RAAPP - The Role of Antidepressants or Antipsychotics in Preventing Psychosis

• Applicant: Dr. Britta Galling
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Biological Psychiatry
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251857332

Schizophrenia usually begins in young adulthood and has - even after increasingly refined psychopharmacologic developments - remained one of the most severe and disabling disorders in medicine, which has a huge impact on the quality of life, social integration and the capacity to work. Psychotic symptoms, such as hallucinations, delusions, disordered thinking and emotional withdrawal, are typically preceded by a period of non-psychotic symptoms, known as prodromal symptoms. Since interventions after a first schizophrenia episode have not been able to alter the generally chronic and relapsing disease course (Robinson et al. 2004), the vital goal now is to prevent the onset of schizophrenia in people with prodromal symptoms and to reduce the ultimate severity of the illness by effective treatment in the early stages.Data suggest that - besides psychotherapeutic approaches (most importantly cognitive-behavioral therapy, see Stafford et al. 2013) - antipsychotic drugs as well as antidepressants may reduce prepsychotic symptoms, improve functioning and reduce progression to full blown psychosis (Correll et al. 2010).The data of an open label, non-randomized pilot study that compared treatment response to the class of antidepressants versus antipsychotic drug treatment (n= 48) suggested that the antidepressants were associated with less conversion to psychosis as compared with second-generation antipsychotic treatment. It appeared that the advantage of antidepressants in preventing transition to psychosis was mediated by a significantly higher rate of non-adherence associated with antipsychotic treatment (Cornblatt et al. 2007). While these first findings suggest that antidepressants, which have a favorable risk-benefit ratio, may reduce the development of psychosis, the lack of randomization and potential of prescriber bias reduce the interpretability of these early data.Therefore the applicant designed a 6-month, randomized, double-blind study in 48 subjects aged 12-25 years with at least moderate attenuated positive symptoms that developed within the past five years, focusing on intermediate outcomes of antipsychotic and antidepressant treatment (in addition to psychosocial background treatment), including the composite of all-cause-discontinuation and/or addition of a major psychotropic medication, symptom change, safety, and adherence. The specific aim of the proposed study is to compare fluoxetine and aripiprazole:1. on the likelihood of and time to a) all-cause discontinuation, b) need to add another psychiatric medication, c) symptomatic improvement, and d) adverse effects. 2. on social and role functioning and subjective well-being in individuals at risk for schizophrenia.3. on peripherally measured levels of brain derived neurotrophic factor (BDNF), which supports neuronal cell integrity and functioning (processes that appear to be disturbed during the transition from the prodrome to full psychosis)

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Christoph U. Correll