Epidemiology, Diagnosis and Management of Mixed Mania

The presence of depressive symptomatology during acute mania has been termed mixed mania, dysphoric mania, depressive mania or mixed bipolar disorder. Highly prevalent, mixed mania occurs in at least 30% of bipolar patients. Correct diagnosis is a major challenge. The DSM diagnostic criteria, the most widely adopted clinical convention, require a complete manic and complete depressive syndrome co-occurring for at least 1 week. However, recent alternative categorical and dimensional studies of manic phenomenology have shown that there are certain depressive symptoms or constellations that have special clinical importance when describing mixed states, such as depressed mood and anxiety symptomatology that do not overlap with manic symptoms.

Patients with mixed mania are over-represented in the subgroup with severe and treatment-resistant symptoms. The course and prognosis of mixed mania are worse than that of pure manic forms in the medium and long term, with higher recurrence rates, higher frequency of co-morbid substance abuse and greater risk of suicidal ideation and attempts. Moreover, mixed manic episodes are usually associated with increased depression during follow-up, greater risk of rapid cycling course and higher prevalence of physical co-morbidities, principally related to thyroid function. All these factors are very relevant to selection of treatment.

There are three crucial steps in the treatment of mixed mania — making the correct diagnosis, starting treatment early, and considering not only the acute state but also maintenance treatment and the patient’s long-term outcome. Although challenging, acute mixed episodes are treatable. To date there have been no controlled studies devoted exclusively to treatment of mixed mania, and the only controlled data available therefore derive from sub-analyses of randomised clinical trials. Both short-term and maintenance treatments of patients with mixed mania requires experience and usually involves the combination of different treatments. As a general rule, there is some consensus about discontinuing antidepressants during mixed mania. Olanzapine, aripiprazole or valproate semisodium (divalproex sodium) are first-line drugs for mild episodes; severe episodes of mixed mania usually require treatment with a combination of valproate semisodium or lithium plus an antipsychotic, preferably an atypical agent. Carbamazepine is also useful for the treatment of mixed mania. High-dose medications are sometimes needed to control the episode, and time to remission is usually longer than in pure mania. Importantly, patients with mixed manic episodes have more adverse events of psychopharmacological treatment. In some cases, electroconvulsive therapy is required.