‘Mood stabilizers’ as the royal road to nirvana or a narrow bridge to well-being?

Words make worlds

Malhi et al. (2017) make several salient points about the limitations and usefulness of using the words ‘mood stabilizer’ to classify medications used for bipolar disorder—that such a classification should (obviously) stabilize mood, acutely and more importantly, for the long term; that stabilization should mean treating acute episodes and prevent future episodes; and that ultimately, we should consider domains other than mood as important—specifically activity and cognition. They claim that only lithium appears to meet the designation of a true mood stabilizer so that patients can be free from repeated mood episodes. Other medications which proclaim that they, too, are mood stabilizers (e.g. divalproex and carbamazepine) may not actually deserve that designation. Nevertheless, if clinicians call them mood stabilizers and use them as mood stabilizers, they start to smell like mood stabilizers regardless of contrary data. It becomes difficult to shift opinions once a world is formed.

Who’s in and who’s out?

Malhi and colleagues use the delightful metaphor of car racing—‘lithium’s pole position in guidelines has been retained’—to describe more recent data from the BALANCE study to support classifying lithium as a mood stabilizer (Geddes et al., 2002). But they do concede that lithium may have a weaker effect on treating and preventing depressive episodes compared to manic episodes. Conversely, lamotrigine may have a weaker effect on treating and preventing mania compared to depressive episodes. One could argue that quetiapine may be the most stabilizing of the mood stabilizers because it treats and prevents mania and depression. And here is where Buddha may have to meet the devil of the details—and the details would be found in randomized comparative effectiveness studies—Bipolar CHOICE (Nierenberg et al., 2016) and a more recent study (which lacks a clever acronym) by Berk et al. (2017). Both studies found lithium and quetiapine equally effective over 6 months, but the Berk study found that after 6 months, lithium was superior.

What about that other so-called mood stabilizer divalproex? It did not do particularly well in the BALANCE study and other studies have failed to show it works, on average, in the long run. And what about carbamazepine (or its cousin oxcarbazepine)? Surprisingly, little data support their short- or long-term use.

So if lithium is at the top of the heap, the king of the hill, the one and only, then why aren’t more people taking lithium monotherapy? And if quetiapine has at least some data to support the moniker of mood stabilizer, why aren’t more people taking quetiapine monotherapy?

How stable is stable and how long is long?

It’s usually a good idea to begin at the beginning. Mahli and colleagues define mood stabilization as a reasonable mix of acutely treating and preventing discrete mood episodes and with helping with activity and cognition as well as functioning. But the authors omit any mention of what would define stability—a complete absence of any mood episode, even subthreshold? And while they add cognition, activity and functioning, they leave out many of the problems which our patients face—suboptimal resiliency to stress, a tendency to become anxious and to ruminate on good and bad thoughts, persistent problems with sleep and motivation, irritability, mood lability, as well as subtle psychotic thoughts.

One more problem for mood stabilizers is that a lack of pathology is not the presence of wellness. Psychological well-being as defined by Marie Jahoda and Carol Ryff (Ryff and Singer, 1996) includes Self-Acceptance—the capacity to see and accept one’s strengths and weaknesses; Purpose in Life—having goals and objectives that give life meaning and direction; Personal Growth—feeling that personal talents and potential are being realized over time; Positive Relations with Others—having close, valued connections with significant others; Environmental Mastery—being able to manage the demands of everyday life; and Autonomy—having the strength to follow personal convictions, even if they go against conventional wisdom.

Maybe it is asking too much of mood stabilizers to bring people to wellness. But it’s what our patients want.

The other challenge is time. Should a mood stabilizer keep people free of mood episodes, then if so, for how long? Even with lithium, only a small minority of people who respond get well and stay well for 1–5 years. We can be accused of being harsh here—and perhaps the outcomes we suggest are not realistic and no worse than outcomes for people with epilepsy. But at least as far as a definition, we need to have a precise definition of how long is long enough.

Reality tends to assert itself regardless of our words

Buddha acknowledged the Four Noble Truths—the truth of suffering, the cause of suffering, the cessation of suffering and the paths to end suffering. Rabbi Nachman of Bratslav wrote that ‘The whole world is a very narrow bridge; the important thing is not to be afraid’. People with bipolar disorder experience more suffering than most—they did not ask for it. Our job is to help reduce their suffering regardless of what we call our medications and to discover better treatments. Our so-called mood stabilizers are all too often not good enough.

See Editorial by Malhi et al., 51: 434–435.