![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 36. This is the beginning of the thread.
Posted by Squiggles on July 27, 2007, at 8:49:38
I know that there are social advantages to
generic drugs, but I am uncertain about the
safety of some them meeting the therapeutic
index. Do the same drug companies make them as
well as the non-generic? It would be kind of
redundant wouldn't it, if they did. Why not
make all drugs generic at the lower price?Squiggles
Posted by med_empowered on July 27, 2007, at 11:02:19
In reply to Should all drugs be generic?, posted by Squiggles on July 27, 2007, at 8:49:38
the laws on the vary from country to country. In India, a patent is issued only for the process to get a certain molecule. So, for zyprexa, India only recognizes Eli Lilly's process to get the olanzapine molecule. Other companies have found other ways to get the same molecule, so they can market their versions of Olanzapine.
There are some companies, like Teva, that seem to specialize in generics. There's lots of $$$ to be made, especially in the US, if they can get the first rights to a generic. Then they have 6months of being the only manufacturer of that generic product, which means: a)they can charge more and b)they can establish market dominance for a particular drug, especially if its got a somewhat limited market.
Posted by Squiggles on July 27, 2007, at 11:36:07
In reply to Re: Should all drugs be generic?, posted by med_empowered on July 27, 2007, at 11:02:19
> the laws on the vary from country to country. In India, a patent is issued only for the process to get a certain molecule. So, for zyprexa, India only recognizes Eli Lilly's process to get the olanzapine molecule. Other companies have found other ways to get the same molecule, so they can market their versions of Olanzapine.
> There are some companies, like Teva, that seem to specialize in generics. There's lots of $$$ to be made, especially in the US, if they can get the first rights to a generic. Then they have 6months of being the only manufacturer of that generic product, which means: a)they can charge more and b)they can establish market dominance for a particular drug, especially if its got a somewhat limited market.
>
It is unfortunate that the FDA or other gov. agencies do not put a limit on competition
in medical products. I think marketing competition is healthy for most products because it allows countries to be productive and there is always a percentage of corruption that goes along with that, but the benefits to welfare and prospertity outweight that. In the case of medical products, and maybe even human parts, i think it can easily enter into a violation of human rights and even criminality.BTW, is there a restriction on patents for elements rather than molecules? I guess not if lithium was patented at one time-- or was it patented along with some other ingredients changing its legal status;
Squiggles
Posted by Phillipa on July 27, 2007, at 12:07:21
In reply to Re: Should all drugs be generic? » med_empowered, posted by Squiggles on July 27, 2007, at 11:36:07
Squiggles I'm sure you read that synthroid is going generic this year no formal announcement that I know of just the endo telling me and that the deviation will only be 5%. Love Phillipa
Posted by Squiggles on July 27, 2007, at 12:13:13
In reply to Re: Should all drugs be generic? » Squiggles, posted by Phillipa on July 27, 2007, at 12:07:21
> Squiggles I'm sure you read that synthroid is going generic this year no formal announcement that I know of just the endo telling me and that the deviation will only be 5%. Love Phillipa
Yup, i read the post; but i am not sure of
the countries? Also, is synthroid as a natural
hormone, going to be the same in generic and non-generic preparations? I know they say they are identical but with sensitive drugs like that, there may be enough variation to make a subjective difference.Squiggles
Posted by Phillipa on July 27, 2007, at 19:31:07
In reply to Re: Should all drugs be generic? » Phillipa, posted by Squiggles on July 27, 2007, at 12:13:13
Squiggles I have absolutely no idea. Wonder is anyone else does. Love Phillipa
Posted by Jedi on July 28, 2007, at 1:28:45
In reply to Should all drugs be generic?, posted by Squiggles on July 27, 2007, at 8:49:38
...
> Why not make all drugs generic at the lower price?
>
> SquigglesIf you take away the profit motivation there would be no reason for these companies to spend millions developing new medications. Mental health medications have lagged behind because of the awesome complexity of the human brain. But without the profit motivation there would be very little advancement in any medications.
Just my opinion,
Jedi
Posted by Squiggles on July 28, 2007, at 6:41:25
In reply to Re: Should all drugs be generic? » Squiggles, posted by Jedi on July 28, 2007, at 1:28:45
> ...
