Lithium to Treat Bipolar - The Evidence
Here’s a monster irony for you: Lithium, by far the most-studied of the bipolar meds, is also the one that doctors manifest the most ignorance and likewise the greatest reluctance to prescribe.
An earlier piece, A Brief History of Lithium, detailed some of the reasons. Essentially, these boil down to: 1) Lithium, due to toxicity considerations, requires greater clinician oversight; 2) Lithium, because it is a natural element that lacks patent protection, is not championed by the drug companies.
A quick overview ...
The study evidence indicates that lithium has a strong anti-manic effect, both short-term and long-term, and a weaker antidepressant effect, short-term and long. This singular ability to treat all phases of bipolar gives the drug significant advantages over other meds in certain situations.
In addition, studies have linked lithium use to reduced risk of suicide.
Short-term, lithium compares favorably with other bipolar meds, but the true test of any bipolar med is how it works in the long term. In this regard, only lithium has credible evidence.
The long term evidence ...
The story is laid out in Goodwin and Jamison’s Manic-Depressive Illness (2nd Edition, 2007). In brief:
A 1967 retrospective study by Baastrup and Schou found patients were ill 13 weeks a year before taking lithium and just two weeks a year while on lithium. By 1972, more than 60 open clinical trials had been conducted, comparing before-and-after results, virtually all showing that lithium decreased the frequency, duration, and severity of episodes.
These were buttressed by placebo-controlled studies yielding similar results, but commentators from the mid-80s onward started calling these results into question, particularly with the emergence of newer studies revealing more problematic outcomes.
Goodwin and Jamison note that lithium’s bad press coincided with the arrival of new meds such as Depakote. It is worth noting that Depakote has only two short-term studies going for it, nothing long-term, with demonstrated efficacy only for mania.
The authors cite more recent studies in support of lithium’s utility over the long term. It is worth taking a closer look at one of these, from 2001 (Tondo et al):
The researchers tracked a group of 360 patients taking lithium for a period of one year. Over that time, only about a quarter of the patients achieved complete remission. Nevertheless, at least 60 percent experienced reductions in episode frequency and cut their time being ill in half. The most encouraging result - the rate of hospitalizations fell by 82 percent.
Some head-to-head studies ...
After 2000, some of the drug companies sought to establish long-term efficacy for their meds. In addition to a placebo group, some of these trials also added a lithium group as a comparison drug.
The first of these involved a 12-month face-off with Depakote (Bowden et al, 2000). In its primary outcome measure - length of time to either a depressive or manic episode - neither drug succeeded in outperforming the placebo.
Drugs often fail in trials through no fault of their own. But, with regard to demonstrating long-term efficacy, Depakote never got a second chance.
A couple of years later, Bowden led a similar set of trials, this time over a period of 18 months comparing lithium to Lamictal. One result showed that the patients on Lamictal took longer than those on lithium or the placebo to relapse into depression. Lithium performed better than the placebo.
The other result showed that the patients on lithium took longer to relapse into mania. Lamictal failed to outperform the placebo.
Significantly, it was this set of trials that won Lamictal its FDA indication for treating bipolar. Several short-term trials testing Lamictal for bipolar depression had failed.
In June this year, Medscape reported on a study that compared Seroquel to lithium over a six-month period. Both drugs performed about the same on all the main outcome measures. Significantly, though, only about a quarter of the patients were truly well at the end of the study.
The introduction of mood stabilizers and atypical antipsychotics in the nineties led to the mistaken notion that newer equated to better. The reality is that lithium holds its own against the newer meds.
As a general rule, bipolar meds over the long term reduce severity of symptoms and time being ill and cut down on hospitalizations. For all these results, lithium has by far the best evidence going for it. By the same token, however, whether on lithium or another drug, for most patients complete recovery remains an elusive goal.
A good doctor will seek to match the right patient to the right med. Unfortunately, these days many psychiatrists lack experience in using lithium, so that right med for you may be the one your doctor fails to recommend.