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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 2 to 26 of 40. Go back in thread:
Posted by jrbecker on May 22, 2003, at 16:44:50
In reply to You CANNOT lower CORTISOL directly, posted by davpet on May 22, 2003, at 15:44:57
thus, the continuing CRF antagonism research. Organon is taking another approach to this, it's clinical trial drug ORG 34517 (a glucocorticoid receptor antagonist) also works by reducing cortisol. ORG 34517 was found to be comparable to paroxetine in a double-blinded, paroxetine controlled trial with 142 patients. Nemifitide is a drug in the class of novel brain peptides (synthetic) currently in Phase II (efficacy) and III (large scale) clinical trials. The company manufacturing nemifitide (Innapharma) claims this class of drugs offer benefits over SSRI agents, including rapid onset of action and better side effect profile. How this class of drugs act is still under investigation.
JB
Posted by CamW. on May 24, 2003, at 15:54:26
In reply to Re: You CANNOT lower CORTISOL directly, posted by jrbecker on May 22, 2003, at 16:44:50
Geez, I thought that Florian Holsboer had laid the CRF-antagonists research to rest. The only use they would be is in the initial treatment phase of depression, until standard therapies had a chance to kick in. Adjusting cortisol levels to relieve depressive symptoms just doesn't work.
I also seem to remember that CRF-antagonists were tried (unsuccessfully) as anxiolytics.
Just thinking out loud. - Cam
Posted by Shawn. T. on May 25, 2003, at 18:09:28
In reply to Re: You CANNOT lower CORTISOL directly » jrbecker, posted by CamW. on May 24, 2003, at 15:54:26
Which Holsboer articles are you referring to? I looked through PubMed and couldn't find anything. If you believe that the matter has been laid to rest, could you please provide the references that you're discussing? Does his finding apply to R121919 or to all CRF antagonists? Do you know if any other researchers have verified Holsboer's findings? If the results are so clear cut, wouldn't other research groups be able to easily verify them?
Shawn
Posted by jrbecker on May 26, 2003, at 12:22:37
In reply to Re: You CANNOT lower CORTISOL directly » jrbecker, posted by CamW. on May 24, 2003, at 15:54:26
> Geez, I thought that Florian Holsboer had laid the CRF-antagonists research to rest. The only use they would be is in the initial treatment phase of depression, until standard therapies had a chance to kick in. Adjusting cortisol levels to relieve depressive symptoms just doesn't work.
>
> I also seem to remember that CRF-antagonists were tried (unsuccessfully) as anxiolytics.
>
> Just thinking out loud. - CamHuh? It is my understanding that Holsboer is one of the biggest proponents of CRF1 antagonism R&D (please see below). I'd be very interested in hearing any news to the contrary. Thanks.
www.neurocrine.com/html/clin_anxietyDepression.html
Neurocrine Clinical Development Program Status
A first generation CRF1 non-peptide antagonist that was previously in development with Janssen Pharmaceutica (R121919) was studied in a Phase IIa clinical trial. This study, conducted by Dr. Florian Holsboer, Director of the Department of Psychiatry at the Max Planck Institute in Munich Germany, treated two groups of 20 patients suffering from major depression. Although the trial did not include a control placebo group and involved too few patients to draw definitive conclusions, a dose dependent improvement in measurements of both anxiety and depression were noted in 80% of patients providing the first indications of a CRF1 receptor antagonist effect using a novel mechanism for major depression. These results, "The First Human Experience with CRF Antagonists" were published in the Journal of Psychiatric Research and were presented at scientific meetings throughout 2000.
http://www.eneassoc.org/enea2002.htmProf. Florian Holsboer (Munich) demonstrated on the basis of CRH the way from basic research on depression to the development of novel therapeutical approaches in the treatment of this disease. Mice overexpressing CRH show signs and symptoms of affective disorders, whereas CRH receptor type-1 (CRHR1) knock-out mice show reduced anxiety-like behaviour. In vivo studies in innate high-anxiety rat strains with a novel CRHR1 antagonist (R121919) reduced anxiety-like behaviour. In patients with major depression R121919 was as effective as standard antidepressants. This indicates that CRHR1 antagonists represent powerful future tools for the individual pharmacological treatment of patients with affective disorders.
