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Neurocognitive Effects of Agomelatine Treatment in Schizophrenia Patients Suffering From Comorbid Depression

Results From the AGOPSYCH Study

Englisch, Susanne, MD*†; Jung, Hanna Sophie; Eisenacher, Sarah, MSc, PhD*; Lewien, Antje, MD§; Becker, Anna, MD*; Nowak, Ulrike, MSc; Braun, Hanna, MSc*; Thiem, Jascha, MSc*; Meyer-Lindenberg, Andreas, MD, PhD*; Zink, Mathias, MD

Journal of Clinical Psychopharmacology: August 2018 - Volume 38 - Issue 4 - p 357–361
doi: 10.1097/JCP.0000000000000909
Brief Reports

Background Cognitive impairment in schizophrenia is highly disabling and remains one of the major therapeutic challenges. Agomelatine (AGO), an agonist at melatonergic MT1/MT2 receptors and antagonist at 5-HT2C receptors, increases dopamine and norepinephrine in the prefrontal cortex and may therefore have the potential of improving neurocognition in patients with schizophrenia.

Methods Twenty-seven patients with schizophrenia and comorbid depression were treated with AGO in addition to stable doses of antipsychotic drugs. Cognitive abilities were assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) at study entry and after 12 weeks of AGO treatment after the intention-to-treat principle.

Results We observed statistically significant yet clinically negligible increases of the MCCB composite score and the reasoning/problem solving subscore. Patients with unimpaired sleep at baseline showed greater improvements over time than those with sleep disturbances. Changes on the MCCB were not correlated with other psychometric variables.

Conclusions Despite statistically significant, cognitive improvements after 12 weeks of AGO treatment were clinically irrelevant. Our findings may be limited by baseline properties of the study sample and the study design. In particular, lacking a control group, it cannot be ruled out that improvements were unrelated to AGO treatment. That is why randomized controlled trials are needed to validate the relevance of AGO as a cognitive enhancer in schizophrenia.

From the *Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim;

University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz;

Municipal Hospital Karlsruhe, Department of Psychiatry and Psychotherapy, Karlsruhe;

§Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen;

Institute of Psychology, Clinical Psychology and Psychotherapy, University of Hamburg, Hamburg; and

District Hospital Ansbach, Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Ansbach, Germany.

Received November 8, 2017; accepted after revision April 30, 2018.

Reprints: Susanne Englisch, MD, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, PO Box 12 21 20, 68072 Mannheim, Germany (e-mail:

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