Clinical trial NCT01822418: Agomelatine Treatment of Depression in Schizophrenia (AGOPSYCH)
Official title: Agomelatine Treatment of Major Depressive Episodes in the Course of Schizophrenic Psychoses (AGOPSYCH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Delusional Disorder
Keywords: Schizophrenia
Depression
Cognition
Agomelatine
Antidepressant
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
Collaborators: name: Servier
First posted: 2013-04-02
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Antidepressive efficacy
timeFrame: 6 weeks
Secondary outcomes:
measure: Secondary efficacy measures: Response rates
timeFrame: 6 weeks and 3 months
measure: Secondary efficacy measures: Long-term efficacy
timeFrame: 6 weeks and 3 months
measure: Secondary efficacy measures: Psychosocial functioning
timeFrame: 6 weeks and 3 months
measure: Secondary tolerability and safety measures: Psychotic symptoms
timeFrame: 6 weeks and 3 months
measure: Secondary tolerability and safety measures: General tolerability
timeFrame: 6 weeks and 3 months
measure: Secondary tolerability and safety measures: Pharmacokinetic interactions between AGO and antipsychotic agents
timeFrame: 6 weeks and 3 months
measure: Secondary efficacy measures: Remission rates
timeFrame: 6 weeks and 3 months
measure: Secondary efficacy measures: Cognitive functioning
timeFrame: 3 months
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
state: Baden-Württemberg
Study officials:
affiliation: Central Institute of Mental Health, Department of Psychiatry and Psychotherapy
name: Mathias Zink, MD
role: PRINCIPAL_INVESTIGATOR
References: