach the lower level and 130 of them to reach the higher. Turmeric may be a good antidepressant, but it's certainly not a very practical one.
> Thats why Turmeric is such a good antidepressant. It is both a COX-2 inhibitor and a monamine oxidase inhibitor.
>
> This study found it more potent that prozac in mice. Though you won't hear much about that.
>
> http://www.moodfoods.com/turmeric.html
>
>
> Linkadge
>
>
>
Posted by Declan on August 30, 2006, at 0:11:41
In reply to Re: Cox-II inhibitors for depression » Declan, posted by Iansf on August 29, 2006, at 10:56:12
Yes, I've read that nobelitin and tangeritin are COX2 inhibitors and I find that they keep my arthritis/knee condition stabilised (which basically means keeping me out of hospital). Actually, I might be wrong. I have also heard they affect gene expressiion. Then there's
boswellia
tumeric
(celery seed and giger, which we can ignore)
Posted by Iansf on August 30, 2006, at 9:22:49
In reply to Re: Cox-II inhibitors for depression » Iansf, posted by Declan on August 30, 2006, at 0:11:41
> Yes, I've read that nobelitin and tangeritin are COX2 inhibitors and I find that they keep my arthritis/knee condition stabilised (which basically means keeping me out of hospital). Actually, I might be wrong. I have also heard they affect gene expressiion. Then there's
> boswellia
> tumeric
> (celery seed and giger, which we can ignore)
>I've never come across nobelitin and tangeritin in supplement stores or catalogs. Are they widely available in capsule or pill form?
Posted by linkadge on August 30, 2006, at 17:38:20
In reply to Re: Cox-II inhibitors for depression » linkadge, posted by Iansf on August 29, 2006, at 22:00:39
Not necessarily so. At my weight, I'd need about 11 grams of it per day. I figured a gram was about 1/4 teaspoon, so I throw 4 of those in hot water swig it down, then do the same at lunch and dinner.
Theres not to say that it couldn't be an effective antidepressant at lower doses too. I found that it had mood elevating effects at even half of that.
Just don't combine it with other antidepressants, cause it will potentiate their action, being an MAOI.
Linkadge
Posted by Iansf on August 30, 2006, at 18:26:33
In reply to Re: Cox-II inhibitors for depression » Iansf, posted by linkadge on August 30, 2006, at 17:38:20
> Just don't combine it with other antidepressants, cause it will potentiate their action, being an MAOI.
>
> LinkadgeBeing an MAOI, does that mean it has risky food and drug interactions as well?
Posted by Declan on August 30, 2006, at 18:33:17
In reply to Re: Cox-II inhibitors for depression » Declan, posted by Iansf on August 30, 2006, at 9:22:49
I get it in Arthromax from Life Extension Foundation. It's one of several ingedients in that.
For a while LEF was putting it into Cognitex.
Posted by linkadge on August 31, 2006, at 16:30:28
In reply to Re: Cox-II inhibitors for depression » linkadge, posted by Iansf on August 30, 2006, at 18:26:33
I asked a smart doctor/herbalist who said no, due to the fact that it was a reversable MAOI like moclobeminde, it would not need dietary restrictions.
This is the end of the thread.
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