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Dr. Bob is Robert Hsiung, MD,
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Posted by SLS on July 4, 2009, at 3:32:15
In reply to Re: Going back to old-school - lithium., posted by linkadge on July 3, 2009, at 18:11:33
> >I don't understand. What exactly would upset the >integrity of psychiatry if it were found that >drug-induced manias were not necessarily the >result of an underlying bipolar disorder.
> Then, it could be seen as (what I believe it is) a side effect of certain drugs in certain patients.
Yeah. Those with occult bipolar spectrum disorders.
> Biology is way too complex to classify a disorder based on a reaction to a drug IMHO.
It is done all the time for diagnostic purposes in many different fields of medicine. I can't give you an example right off the top of my head. Even depression can be parsed using the body's reaction or non-reaction to the administration of the drug, dexamethasone.
> If it is the patient and not the drug, there is no fault with psychiatry.
I just don't think that this kind of mentality went into the decision reached by William Potter (NIH) in 1992 to understand my illness as being a variety of bipolar disorder.
> > They are probably more heavily >catecholaminergic. Anyway, in what way is this >fact relevant to your beliefs regarding drug->induced manias?
> Well, if all drugs are equally effective in elevating mood, you'd expect them to be equally likely to induce mania.
I would have no expectation of this. I don't find any logic in extrapolating to every antidepressant the same clinical properties, whether they be therapeutic or adverse.
> Because some drugs are more likely to induce mania, suggests to me, that there is some biochemical target which is more fundimentally linked to the manic processes.
Perhaps. The question is whether or not it is downstream from the pharmacological actions of the drug. Wellbutrin and Prozac hit different targets even though many downstream effects are the same.
> Some AD's like survector had to be pulled because it was too good an AD. Basically meaning that it must have induced euphoria as a side effect.
I have never heard that. Stimulating, yes. It might be closer in effect to methylphenidate (Ritalin) or amphetamine (Dexedrine).
> I think there are separate processes for affect and reward.
I think so too.
> Some of the AD's (notably parnate) have effects on affect and reward.
Its all about the brain region that the drug hits.
You are preaching to the choir, my friend.
> If it hits the right (or wrong) brain region, it can be like cocaine - able to give anyone a buzz.
You see, this is where I don't see the execution of the concept. Nice on paper, but show me. I do understand where you are coming from with all of this. If you really want to do some digging, you might want to try some empirical research. For example, at what rate does the general population respond to amphetamine with a manic episode versus people who seek treatment for depression.
If Manji can make rats "depressed", I guess he can make them "manic". How would he go about making a person manic? Where on the Net can I find the Manji quote you cited?
I still believe that if you are treating someone for a depressive disorder, and a drug brings out a manic reaction, the odds are that they are displaying a phenotype that lies somewhere along the bipolar spectrum. These people are not representative of the general population, and I am betting that manic reactions to antidepressants are more likely an indicator of bipolarity than a simple side-effect.
Soon, our debate here will be moot, as functional imaging studies will be able to identify bipolar brains. They already do, but it might be awhile before they see general clinical application.
Oh, well. For now, I guess we must continue to disagree on this one.
- Scott
Posted by SLS on July 4, 2009, at 5:57:26
In reply to Re: Going back to old-school - lithium., posted by SLS on July 4, 2009, at 3:32:15
I found these interesting:
- Scott
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1: Biol Psychiatry. 2006 Nov 1;60(9):1005-12. Epub 2006 Aug 30.Click here to read Links
A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene.
Baumer FM, Howe M, Gallelli K, Simeonova DI, Hallmayer J, Chang KD.Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5540, USA.
BACKGROUND: Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD. METHODS: Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism. RESULTS: Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects. CONCLUSIONS: Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.
PMID: 16945343 [PubMed - indexed for MEDLINE
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1: Arch Gen Psychiatry. 2001 Jun;58(6):539-44.Click here to read Links
The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings.
