Determinants for Effectiveness and Adverse Effects of Mood Stabilizers in Schizoaffective Disorder, Bipolar Type

Schizoaffective disorder (SAD) is a chronic, severe and disabling mental illness characterized by the concurrent presentation of symptoms of schizophrenia and affective disorders. Specific drug treatment for SAD remains a largely unexplored topic although combinations of antipsychotics and mood stabilizers are commonly used in clinical practice. Very recently, the Taiwan Bipolar Consortium discovered glutamate decarboxylase-like 1 (GADL1) variants strongly associated with the response to lithium prophylaxis treatment in type I bipolar disorder with a sensitivity of 93% for predicting a response to lithium. To our knowledge, this is the first study that uses genetic markers with sufficient sensitivity for predicting treatment response in mental disorder. This finding would serve as a milestone in personalized pharmacotherapy in psychiatry. The investigators of this study are from the key members of the Taiwan Bipolar Consortium. We have the best chance to extrapolate these findings from type I bipolar disorder to other affective disorders. This proposed study aims to clarify the role of mood stabilizers in the pharmacotherapy for schizoaffective disorder, bipolar type (SAD-BP), with a specific aim to test the association of lithium response and GADL1 variants. A total of 500 patients with SAD will be recruited for retrospective and/or two-year follow-up study of effects and adverse effects of mood stabilizers. Those who are experiencing an acute exacerbation of illness will be randomized into 8-week acute management with antipsychotic monotherapy or mood stabilizer adjunctive therapy. After management of acute exacerbation, the subjects will enter the maintenance therapy with the regimens they have good response to during acute management. The measure for efficacy of acute management is change in Positive and Negative Syndrome Scale total score from baseline to endpoint. Treatment response for maintenance therapy will be assessed using the Alda Scale. Statistical analyses include effects and adverse effects of mood stabilizers collected retrospectively and prospectively. We will also compare overall allele and genotype frequencies of rs17026688 between lithium responders and non-responders.

Project ID:PC10501-1273
External Project ID:MOST103-2314-B182-011-MY3