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Re: lithium » Squiggles

Posted by Larry Hoover on August 1, 2007, at 11:00:02

In reply to Re: lithium, posted by Squiggles on August 1, 2007, at 9:15:25

> I tried to post the texts but there were too many unacceptable characters,

Just cut and paste into a program like Notepad. It gets rid of all the formatting.

> so here are the url's:
>
> Some articles on renal effects and lithium:
>
> http://sunzi1.lib.hku.hk/hkjo/view/21/2100155.pdf

From 1986.

> http://archpsyc.ama-assn.org/cgi/content/abstract/54/1/9

Personal opionion, with no evidence presented. There is nothing to consider.

> http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=424553

Rabbits, from 1986.

> http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=239687

1987 paper, about diabetes mellitus, a different disorder altogether.

> http://www.emedicine.com/med/topic1313.htm

This paper I already critiqued. It was the one you cherry-picked from. And you've never addressed the findings of the referenced Garofeanu et al meta-analysis.

> http://www.healthieryou.com/mhexpert/exp1120103e.html

This article references Bendz et al:

Nephrol Dial Transplant (1994) 9: 1250-1254
© 1994 European Renal Association-European Dialysis and Transplant Association


Kidney damage in long-term lithium patients: A cross-sectional study of patients with 15 years or more on lithium
H. Bendz1, M. Aurell2,, J. Balldin3, A. A. Mathé4 and I. Sjödin5
1Department of Psychiatry, University of Lund Lund 2Nephrology, University of Göteborg Göteborg 3Psychiatry and Neurochemistry, University of Göteborg Göteborg 4Department of Psychiatry, Karolinska Institute Stockholm 5Department of Psychiatry, University of Linköping Linköping, Sweden

Correspondence and offprint requests to: Correspondence and offprint requests to: Dr M. Aurell, Njurkliniken Göteborg liniversitet, Sahlgrenska Sjukhuset, 41345 Goteborg, Sweden

The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.

You really ought to read everything Bendz has published.

> http://www.antenna.nl/lithium/english/postgrad/vasopressin_ep.htm

Neither evidence nor arguments provided, unless you think "further research required" is noteworthy.

> http://jpet.aspetjournals.org/cgi/content/full/289/1/443

The article is really about another drug, amiloride, and the subjects are rats. We already knew that lithium affected aldosterone responsiveness.

> I think I will stop here now.

Where is your argument? What have you shown?

> You can go on with the appropriate key words, and you may already
> have. Obviously, the research shows that as far as renal effects go, there is substantial evidence
> that the kidneys are affected.

I think that's *my* argument.

> This is just one of the effects that lithium has.

I recall making that argument myself, also.

> Personally, I would be
> more concerned with the bradycardia that is induced by lithium and does not receive as lengthy
> study (as far as i have seen on the net).

I also mentioned that there were other adverse effects, which I had yet to list or consider.

> I have had periods of such an occurrence and neither clinics
> nor doctors considered it as significant enough as renal checks.

Okay.

> Regarding renal clearance and kidney changes, my question would be, to what extent this is
> a serious pathology enough to change from lithium to say depakote, wich has its own can of worms,
> raising weight about 3 to 4 times than lithium and affecting the liver, and causing neurological damage
> upon withdrawal.

Usually when the kidneys are so damaged as they can no longer tolerate continued lithium exposures.

> At least with lithium it is possible to have a clearance by stopping it for some time.

Only to re-expose to the toxin, thereafter?

> Also, the effects of lithium toxicity are detectable both personally and through lab tests, and therefore
> easy to monitor.

So you acknowledge lithium toxicosis is real?

> In seniors or women, the dose may be lowered, or an adjunct given.
>
> Given the incomparable specificity, mental clarity, and suicide prevention that this drug can provide,
> the physiological effects should be compared and weighed against other drugs, which can be researched
> for more severe side effects.

Oh, really? Cochrane disagrees with your conclusions.

Cochrane Database Syst Rev. 2001;(3):CD003013

Lithium for maintenance treatment of mood disorders.Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G.
Department of Psychiatry, University of Oxford, Oxford, UK, OX3 7JX. [email protected]

BACKGROUND: Mood disorders are common, disabling and tend to be recurrent. They carry a high risk of suicide. Maintenance treatment, aimed at the prevention of relapse, is therefore of vital importance. Lithium has been used for some years as the mainstay of maintenance treatment in bipolar affective disorder, and to a lesser extent in unipolar disorder. However, the efficacy and effectiveness of prophylactic lithium therapy has been disputed. Low suicide rates in lithium-treated patients have led to claims that lithium has a specific anti-suicidal effect. If so, this is of considerable importance as treatments for mental disorders in general have not been shown convincingly to be effective in suicide prevention. OBJECTIVES: 1. To investigate the efficacy of lithium treatment in the prevention of relapse in recurrent mood disorders. 2. To examine the effect of lithium treatment on consumers' general health and social functioning, its acceptability to consumers, and the side-effects of treatment. 3. To investigate the hypothesis that lithium has a specific effect in reducing the incidence of suicide and deliberate self-harm in persons with mood disorders. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) and The Cochrane Controlled Clinical Trials Register (CCTR) were searched. Reference lists of relevant papers and major text books of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. Specialist journals concerning lithium were hand searched. SELECTION CRITERIA: Randomised controlled trials comparing lithium with placebo, where the stated intent of treatment was maintenance or prophylaxis. Participants were males and females of all ages with diagnoses of mood disorder. Discontinuation studies (in which all participants had been stable on lithium for some time before being randomised to either continued lithium treatment or placebo substitution) were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. The main outcomes studied were related to the objectives stated above. Data were analysed for all diagnoses of mood disorder and for bipolar and unipolar disorder separately. Data were analysed using Review Manager version 4.0. MAIN RESULTS: Nine studies were included in the review, reporting on 825 participants randomly allocated to lithium or placebo. Lithium was found to be more effective than placebo in preventing relapse in mood disorder overall, and in bipolar disorder. The most consistent effect was found in bipolar disorder (random effects OR 0.29; 95% CI 0.09 to 0.93 ). In unipolar disorder, the direction of effect was in favour of lithium, but the result (when heterogeneity between studies was allowed for) did not reach statistical significance. Considerable heterogeneity was found between studies in all groups of patients. The direction of effect was the same in all studies; no study found a negative effect for lithium. Heterogeneity may have been due to differences in selection of participants, and to differing exposures to lithium in the pre-study phase resulting in variable influence of a discontinuation effect. There was little reported data on overall health and social functioning of participants under the different treatment conditions, or on the participants' own views of their treatment. Descriptive analysis showed that assessments of general health and social functioning generally favoured lithium. Small absolute numbers of deaths and suicides, and the absence of data on non-fatal suicidal behaviours, made it impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention. REVIEWER'S CONCLUSIONS: This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behaviour should be included in all future maintenance studies of mood disorder.


In fact, lithium is the most poorly studied common psych medication in use today. Oh, there's been a lot written *about* it, but it has not been subjected to rigourous controlled studies of good quality.

We view lithium differently because it was grandfathered into use. Just like ECT. Neither one would stand a hope of being approved as a treatment under today's perceptions of acceptable medical risk.

I would argue that medical complications arising from lithium are vastly under-reported. Doctors "know" that lithium messes with the heart and brain and kidney and thyroid and parathyroid etc., so what's there to report? They just go on to treat the problem as best they can. And there's no big pharma big wallet to get sued, either.

Lar

 

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poster:Larry Hoover thread:772306
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