http://atlas.pharmalicensing.com/news/adisp/955314491_38f0f13bb4d9b
Florian Holsboer, M.D., Ph.D., and director at the Max Planck Institute fur Psychiatrie in Munich, Germany commented, "The results of an unrelated open label Phase IIa study conducted at the Max Planck Institute have provided encouraging results regarding the validity of the CRF mechanism as a potential therapeutic target for anxiety and depression.
http://www.cmeondemand.net/CNS/novelperspectives/CNS701_Holsboer.html
CRHR1 Antagonists as Novel Treatment Strategies
By Florian Holsboer, MD, PhD
Abstract
Research has provided considerable evidence for the hypothesis that corticotropin-releasing hormone (CRH), the key central coordinator of stress-hormone homeostasis, also plays a role in the development and course of depression and anxiety disorders. Studies using animal models of anxiety, as well as mouse mutants, in which the gene coding for the CRH type 1 receptor (CRHR1) was genetically deleted supported the notion that enhanced CRH/CRHR1 signaling underlies depression and anxiety disorders. Therefore, a number of small nonpeptide molecules that antagonize CRHR1 have been developed. In animal models, these molecules had anxiolytic and other stress-alleviating effects. An initial clinical study showed that CRHR1 antagonism has beneficial effects on depression and anxiety symptoms at doses unharmful to neuroendocrine stress responsivity.
Posted by MB on May 27, 2003, at 13:36:20
In reply to Re: You CANNOT lower CORTISOL directly, posted by jrbecker on May 26, 2003, at 12:22:37
How would all this stuff apply the the Atypical Depressives (in whom the HPA axis is often underactive)? I fall into the Atypical category. I overeat and crave carbs/chocolate when depressed. I sleep and sleep and sleep when depressed. Also, I have some mood reactivity (a nice event or a cup of coffee might lift my spirits momentarily, but the hopelessness soon comes rushing back followed by two bowls of cereal and a pint of chocolate icecream).
I read an article that manipulating the HPA axis *might* be able to help Atypicals in conjunction with AD therapy:
Being an Atypical Depressive, I find it disheartening that SSRIs further increase my fatigue, increase the time I spend sleeping, and exacerbate my carbohydrate cravings. I know that MAOIs are the best (is that still unanimous?) for Atypicals, but I hear they're not that great, either, for attenuating the reverse vegatative symptoms that are the markers for Atypical Depression (i.e., "Wow, my mood's great, but I'm still sleeping 14 hrs/day, can't work, and am getting even fatter!"). Anyway, I'm reluctant to try them.
Also, parenthetically, opiates energize me, attenuate the reverse vegetative symptoms of my depression (hyperphagia, hypersomnia, leaden fatigue, etc.), and *cure* my depression. Even after I've built a tolorance to the euphorogenic effects of a certain dose of opiate, the antidepressant effects continue. It almost feels like something metabolic is being corrected. I must admit, though, that the opiate dose necessary is pretty high. I was stabalized on 225 mg of morphine/day. That's quite a lot, but after a few months, I was no longer feeling "high," I just felt "corrected"...I felt like I did as a kid before depression hit me in the third grade.
This all seems counterintuitive, since Atypicals seem to have hypoactive HPA axes, and opiates suppress the HPA axis. Shouldn't they make me more depressed, not better? I don't get it, I don't get it, I don't get it, and, furthermore I'm F****** FRUSTRATED.
