Mixed symptoms: a big issue

Alan C. Swann, Professor of Psychiatry and Behavioural Sciences at The University of Texas Medical School at Houston and Director of Research for the UT Harris County Psychiatric Center.

With last year’s launch of the new DSM-5 criteria, one of the big discussions at EPA 2014 is likely to be the introduction of the new ‘mixed’ specifier and the difference that it will make to the recognition of the ‘overlooked’ population of patients suffering with mania with depressive symptoms.

In my opinion though, ‘overlooked’ is slightly the wrong phrase to use. Psychiatrists are familiar with mania with concurrent depressive symptoms – most of us can think of patients we know who fit the description and that we’ve taken steps to treat accordingly – but what is currently underappreciated is the severe impact that the concurrence of manic and depressive symptoms has on these patients. Compared to pure mania, patients experiencing mixed-state report feeling subjectively worse; experiencing driven, rather than pleasure-based, hyperactivity. The combination of this activation with even minimal depressive symptoms is very unpleasant and associated with suicidal ideation.

Patients also state a much greater tendency towards suicidal and other destructive behaviours coupled with a diminished ability to curb these behaviours in manic episodes where depressive symptoms are present.

In addition to increasing disease severity, current evidence suggests that undiagnosed concurrence of symptoms can also reduce treatment efficacy; extending the required duration of treatment and increasing risk of relapse – a double impact.

So why, given these increased risks, have mixed symptoms not been considered a bigger issue before now?

Actually, it is perhaps not so surprising; as we know, depressive symptoms are easily masked by manic ones and may often be subsyndromal, making them more difficult to identify. However, the presence of even one of these subsyndromal depressive symptoms during a manic episode can result in a substantially worse prognosis for a patient.

Given this situation, clinically validated questionnaires can be of great help; encouraging clinicians to pay attention to the possibility of symptoms that may not be initially obvious and greatly facilitating the systematic identification of mixed states, which otherwise can be notoriously hard to detect.

Another approach I have found effective is the use of ‘marker symptoms’, for example, co-existing anxiety, which is rare in manic episodes that are not mixed. Others include dysphoric mood, worry, guilt, hopelessness, and lack of enjoyment of activities (goal-directed hyperactivity that is driven). When any of these symptoms are present during a manic episode, the risk of suicidal behaviour is substantially increased.

As useful as current approaches to identifying mania with depressive symptoms are, we still need more and this is one of the topics that I am most looking forward to discussing at EPA 2014. I’m hoping that primarily focusing on practical means for identifying mixed states during my section of Tuesday’s symposium will give me the opportunity to gather feedback from all of you; combining theoretical, neurobiological, and practical approaches to mood disorders.

I’m also looking forward to discussing with colleagues matters such as pharmacological or nonpharmacological methods to prevent relapse and improve inter-episode function in mixed state individuals. Also of particular interest is the question of whether people susceptible to mixed states have specific patterns of inter-episode cognitive disturbance that could respond to more specific treatments.

EPA always represents a chance for new inputs and new ideas and this year looks to be no exception. So let’s push the conversation forward.