That which we call a mood stabilizer: What’s in a name?

The Editorial by Malhi et al. (2017) invites us to consider whether the term ‘mood stabilizer’ unduly focuses on just one of the core elements of bipolar disorder—namely, mood—proposing instead that the truer path to pharmacodynamic enlightenment arises when treatments embrace the other dimensions of psychopathology that define bipolar illness (notably, dysregulated energy and cognition). In some respects, the issues raised here are largely semantic; mood is indeed only one aspect of the constellation of signs and symptoms that define syndromes in bipolar disorder. The term ‘mood stabilizer’ trivializes the complexity of manic or depressive episodes by placing disproportionate importance on only one component of a multifaceted syndrome. Mood—the momentary subjective experience of an emotional state—may be to bipolar disorder what pain is to angina, or dyspnea is to congestive heart failure. But even a sine qua non symptom of a syndrome is not synonymous with the syndrome itself. Not so long ago, the field designated bipolar disorder as an affective rather than a mood disorder, connoting the importance of its objective behavioral signs as much as its subjective symptoms. ‘Mood instability’ in itself is of course not a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or International Classification of Diseases, Tenth Revision (ICD-10) criterion for bipolar disorder, and overemphasis on its presumed centrality—to the exclusion of sleep, energy, cognition and the other non-mood elements of the disorder—contributes to the overdiagnosis of bipolar disorder in community settings (Goldberg et al., 2008) and encourages its dilution as a meaningful nosologic construct (Baldessarini, 2000).

Ironically, no drug that is popularly or commercially dubbed a ‘mood stabilizer’ has ever been formally studied to treat moment-to-moment shifts in subjective emotional experience. Rather, drugs that we colloquially call ‘mood stabilizers’ have instead been shown to treat or prevent full syndromes of mania or depression—but no placebo-controlled regulatory registration trial of any drug commonly called a ‘mood stabilizer’ has included secondary (much less primary) analyses to assess efficacy for day-to-day or within-day fluctuations in mood. No clinical trial has ever even asked whether, or how much, change from a baseline Young Mania Rating Scale Item #1 (‘elevated mood’) or Item 5 (‘irritability’), or Montgomery-Åsberg Depression Rating Scale Item #2 (‘reported sadness’) rating is necessary to leverage a clinically meaningful overall improvement, or how much the proportion of variance in total symptom severity scores is explainable just from changes in mood alone. In theory, at least, a highly effective mood stabilizer could markedly reduce agitation, restore sleep and slow racing thoughts, but have absolutely no effect on mood itself. When patients, or even some clinicians, presume that ‘mood stabilizer’ is shorthand for a drug that will expectably curtail the magnitude of day-to-day mood ‘swings’, the proposition is not only non-evidence-based but scientifically disingenuous.

Overattention to mood, rather than affect and its associated signs, has perhaps fostered lay misperceptions about what the construct of bipolar disorder even implies. In ways that neither Karl Leonhard nor Robert Spitzer likely ever intended, the term ‘bipolar’ has entered vernacular parlance as an adjective to signify anyone or anything that is quirky, outrageous, radical or mercurial. Differential diagnosis, and differential therapeutics, quickly fall by the wayside as everything from rage attacks to distress intolerance to hardcore addictions increasingly falls under the nebulous heading of ‘soft bipolarity’, irrespective of changes in sleep/energy or cognition, or of Kraepelin’s emphasis on periodicity (i.e. departures from someone’s baseline mental state that then revert back to that usual baseline). Syndromality, if the neologism fits, has been replaced by a singular focus on mood and its vicissitudes, regardless of context or associated features of psychomotor activation.

Malhi and colleagues’ definition of pharmacological nirvana is really just a more accurate description of the appropriate treatment goals in bipolar disorder. That bipolar disorder involves not only changes in mood but also in cognition and energy/activity should (hopefully) come as no epiphany to anyone who studies or treats the condition; indeed, a recent meta-analysis by Scott et al. (2017) affirmed that mood and activation are distinct yet equally fundamental domains of pathology in bipolar disorder. Rather disturbingly, Malhi et al.’s editorial implies that the field could profit by rediscovering something that never should have become lost in the first place. Proper treatments are keyed not to symptoms but to definable medical syndromes, in the truest of Hippocratic and Oslerian traditions (Ghaemi, 2008). Much as the ideal cold medicine does more than treat nasal congestion, or nitroglycerin for angina is not simply an antinocioceptive, and even antipsychotics used in schizophrenia are usually expected to address more aspects of the illness than just delusions and hallucinations, so too are the core medications used in bipolar disorder expected to accomplish more (or other) things than modulate dramatic mood ‘swings’ from one emotion to another—at least until somebody first undertakes a study to find out whether or not mood stabilizers actually stabilize mood.