MB
Posted by davpet on May 28, 2003, at 12:47:45
In reply to HPA, Atypicals and Opiates?--Cam??, posted by MB on May 27, 2003, at 13:36:20
MB i think Prednisone augmentation would only be useful in the short term , in the long term it would then cause further down-regulation of the Glucocorticoid-Receptors (GR) and make matters worse
(I've seen this when my dog had cancer they gave her Prednisone her swelling virtually disappeared and then rebounded much worse 10 days later)
Posted by cybercafe on May 28, 2003, at 14:54:05
In reply to HPA, Atypicals and Opiates?--Cam??, posted by MB on May 27, 2003, at 13:36:20
> How would all this stuff apply the the Atypical Depressives (in whom the HPA axis is often underactive)? I fall into the Atypical
interesting... i'm atypical (bipolar) and have noticed my cortisol is low normal too
> Being an Atypical Depressive, I find it disheartening that SSRIs further increase my fatigue, increase the time I spend sleeping, and exacerbate my carbohydrate cravings. I know that
i find SSRIs give me more energy, and i spend less time sleeping
>MAOIs are the best (is that still unanimous?) for Atypicals, but I hear they're not that great, either, for attenuating the reverse vegatative symptoms that are the markers for Atypical
actually i think most people who take parnate will eat less and definately sleep less
Posted by jrbecker on May 29, 2003, at 16:13:19
In reply to HPA, Atypicals and Opiates?--Cam??, posted by MB on May 27, 2003, at 13:36:20
> How would all this stuff apply the the Atypical Depressives (in whom the HPA axis is often underactive)? I fall into the Atypical category. I overeat and crave carbs/chocolate when depressed. I sleep and sleep and sleep when depressed. Also, I have some mood reactivity (a nice event or a cup of coffee might lift my spirits momentarily, but the hopelessness soon comes rushing back followed by two bowls of cereal and a pint of chocolate icecream).
>
> I read an article that manipulating the HPA axis *might* be able to help Atypicals in conjunction with AD therapy:
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10999245&dopt=Abstract
>
> Being an Atypical Depressive, I find it disheartening that SSRIs further increase my fatigue, increase the time I spend sleeping, and exacerbate my carbohydrate cravings. I know that MAOIs are the best (is that still unanimous?) for Atypicals, but I hear they're not that great, either, for attenuating the reverse vegatative symptoms that are the markers for Atypical Depression (i.e., "Wow, my mood's great, but I'm still sleeping 14 hrs/day, can't work, and am getting even fatter!"). Anyway, I'm reluctant to try them.
>
> Also, parenthetically, opiates energize me, attenuate the reverse vegetative symptoms of my depression (hyperphagia, hypersomnia, leaden fatigue, etc.), and *cure* my depression. Even after I've built a tolorance to the euphorogenic effects of a certain dose of opiate, the antidepressant effects continue. It almost feels like something metabolic is being corrected. I must admit, though, that the opiate dose necessary is pretty high. I was stabalized on 225 mg of morphine/day. That's quite a lot, but after a few months, I was no longer feeling "high," I just felt "corrected"...I felt like I did as a kid before depression hit me in the third grade.
>
> This all seems counterintuitive, since Atypicals seem to have hypoactive HPA axes, and opiates suppress the HPA axis. Shouldn't they make me more depressed, not better? I don't get it, I don't get it, I don't get it, and, furthermore I'm F****** FRUSTRATED.
>
> MB
MB,you pose a lot of interesting questions. I myself am an atypical depressive. As for cortisol replacement therapy, I would agree with davpet in that this is really only a short-term solution. I once emailed Charles Nemeroff himself on this issue, and he responded that a low dose of prednisone might be beneficial. However, I really don't think that such a therapy is getting to the root of the problem and the side effects of this drug might be more trouble than it is worth. Levels of cortisol have been inconclusive when measured in atypicals (some find them normal, some too high, some too low). Also, cortisol acts as a negative feedback mechanism for CRF, so more cortisol isn't necessarily a good thing. Some experts believe that a potentiator of CRH might be beneficial for atypical depressives, while others disagree.
Perhaps with the advent of the CRF antagonists, more research will be dedicated to finding compounds that modulate or slightly enhance CRF to see what effect this will have in treating our condition. And this is most likely the next step in the CRF research.
But this just begins to tell only part of the story of atypical depression. The question remains, why are some depressed people not able to sleep, eat, etc., and why do some react oppositely? There are two hypothesis to answer this question: 1) Atypical depressives are those individuals whose stress system have crashed, meaning that high levels of HPA output have desensitized the receptors and made them less able to respond in normal day-to-day life situations; 2) Atypical depressives are really an offshoot of bipolar depression and the symptoms atypical depressives exhibit are manifestations of larger cortical dysregulation found to be typical of the bipolar illness as whole. Considering that there have been genetic differences seen between the two different unipolar conditions (melancholic vs atypical), then this theory might hold some water.