> > Why not make all drugs generic at the lower price?
> >
> > Squiggles
>
> If you take away the profit motivation there would be no reason for these companies to spend millions developing new medications. Mental health medications have lagged behind because of the awesome complexity of the human brain. But without the profit motivation there would be very little advancement in any medications.
> Just my opinion,
> Jedi
>
>Putting aside the ethics of marketing, the problem is that even with fiercely competitive strategies, there isn't much scientific progress going on, but rather a reliance on cloning formulas from 30 year old prototypes. Even the the drugs from the 50s are now being compared favourably and they certainly didn't sink millions into those at that time.
Squiggles
Posted by Larry Hoover on July 28, 2007, at 10:11:31
In reply to Should all drugs be generic?, posted by Squiggles on July 27, 2007, at 8:49:38
IMHO, the word should should not even be applied to this issue. The world is a certain way, and has become this way by a complicated path of decision after decision, each made with good intention. My direct answer to your question is, "In your dreams."
> I know that there are social advantages to
> generic drugs, but I am uncertain about the
> safety of some them meeting the therapeutic
> index.If you intend to use medical jargon, please ensure that you are using it correctly. Therapeutic index is the ratio of a drug's toxic dose to its therapeutic dose. What you are (likely) trying to reference is called bioequivalency, or sometimes, therapeutic equivalency. The latter subsumes the former, but often only bioequivalency is formally tested.
> Do the same drug companies make them as
> well as the non-generic?Sometimes. Usually not.
> It would be kind of
> redundant wouldn't it, if they did.How so? Stealing away a portion of the generic market with what one would assume to be a high quality copy of the branded form makes good business sense. It's usually done through a subsidiary, though, if it is done.
> Why not
> make all drugs generic at the lower price?
>
> SquigglesAnd who is going to do any research thereafter?
The existing system has evolved in this particular format. It can costs 100's of millions of dollars to bring a single drug to market. It costs that much because the system has evolved to require multiple "phases" of research, each subsequent level depending on approval of the one before it. Remember thalidomide? Only the drug companies have the money to bridge the distance between academia/basic research and approved drugs. Social pressures are the cause of this expensive process.
You later make a comment about how drugs of fifty years ago were neither so expensive, nor so exclusively marketed. The first point is true, but the latter is false. Patented medicine, from Doan's Little Liver Pills, through to lithium carbonate, and on to Vioxx et al, has always been the way it's done.
Your beloved lithium could not pass current clinical trial requirements, IMHO. Just be thankful it got approved before the lawyers could sue the makers for thyroid toxicosis and kidney damage. Just consider how we accept *these* toxic effects without batting an eye, but we howl if one of the mose effective anti-inflammatory drugs in existence shows a correlation with heart attack. The causative link has never been demonstrated (unlike with lithium salts), as there are a number of possible alternative explanations for the statistical finding (e.g. subject selection bias), yet Vioxx is toast. And the lawyers get rich.
Lar
Time flies like an arrow. Fruit flies like a banana.
Posted by Squiggles on July 28, 2007, at 12:06:04
In reply to Re: Should all drugs be generic? » Squiggles, posted by Larry Hoover on July 28, 2007, at 10:11:31
> IMHO, the word should should not even be applied to this issue. The world is a certain way, and has become this way by a complicated path of decision after decision, each made with good intention. My direct answer to your question is, "In your dreams."
>
> > I know that there are social advantages to
> > generic drugs, but I am uncertain about the
> > safety of some them meeting the therapeutic
> > index.
>
> If you intend to use medical jargon, please ensure that you are using it correctly. Therapeutic index is the ratio of a drug's toxic dose to its therapeutic dose. What you are (likely) trying to reference is called bioequivalency, or sometimes, therapeutic equivalency. The latter subsumes the former, but often only bioequivalency is formally tested.
>I'm a layman, you sound like a doctor. Therapeutic index is primarily a toxicity measure, but bioequivalence will have to play a role in the making of copies of drugs as well as variability in generics.
> > Do the same drug companies make them as
> > well as the non-generic?
>
> Sometimes. Usually not.That's interesting. So, some companies make generics for the poor, and they are bioequivalent to non-generics? Do you now of such a company?
>
> > It would be kind of
> > redundant wouldn't it, if they did.