Mundo E, Walker M, Cate T, Macciardi F, Kennedy JL.Neurogenetics Section, R-31, Centre for Addiction and Mental Health, Clarke Site, 250 College St, Toronto, Ontario, Canada M5T 1R8. James_Kennedy@CAMH.net
BACKGROUND: The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP. METHODS: Twenty-seven patients with a DSM-IV diagnosis of BP I or II, with at least 1 manic or hypomanic episode induced by treatment with proserotonergic antidepressants (IM+ group), were compared with 29 unrelated, matched patients with a diagnosis of BP I or II, who had been exposed to proserotonergic antidepressants without development of manic or hypomanic symptoms (IM- group). The 2 known polymorphisms of the SLC6A4 were genotyped, and allelic and genotypic association analyses were performed. RESULTS: With respect to the polymorphism in the promoter region (5HTTLPR), IM+ patients had an excess of the short allele (n = 34 [63%]) compared with IM- patients (n = 17 [29%]) (chi(2)(1), 12.77; P <.001). The genotypic association analysis showed a higher rate of homozygosity for the short variant in the IM+ group (n = 10 [37%]) than in the IM- group (n = 2 [7%]) and a lower rate of homozygosity for the long variant in the IM+ group (n = 3 [11%]) compared with the IM- group (n = 14 [48%]) (chi(2)(2), 12.43; P =.002). No associations were found for the polymorphism involving a variable number of tandem repeats. CONCLUSION: If these results are replicated, the 5HTTLPR polymorphism may become an important predictor of abnormal response to medication in patients with BP.
Posted by linkadge on July 4, 2009, at 7:42:42
In reply to Re: Going back to old-school - lithium., posted by SLS on July 4, 2009, at 3:32:15
>Yeah. Those with occult bipolar spectrum >disorders.
Well if your definition of bipolar is an individual who has a manic epsode in response to an antidepressant then yes. Otherwise its just a drug reaction.
>Even depression can be parsed using the
>body's reaction or non-reaction to the >administration of the drug, dexamethasone.This is rarely used for diagnostic purposes. Even such, a certain response to dexamethasone does not conclusively indicate depression. The patient could have cushings disease for instance and react to dexamethasone in a similar manner to depression. Do they necessarily have depression? No. That is the danger in trying to classify drug reactions as diseases.
>I just don't think that this kind of mentality >went into the decision reached by William Potter >(NIH) in 1992 to understand my illness as being >a variety of bipolar disorder.
Who knows peoples motives. Have you ever noticed that ever since drugs like seroquel have been approved for bipolar depression, there is this big push on internet banners for patients to consider whether they might have bipolar depression. The drug de jour defines how we classify mental illnesses. We are in a perod of AD backlash. Everyone's got bipolar depression now because a) their SSRI pooped out or b) they had a manic response to an antdidepressant. Keep in mind the SSRI's can cause extreme akathesia for some patients. Many of the symptoms of extreme akathesia overlap well with mania - namely irritability, psychomotor agiation, insomnia, etc. etc.
>Perhaps. The question is whether or not it is >downstream from the pharmacological actions of >the drug. Wellbutrin and Prozac hit different >targets even though many downstream effects are >the same.
This is exaclty what I am saying though. If the patient was bipolar already, one would expect the mood elevation itself to accelerate the cycle.
>I have never heard that. Stimulating, yes. It >might be closer in effect to methylphenidate
>(Ritalin) or amphetamine (Dexedrine).Exaclty, drugs which people abuse to get high. People high on stimulants have symtpoms identical to manic episodes.
>I do understand where you are coming from with >all of this. If you really want to do some >digging, you might want to try some empirical >research. For example, at what rate does the >general population respond to amphetamine with a >manic episode versus people who seek treatment >for depression.
Anyone who abuses amphetamine is more or less having a manic episode. Elevated mood, increased energy, goal directed behaviors, increased hedonic capacity, less need for sleep, pressure of speech, grandiose ideas, you name it - its all the same thing.
>If Manji can make rats "depressed", I guess he >can make them "manic". How would he go about >making a person manic? Where on the Net can I >find the Manji quote you cited?
