|- candidate number||1355|
|- NTR Number||NTR193|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||8-sep-2005|
|- Secondary IDs||N/A |
|- Public Title||DELPHI-trial and DELPHI-SPECT.|
|- Scientific Title||Dose Escalation Legitimate?
Pharmacology and Imaging studies in depression.
|- hypothesis||Dose-escalation of paroxetine (up to 50 mg/day) does not increase efficacy of treatment of Major Depressive Disorder in patients who did not respond to a 6 week trial of paroxetine in a standard dose (20 mg/day).|
|- Healt Condition(s) or Problem(s) studied||Depression, Depressive Disorder |
|- Inclusion criteria||1. Major Depressive Disorder according to DSM-IV (determined by Structured Interview for DSM-IV (SCID-I)); |
2. 17-item Hamilton Depression Rating Scale (HDRS-17) >18;
3. Age 18 to 70 years;
4. Maximally 1 previous treatment-trial with an antidepressant (of adequate duration [6 weeks] and dosage [maximum recommended dose]) for the current MDD episode.
|- Exclusion criteria||1. Bipolar disorder, psychosis or cognitive impairment (dementia or low IQ);|
2. Use of psychoactive medication (except low doses of benzodiazepines);
3. Previous adequate trial with paroxetine with insufficient response for the current episode;
4. Primary alcohol- or drugs abuse;
5. MDD secundary to comorbid anxiety- or somatophorm disorder;
6. Somatic illnesses (e.g. untreated thyroid or other endocrine illnesses, systemic illnesses);
7. Pregnancy or wish to become pregnant;
8. Severe and acute suicidality;
9. Insufficient knowledge of Dutrch to fill in questionnaires.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-nov-2003|
|- planned closingdate||31-dec-2006|
|- Target number of participants||500|
|- Interventions||After 6 weeks of open treatment with a standard dose of paroxetine (20 mg/day) the patients who have not responded (<50% decrease in baseline HDRS-17) will be randomised to receive either a true or a placebo increase (by capsules) in addition to the standard dose.|
|- Primary outcome||1. Response and remission rates (decrease of >= 50% in HDRS-17 and HDRS-17 <= 7 respectively);|
2. Total and specific (due to side-effects or inefficacy) drop-out.
|- Secondary outcome||1. Occurence of side-effects (physical and sexual);|
2. Subjective well-being and MOS-SF36 quality of life;
3. Direct and indirect costs (TiC-P).
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. A.H. Schene|
|- CONTACT for SCIENTIFIC QUERIES||Dr. H.G. Ruhe|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Background:|
Major depression is a major illness, with a year-prevalence of 5.8% in The Netherlands, and accounting for high costs regarding treatment and disability. Pharmacotherapy with Selective Serotonin Reuptake Inhibitors (SSRI) has become the first-choice treatment, but 50% of the patients treated show insufficient response to a first treatment of 6 weeks standard dose of a SSRI.
An often-used next-step strategy is dose-escalation: standard-dosages are doubled or tripled. After a systematic review, very little evidence for the efficacy of dose-escalation was found, previous studies investigated dose-escalation 3 weeks after initiation of treatment, which appears to be too early. Side effects undoubtedly increase with higher dosages. Patients are often reluctant to this strategy, but there is no systematic study of their perspectives. Additionally genetic polymorphisms of the serotonergic system are under examination as a possible explanation of the response rate to SSRIs. Prognostic factors to predict the efficacy of dose-escalation after several weeks of a standard-dose (meaning a form of patient-selection) would increase efficiency of this strategy.
To add evidence concerning efficacy, effectiveness and prognostic factors for the strategy of dose-escalation after 6 weeks on a standard dose of paroxetine.
To quantify patient perspectives regarding dose-escalation.
Randomized placebo-controlled trial of dose-maximization in depressed non- and partial responders after 6 weeks of a standard dose of a SSRI; Explorative study of prognostic factors (including genetic polymorphisms) for final response after dose-maximization.
1. & 2. Response (> 50% decrease in 17-item Hamilton Depression Rating Scale (HDRS)), Remission (HDRS <8), Overall and specific drop-out, Subjective Well-being.
Rates of dichotic outcomes and decreases in HDRS-scores during 6 weeks of follow-up in patients receiving increased dosages versus placebo-increase. Associations (in regression-models) of prognostic factors (demographic, genotypes of monoaminergic enzymes, Serotonin-Transporter and -receptors) with final response and interaction with dosage.
|- Main changes (audit trail)|
|- RECORD||1-sep-2005 - 14-sep-2009|