>
> How so? Stealing away a portion of the generic market with what one would assume to be a high quality copy of the branded form makes good business sense. It's usually done through a subsidiary, though, if it is done.More good moral sense for those who cannot afford the non-generics; unless you mean good advertising and PR by good business sense.
>
> > Why not
> > make all drugs generic at the lower price?
> >
> > Squiggles
>
> And who is going to do any research thereafter?Is research that expensive? Their profits are superflous when you compare them to the top companies in the world.
>
> The existing system has evolved in this particular format. It can costs 100's of millions of dollars to bring a single drug to market. It costs that much because the system has evolved to require multiple "phases" of research, each subsequent level depending on approval of the one before it. Remember thalidomide? Only the drug companies have the money to bridge the distance between academia/basic research and approved drugs. Social pressures are the cause of this expensive process.I think that they could economizie by cutting down on the unnecessary number of drugs which share the same chemical composition and backround in neuropsychiatric research.
>
> You later make a comment about how drugs of fifty years ago were neither so expensive, nor so exclusively marketed. The first point is true, but the latter is false. Patented medicine, from Doan's Little Liver Pills, through to lithium carbonate, and on to Vioxx et al, has always been the way it's done.
>
> Your beloved lithium could not pass current clinical trial requirements, IMHO. Just be thankful it got approved before the lawyers could sue the makers for thyroid toxicosis and kidney damage. Just consider how we accept *these* toxic effects without batting an eye, but we howl if one of the mose effective anti-inflammatory drugs in existence shows a correlation with heart attack. The causative link has never been demonstrated (unlike with lithium salts), as there are a number of possible alternative explanations for the statistical finding (e.g. subject selection bias), yet Vioxx is toast. And the lawyers get rich.
>I don't understand the thyrotoxicosis point-- lithium lowers the thyroid hormone not elevates it. Infact, lithium is used to thyrotoxicosis.
As for kidney damage, barring dehydration and initial kidney problems, lithium does not affect the kidneys if you drink adequate fluids. It is a side effect that has an urban pharmacology legend history.
> Lar
>
> Time flies like an arrow. Fruit flies like a banana.I'm not sure how profound that is.
Squiggles
Posted by Larry Hoover on July 28, 2007, at 12:51:03
In reply to Re: Should all drugs be generic? » Larry Hoover, posted by Squiggles on July 28, 2007, at 12:06:04
> I'm a layman, you sound like a doctor.
Then please speak without using jargon you don't understand. I could only sound like a doctor if I use the jargon properly, n'est-ce pas?
> Therapeutic index is primarily a toxicity measure,
Which is exactly what I just said.
> but bioequivalence will have to play a role in the making of copies of drugs as well as variability in generics.
Which is exactly what I just said, although more concisely than did you.
> So, some companies make generics for the poor, and they are bioequivalent to non-generics? Do you now of such a company?
They don't make generics for the poor. They make generics to try to maintain market share, after their patent expires. I do know of such a company, but I don't wish to become excessively tangential in this discussion. So, forget I said it.
> > Stealing away a portion of the generic market with what one would assume to be a high quality copy of the branded form makes good business sense.
>
> More good moral sense for those who cannot afford the non-generics; unless you mean good advertising and PR by good business sense.It's about selling drugs. Generics are only on the market after a drug goes off patent.
> > And who is going to do any research thereafter?
>
> Is research that expensive?Yes!
> Their profits are superflous when you compare them to the top companies in the world.
There are no more profitable companies than the pharmaceutical companies, within the realm of manufacturing as a whole. There are commodity companies (mining, especially), which are more profitable. I repeat, pharmaceutical companies are the most profitable among all manufacturing companies (earnings as percentage of revenue basis).
> I think that they could economizie by cutting down on the unnecessary number of drugs which share the same chemical composition and backround in neuropsychiatric research.
Your comment has no basis. A consumer need only choose from the least expensive drugs in a class, if your premise has any validity. However, supposedly similar drugs are not interchangeable in practise, so I cannot agree with you in any sense.
> > Your beloved lithium could not pass current clinical trial requirements, IMHO. Just be thankful it got approved before the lawyers could sue the makers for thyroid toxicosis and kidney damage.