He has done losts of work in rats and what he notices is that high dose amphetamines do cause behavior which is used as a model for amphetamines. How do you think all of these bipolar and schizophrenic drugs are identified? By they activity in reducing the manic like excitement caused by stimulants. Stimulants cause a more rapid elevation in signal transduction systems than antidepressants do. Lithium and valproate direclty block the transducton wherase the AP's block the receptor induced transduction.
Antidepressants also elevate protein kinase C. Actually, the SSRI's have more potent effects on PKC than bupropion does.If you could relieve depression without causing mania then do you really have bipolar?
Take yourself for instance, what if you initially took (and got well on) bupropion and not nortriptyline. If you never had a manic response to this drug and remained well, would you still be bipolar????
What about agomelatine? I personally think this drug will have an extrelly low propensity to cause mania. No monoamine reuptake. 5-ht receptor blockade. Completely different profile. I think if drugs like this were used more often for depression we'd have fewer manic reactions and ultimately fewer bipolar diagnosis.
Linkadge
Posted by Frustratedmama on July 4, 2009, at 8:52:33
In reply to Re: Going back to old-school - lithium. » Frustratedmama, posted by SLS on July 4, 2009, at 2:52:31
Scott, how are you feeling today? FM
Posted by SLS on July 4, 2009, at 10:04:28
In reply to Re: Going back to old-school - lithium. » SLS, posted by Frustratedmama on July 4, 2009, at 8:52:33
> Scott, how are you feeling today? FM
Hi.
I was more energetic than usual yesterday and accomplished a few things around my apartment that I haven't gone near in years. I am convinced that this was an effect of lithium. I am tired today for lack of sleep. I really don't know what's going on today yet.
Thanks for asking.
:-)
- Scott
Posted by SLS on July 4, 2009, at 10:32:28
In reply to Re: Going back to old-school - lithium., posted by linkadge on July 4, 2009, at 7:42:42
Hi Linkadge.
Thanks for giving the example of using a drug (dexamethasone) to diagnose a disease (Cushings). You pretty much proved my point. I tested positive for the DST very early in my history. It would be interesting to see where I'm at now. I don't know if DST non-suppression is a state-specific or trait specific phenomenon. Unfortunately, it is not specific enough to be of much value if one would use it to attempt to diagnose all of the subtypes of depression. My guess is that it is more selective for depressions with anergia and psychomotor retardation than it is for the more atypical types. I don't know if DST non-suppressors respond better to certain drugs than suppressors. I don't recall coming across any studies of this. If there are any, they were probably performed in the late 1970s or early 1980s.
There is really too much to cover here, and it would take quite a bit of work to treat this important issue thoroughly. I don't really have the energy to do that right now. Maybe we can revisit this another time.
You did a nice job with your last post.
- Scott
Posted by SLS on July 4, 2009, at 10:39:20
In reply to Re: Going back to old-school - lithium., posted by linkadge on July 4, 2009, at 7:42:42
Do you think the ability for low dosages of lithium to augment antidepressants has anything to do with it perhaps reducing the excitability of neurons along the pathways that flow through the subgenual cingulate (Brodman's) area 25? Maybe it is acting like DBS in this regard.
- Scott
Posted by bleauberry on July 4, 2009, at 19:36:14
In reply to Going back to old-school - lithium., posted by SLS on July 3, 2009, at 6:42:30
I know my comments sometimes go against the grain of academia. But I believe shooting for a predetermined target dose of anything, including lithium, based on a general consensus of what happens in the general population, is bogus. I think it causes more failure than success. I think more success is attainable by slowing increasing doses, after starting at very low doses, so as to find "the" place and not shoot past it. If the mind numbing stuff of lithium is already kicking in, the dose in my opinion is already too high. It perhaps needs a lower dose and longer time, versus higher dose and shorter time. Lithium should feel invisible at the right dose.
Totally different drug, but an example. My LLMD claims to have never had a failure at fixing anyone's depression. His arsenal consists mostly of just lexapro or zoloft. The trick is not the drugs, but the doses. He has patients in complete remission from treatment resistant drug sensitive depression on things like: 1 drop of liquid lexapro up to 5mg of lexapro. 1 drop is 1/10th of 1mg. Psychiatrists and pharmicists would scoff at the idea and probably laugh hysterically. The only problem is, it works over and over in very difficult populations.
