Agomelatine Treatment of Depression in Schizophrenia (AGOPSYCH)

Schizophrenia Clinical Trial

— AGOPSYCH  

Official title:

Agomelatine Treatment of Major Depressive Episodes in the Course of Schizophrenic Psychoses (AGOPSYCH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01822418
• Other study ID #: 01112012
• Status: Completed
• Phase: Phase 4
• First received: March 11, 2013
• Last updated: March 7, 2018
• Start date: January 2013
• Est. completion date: December 2015

Study information

• Verified date: March 2018
• Source: Central Institute of Mental Health, Mannheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 60 years.

2. Presence of an MDE according to ICD-10 criteria (HAMD17 = 18 or CDSS-Score = 8 points).

3. Lifetime diagnosis of schizophrenia-spectrum disorder according to ICD-10 (F 20, F22, F23, F25).

4. Partial remission of psychotic positive symptoms (PANSS positive subscore = 15 points).

5. Stable antipsychotic medication for at least 2 weeks (tolerable quantitative changes of daily dosage = 25%).

6. The patient is able to give an informed consent. In case of legal guardianship, the custodian will have to agree to the patient's participation.

Exclusion Criteria:

1. Contraindications against AGO treatment

2. Insufficient contraception in women of childbearing potential when sexually active.

3. Gravidity or breastfeeding.

4. Addiction to alcohol

5. Current abuse of THC and other illegal substances according to ICD-10

6. Dementia

Related Conditions & MeSH terms

• Delusional Disorder
• Disease
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophrenia, Paranoid

Intervention

Drug:
• agomelatine
Augmentation of antipsychotic therapy with 25 to 50 mg agomelatine as a single oral dosage per day

Locations

Country	Name	City	State
Germany	Central Institute of Mental Health	Mannheim	Baden-Württemberg

Sponsors (2)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim	Servier

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 weeks
Secondary	Secondary efficacy measures: Response rates	We will determine the percentage of responses (decrease of HAMD by at least 50 %)	6 weeks and 3 months
Secondary	Secondary efficacy measures: Long-term efficacy	After 12 weeks of treatment we plan to compare means of HAMD and CDSS with baseline data.	6 weeks and 3 months
Secondary	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.	6 weeks and 3 months
Secondary	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.	6 weeks and 3 months
Secondary	Secondary tolerability and safety measures: General tolerability	The general tolerability measures include the exploration and documentation of adverse events.	6 weeks and 3 months
Secondary	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.	6 weeks and 3 months
Secondary	Secondary efficacy measures: Remission rates	We will determine the percentage of remissions (decrease of HAMD below 8)	6 weeks and 3 months
Secondary	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.	3 months

External Links

•   Central Institute of Mental Health. Non-profit University hospital