But which hypothesis makes more sense? Actually, I think both are probable factors in the disorder, one nature in causation, the other one nuture in theory. Hypothesis #1 (the stress overload theory) is really the environmental stressor, and #2 (the genetic predisposition to it). Bipolars are usually atypical in nature and their energy levels do not respond naturely to the normal biological clock of night and day that most people do. Also, the fact that atypicals tend to have sleep disruption (usually seen in HPA overactivity) despite being overly tired most of the day, points to further chinks in the armor of the theory that the cause of atypical depression is purely that of HPA underactivity.
http://www.psycheducation.org/depression/clock.htm
So what does this mean? Perhaps underactivity of the stress system isn't the only part of the issue (or maybe not the direct issue at all). Maybe it's also about realigning the biological clock as well. Subjectively, this makes a lot of sense to me. I remain sleepy throughout the day and have a lot more rebound energy at night. I've even found that if I push my sleep cycle further into the night and wake up later in the day, that I have a much a more normal circadian clock. And remember, circadian rhythm just doesn't effect feeling "tired" or "awake" but also plays a very major role in your mood state.
So what does this mean in terms of treatment? It means there's still a lot more work to do. But, we do know that mood stabilizers like depakote and lithium help to reset the circadian clock. In other areas, 5HT1A post-synaptic agonism also helps create an advance-sleep shift through release of ACTH (and by metabolization, cortisol). This is why a few of the 5HT1A partial agonists coming out in the next few years will probably be good for atypical depression. Gepirone, a 5HT1A partial agonist (probably going to be approved next year), has been shown to be effective against atypical depression. This is probably due not only due to its 5HT1A action but also because one of its metabolites is an alpha-2 adrenergic antagonist (which increases NE and dopamine). Other 5HT1A compounds in trials will hopefully further delineate the role of these drugs for atypical depression. Another serotonergic subreceptor, the 5HT7 receptor, also will likely play a role since it has a very specific function in regulating circadian rhythm.
And back to the CRF antagonists. There is really no real data to believe that this sort of treatment might not be beneficial to some atypical depressives as well. After all, the stress system of the atypical condition is still not clear, since as mentioned before, it is not certain whether a circadian clock dysfunction is at fault or whether it's a failure of CRH to respond properly (most likely both). In bipolar disorder, there is hypermetabolic activity in the subcortical regions responsible for CRH output. So perhaps, some form of CRF antagonist might play a more positive role than a negative one in treating atypical depression. CRF antagonist research has shown no signs of suppressed basal, stimulated ACTH, and/or cortisol secretion after administration. Thus, it means there is no endocrine side effects such as adrenal insufficiency from taking them. It was also found that the beneficial response to a CRHR1 antagonist is not limited to patients with elevations in plasma cortisol concentrations (e.g., melancholic types).
http://www.cmeondemand.net/CNS/novelperspectives/CNS701_Holsboer.html
All in all, CRF antagonism will be a giant leap for treating the "typical" unipolar population. As atypicals though, we will probably have to just hope that CRF antagonists are a more tolerable drug class -- with less exacerbation of sleepiness, anergia, apathy, and hyperphagia that you speak of MB. And most likely, they will be.As touched on before, compounds that effect the stress system via glutamate and the glucocorticoid receptor are also being developed. These will hopefully provide us with some other options in the arsenal as well.
