Understanding mania with depressive symptoms

Professor Suppes reminded us that bipolar I disorder often presents in complex ways. Even back in 1899, Kraepelin was already considering the multifaceted presentations of bipolar I disorder including anxious mania, excited depression, manic stupor and depression with flight of ideas. However, where are we now in our thinking? The ‘mixed episode’ criteria from DSM-IV were found to be too restrictive, leading to a great deal of confusion and a lack of precision when diagnosing and treating patients. The consequences of the wrong diagnosis include underestimation of suicide risk, inappropriate treatment selection and failure to identify those with depression who are at increased risk of progression to bipolar I disorder. The higher suicide risk for patients with mixed features compared with purely manic episodes was a recurrent, sobering issue throughout the whole symposium.

The changes in DSM-5

DSM-IV was focused on categorising patients, whereas DSM-5 aimed to improve and provide a more accurate basis for diagnosis with a more dimensional approach. The new DSM-5 mixed features specifier requires a patient to have mania with at least three depressive symptoms. Prof. Suppes noted that the depressive symptoms don’t have to be present constantly throughout the day but often will only be present for a portion of the day, better reflecting the everyday life of the patient.

The DSM-5 mixed specifier in real-world practice

In a real-world global study evaluating the mixed specifier in over 1,000 patients, a third were found to have mania with at least three depressive symptoms and the overlapping symptoms of anxiety, agitation and irritability were significantly more prevalent in patients with at least three depressive symptoms.

Can we still improve further?

From the real-world study, it seems that the specifier should capture anxiety and irritability. Prof. Suppes acknowledged that DSM-5 may not capture the complexity of each patient, including other concomitant symptoms, and also does not refer to the underlying biology of the disorder. However as our knowledge of neuroscience progresses, so will our ability to understand and diagnose this difficult patient type.

Professor Alan Swann of Baylor College of Medicine, Texas moved the conversation on to ‘The pathophysiology of depressive symptoms in mania’. He reinforced that the deadliest combination of symptoms for patients is the depression with activation found in mixed states. Just as the brightness of a full moon may obscure the stars around it, he mused, the more obvious symptoms of depression may hide the underlying manic symptoms that could lead to suicide.

The impact of mixed features on patients

Not only is there a higher risk of suicide attempts with mixed states, but patients are more likely to suffer more frequent episodes, hospitalisation, work impairment and a lowered satisfaction with life. This really hammered home the importance of managing these patients in the most effective way.

From a physiological point of view, it appears both cortisol levels and norepinephrine are elevated in mixed states. Could these be a driving force behind these mixed features episodes?

Prof. Swann finished his talk by discussing the complexity of psychiatric treatments, as there is such a huge variety in receptor affinity for each antipsychotic. This was a topic that was swiftly picked up by Professor Andrea Fagiolini, Italy in his talk on ‘'Clinical management of mania with depressive symptoms’.

Prof. Fagiolini acknowledged that it is difficult to establish which treatment to use as each patient presents with very different symptoms. Perhaps in the future biological markers will help deliver personalised treatments for patients.

Real-world treatment of mixed states

A real-world global study evaluating the treatment of mixed states revealed that the majority of patients were treated with antipsychotics but interestingly, patients received an average of 3.17 medications. This perhaps reflects clinical practice in that it is rare to be able to use just one drug to treat a patient suffering from mixed features.

So how should we treat patients with mixed features?

Prof. Fagiolini went on to discuss the treatment of mixed features and presented data from several antipsychotics. He reinforced that the antipsychotics are profoundly different to each other, most likely due to different receptor fingerprints.

He finished by concluding that while antipsychotics clearly have a place in the treatment of mania with depressive symptoms, psychoeducation is also vital for the prevention and treatment of these patients.