> I don't understand the thyrotoxicosis point-- lithium lowers the thyroid hormone not elevates it. Infact, lithium is used to thyrotoxicosis.
You do understand. You're repeating what I just said. Lithium is thyrotoxic. End of story.
> As for kidney damage, barring dehydration and initial kidney problems, lithium does not affect the kidneys if you drink adequate fluids. It is a side effect that has an urban pharmacology legend history.False! There are numerous nephritic complications of lithium prophylaxis in bipolar disorder. Just do a search on one of them, nephritic diabetes insipidus, and you'll know you're mistaken. Here, I'll even start you off:
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11999908
Lar
Posted by Squiggles on July 28, 2007, at 13:14:22
In reply to Re: Should all drugs be generic? » Squiggles, posted by Larry Hoover on July 28, 2007, at 12:51:03
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11999908
>
> LarI can find many articles and recent researches on this (see LITHIUM IN NEUROPSYCHIATRY - Bauer, Grof, and Mu[..]ller-Oerlignhausen) that say the contrary.
In the majority of cases, lithium inhibits thyroid hormone secretion rate by an increase in TSH concentration. Sometimes goiter and enlargement of the thyroid results. In some interesting, rare case there is the phenomenon of hyperthyroidism-- but that is a clinical oddity; is this what you are referring to by toxicity?
Also, let me remind you that patients on lithium are regularly checked for TSH function.
And in my case, i have been on lithium since i think about 1986, and have a steady level of creatine clearance, and TSH, with the TSH lowered in the first couple of years and remaining at a level where Synthroid was required, and the dose changed 2 or 3 x since. Therefore, you could say I am stable.
Furthermore, if i did try to get off lithium, given a stable state which others might envy on other drugs, it is not a certain that the thyroid gland could be reversed to its initial natural state.
P.S. Could you please approach a milder tone with me; you seem irritated by my posts or me.
Squiggles
Posted by Klavot on July 28, 2007, at 15:26:23
In reply to Re: Should all drugs be generic? » Larry Hoover, posted by Squiggles on July 28, 2007, at 12:06:04
> That's interesting. So, some companies make generics for the poor, and they are bioequivalent to non-generics? Do you now of such a company?
Hi Squiggles
To paraphrase Shakespeare, a molecule by any name is still the same molecule. Generally speaking, generics are not of inferior quality, and they are not targeted at poor people. By law, they need to be bioequivalent to within a certain margin with the brand-name drug. So you're getting pretty much the same chemicals but at a much lower price.
Klavot
Posted by Squiggles on July 28, 2007, at 15:31:10
In reply to Re: Should all drugs be generic? » Squiggles, posted by Klavot on July 28, 2007, at 15:26:23
> > That's interesting. So, some companies make generics for the poor, and they are bioequivalent to non-generics? Do you now of such a company?
>
> Hi Squiggles
>
> To paraphrase Shakespeare, a molecule by any name is still the same molecule. Generally speaking, generics are not of inferior quality, and they are not targeted at poor people. By law, they need to be bioequivalent to within a certain margin with the brand-name drug. So you're getting pretty much the same chemicals but at a much lower price.
>
> Klavot
So, if they are bioequivalent, as the FDA assures us, and they are not targeted at poor people, then why make them at all?Squiggles
p.s. it takes more than a molecule to make a drug in most cases i would think;
Posted by Klavot on July 28, 2007, at 15:51:49
In reply to Re: Should all drugs be generic? » Klavot, posted by Squiggles on July 28, 2007, at 15:31:10
Hi Squiggles
> So, if they are bioequivalent, as the FDA assures us, and they are not targeted at poor people, then why make them at all?
Once the patent to a drug expires, other pharmaceutical companies are able to profit by selling a generic version of that drug at a cheaper price.
> p.s. it takes more than a molecule to make a drug in most cases i would think;
Yes, but the active molecule is where most of the innovation lies.
Klavot
Posted by Squiggles on July 28, 2007, at 16:01:23
In reply to Re: Should all drugs be generic?, posted by Klavot on July 28, 2007, at 15:51:49
> Hi Squiggles
>
> > So, if they are bioequivalent, as the FDA assures us, and they are not targeted at poor people, then why make them at all?