And if you want to look even more ahead, there is already a lot of research that ties in
diabetes and Alzheimer's with depression treatment as well research as that is looking towards brain cell regeneration -- all of which seems applicable to the atypical cause. New areas for research are being discovered every month.But enough future soothsaying, unfortunately all this talk doesn't help you today. My only advice to you would be to talk to your doc about maybe lowering your SSRI if the effects are too sedating, or maybe switching onto a new one, or adjuncting with something else (e.g., Wellbutrin). Don't know what to tell you about the opioids. If you can get a doc to prescribe one, all the more power to you. Perhaps one way to do this is to email Dr. Alec Bodkin at McLean Hospital and have him consult with your doc (he would most likely be willing to do so). Recognize though that opioid tx is still very outre. I would definitely read up on it as much as possible so you have an idea of what it entails. On another note, have you experimented with supplements -- SAMe, Folate, Fish oil, DHEA, NADH. What about light therapy (it's actually helped my energy levels). And what about CBT? Given it any thought? There's lots of proof that atypical depression responds to it.
There's a bunch of things to try. Keep optimistic
JB
Posted by johnj on May 29, 2003, at 17:02:15
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
d
Posted by Pfinstegg on May 29, 2003, at 18:05:39
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
Yes, thank you for posting-just an excellent post summarizing present knowledge and future directions for research and treatment.
Pfinstegg
Posted by BekkaH on May 29, 2003, at 18:23:11
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
jrbecker,
We are very fortunate to have you here on PB. I learn so much from your posts. Thank you.
Bekka
Posted by SLS on May 29, 2003, at 19:25:38
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
I have never had my baseline cortisol measured, but I have repeatedly demonstrated DST non-suppression. My depressive state exhibits reverse vegetative features (atypical depression), although it can be argued that I am bipolar because MAOIs can trigger severe mania.
I was under the impression that most depressives, melancholic and atypical both, showed positive DST as non-suppressors.
- Scott
Posted by Shawn. T. on May 29, 2003, at 19:32:06
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
"As for cortisol replacement therapy, I would agree with davpet in that this is really only a short-term solution. I once emailed Charles Nemeroff himself on this issue, and he responded that a low dose of prednisone might be beneficial. However, I really don't think that such a therapy is getting to the root of the problem and the side effects of this drug might be more trouble than it is worth."
Agreed.
"Levels of cortisol have been inconclusive when measured in atypicals (some find them normal, some too high, some too low). Also, cortisol acts as a negative feedback mechanism for CRF, so more cortisol isn't necessarily a good thing. Some experts believe that a potentiator of CRH might be beneficial for atypical depressives, while others disagree."
Good article. Note that they mention that it would not be surprising to note normal cortisol levels in people with CRF deficiency. Multiple feedback systems exist to keep cortisol levels within a certain range; decreased CRF excretion would likely be compensated for in many cases. I've gathered the following observations on atypical depressive patients from four different articles: {high ACTH, low cortisol}; {low ACTH, normal cortisol, low CRF}; {low ACTH, normal cortisol}; {normal ACTH, normal cortisol}. Assuming that the most important factor involved in atypical depression is hypofunction of CRF neurons, all of this data does not nullify that hypothesis. I've also read that some people with atypical depression exhibit exaggerated suppresion of cortisol in response to dexamethasone (Levitan et al., 2002). I'm not sure how CRF deficiency might lead to such responses, but there may be some connection.
"But this just begins to tell only part of the story of atypical depression. The question remains, why are some depressed people not able to sleep, eat, etc., and why do some react oppositely? There are two hypothesis to answer this question: 1) Atypical depressives are those individuals whose stress system have crashed, meaning that high levels of HPA output have desensitized the receptors and made them less able to respond in normal day-to-day life situations; 2) Atypical depressives are really an offshoot of bipolar depression and the symptoms atypical depressives exhibit are manifestations of larger cortical dysregulation found to be typical of the bipolar illness as whole. Considering that there have been genetic differences seen between the two different unipolar conditions (melancholic vs atypical), then this theory might hold some water."See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12658618&dopt=Abstract for some recent information on the link between early onset unipolar and bipolar II. I haven't yet seen enough evidence to lump all early onset atypicals into the bipolar II category; I'm sure we'll see a lot more on this in the next few years. I think it's also important to note that not all bipolars experience atypical depression; I haven't seen any exact figures on the prevalence of atypical depression in bipolar disorder, but a very significant percentage of bipolars do not experience atypical symptoms. With regard to genetic differences, the availability of genetic research on atypical depression is extremely scarce. I'm still baffled by the situation. In the long term, the optimal treatment options for people with any psychiatric disorder will be determined from genetic evidence. Unfortunately, atypical depression genetic research lags far behind every other disorder. Perhaps research that further identifies exactly which groups of people do experience atypical depression will fuel genetic studies involving those groups. Until then, I do believe that progress in other areas is being made. More studies involving CRF/NE deficiency should do much to clarify the biological aspects of atypical depression.