We accept dosing targets as if they came out of a bible. They didn't. They are just as flawed as the clinical studies they came from.
I see no problem with lithium except in two areas:
1)When it is combined with a serotonin med, which in your case doesn't apply, so that's cool. I think it works best in norepinephrine or multi-neurotransmitter meds, but not pure serotonin meds.
2)When a preconceived dose target is set, as if anyone on the planet could have the slightest clue how much lithium you need. Example, I know someone who had the lithium numbing at 300mg, totally zombied at 600mg, but pleasantly energized and feeling good at 75mg.
I think the version of lithium you take is also important. They are not the same. If one bombs, try the other. I don't know if you have the citrate version or what, but they are different.
Posted by SLS on July 4, 2009, at 20:23:01
In reply to Re: Going back to old-school - lithium., posted by bleauberry on July 4, 2009, at 19:36:14
> 2)When a preconceived dose target is set, as if anyone on the planet could have the slightest clue how much lithium you need. Example, I know someone who had the lithium numbing at 300mg, totally zombied at 600mg, but pleasantly energized and feeling good at 75mg.
Hmm. Thanks, Bleauberry. Maybe I'll give 150mg a shot. That was also the advice Linkadge gave.
- Scott
Posted by Phillipa on July 4, 2009, at 23:51:25
In reply to Re: Going back to old-school - lithium. » linkadge, posted by SLS on July 4, 2009, at 10:32:28
Scott just home but what is DST? know you're sleeping. Love Phillipa
Posted by SLS on July 5, 2009, at 6:03:52
In reply to Re: Going back to old-school - lithium. » SLS, posted by Phillipa on July 4, 2009, at 23:51:25
> Scott just home but what is DST? know you're sleeping. Love Phillipa
DST = dexamethasone suppression test
If you give a healthy person dexamethasone, it turns off the production of cortisol (suppressors), which is measurable in the blood. If a person does not react to dexamethasone this way (non-suppressors), it indicates that something is wrong. It is used to diagnose Cushings Disease, a condition where the body produces too much cortisol. Cortisol is secreted by the adrenal cortex, not the adrenal medulla where adrenalin is secreted.
It was found that a major portion of people seeking treatment for depression are DST non-suppressors. This test was used frequently in the 1980s. Because it doesn't "catch" all cases, it is not considered valid anymore. It is my guess that the DST is selective for certain subtypes of depression and bipolar depression. I think it might be useful to help diagnose, however, it would be only to confirm certain presentations. It might not work for atypical depression without psychomotor retardation. I haven't followed it for a long time.
- Scott
Posted by linkadge on July 5, 2009, at 11:16:28
In reply to Re: Going back to old-school - lithium. » linkadge, posted by SLS on July 4, 2009, at 10:39:20
>Do you think the ability for low dosages of >lithium to augment antidepressants has anything >to do with it perhaps reducing the excitability >of neurons along the pathways that flow through >the subgenual cingulate (Brodman's) area 25? >Maybe it is acting like DBS in this regard.
Could be. Lithium has a stabilizing effect on glutamate reuptake.
Linkadge
Posted by linkadge on July 5, 2009, at 11:18:33
In reply to Re: Going back to old-school - lithium., posted by bleauberry on July 4, 2009, at 19:36:14
SSRI's have been shown to substantially increase allopregnanalone at doses much lower than needed to significantly affect serotoin reuptake.
I can notice as little as 1mg of citalopram or about 5mg of venlafaxine.
Linkadge
Posted by linkadge on July 5, 2009, at 11:19:45
In reply to Re: Going back to old-school - lithium. » Phillipa, posted by SLS on July 5, 2009, at 6:03:52
I have been having some definate improvement with about 50mcg of chromium.
Linkadge
Posted by SLS on July 5, 2009, at 11:34:03
In reply to Re: Going back to old-school - lithium., posted by linkadge on July 5, 2009, at 11:19:45
> I have been having some definate improvement with about 50mcg of chromium.
