Major depressive episode
Conditions
Interventions
Trade Name: Valdoxan 25 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: AGOMELATINE
CAS Number: 138112-76-2
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 25-
Sponsors
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy
Eligibility
Sex/Gender
All
Inclusion 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Contraindications against AGO treatment [compare study protocol section 1.4.5: bipolar depression, mania, suicidality (see 3.2.4), hepatic dysfunction with increased serum transminases above threefold upper limits of normal values, concomitant prescription of moderate CYP1A2 inhibitors (e.g. propranolol, grepafloxacine, enoxacine)] 2. Insufficient contraception in women of childbearing potential when sexually active. Adequate methods of contraception are: intrauterine devices (IUD), oral or depot anticontraceptives 3. Gravidity or breastfeeding. 4. Addiction to alcohol 5. Abuse of THC and other illegal substances according to ICD-10 (anamnestic data). 6. Dementia according to ICD-10.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of MDE severity before and after six weeks of treatment with Agomelatine (AGO) in patients with schizophrenia-spectrum disorder. HAM-D17 and CDSS will be applied at baseline and regularly over a period of 6 weeks after treatment initiation. In order to assess the treatment success, means in 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 =0.05. ;Secondary Objective: Efficacy: a) Responses, remission rates represented in HAM-D17-improvement by 50% or below 8 points. b) Long-term-efficacy due to follow-up-investigations after 12 weeks of treatment (HAMD17 and CDSS) c) Personal and social functioning (according to CGI and PSP) Safety and tolerability: a) Stability of the psychotic syndrome according to PANSS b) General tolerability (physical examination, ECG, laboratory testing) c) Pharmacokinetic interaction (regarding serum levels of antipsychotics) Neurocognition: Improvement of cognitive deficits associated with schizophrenia (MATRICS);Primary end point(s): Comparison of MDE severity before and after six weeks of treatment with AGO in patients with schizophrenia-spectrum psychosis. HAM-D17 and CDSS will be applied at baseline and regularly over a period of 6 weeks after treatment initiation. In order to assess the treatment success, means in 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 =0.05. ;Timepoint(s) of evaluation of this end point: Baseline (before start of treatment with agomelatine) and after 6 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: a) Responses, remission rates: HAM-D17 and CDSS will be applied regularly over a 6-week observation period after AGO initiation in order to evaluate treatment response. Proportion of patients responding to treatment (reduction of HAM-D17 by 50%) or even experiencing remission (HAM-D17 < 8 points) will be determined. b) Long-term-efficacy (follow-up after 12 weeks): In order to assess the long-term efficacy of AGO, a follow-up visit will be scheduled 3 months after treatment initiation. Changes in HAM-D17 and CDSS scores will also be evaluated (long-term follow-up). Suicidal ideations and their changes during treatment will be monitored with the CSSRS (Columbia Suicide Severity Rating Scale). c) Personal and social functioning: Personal and social performance will be evaluated with the PSP; all-over clinical impression will be rated on the CGI-S, and the level of improvement will be assessed by CGI-I and CGI-CB. Safety and tolerability: a) Stability of the psychotic syndrome: Psychotic positive symptoms will be monitored by regular PANSS ratings; negative symptoms will be assessed by PANSS (negative subscale) and SANS. An increase of PANSS positive subscores by = 5 points will be regarded as a clinically relevant psychotic deterioration and result in an early drop-out. b) General tolerability: Clinical measures (e.g. body weight, BMI, heart rate, blood pressure) and routine laboratory parameters, serum prolactin levels as well as ECGs will be examined. Sleep quality will be monitored by self-rating (LSEQ scores), sexual functioning will be evaluated by the administration of the SFQ scale; general well-being under psychopharmacological treatment will be assessed by SWN. Investigators will evaluate treatment AEs with the instruments BAR, SAS and ANNSERS. c) Pharmacokinetic interactions: Serum antipsychotic levels will be obtained prior to augmentation with AGO, 6 weeks and 3 months after treatment initiation. N | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Mathias Zink, PI
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy
Outcome results
None listed