>
> Once the patent to a drug expires, other pharmaceutical companies are able to profit by selling a generic version of that drug at a cheaper price.
>
> > p.s. it takes more than a molecule to make a drug in most cases i would think;
>
> Yes, but the active molecule is where most of the innovation lies.
>
> Klavot
Can't help it but my mind turns to biology and
parisitic opportunism. I wonder if there is a concept for that in Marketing Management.Squiggles
Posted by Larry Hoover on July 29, 2007, at 10:33:01
In reply to Re: Should all drugs be generic? » Larry Hoover, posted by Squiggles on July 28, 2007, at 13:14:22
> http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11999908
> >
> > Lar
>
> I can find many articles and recent researches on this (see LITHIUM IN NEUROPSYCHIATRY - Bauer, Grof, and Mu[..]ller-Oerlignhausen) that say the contrary.??
I presented empirical evidence of kidney function disturbance by lithium, which took me less than 10 seconds to find. It is irrelevant that others exclude data to reach contrary conclusions.
Moreover, I showed one of many kidney disturbances from lithium intake. I've already shown your supposition to be false.
> > Time flies like an arrow. Fruit flies like a banana.
> I'm not sure how profound that is.
It's not meant to be profound. It's a simple word play. The first statement primes the mind into considering one option, whereas the second statement is about something else entirely. It is not that 'fruit (collective noun)' 'flies (verb intransitive)', but that 'fruit flies (noun plural)' 'like (verb intransitive)'.....
> P.S. Could you please approach a milder tone with me; you seem irritated by my posts or me.
>
> SquigglesI think that's your perception.
Lar
Posted by Larry Hoover on July 29, 2007, at 10:36:08
In reply to Re: Should all drugs be generic? » Squiggles, posted by Larry Hoover on July 29, 2007, at 10:33:01
> It's not meant to be profound. It's a simple word play. The first statement primes the mind into considering one option, whereas the second statement is about something else entirely. It is not that 'fruit (collective noun)' 'flies (verb intransitive)', but that 'fruit flies (noun plural)' 'like (verb intransitive)'.....
Ooops. I meant the latter was transitive, or I'd not have included the descriptor.
Lar
Posted by Squiggles on July 29, 2007, at 10:49:58
In reply to Re: Should all drugs be generic? » Squiggles, posted by Larry Hoover on July 29, 2007, at 10:33:01
> > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11999908
> > >
> > > Lar
> >
> > I can find many articles and recent researches on this (see LITHIUM IN NEUROPSYCHIATRY - Bauer, Grof, and Mu[..]ller-Oerlignhausen) that say the contrary.
>
> ??
>
> I presented empirical evidence of kidney function disturbance by lithium, which took me less than 10 seconds to find. It is irrelevant that others exclude data to reach contrary conclusions.
>
> Moreover, I showed one of many kidney disturbances from lithium intake. I've already shown your supposition to be false.
REPLY:
Is it "disturbance" or is it "toxicity" or both--
you seem to be wavering.http://www.emedicine.com/med/topic1313.htm
"The role of lithium in the production of acute renal failure is well accepted. The cause is generally due to severe dehydration and volume depletion due to the combination of natriuresis and water diuresis accompanied by elevated lithium levels, altered mental status, and subsequent poor oral intake. Acute renal failure has also been described as a result of lithium-induced neuroleptic malignant syndrome. However, controversy still exists over its role in chronic renal failure. Boton et al estimated (from an analysis of more than 1000 patients) that 85% of patients on long-term lithium therapy had normal glomerular filtration rates (GFRs); the remaining 15% had GFRs of more than 2 standard deviations below the age-corrected normal values, but very few patients had values less than 60 mL/min.
Extensive reviews in 1988 and 1989 suggested that monitored long-term lithium treatment does not adversely affect the GFR, despite other reports of concurrent histological damage. Prospective studies of patients taking stable lithium also failed to show a decline in GFR in the absence of acute lithium intoxication. Although a minimal increase in the protein excretion rate has been reported in some patients who were taking lithium for at least 2 years, overt proteinuria is not a common complication. A rare association between minimal-change nephrotic syndrome and lithium administration has also been described.
Lithium does not appear to adversely affect proximal tubular function."
-----
Please not Larry, that if you are referring to
nephrogenic diabetes insipidus, i have been tested for that. I am monitored. And, my voiding is almost clockwork regular. See the conditions which may lead to renal failure above.
And keep in mind that other psychiatric drugs also lead to "toxic" effects, under certain conditions; for example cardiac arrest due to prolonged or large dose of some tricyclics.Squiggles
Posted by Larry Hoover on July 29, 2007, at 11:29:18
In reply to Re: Should all drugs be generic? » Larry Hoover, posted by Squiggles on July 28, 2007, at 12:06:04
> > Your beloved lithium could not pass current clinical trial requirements, IMHO. Just be thankful it got approved before the lawyers could sue the makers for thyroid toxicosis and kidney damage. Just consider how we accept *these* toxic effects without batting an eye, but we howl if one of the mose effective anti-inflammatory drugs in existence shows a correlation with heart attack. The causative link has never been demonstrated (unlike with lithium salts), as there are a number of possible alternative explanations for the statistical finding (e.g. subject selection bias), yet Vioxx is toast. And the lawyers get rich.
> >
>
> I don't understand the thyrotoxicosis point-- lithium lowers the thyroid hormone not elevates it. Infact, lithium is used to thyrotoxicosis.Here we go again, with the jargon issue. I apologize for not being 100% rigorous with my semantics, but I did not ever mention thyrotoxicosis. I mentioned thyroid toxicosis, whereby what I meant was "lithium-induced toxicosis of the thyroid", i.e. that the thyroid was the specific organ affected by toxic lithium exposure.
Thyrotoxicosis is a specific effect of hyperthyroidism. That is not what I meant at all, and I apologize for opening the door on that misinterpretation of my words.
Lithium influences iodine uptake and storage in the thyroid. Goiter is a common result of lithium therapy (about 1 in 4 users). Frank hypothyroidism is far more common among lithium users than in the broader population. I dispute that TSH influences the thyroid, but that TSH is a result of thyroid defects caused by lithium. In the end, the argument is moot, IMHO, as I intended the broadest possible interpretation of the thyro-toxic effects of lithium. Mechanisms were not my concern.
Lar
Posted by Larry Hoover on July 29, 2007, at 12:00:52
In reply to Re: Should all drugs be generic? » Larry Hoover, posted by Squiggles on July 29, 2007, at 10:49:58
> > I presented empirical evidence of kidney function disturbance by lithium, which took me less than 10 seconds to find. It is irrelevant that others exclude data to reach contrary conclusions.
> >
> > Moreover, I showed one of many kidney disturbances from lithium intake. I've already shown your supposition to be false.
>
>
> REPLY:
>
>
> Is it "disturbance" or is it "toxicity" or both--
> you seem to be wavering.I am not wavering in the least.
>
> http://www.emedicine.com/med/topic1313.htm
>
> "The role of lithium in the production of acute renal failure is well accepted...."Let's stop right there. For a moment, and let that sink in. Your reference, right?
As I stated in the quoted portion of my prior post, above, "It is irrelevant that others exclude data to reach contrary conclusions."
The segment of the article you reference was cherry-picked, and it thus is out of context. It is common in the introduction to a review article to lay out the pros and cons of an argument. You have quoted only one side of the story.
If you were to only review the referenced articles for this one piece (rather than the entire body of medical literature), this, in part, is what you would find:
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=3314489
Am J Kidney Dis. 1987 Nov;10(5):329-45.
Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy.
Boton R, Gaviria M, Batlle DC.
Department of Psychiatry, University of Illinois at Chicago."...The most prevalent renal effect of lithium is impairment of concentrating ability, which we estimated to be present in at least 54% of 1,105 unselected patients on chronic lithium therapy. This defect translated into overt polyuria in only 19% of unselected cases. A renal lesion confined to the collecting tubule has been described in humans who have taken lithium for short periods of time. This lesion may represent the collecting tubule's response to the intracellular accumulation of lithium, which interferes with cAMP formation and results in an early and probably reversible inhibition of antidiuretic hormone (ADH)-mediated water transport. However, long-term lithium therapy may induce a progressive and partly irreversible defect in concentrating ability...."
So, in 1987, they presume a partly irreversible defect, but by 2005, that changes to "CONCLUSION: ...Long-term treatment with lithium seemed to result in irreversible NDI."