Shawn
Posted by Shawn. T. on May 29, 2003, at 19:39:25
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by SLS on May 29, 2003, at 19:25:38
> I was under the impression that most depressives, melancholic and atypical both, showed positive DST as non-suppressors.
>
> - ScottNot all melancholic depressives are non-suppressors. A significant percentage are not. I only know of one study involving DST and people with atypical depression. They were found to be hypersuppressors; however, the study involved only women. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11836976&dopt=Abstract
Shawn
Posted by Pfinstegg on May 29, 2003, at 20:22:44
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » SLS, posted by Shawn. T. on May 29, 2003, at 19:39:25
Just to add my two cents worth, I'm mixed melancholic-atypical, but more atypical. I was a non-suppressor with a low-normal 24-hour cortisol; after TMS, I became a suppressor, and am trying hard to stay that way-for me, this coincided with a remission. (I'm female).
Pfinstegg
Posted by MB on May 29, 2003, at 20:29:55
In reply to Re: HPA, Atypicals and Opiates?, posted by davpet on May 28, 2003, at 12:47:45
Hmmm, yeah, that makes sense. Is that why they down-taper your doses after a Prednisone cycle? The whole negative feedback mechanism inherent in the HPA axis seems like it would make modulating this system difficult! Also, I guess another question is: which is primary, the physiochemical dysfunction of the brain, or the dysfunction of the HPA. It's like the "chicken and egg" riddle. Maybe we can't separate the endocrine system from the nervous system as strictly as it would seem. Glands have receptors for monoamines, and the brain has receptors for hormones, and the whole thing is so confusing *I* sure as heck can't figure it out...
MB
> MB i think Prednisone augmentation would only be useful in the short term , in the long term it would then cause further down-regulation of the Glucocorticoid-Receptors (GR) and make matters worse
>
> (I've seen this when my dog had cancer they gave her Prednisone her swelling virtually disappeared and then rebounded much worse 10 days later)
>
>
Posted by MB on May 29, 2003, at 20:35:52
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by cybercafe on May 28, 2003, at 14:54:05
> actually i think most people who take parnate will eat less and definately sleep less
Really? That's good news. My misconception might have come from so many reports of people gaining weight on MAOIs (including Parnate) I just figured they must slow you down and increase appetite.Anyway, you said SSRIs give you *more* energy? You're lucky. They drain me. At first I feel agitated and fatigued at the same time, and then, after a few months, I just feel fatigued. Unfortunately, increasing the dose brings back the agitation and worsens the fatigue. Uggg
MB
ps. I'm glad they work for you, though.
Posted by MB on May 29, 2003, at 21:08:46
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » MB, posted by jrbecker on May 29, 2003, at 16:13:19
<cut>
> Some experts believe that a potentiator of CRH might be beneficial for atypical depressives, while others disagree.
I think I read somewhere that naltrexone might help in this area...stimulating the hypothalamus to release CRF...
<cut>
> I remain sleepy throughout the day and have a lot more rebound energy at night. I've even found that if I push my sleep cycle further into the night and wake up later in the day, that I have a much a more normal circadian clock.I've noticed the same thing. After a night's sleep, I still feel groggy (I also suffer from Restless Leg Syndrome) and my morning .5mg Klonopin dose knocks me on my butt. However, I start to feel rejuvinated as the sun goes down, and I hardly feel my evening 1mg dose of Klonopin at all. Also I've been noticing that my moods cycle in a way opposed to what you would see in someone with Seasonal Affective Disorder: I'm more sluggish, tired, and depressed in the Summer than in the Winter. In the Spring and Summer, I actually *loathe* to go out in the sun, and usually wait until dusk to go outside, to do my shopping, etc. (or if I get up before dawn, and rev up on coffee--which activates the stress system--I can function somewhat normally).
