Treatment resistant depression MedDRA version: 9.1 Level: PT Classification code 10057840 Term: Major depression
Conditions
Interventions
Trade Name: Seroquel Prolong 300 mg Retardtabletten
Product Name: Seroquel Prolong 300 mg Retardtabletten
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: QUETIAPINE
CAS Number: 1119
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed written informed consent before initiation of any study related procedures 2. Male and female patients aged = 18 and = 65 years 3. Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of the following: - 296.2x Major Depressive Disorder, Single Episode - 296.3x Major Depressive Disorder, Recurrent 4. Current episode of depression present, at least 42 days prior to enrolment but not more than 18 months 5. MADRS-Score = 25 at enrolment and randomisation 6. During the current depressive episode history of inadequate response to one or two of the following antidepressants: citalopram, escitalopram, paroxetine, sertraline, or venlafaxine with a maximum dose of 225 mg/day before enrolment to the study. Therefore, patients can be included having failed on one SSRI, Venlafaxine alone, one SSRI then Venlafaxine, Venlafaxine then one SSRI. An inadequate response to treatment is defined as being treated with at least minimum effective dose of an antidepressant according to label for 30 days prior to study inclusions, and with at least one dose increase when permitted according to label without achieving remission from depressive symptoms. 7. Treatment resistance Stage I or II according to Thase ME et al., 1997: Stage I: failure of at least one adequate trial of one major class of antidepressant Stage II: Stage I resistance plus treatment failure of an adequate trial of an antidepressant in a distinctly different class from that used in stage I 8. Outpatient or inpatient status at enrolment (except patients admitted for compulsory treatment). Patients from day hospitals can also be enrolled 9. Female patients of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at enrolment and be willing to use a reliable method of birth control (i.e., barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation) during the study 10. Ability of the patient to understand and comply with the requirements of the study, as judged by the investigator 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation 2. Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient’s current psychiatric status 3. Patients who, in the investigator’s judgment pose a current serious suicidal or homicidal risk, or have made a suicide attempt within the past 6 months 4. Substance or alcohol abuse or dependence within 6 months prior to randomisation (with the exception of caffeine and/or nicotine dependence and/or substance or alcohol dependence in full remission), as defined in DSM-IV criteria. Patients with a positive urine toxicology screen (UTS) will be excluded, with the exception of patients testing positive for cannabinoids or prescribed medications (see Section 7.3.5). Patients can be re-tested if the initial UTS is positive, but should be excluded if the results are still positive at the second test. Patients with a positive UTS for (a) drug(s) legally prescribed, must provide evidence of the prescription 5. Patients receiving treatment with a SNRI other than venlafaxine or any other substance not allowed according to the protocol 6. Patients prescribed venlafaxine at a dose higher than 225 mg/day 7. Concomitant use of any medication or herbal supplement that may induce or inhibit the hepatic metabolising cytochrome P450 and P3A4 enzymes within 14 days prior to randomisation, e.g., - inducers: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, rafabutin, thioridazine, and St John’s Wort - inhibitors: ketoconazole (except for topical use), itraconazole, fluconazole, erythromycin, clarithromycin, fluvoxamine, nefazodone, troleandomycin, indinavir, nelfinavir, ritonavir, and saquinavir 8. Use of mood stabilisers other than those allowed according to the protocol, other antipsychotic or psychoactive drugs within 7 days prior to randomisation. The use of MAO inhibitors, anxiolytic drugs or hypnotics (except medications specified in Table 4) within 14 days before randomisation, or the use of an antipsychotic depot injection within two dosing intervals prior to randomisation 9. Patients who in the investigators opinion will require psychotherapy (other than supportive psychotherapy) during the study period. Psychotherapy initiated more than 90 days prior to randomisation is allowed 10. Pregnant or breast-feeding women 11. Low sodium diet 12. Psoriasis 13. Use of diuretic medication (thiazides, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors), ACE inhibitors, cyclooxygenase II inhibitors, angiotensin receptor II antagonists, calcium-blocking agents, methyldopa, theophylline, pentoxifylline, xanthinol nicotinate, non-steroidal antiflammatory drugs, non-steroidal antirheumatic agents, triptans, metronidazole, tetracyclines and alkalescent substances 14. Evidence of clinically relevant diseases, e.g., renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome (AIDS) 15. Any unstable clinical finding (e.g., hypertension, poorly controlled diabetes, unstable angina) or finding that in the investigator’s opinion, would negatively be affected by the study medication or affect the efficacy or tolerability of the study medication 16. Conditions that could affect absorption and metabolism of study medication (e.g., malabsorption syndrome, liver disease) 17. A current diagnosis of cancer (except basal or squ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of Quetiapine extended release in combination with an SSRI or Venlafaxine versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine versus Quetiapine extended release monotherapy in subjects with treatment resistant depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. As an independent objective, the primary objective will also be evaluated in two subgroups of patients: (1) patients who were resistant to two previous antidepressant therapies and (2) in the subgroup of patients with one previous failure.;Secondary Objective: The secondary objectives of the study are to compare the effects of the three different treatment regimen as assessed by the following variables and, if applicable, by their changes from randomisation to week 6 (end of study). Additionally the time of onset of therapeutic effect will be assessed by evaluating efficacy data after the first four days (Day 4) of treatment as well as after the first week of treatment (Day 8). These analyses will also be performed in the subgroups of patients with 2 failed previous antidepressants and patients with 1 failure.;Primary end point(s): The primary efficacy variable is the change in depressive symptoms between randomisation and week 6 as measured by the MADRS. | — |
Countries
Austria, Bulgaria, Denmark, Germany, Hungary, Italy, Portugal, Slovakia, United Kingdom
Outcome results
None listed