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15806465
Am J Kidney Dis. 2005 Apr;45(4):626-37.
Causes of reversible nephrogenic diabetes insipidus: a systematic review.
Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF.
Division of Nephrology, Walkerton Health Study, London Health Science Centre, Westminster Campus, Canada.BACKGROUND: In nephrogenic diabetes insipidus (NDI), the kidney is unable to produce concentrated urine because of the insensitivity of the distal nephron to antidiuretic hormone (arginine vasopressin). In settings in which fluid intake cannot be maintained, this may result in severe dehydration and electrolyte imbalances. The risk for conversion of reversible to irreversible NDI seems to be a potential complication. This review summarizes the reversible causes of acquired NDI to facilitate earlier recognition and more effective treatment by clinicians. METHODS: Two reviewers independently searched MEDLINE, Experta Medica (EMBASE), and ISI bibliographic databases. Human studies that described NDI caused by drugs, substances, or metabolic disturbances were included. To evaluate the causal role of the risk factor, data were abstracted according to Koch's postulates. RESULTS: One hundred fifty-five studies published between 1957 and March 2004 described 30 risk factors. Of 155 studies, 58 studies provided a "definite" diagnosis of NDI; 83 studies, a "probable" diagnosis; and 14 studies, a "possible" diagnosis. Nine factors were considered "definite" causes of NDI; 15 factors, "probable" causes; and 6 factors, "possible" causes. The most reported risk factors were lithium (84 studies), antibiotics (16 studies), antifungals (11 studies), antineoplastic agents (9 studies), antivirals (8 studies), and metabolic disturbances (8 studies). Duration of NDI reversal, as well as conversion to irreversible symptoms, seemed to depend on the duration of exposure. CONCLUSION: Most risk factors for reversible NDI were medications, and their identification and removal resulted in resolution of the condition. Long-term treatment with lithium seemed to result in irreversible NDI.
Nota bene that last sentence. Remember, this was your reference. I didn't even have to show you the ones I found.
And about thyrotoxicosis, there is a significant increase over baseline in lithium-exposed patients:
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11678833
Clin Endocrinol (Oxf). 2001 Oct;55(4):501-8.
Association between lithium use and thyrotoxicosis caused by silent thyroiditis.
Miller KK, Daniels GH.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.OBJECTIVE: To determine the incidence of silent thyroiditis in lithium users and characterize lithium-associated thyrotoxicosis. DESIGN: Retrospective record review. PATIENTS: 400 consecutive patients (300 with Graves' disease and 100 with silent thyroiditis) who underwent radioiodine scanning of the thyroid. MEASUREMENTS: Odds of lithium exposure. RESULTS: The odds of lithium exposure were increased 4.7-fold in patients with silent thyroiditis compared with those with Graves' disease (95% CI: 1.3, 17). Lithium-associated silent thyroiditis occurred with an incidence rate of approximately 1.3 cases per 1000 person-years, and lithium-associated thyrotoxicosis occurred with an incidence rate of approximately 2.7 cases per 1000 person-years, higher than the reported incidence rates of silent thyroiditis (< 0.03-0.28 cases per 1000 person-years) and of thyrotoxicosis (0.8-1.2 cases per 1000 person-years) in the general population. CONCLUSION: Thyrotoxicosis caused by silent thyroiditis might be associated with lithium use.
The thing is, Squiggles, a valid theory must account for all empirical findings. I'm trying to account for the evidence that is available for consideration. The Garofeanu et al study is a meta-analysis. That's not cherry-picking. Although the title of the review is about reversible NDI, they yet conclude that lithium causes irreversible NDI.Lar
Posted by Squiggles on July 29, 2007, at 12:10:36
In reply to Re: lithium » Squiggles, posted by Larry Hoover on July 29, 2007, at 12:00:52
I think you cherry-pick too. You're bright
alright, and you have been in the clinical
settings, but i think you have an agenda.Squiggles
Posted by Larry Hoover on July 29, 2007, at 12:31:52
In reply to Re: lithium » Larry Hoover, posted by Squiggles on July 29, 2007, at 12:10:36
> I think you cherry-pick too. You're bright
> alright, and you have been in the clinical
> settings, but i think you have an agenda.
>
> SquigglesHow so?