<cut> (re: Gepirone)
> This is probably due not only due to its 5HT1A action but also because one of its metabolites is an alpha-2 adrenergic antagonist (which increases NE and dopamine).
Would this make it like a BuSpar/Remeron hybrid in terms of action?
<cut>> On another note, have you experimented with supplements -- SAMe, Folate, Fish oil, DHEA, NADH. What about light therapy (it's actually helped my energy levels). And what about CBT? Given it any thought? There's lots of proof that atypical depression responds to it.
I've experimented very little with the above supplements. SAMe made me restless and irritible (much in the way SSRIs do, hence the Klonopin ingredient in my cocktail). I'd really like to try CBT.
Thanks for the hopeful/informative input and the links...
MB
Posted by cybercafe on May 30, 2003, at 16:36:35
In reply to Re: HPA, Atypicals and Opiates?--Cam?? » cybercafe, posted by MB on May 29, 2003, at 20:35:52
> > actually i think most people who take parnate will eat less and definately sleep less
>
>
> Really? That's good news. My misconception might have come from so many reports of people gaining weight on MAOIs (including Parnate) I just figured they must slow you down and increase appetite.i know there are some people who gain weight on parnate or even fatigue but it is much much more likely that a person will lose weight and sleep much less... i'm sure you've read the many many posts about people wondering what med to take to help with parnate insomnia (which i loved btw as someone who used to sleep 10, 12, 14 hours a day)
parnate i found very stimulating.... great.... libido really goes up to
> Anyway, you said SSRIs give you *more* energy? You're lucky. They drain me. At first I feel agitated and fatigued at the same time, and then, after a few months, I just feel fatigued. Unfortunately, increasing the dose brings back the agitation and worsens the fatigue. Uggg
well it's actually more like... when i'm feeling okay i have thoughts come into my head "hey doing ___ would be fun" "hey this is fun" ... "i should do ___ today" ... without an AD i do not have any happy thoughts... so i wake up in the morning, no thoughts come into my head as per things i should do, so i just go back to sleep....
maybe i'm fatigued and don't notice it because there are all these things that seem interesting/fun that i want to do and am too busy doing ... when i was depressed *everything* bored me so i didn't actually do anything
anyways.... yeah i would definately recommend MAOIs... they're great drugs
Posted by Jota on May 30, 2003, at 21:14:54
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by cybercafe on May 30, 2003, at 16:36:35
Might there be any link between high cortisol levels and the low testosterone levels found in a substantial subset of depressed men? (Pope et. al., American Journal of Psychiatry, Jan. 2003)
Posted by davpet on May 30, 2003, at 23:12:17
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by Jota on May 30, 2003, at 21:14:54
You say you crave carbohydrates and that coffee brings temporary relief to your symptoms - these are classic signs of Reactive Hypoglycemia , have you ruled that out as a possibility
Posted by cybercafe on May 30, 2003, at 23:16:39
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by Jota on May 30, 2003, at 21:14:54
> Might there be any link between high cortisol levels and the low testosterone levels found in a substantial subset of depressed men? (Pope et. al., American Journal of Psychiatry, Jan. 2003)
interesting.... i had low normal cortisol and high normal testosterone (atypical depression)
Posted by MB on May 31, 2003, at 19:13:48
In reply to Re: HPA, Atypicals and Opiates?--Cam??, posted by cybercafe on May 30, 2003, at 16:36:35
> i know there are some people who gain weight on parnate or even fatigue but it is much much more likely that a person will lose weight and sleep much less... i'm sure you've read the many many posts about people wondering what med to take to help with parnate insomnia (which i loved btw as someone who used to sleep 10, 12, 14 hours a day)
I *have* read the reports about Parnate and insomnia, but after years on the med-go-round, I have become very careful to not equate "insomnia" or "activation" with "energizing." For example, Effexor gave me horrible insomnia, and it was extremely activating (in that I had to keep wiggling my legs, etc.) but I was not energized; I was fatigued. Wired and tired, like a strung out coke-head. I hated it. I'd rather be fatigued and able to sleep, than fatigued and agitated...anyway, that's my explanation for having misgivings about Parnate despite the insomnia reports.
