major depressive disorder
Conditions
Interventions
Using a genetic test, genetic variants that have an impact on the metabolizing
capacity of CYP2D6 and CYP2C19 will be determined. These variants explain
90-95% of the cases with changes in CYP2D6 an
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients are in- and outpatients, having a primary diagnosis of severe major depressive disorder (SCID-I diagnosis in agreement with DSM-5 criteria and a Hamilton Rating Scale for Depression score * 19 (HRSD-17-item version), aged 18-65 years, who, according to their physician, are eligible for treatment with a TCA (Nortriptyline (NOR), Clomipramine (CLOMI) or Imipramine (IMI)). The choice of the specific TCA is at the discretion of the physician in attendance.
Exclusion criteria
Exclusion criteria: (1) Psychotic depression (2) Bipolar I or II disorder. (3) Schizophrenia or other primary psychotic disorder.(4) Drug or alcohol dependence in the past 3 months. (5) Mental Retardation (IQ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome measure: Time to TCA plasma concentration in the therapeutic range (primary outcome measure). Blood for plasma concentration measurements will be taken in the morning, at 12 (+/-) 1 hours after the last evening dose. When a patient attains a plasma level within the therapeutic range at steady state, the primary endpoint has been reached (for nortriptyline 0.05*0.15 mg/l; for clomipramine: 0.15*0.30 mg/l (clomipramine plus desmethylclomipramine) and for imipramine 0.15-0.25 mg/l (imipramine plus desipramine). | — |
Secondary
| Measure | Time frame |
|---|---|
| a. Reduction of depressive symptoms after 7 weeks of treatment (defined as the baseline HDRS score minus the HDRS score at the 7 weeks assessment.) rated by a blinded investigator. b. Highest level of side effects based on the Antidepressant Side Effect Checklist (ASE, Uher et al. 2009) and the FIBSER (Frequency, Intensity, and Burden of Side Effects Rating FIBSER (Wisniewski et al. 2006)) rated by the patient. c. Economic Evaluation: The impact of the intervention on the quality of life of patients will be assessed both by the EuroQol 5 dimensions with 5 levels (EQ5D5L) and the The Short Form (36) Health Survey (SF36) at weeks 0, 2,4,6,13 and 26 following randomization. Cost analysis: The cost analysis consists of two main parts. First, at patient level, volumes of care related to MDD and TCA therapy will be measured by means of the iMTA Medical Consumption Questionnaire. This questionnaire measures all relevant health care related costs like outpatient visits at any medical specialist and hospitalizations. In addition the medication use will be derived from the electronic patient records. Loss of productivity due to illness or recovery, will be estimated based on patient reported absences from paid (or unpaid) labour measured with the Productivity Cost Questionnaire. The second part of the cost analysis consists of determining the cost prices for each volume of consumption. The standard cost prices from the 'Dutch Guidelines for Cost Analyses* and www.medicijnkosten.nl will be used. For units of care where no standard prices are available real costs prices will be determined on the basis of full cost pricing. Productivity losses will be valued by means of the friction cost method. In the end volumes of care will be multiplied with the cost prices for each volume of care to calculate costs. | — |
Countries
Netherlands
Outcome results
None listed