I hope it continues.Good luck.
- Scott
Posted by SLS on July 5, 2009, at 11:39:00
In reply to Re: Going back to old-school - lithium., posted by linkadge on July 5, 2009, at 11:16:28
> Lithium has a stabilizing effect on glutamate reuptake.
I didn't know that. That is HUGE.
It might not be too far-fetched to combine Lamictal and lithium for some people.
- Scott
Posted by Phillipa on July 5, 2009, at 19:36:42
In reply to Re: Going back to old-school - lithium. » Phillipa, posted by SLS on July 5, 2009, at 6:03:52
Scott thanks thyroid normal? Phillipa
Posted by SLS on July 5, 2009, at 19:43:05
In reply to Re: Going back to old-school - lithium. » SLS, posted by Phillipa on July 5, 2009, at 19:36:42
> Scott thanks thyroid normal? Phillipa
Yeah. The last time I had it checked was about a year ago. It was normal at that time.
- Scott
Posted by SLS on July 8, 2009, at 14:42:11
In reply to Re: Going back to old-school - lithium. » Phillipa, posted by SLS on July 5, 2009, at 19:43:05
I actually began to feel better within 36 hours of adding lithium.
I am now feeling better, although not great. That I am improved at all is extremely encouraging. It has been less than a week since I added lithium. My best guess is that, even under the most optimum of conditions, it will be a very gradual process of recovery. I have to expect that it will take months to experience a robust improvement. I will evaluate my improvement week by week rather than day by day. If I attain remission, it will be well worth the wait.
That disgusting lithium malaise that I experience at higher dosages is dissipating quickly.
Currently:Parnate 80mg
nortriptyline 150mg
Lamcital 200mg
Abilify 20mg
lithium 300mg
- Scott
Posted by Frustratedmama on July 8, 2009, at 16:11:50
In reply to Re: Going back to old-school - lithium., posted by SLS on July 8, 2009, at 14:42:11
Posted by floatingbridge on July 8, 2009, at 17:11:53
In reply to Re: Going back to old-school - lithium., posted by SLS on July 8, 2009, at 14:42:11
Posted by Phillipa on July 8, 2009, at 19:50:20
In reply to Re: Going back to old-school - lithium., posted by SLS on July 8, 2009, at 14:42:11
Scott that is fabulous. Love Phillipa
Posted by SLS on July 9, 2009, at 5:17:24
In reply to Re: Going back to old-school - lithium. » SLS, posted by Phillipa on July 8, 2009, at 19:50:20
> Scott that is fabulous. Love Phillipa
We'll have to see. I have been disappointed before when something would begin to work well, only to stop working 3-4 days later.
Perhaps I spoke too soon.
- Scott
Posted by Phillipa on July 9, 2009, at 20:41:04
In reply to Re: Going back to old-school - lithium. » Phillipa, posted by SLS on July 9, 2009, at 5:17:24
Scott program you brain l000 times repeat lithium is working and I'm in remission and it is going to last for many years to come. Love Phillipa
Posted by SLS on July 12, 2009, at 7:46:30
In reply to Re: Going back to old-school - lithium. » SLS, posted by ricker on July 3, 2009, at 19:14:35
> Wouldn't that be a kick in the butt if, after having tried countless exotic treatments, it turns out that lithium ended up being the last key necessary to unlock the cage door?
No such luck.
Lithium stopped helping me after three days had passed. I had been feeling significantly improved.
I wonder what this three-day remission thing is all about with me. It doesn't matter what I take or how much of it I take. Like clockwork, when something triggers an antidepressant response, it always poops-out after three days.
Does three days ring a bell for anyone? What physiological process takes three days to occur?
I wonder if this is hypothalamus stuff. Bipolar disorder seems to be oscillatory, especially when one looks at ultra-rapid cyclers. I was an ultra-rapid cycler for a number of years prior to my first exposure to lithium. Lithium took away my upswings and left me in a state of severe depression. My 11 day cycle had been comprised of 8 days of depression followed by 3 days of euthymia. There's that three-day thing again.
- Scott
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