WPA 2014: Making a feature of mixed episodes

After Prof McIntyre’s introduction, the presentations started with Professor Trisha Suppes’s talk on DSM-5, mixed features and the potential to recognise anxiety, irritability and agitation as gateway symptoms for patients suffering from mania with depressive symptoms.

For this correspondent, the inclusion of Prof Suppes was of particular interest due to her role as the Chair of the Bipolar Disorders subcommittee of DSM-5. It was fascinating to hear the point of view of someone so intimately involved with one of the most transformative, and controversial, changes to bipolar practice in recent years.

Defining DSM-5

Starting with the historical context of mixed states, Prof Suppes noted that Jules Falret first used the term ‘mixed states’ in 1861. However, despite this early understanding, by the introduction of DSM-IV, the criteria for mixed states were still too restrictive.

As a consequence of this limited definition, there was:

• An underestimate of suicide risk
• An increased likelihood of inappropriate treatment
• A failure to identify those patients with depression who were at increased risk of progression to bipolar

As a leading light in shaping how DSM-5 would reflect current thinking on bipolar, Prof Suppes was aware of the challenges facing them, and told the rapt auditorium that even though decisions were based on relative considerations and the available data, there were always going to be unintended consequences. One of these consequences was the fact that DSM-5 didn’t capture the quickly changing quality of mixed symptoms, and as a result, it implies more symptom stability than was intended.

In addition to her astute analysis of potential weaknesses of DSM-5, Prof Suppes also pointed to the strengths of the new approach, in particular the importance of the mixed specifier in properly identifying and treating patients with mania with depressive symptoms.

The burden of bipolar

We are well aware of difficulties with diagnosis of patients with mixed features, but Prof McIntyre’s presentation took this one step further when he discussed the burden that suffering from mania with depressive symptoms places on the patient.

As well as the more obvious impacts, such as an earlier age of onset and a significantly higher rate of suicide than pure mania patients, your correspondent was surprised to find that mixed patients are also significantly more likely to be unemployed (70% vs. 44%), and even more surprisingly, are significantly more likely to suffer from cardiovascular disease (37% vs. 14%).

This data really brought home ever-widening spiral of impact that depressive symptoms in mania can have on patients, and crystallised the need for effective identification and treatment of these patients.

MINI me

Fortunately, our next presentation by Professor Allan Young was about exactly that – evaluating depressive symptoms in mania with the MINI module.

The MINI (Mini International Neuropsychiatric Interview) is a well-known and well-used tool, designed to assist diagnoses according to DSM-IV. In order to better serve the needs of patients with mixed specifiers, Prof Young and colleagues developed the MINI module, a patient-completed questionnaire whose questions map onto DSM-5 criteria.

Prof Young then discussed assessing the validity of the MINI module, and how it was shown to have a good degree of concurrent validity with physicians’ evaluations of DSM-5 mixed features in manic patients. The module also showed a high capacity to detect symptoms, while maintaining a low incidence of over-diagnosis, and as a result, Prof Young urged the audience to consider using the MINI module in their own practice.

Two A's, one I

Both Prof Suppes and Prof Young focused on anxiety, irritability and agitation as a gateway indicator of mixed states.

Prof Young expanded on the discussion of these symptoms with data showing that anxiety, irritability and agitation were significantly more prevalent and severe in patients with 3 or more depressive symptoms than those with 0-2 depressive symptoms.

Question time

After three engaging and illuminating sessions, I was thoroughly energised, and obviously so was the rest of the audience, as the panel faced a series of astute questions.

The first question from a doctor based in Singapore brought up what would become a continuing thread throughout the questions – how ‘mixed features’ fit with the changing definitions of bipolar. In this particular case, the question was regarding the differences between rapid cycling, ultra-rapid cycling and mixed states.

Prof Suppes answered for the panel, explaining that rapid cycling is defined by the rate of changes of the patient’s state, whereas ‘mixed features’ occur within a state. Both Prof Young and Prof McIntyre noted that this is why we need to stay vigilant in looking for mixed features, and the importance of granularity, which was highlighted by the impact of 3 or more depressive features vs. 0-2, as seen in Prof Young’s presentation.

The next question, from a US psychiatrist, queried the on-going use of categories in describing bipolar, as opposed to assessing along dimensions and domains. The panel acknowledged that the current assessment methods are by no means perfect, but that categories are still needed, as complicated dimensional frameworks are just not practical or workable for current clinical practice.

The final question of the session, on the changing definitions of bipolar over the years, prompted some fascinating insights from the panel. Prof Young observed that generational changes in the observation of bipolar may be due to an artefact of reporting, or may be due to genuine brain changes (possibly related to increased rates of substance abuse).

Prof McIntyre expanded on this, by pondering whether the phenotype of bipolar may actually be changing, with decreasing rates of euphoric mania and increasing rates of dysphoric mania/mixed states being observed. He then pointed to the impact of obesity on the regions of the brain that control affect regulation and impulse control, and the fact that obese patients are more likely to show mixed depressive states. Yet another reason that intervention in the growing problem of obesity is desperately needed.

It’s a wrap

Day one of WPA and already this correspondent has been enlightened, educated and engaged by an engrossing symposium.