Semantics and expanding the treatment goals in bipolar disorder

Psychiatry has always been a field in which the meaning of words has been particularly challenging. One might argue that the core mission of the modern Diagnostic and Statistical Manuals of Mental Disorders (DSMs), beginning with Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) in 1980, was to create a dictionary of diagnoses such that describing a patient’s diagnosis as major depression would mean the same (reliability) to all clinicians and researchers, regardless of whether the definition was optimal (validity). In their recent editorial, Malhi et al. (2017) suggest that we rethink the meaning of the term ‘mood stabilizer’, proposing that we expand the definition from its usual current meaning of describing a treatment that (optimally) treats acute mania and acute depression and prevents both manic and depressive episodes, highlighting the preventive efficacy as the most critical effect. Activity and cognition are proposed as two other domains of psychopathology that might profitably be considered as targets of intervention and that efficacy in these areas be part of the goal of mood stabilizers.

Reconsidering the goals of treatment in bipolar disorder seems to me rather timely and is consistent with conceptual and clinical work in other psychiatric disorders such as schizophrenia for which multiple domains of psychopathology – not just psychosis/positive symptoms but also negative symptoms, cognitive impairment and even depression – are considered legitimate targets as outcome variables and in treatment development. (See, as an example, the considerable recent efforts in developing new molecules to combat the cognitive symptoms that are as intrinsic to schizophrenia as are delusions and hallucinations (Keefe et al., 2013).)

Cognitive impairment, although less severe and less prevalent in bipolar disorder than in schizophrenia, would seem to be a legitimate treatment target and a key outcome variable for any psychotropic medication beyond classic mood-stabilizing effects (Porter et al., 2015). Additionally, cognitive impairment does not routinely co-vary with mood symptoms and should therefore be considered a more independent domain of psychopathology. Enhancing cognition would seem to be especially relevant given the clear and independent relationship between cognitive impairment in bipolar disorder and functional outcome (Gitlin and Miklowitz, 2017). As with schizophrenia, it may be simpler to acknowledge that cognition is a separate domain of psychopathology within bipolar disorder and that it should be a separate target of treatment intervention, rather than require a mood stabilizer to show efficacy in the cognitive domain beyond its effects on mood symptoms and syndromes.

In contrast, considering activity as another separate domain of psychopathology and as an outcome variable seems less useful to me, given the lack of data showing that it is independent of other mood symptoms or that it predicts functional outcome.

The core underlying concept proposed by Malhi et al. (2017) is to broaden our goals of treatment in bipolar disorder from simply measuring symptoms and syndromes to other variables. Another way of considering this suggestion is to acknowledge that mood symptoms/syndromes reflect only the most basic of outcomes for mood disorders. Aside from cognition, the two other long-term outcome measures that seem most important and should therefore be considered more routinely are function and Quality of Life (QoL). Function reflects the degree of success of patients’ lives in the two core domains of role function and social activity. Function can be measured reliably and reflects a person’s activity using somewhat objective markers (Rosa et al., 2007). In contrast, QoL measures a more purely subjective assessment – whether an individual feels satisfied or fulfilled. Arguably, patients and families alike are concerned less about symptoms and syndromes than about the ways in which mood disorders interfere with the ability to lead a full life – in role function (occupation/school/parenting/taking care of a home) and interpersonally (in a primary relationship, more extended family relationships and social interactions). Thus, a maintenance treatment, whether medication or medication plus psychotherapy, could be easily evaluated using function and QoL measures as richer and more complex methods of evaluating outcome. Therefore, I would propose that at least in long-term/maintenance treatment studies, functional outcome and QoL be routine or even mandatory variables to measure, i.e., that every long-term study be required to report functional outcome and QoL as they do time to relapse and other syndrome-based measurement.

This suggestion is entirely in keeping with the proposal of Malhi et al. to broaden our notion of what mood stabilizers can and should do. If these other measures were included in future studies, the nirvana for those with bipolar disorder proposed in the editorial by Malhi et al. could be defined as having no more than minor mood symptoms, functioning at a level near to or at the same level as a control population and achieving a QoL that is as satisfying as those without a mood disorder. That would be nirvana indeed!

See Editorial by Malhi et al. (2017) 51: 434–435.