There are some basic scientific principles at play, here. It is impossible to prove a negative. It appears that your premise is that lithium doesn't do certain things. Yet, significant findings are abundant which are inconsistent with the null hypothesis.
I don't think that I'm the one with the agenda.
Lar
Posted by Squiggles on July 29, 2007, at 13:41:12
In reply to Re: lithium » Squiggles, posted by Larry Hoover on July 29, 2007, at 12:31:52
> I don't think that I'm the one with the agenda.
>
> Lar
>
>If not agenda, at least a question of interpretation to support your questionable
certainty that lithium IS AND MUST do serious
renal damage. All drugs do damage after a chronic period of use. Lithium should be
weighed against them, and see if it does not
infact come up as one of the best for lifelong treatment.
---------------------------------------------
1: Drug Saf. 1999 Mar;20(3):231-43.Links
Lithium and the kidney: an updated review.
Gitlin M.University of California, Los Angeles, Department of Psychiatry, USA. MGitlin@NPIH.medsch.ucla.edu
Despite the availability of alternative agents, lithium continues to be the standard against which all mood stabilisers, prescribed for acute and maintenance treatment of bipolar (and, to a lesser extent, unipolar) mood disorders, are compared. As a medication often used on a maintenance basis for a lifelong disorder, the potential for lithium to cause long term organ toxicity has generated appropriate concern. Foremost among these concerns are its renal effects. Lithium adversely affects renal tubular function, causing polyuria secondary to a deficit in urine concentrating ability. This effect is probably progressive for the first decade of lithium therapy, i.e. it correlates with duration of lithium therapy. Although this effect of lithium is probably functional and reversible early in treatment, it may become structural and irreversible over time. In contrast, the effect of lithium on glomerular function is not progressive. Conclusions in this area are hampered by the evidence that patients with psychiatric disorders who are not receiving lithium also show defects in certain aspects of renal function. Despite the generally sanguine data on glomerular function, a very small group of patients may develop renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, for the vast majority of patients, the renal effects of lithium are benign. Current strategies for minimising the renal effects of lithium include: (i) assiduously avoiding episodes of renal toxicity; (ii) monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentration; (iii) monitoring serum creatinine levels on a yearly basis, getting further medical evaluation when the serum creatinine level consistently rises above 140 mmol/L (1.6 mg/dl); and (iv) possibly administering lithium once a day.
------------------------------------------------
PMID: 10221853 [PubMed - indexed for MEDLINE]
Posted by Larry Hoover on July 29, 2007, at 14:15:04
In reply to Re: lithium » Larry Hoover, posted by Squiggles on July 29, 2007, at 13:41:12
>
> > I don't think that I'm the one with the agenda.
> >
> > Lar
> >
> >
>
> If not agenda, at least a question of interpretation to support your questionable
> certainty that lithium IS AND MUST do serious
> renal damage.I did not say anything of the sort. I would never use such language.
From your referenced piece: "Although this effect of lithium is probably functional and reversible early in treatment, it may become structural and irreversible over time."
Let's recap the sequence of debated issues.
You initially questioned the sociological value of patented drugs, arguing that generics would be of greater value to society.
You then questioned if lithium could have been patented, and suggested that drugs (such as lithium) from the 1950's were somehow both cheaper and superior to later developments.
I then entered the discussion, suggesting that doing away with drug patents would destroy drug research and development as it is presently conducted. Furthermore, I declared that lithium would never be approved under current drug testing guidelines. Although a minor point in what I had written, you chose to focus on that one issue.
I won't re-argue the presentation of evidence, but I believe that the null hypothesis is inconsistent with the body of evidence. I reserve my conclusions until after studying the data, to avoid confirmation bias. (However, I also accept that to believe that might also demonstrate bias. I am reminded of Escher, but I digress....)
What is most interesting to me is that, despite your protestations that lithium is safe to the thyroid and the kidney, your own doctor routinely tests these functions. You seem to derive some comfort from this. I suggest that you have simply been lucky, both in having the doctor you have (only about 1/3 of lithium-treated patients even get routine thyroid testing), and in the negative results therefrom.
Generalizing from your experience, one might conclude that lithium is safe. However, the experience of others is also relevant to the issue of safety.
Lar
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