Major depressive episodes (MDEs) occur frequently during the course of psychotic disorders, and several antidepressive agents have been successfully applied. The new melatonergic antidepressant agomelatine (AGO) appears promising for the treatment of MDEs in schizophrenia for several reasons. The investigators plan to test the efficacy and tolerability of AGO for antidepressive treatment in schizophrenia. For this task, the investigators plan to enrol 27 schizophrenic patients into an open, single-armed, prospective clinical trial with agomelatine.
Major depressive episodes (MDEs) occur frequently during the course of psychotic disorders, and several antidepressive agents have been successfully applied. The new melatonergic antidepressant agomelatine (AGO) appears promising for the treatment of MDEs in schizophrenia for several reasons: 1. AGO provides a unique pharmacological profile by combining antidepressive potency, sleep regulation and enhancement of frontocortical dopaminergic activity by 5-HT-2C-blockade. 2. AGO might exert favourable effects on cognition. 3. While pharmacokinetic interactions are generally possible, major influences on antipsychotic substances are unlikely due to metabolism by cytochrome isoenzymes CYP1A2 and CYP2C9/19. 4. AGO is characterized by a favourable range of adverse events (AE) which do not overlap with typical antipsychotic AEs such as weight gain and sexual dysfunction. Thus, the risk of additive effects seems to be small. The investigators plan to enroll 27 schizophrenic patients into an open, single-armed, prospective clinical trial with agomelatine. As predefined primary and secondary endpoints, we are going to investigate whether AGO is able to improve MDE severity, sleep quality, general and psychosocial functioning as well as cognitive function in schizophrenia without detrimental effects on the psychotic syndrome. Moreover, we intend to monitor for pharmacokinetic interactions. The results obtained will allow designing future randomized and controlled clinical trials in order to improve the range of therapeutic options for affective and cognitive deficits in schizophrenia.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Augmentation of antipsychotic therapy with 25 to 50 mg agomelatine as a single oral dosage per day
Central Institute of Mental Health
Mannheim, Baden-Wurttemberg, Germany
Antidepressive efficacy
Comparison of MDE severity before and after six weeks of treatment with AGO. In order to assess the treatment success, means of HAM-D17 and CDSS scores at both baseline and week 6 will be compared within the efficacy sample (at least one application of AGO, LOCF). The primary endpoint will be tested with a two-sided student's t-test at a level of statistical significance of ≤.05.
Time frame: 6 weeks
Secondary efficacy measures: Response rates
We will determine the percentage of responses (decrease of HAMD by at least 50 %)
Time frame: 6 weeks and 3 months
Secondary efficacy measures: Long-term efficacy
After 12 weeks of treatment we plan to compare means of HAMD and CDSS with baseline data.
Time frame: 6 weeks and 3 months
Secondary efficacy measures: Psychosocial functioning
During treatment psychosocial functioning might improve. We plan to compare means of PSP scale assessed after 6 weeks and 3 months with baseline data.
Time frame: 6 weeks and 3 months
Secondary tolerability and safety measures: Psychotic symptoms
The stability of the psychotic syndrome during treatment with AGO will be evaluated comparing means of PANSS after 6 weeks and 3 months with baseline.
Time frame: 6 weeks and 3 months
Secondary tolerability and safety measures: General tolerability
The general tolerability measures include the exploration and documentation of adverse events.
Time frame: 6 weeks and 3 months
Secondary tolerability and safety measures: Pharmacokinetic interactions between AGO and antipsychotic agents
Effects of AGO treatment on serum drug levels of antipsychotic agents will be evaluated by comparing the SDLs at baseline with values obtained after 6 weeks and 3 months.
Time frame: 6 weeks and 3 months
Secondary efficacy measures: Remission rates
We will determine the percentage of remissions (decrease of HAMD below 8)
Time frame: 6 weeks and 3 months
Secondary efficacy measures: Cognitive functioning
During treatment neurocognitive deficits might improve. We plan to compare means in the MCCB assessed after 3 months with baseline data.
Time frame: 3 months
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