As the treatment arsenal for bipolar (manic-depressive) disorder has expanded in recent years, some experts have become concerned that lithium — a mainstay of treatment since FDA approval in 1970 and still considered the most effective option for long-term therapy — may be falling out of favor.
Treatment options besides lithium include anticonvulsants with mood-altering properties, notably valproate (Depakene, Depakote), carbamazepine (Epitol, Tegretol), and lamotrigine (Lamictal), as well as antipsychotics and antidepressants. As the options have multiplied, prescribing patterns have shifted.
In the United States, valproate is now being used twice as often as lithium as a treatment for bipolar disorder, especially for long-term maintenance therapy, despite questions about its relative effectiveness. And antidepressants are being used more often than any other medications to treat patients with bipolar disorder. As more new drugs become available, the trend in treating bipolar disorder is toward increasingly complex regimens, involving untested combinations of a variety of drugs.
This trend concerns a number of leading experts, because studies have found that people with bipolar disorder taking lithium were significantly less likely to die by suicide than others not treated with lithium, or given other treatments. Even so, their suicide rate was still significantly higher than that of the general population.
Why lithium reduces the risk of suicide in people with bipolar disorder is not entirely clear, but it is likely that the drug's mood-stabilizing properties contribute.
To be used safely, however, lithium treatment requires regular monitoring by a doctor or a qualified nurse, including regular visits and blood tests.
Lithium has a narrow "therapeutic window," which means there is a small difference between a helpful dose and a harmful one. In other words, it can become toxic if blood levels increase much above the therapeutic range (between 0.6 and 1.2 millimoles per liter, or mmol/L). Blood levels only two to three times greater can cause medical problems, and somewhat higher levels may be deadly. Long-term lithium treatment also carries some risk of weakening the functioning of the kidneys or the thyroid gland.
To avoid toxicity, lithium is started at relatively low doses and increased gradually. Blood levels are monitored more regularly during the first months of therapy. Clinicians usually order lithium blood tests every few days at first, then weekly, monthly, and — assuming a reliable individualized dose has been established — every 3 to 6 months. The American Psychiatric Association (APA) recommends that doctors perform baseline tests of kidney, heart, and thyroid function on any patient over age 40. The APA also recommends testing kidney function every two to three months for the first six months of lithium treatment, and then following up with kidney and thyroid function tests at least once or twice a year afterward, unless more frequent testing is indicated medically.
Patients find the most bothersome side effects of lithium are weight gain, cognitive impairment, clumsiness, and tremors. Although the cognitive impairment is generally mild when it is measured by formal tests, it can be frustrating to patients, especially those with professional or creative jobs. As many as 65% of patients taking lithium develop tremors.
One approach to lessening these side effects is to reduce the lithium dose during long-term treatment. Another way to ease side effects during the day is for patients to take most of their lithium dose at night. However, some patients may not be able to tolerate gastrointestinal side effects of large single doses.
Patients with bipolar disorder should not stop taking lithium abruptly. Rather, it's important to lower the dose slowly. Otherwise, patients greatly increase their risks of relapse and of suicide.
Lithium is far from being an ideal medicine, but the evidence establishes it as the best agent we have for diminishing the risk of suicide in bipolar disorder. The side effects may be hard to tolerate, but in some cases lithium's helpful effects may be lifesaving.
Have you ever taken lithium? What has your experience been?
Dr. Michael Miller has been on staff of the Beth Israel Deaconess Medical Center, a large teaching hospital in Boston, for more than 25 years. He is also an Assistant Professor of Psychiatry at Harvard Medical School.
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Comments: 9
Regarding your question about epileptics, the short answer is maybe.
I find myself gravitating toward the term "seizure disorder" rather than epilepsy -- not sure why -- maybe because it is more directly descriptive.
And these medications that Donald asks about (Tegretol, Phenobarbital & Valium) are all used to treat seizures.
The question is relevant because some studies have shown that the risk of suicide is higher in people who have seizure disorders.
Whether or not lithium would be helpful in someone who has a seizure disorder is something that would have to be examined on a case by case basis. That is, it's possible to have BOTH a seizure disorder AND a mood disorder -- and in those cases, lithium might be worthwhile.
Just as no two mood disorders are the same, no two seizure disorders are the same, so individualized treatment is very important.
It's not surprising to read that lithium didn't work for you, Vivian. And Lora, Abilify (the generic name is aripiprazole) is a newer drug that can be very good treatment for bipolar disorder, depression, and other mood disorders.
I know I'm repeating myself, but it is an important point that can't be repeated too much in my view — in all mental disorders, the underlying biology is potentially very different from person to person. That holds true even if the outward symptoms are the same. So you can have two people with identical symptoms who end up having very different medication experiences.
That's why it is so important to keep trying different approaches to treatment. It's hard to predict which approach will be best until you try.
You have accurately described a couple of very common lithium side effects. If tremor and dry mouth are mild, some people can bear it. Some find it pretty uncomfortable, no matter how mild it is. And others feel (understandably) self-conscious about the tremor.
Of course, you raise a good point about caffeine and lithium together.
Caffeine can also cause tremors, especially in high doses. So here's an example of a trade-off. Let's say someone is helped very much by lithium, but it causes a tremor. The doctor might ask about caffeine consumption. If it's high, it can be worth trying to limit the amount of caffeine to see if that reduces or even eliminates the tremor problem.
Tremor aside — a person taking lithium doesn't necessarily have to avoid caffeine. But it's important to be aware that caffeine and lithium can interact with one another.
Caffeine can lower the level of lithium in the blood. If a person on lithium suddenly stops taking caffeine, the lithium level can go up. And the reverse is true, too — increased caffeine intake can drive the lithium level down.
In practice, this turns out not to be a big problem, because most people have a stable pattern of caffeine intake.
This, above, is the end of your article in quotes. It all boils down to saving lifes. However, somehow we also want to give persons valuable lifes, not just avoid premature deaths.
That's tougher and would involve larger studies asking patients about life quality, how lithium helps them in their daily life or if they feel it is great that they avoid/diminish the risk of psychosis, suicide. The answer may that all do, or not. We will never know, I guess, since it is very unlikely we would talk to and listen to our patients. Instead, we continue with our analyzing their lifes, making choices for lots of people, and saving them and us from the horror of mass suicides.