Depressive Disorder, Major
Conditions
Brief summary
The purpose of this study was to investigate the efficacy of duloxetine versus placebo on pain in outpatients with major depressive disorder (MDD): change in Brief Pain Inventory Short Form (BPI-SF) 24-hour average pain score from baseline over the 8 weeks of treatment
Interventions
DRUGDuloxetine
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients who meet the criteria for MDD according to the Diagnostic and Statistic Manual of mental disorders, 4th edition (DSM-IV) criteria and confirmed by Mini International Neuropsychiatric Interview (MINI) * Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20 at screening and baseline (Visits 1 and 2) * Patients must have had at least one previous episode of depression in their medical history * Painful physical symptoms (PPS) with a score ≥ 3 on the BPI-SF scale for average pain at screening and baseline * Patient aged 18 years or older at the screening visit * CGI-Severity score ≥ 4 at Visits 1 and 2 * Patients willing and able to comply with the scheduled visits, tests and procedures required by the protocol * Written informed consent obtained at the screening visit, in accordance with Good clinical practice (GCP) and local regulatory requirements, prior to any study procedure
Exclusion criteria
Neuro-psychiatric exclusions * Lack of response of the current episode to 2 or more adequate courses of antidepressant therapy given at a clinically appropriate dose and for a sufficient length of time in the judgement of the investigator * Any anxiety disorder as a primary diagnosis within the past 6 months (including panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia). Note: Specific phobias (i.e. agoraphobia, arachnophobia, etc.) will be allowed * Any diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders * Presence of an Axis II disorder which, in the judgement of the investigator, would interfere with compliance with the study protocol * History of serious suicide attempt or patient judged to be at serious suicidal risk in the opinion of the investigator and / or score \> 2 for question 10 (suicide) of the MADRS * History of drug dependence, including alcohol or benzodiazepines, according to DSM-IV, in the previous year * Positive urine screen for drug abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, amphetamines) Other medical exclusions * Patients requiring continuous treatment with analgesics (\> step 2 WHO definition) because of chronic pain (\> 6 months) * Patients with organic pain syndromes * Epilepsy or history of seizure disorder or of a treatment with anticonvulsant medication for epilepsy or seizures * Patients with a known diagnosis of raised intraocular pressure or at risk of acute narrow-angle glaucoma * Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption syndrome, or lactose deficiency * Patients with severely impaired renal function, defined by a creatinine clearance \< 30 mL/min (creatinine clearance was calculated by the central laboratory from the screening safety laboratory test * Acute liver injury (such as hepatitis) or severe (Child-Pugh Class C) cirrhosis * Abnormal initial ECG findings according to investigator's judgement * Serious medical illness or clinically significant laboratory abnormalities which, in the judgement of the investigator, are likely to require medication/ intervention or hospitalization during the course of the study * Women of childbearing potential not using a medically accepted means of contraception when engaging in sexual intercourse (e.g. intrauterine device, oral contraceptive, contraceptive patch, implant, or barrier devices) * Women who are pregnant or breast-feeding Pharmacological and other exclusions * Participation in another clinical trial within 30 days prior to screening (Visit 1) * Patients who have previously completed or withdrawn from this or any other study investigating duloxetine or have previously been treated with duloxetine * Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 or potential need to use a MAOI within 5 days after discontinuation of study drug * Treatment with fluoxetine within 28 days prior to Visit 2 * Treatment with any of excluded medications (listed in Protocol) within 7 days prior to Visit 2 * (excepted MAOI within 14 days and fluoxetine within 28 days) * Frequent and/or severe allergic reactions with multiple medications. Known hypersensitivity to duloxetine or any of the inactive ingredients * Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one year prior to screening * Initiation or discontinuation of depression-oriented psychotherapeutic treatment (e.g. behavioural therapy, psychoanalytic therapy, cognitive therapy etc.) within 6 weeks prior to screening visit or planned use of such treatment at any time during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of 24-hour average pain rated on Brief Pain Inventory-Short Form (BPI-SF) score | Up to 8 weeks after drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to sustained clinical response for Painful Physical Symptoms (PPS) according BPI-SF score | Up to 8 weeks after drug administration | as defined by 30% reduction from baseline in question 5 (average pain) of the BPI-SF score |
| Change of patient symptoms rated on Symptom Checklist 90 Revised (SCL-90-R) scale | Up to 8 weeks after drug administration | — |
| Patients Global Impression (PGI) rated on PGI-improvement scale | Up to 8 weeks after drug administration | — |
| Clinical Global Impressions (CGIs) by investigator rated on CGI-severity score | Up to 8 weeks after drug administration | — |
| Clinical Global Impressions (CGIs) by investigator rated on CGI-improvement scale | Up to 8 weeks after drug administration | — |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score | Up to 8 weeks after drug administration | — |
| Number of patients with adverse events | Up to 8 weeks after drug administration | — |
| Number of patients withdrawing due to adverse event | Up to 8 weeks after drug administration | — |
| Number of patients with clinical significant findings in vital signs | Up to 8 weeks after drug administration | blood pressure, pulse rate |
| Number of patients with clinical significant findings in weight | Up to 8 weeks after drug administration | — |
| Number of patients with clinical significant findings in laboratory values | Up to 8 weeks after drug administration | — |
| Time to sustained clinical response for overall depression symptoms | Up to 8 weeks after drug administration | as defined by a 50% reduction from baseline in MADRS score |
Outcome results
None listed