Wednesday, April 13, 2011

Bipolar Disorder: Lithium Posts


May 09, 2008


Nanking Poster: THINKFilm
On July 2, 1996, the anniversary of Ernest Hemingway’s own suicide, Margaux Louise Hemingway, his grand daughter was found dead in her studio apartment in Santa Monica, California at age 41.

On November 9, 2004, Iris Chang (張純如), who was propelled into the limelight by her 1997 best-selling account of the Nanking Massacre “
The Rape of Nanking: The Forgotten Holocaust of World War II”, committed suicide. Earlier she had a nervous breakdown and was said to be at the risk of developing Bipolar illness. She was on the mood stabilizer divalproex and Risperidone, an antipsychotic drug commonly used to control mania. There was a detailed report in San Francisco Chronicle.

My sentiments about the treatment of bipolar illness are expressed in The Cockroach Catcher:
“I am a traditionalist who believes that Lithium is still the drug of choice for Bipolar disorder. Tara’s mother was well for ten years. She was taking only Lithium and no other medication.”

The anti-suicidal effect of lithium has been confirmed by a number of recent studies in both the U.S. and in Europe.


According to the results of a population-based study published in the 2003 Sept. 17 issue of The Journal of the American Medical Association (JAMA. 2003;290:1467-1473, 1517-1519), Lithium reduced suicide rates of patients with bipolar disorder but divalproex did not. Risk of suicide death was about 2.5-fold higher with divalproex than with lithium.

Another paper published in 2005 
(Arch Suicide Res. 2005;9(3):307-19) reviewed the existing evidence.

“The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithium's episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.”

The JAMA paper highlighted the declining use of lithium by psychiatrists in the United States and observed that:


"Many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."

One might ask why there has been such a shift from Lithium.

Could it be the simplicity of the salt that is causing problems for the younger generation of psychiatrists brought up on various neuro-transmitters?

Could it be the fact that 
Lithium was discovered in Australia? Look at the time it took for Helicobacter pylori to be accepted.

Some felt it has to do with how little money is to be made from Lithium.

My questions are: Will the new generation of psychiatrists come round to Lithium again? How many talented individuals could have been saved by lithium?

May 19, 2009


Just before I retired, it has become fashionable to use anticonvulsants as a mood stabiliser. Being a traditionalist, I felt then that the evidence was not clear and I tended to stick with the trusted lithium.

Well my doubts were confirmed:
Journal of the American Academy of Child & Adolescent Psychiatry:
May 2009 - Volume 48 - Issue 5 - pp 519-532
doi: 10.1097/CHI.0b013e31819c55ec
New Research


A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents
WAGNER, KAREN DINEEN M.D. et al.
AbstractObjective: To compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study.
Method: In the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 μg/mL. Sixty-six patients enrolled in the extension study.
Results: In the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER -8.8 [n = 74]; placebo -7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting.
Conclusions: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(5):519-532.

An earlier Harvard study showed that Lithium reduced suicide risks by as much as 9 fold.


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