> parnate i found very stimulating.... great.... libido really goes up toThat's great that you found it both stimulating and non-fatiguing. The only med I've found like that was Adderall. It gave me insomnia, but I didn't care, because there wasn't fatigue mixed with the insomnia. Maybe Parnate would be like this.
> well it's actually more like... when i'm feeling okay i have thoughts come into my head "hey doing ___ would be fun" "hey this is fun" ... "i should do ___ today" ... without an AD i do not have any happy thoughts... so i wake up in the morning, no thoughts come into my head as per things i should do, so i just go back to sleep....
>
> maybe i'm fatigued and don't notice it because there are all these things that seem interesting/fun that i want to do and am too busy doing ... when i was depressed *everything* bored me so i didn't actually do anything
Well, I think you might be onto something regarding not noticing the fatigue due to busyness. When I'm up and moving, the fatigue is definitely less. It's just hard to get up and moving. This Lexapro/Klonopin combo I'm on is very unmotivating. If I have an appointment where I'm *committed* to get off of my lazy butt, then the fatigue isn't so bad (but moving around *does* give me tachycardia and head-rushes). I guess its all about compromises (e.g. "Would I rather think of killing myself 24/7 or would I rather be numb, anhedonic, and amotivated?"). Recreational drugs are nice, but they quit working very quickly and then there are two problems: a mood disorder + a chemical dependency. Woa, I'm getting off topic, ramble, ramble, ramble...> anyways.... yeah i would definately recommend MAOIs... they're great drugs
My GP "doesn't prescribe" Parnate, and my pharmacy doesn't carry it. I've alienated myself from all the pdocs in my town because I'm a non-compliant know-it-all, so getting help from a psych professional isn't an option. I might have to go out of state.
MB
Posted by MB on May 31, 2003, at 19:24:10
In reply to MB is this possible, posted by davpet on May 30, 2003, at 23:12:17
> You say you crave carbohydrates and that coffee brings temporary relief to your symptoms - these are classic signs of Reactive Hypoglycemia , have you ruled that out as a possibility
This is very much a possibility. I had a glucose tolorance test done, and they told me I was normal. However, it was the short test, not the long one (they checked me a few times over the period of an hour). I almost passed out in the parking lot on the way home, so I don't think they waited long enough to witness and measure the crash. The next time I had fasting blood work done (this time without drinking that sugar drink) my blood glucose level was 51 mg/dL, which the doc seemed concerned about. I know I have hypoglycemia, because sometimes I get shaky and weak and sweaty, and eating someting sweet corrects it immediately. However, the fatigue I described in the above post is subjectively different (it is annoying, but no where near as uncomfortable as a hypoglycemic attack). Also, after a hypoglycemic attack, eating sugar or carbohydrates will make me feel better immediately. While the fatigue I mentioned in the previous post is often exacerbated by munchi9ng out on carbs. I *do* think I have problems with low blood sugar, but I think there is something else going on as well. Two different types of fatigue...one gets better with eating, the other doesn't.
MB
Posted by davpet on June 1, 2003, at 4:14:15
In reply to Re: MB is this possible » davpet, posted by MB on May 31, 2003, at 19:24:10
The term hypoglycemia , doesn't just mean your blood sugar runs low sometimes , it means there is a problem with the hormones that regulate blood sugar (after the ingestion of high glycemic meal) . You said you have a hypoactive HPA axis thats another classic sign . You were right the correct glucose tolerance test is for four hours taken every half hour , to catch the peak and trough . Eating sugar to alleviate a hypoglycemic attack is only a quick fix as your body will then produce more insulin in response to the sugar lowering your blood sugar once more . The fatigue you talk about can definitely be attributed to hypoglycemia as your body is not able to efficiently metabolise its chief energy source , namely carbohydrates . The first rule of hypoglycemia is absolutely no sugar (or caffeine) of any kind . It takes at least six weeks of following a strict diet of controlled complex carbohydrates ,protein , fibre and fat , to break the sugar cycle and improve your symptoms .
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