In recent times psychiatrists have begun moving away from Lithium and toward anti-convulsant drugs for long term stabilization of mood in patients with bipolar disorder. Anti-convulsants are drugs which were initially designed and FDA approved to prevent seizures in persons with epilepsy. Although anti-convulsants appear to work as a mood stabilizer for bipolar patients, questions have been raised about their safety, because some studies showed they increased the probability of suicide in the patients who take them. In December 2008 the FDA required all manufacturers of anti-convulsants to insert a warning about increased risk of suicide in the box without specifying the relative risks of particular brands. This move by the FDA was precipitated by its analysis of 199 clinical trials of 11 anti-epileptic drugs which showed that patients receiving anti-epileptic drugs had almost twice the risk of suicidal behavior or thoughts compared to patients receiving a placebo.
Bipolar I involves shifting back and forth from mania to depression, while Bipolar II involves shifting back and forth from hypomania (a less intense form of mania) to depression. Since bipolar disorder involves a depressive phase which can be highly serious and lead to suicidal thoughts, acts of self-harm or even completed suicide, it’s necessary to treat bipolar patients with an anti-depressant. These days anti-depressants are the most commonly prescribed drugs for people with bipolar disorder. On the other hand, psychiatrists have found that anti-depressants alone are not adequate to treat bipolar disorder. That’s because an anti-depressant can mask a manic episode or even shoot a bipolar patient into mania. On the medication side the appropriate treatment for bipolar patients involves an anti-depressant and a mood stabilizer. On the non-medication side it involves psychotherapy, cognitive-behavioral therapy, exercise, proper sleep and nutrition and helping the patient control his drinking if that is an issue.
After it was approved for treatment of bipolar disorder by the FDA in 1970 Lithium became the universal drug of choice to stabilize mood in bipolar I patients. Lithium had a good safety record. It showed effectiveness in reducing the frequency and severity of manic episodes. It helped relieve depression in some bipolar I patients and reduced the suicide risk in bipolar patients. Lithium also helped manic-depressives control their drinking. It was considered, and still is considered, a good maintenance drug for people with bipolar I.
No drug is perfect. Lithium only works if the blood level is not too high or too low. Long term use can suppress thyroid function and cause kidney damage. Patients taking it are advised to drink 8-12 glasses of water a day and get their blood checked periodically to monitor lithium concentration, which can kill people if it gets too high. Long term use is also associated with mild cognitive impairment, weight gain and tremors.
There is no question that psychiatrists have moved in droves away from Lithium to anti-convulsants. Depakote is prescribed twice as often as Lithium for bipolar patients. As a group anti-convulsants also have significant side effects. Like Lithium, anti-convulsants can cause weight gain, cognitive impairment and tremors and like Lithium they can’t be taken by pregnant women because they cause birth defects. Personally, I’m not entirely clear why there has been this mass movement. It may have something to do with the availability of new drugs, wanting to be on the cutting edge and having drug reps swarm doctor’s offices to push the new drugs. Is this move from Lithium to anti-convulsants a good thing for patients? There are many psychiatrists who say yes.
On the other hand at least one very highly knowledgeable person says no. Dr. Ross Baldessarini is a professor of psychiatry and neuroscience at Harvard Medical School and director of the psychopharmacology program and the International Consortium for Bipolar Disorders Research at McLean Hospital. He knows that reducing risk of suicide is a major public health challenge, and that suicide rates in patients with bipolar disorder are among the highest of any diagnostic group. Three out of every one thousand people with bipolar disorder commit suicide, a rate twenty times higher than the rate in the general population. Dr. Baldessarini says, “Long-term use of lithium is the only treatment we have that is proven to reduce risk of suicides and life-threatening attempts.”
Now lets look a paper which came out in the July 27, 2010 issue of Neurology. A group of investigators led by Frank Anderson, M.D., of Berlin, Germany, wanted to ascertain the relative rise in the suicide risk caused by between different classes of anti-seizure drugs. The reviewed data on 44,300 patients in the United Kingdom who had taken at least one prescription for an epilepsy drug between 1989 and 2005. Participants were followed for an average of 5.5 years. Out of the entire group 453 had harmed themselves or attempted suicide; and 78 died at the time of or within four weeks of the initial attempt. The 453 people were compared to 8,962 sex and age matched peers in the larger group who had not harmed themselves or attempted suicide.
The investigators found that people currently using newer anti-convulsants like Topomax, Keppra, Sabril or Gabatril were three times more likely to harm themselves or attempt suicide than those who were not currently taking any epilepsy drugs. They did not find a statistically significant increase in the risk of suicide from taking Depakote, Tegretol, Dilantin, Neurontin or Lamictal (a drug which carries a small but scary risk of incurring a bizarre, fatal condition that causes all of your skin to slough off). Their finding that Depakote did not increase depression or raise the risk of suicide is a good thing since so many bipolar patients are taking it.
So where does this leave us? For mood stabilization most Bipolar I patients are taking Lithium (which lowers the suicide rate) or Depakote (which the study by Dr. Anderson said doesn’t raise it). For those Bipolar I patients taking Topomax, Keppra, Sabril or Gabatril, I suggest you have a talk with your doctor and tell him about the article. Most Bipolar II patients are taking an anti-convulsant or anti-psychotic for mood stabilization. These patients should also speak with their doctor, especially if they have been prescribed one of the three drugs highlighted by Dr. Anderson’s group. Although anti-psychotics appear to have good mood-stabilizing properties, as a group they tend to cause significant weight gain and increase in blood sugar with increased risk of diabetes. It’s very important to stay informed and to voice any concerns or complaints you have about medication side effects to your psychiatrist so he can assess them and work with you to make a medication adjustment in a safe, thoughtful manner.
