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In this presentation, there will be a demonstration of how changes in the DSM-5 classification have affected the decision-making process for choosing medications, focusing on the problem of differentiating schizophrenia with mood symptoms, schizoaffective disorder, and bipolar disorder with psychosis. In the DSM-5, an important change occurred in the D criterion for schizophrenia, which describes how this differentiation is to be made. The new criterion states that “if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.” In DSM-IV, the duration of such episodes had to “be brief” relative to the total duration of the illness. The text gave an example of what is meant by “brief” and offered a patient who has been ill for 4 years but had a 5 week period of major depression superimposed on the psychotic symptoms. This is about 10% of the total duration of the illness. In the new criterion, the change to the word “minority,” which implies up to 50% of the time, will result in many patients with mood episodes being diagnosed with schizophrenia who previously would have been diagnosed schizoaffective disorder. Please note that in both DSM-IV and DSM-5, patients meeting the A, B and C criteria with significant and even continuous mood symptoms short of meeting criteria for a major depressive or manic episode were and still are diagnosed with schizophrenia. Consistent with the above, the C criterion for schizoaffective disorder has also changed. In DSM-5, the major mood episode must be present for a “majority” of the total duration of active and residual phases of the illness. In DSM-IV, they only had to be present for a “substantial” portion of the time. Schizoaffective disorder had questionable construct validity as defined by the older criteria. Also, there had been very little treatment research focused on patients meeting those criteria. Not enough evidence exists to enable the development of a plausible treatment algorithm. Available evidence indicates that patients meeting these criteria seem to comprise a heterogeneous population of individuals most if not all of whom have variants of either schizophrenia or bipolar disorder. Yet, schizoaffective disorder continues to be an extremely popular diagnosis in the records of patients with combined mood and psychotic symptoms. Many clinicians employ idiosyncratic criteria and treat by clinical experience and improvisation. The Psychopharmacology Algorithm Project at the Harvard South Shore Program has evidence-derived algorithms for the pharmacotherapy of schizophrenia and bipolar disorder. With DSM-5, more patients with mood symptoms will meet criteria for schizophrenia, where the algorithm (in accordance with the evidence-base) recommends minimal use of antidepressants and mood stabilizers. The current algorithms for schizophrenia and for bipolar disorder will be shown and it will be suggested that patients meeting DSM-5 criteria for schizoaffective disorder should be evaluated as to which of these two main diagnoses comes closest to describing them. Then, apply the relevant algorithm. If the algorithm selected is producing an unsatisfactory response, one would consider switching to the other algorithm.