There are still clinical states with uncertainties in psychiatry in terms of diagnosis and treatment. Mixed states in bipolar disorders is one of these states. The Diagnostic and Statistical Manual of Mental Disorders – IV (DSM – IV) defines mixed states as a period in which manic and depressive diagnosis criteria prevail together. However, observing all depressive and manic symptoms together during the mixed episode is not a common occurrence. The Cincinnati criterion has a more şexible approach in terms of diagnosis; a complete manic states together with at least three depression symptoms is enough to diagnose the case as mixed mania. There are studies that identify mixed mania as "a severe form related to mania," "a transition period between manic and depressive episodes," or "a separate emotional state."
15-20% of all manic episodes have characteristics that belong to the mixed mania. In comparison to a classic manic episode, the mixed mania has a more severe psychopathology. Episodes of dysphoria are observed more frequently, and it is frequently reported that dysphoria is an important part of mixed states. In comparison to a classic manic episode, the duration of hospitalization is longer, the number of attacks is higher, and the good periods are shorter during mixed episode. In addition, the psychotic characteristics and catatonic symptoms are more, and the rate of suicide is higher.
The most important element of treating the mixed episode is making the right diagnosis. The basis used to determine the treatment method is the same as those recommended for treating manic episodes. Unfortunately, there are no comprehensive studies that address treating mixed mania. There are limited data related to the efficacy of medications on mixed mania or which medication is better than the other. In general, combining drugs and clinical experiments are required for the short-term and long-term treatment of mixed mania patients. According to the Turkish Psychiatric Association (TPA), the treatment for mixed episodes of bipolar disorder is as follows: The treatment starts with valproate, lithium is added if the decrease in symptoms is not >25% within 4-5 days; in the event that the degree of symptoms do not get better by 50% at the end of three weeks, an alternative is using an atypical antipsychotic and stopping the lithium- valproate combination by gradually reducing the amount given to the patient, or moving on to a lithium – carbamazepine combination, and if >50% progress is not reached at the end of Week 6, it is recommended that patients receive ECT.
In comparison to classic manic episodes, the rate of response to mood stabilizers for mixed episodes is lower. Antidepressants should also not be used to treat symptoms of depression during this period. This situation proves the need for other treatment options. Olanzapine can be used effectively in acute and preventative treatment of mixed mania; however, its disadvantages are weight gain, diabetes, and metabolic syndrome risk. Ziprasidone has a high level of effectiveness that incorporated psychotic and mixed mania. There is evidence that risperidone is effective in treating manic episodes; however, the amount of information related to its efficacy in mixed episodes is limited. The number of studies about the efficacy of quetiapine on mixed episodes is also limited. The efficacy of aripiprazole on manic and mixed episodes is addressed by some studies.
In conclusion, mixed states in bipolar disorder are common clinical reşections. Mood stabilizer treatment strategies are the form of treatment that gives the best results. Mood stabilizer and antipsychotics can be used in the form of monotherapy or combination. Among these mood stabilizers, valproate is the one that has been studied most and is the most recommended. Aripiprazole, ziprasidone, and olanzapine are the antipsychotics that should be utilized first and foremost.