We investigate whether the effects fluoxetine (Prozac®) on the outgrowth of the serotonergic system are dependent on age. In a 16 week multicenter randomized, double-blind, placebo controlled trial with fluoxetine in 80 adolescents and adults suffering from MDD and/or anxiety, the effect of age is investigated using state of the art in vivo Magnetic Resonance Imaging (MRI) techniques that allow determination of the functional status of the 5-HT neurotransmitter system with pharmacological MRI.
Conditions
Interventions
Trade Name: Fluoxetine CF 20, dispergeerbare tabletten 20 mg
Product Name: Fluoxetine CF 20
Product Code: RVG 24609
Pharmaceutical Form: Tablet
INN or Proposed INN: FLUOXETINE
CAS Number: 54910893
Pha
Sponsors
Academic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 40 adolescent (10-14 years of age) and 40 adult (23-30 years of age) female outpatients diagnosed with moderate or severe MDD and/or anxiety disorder, as defined in the DSM-IV, and in need of pharmacotherapy according to existing guidelines. Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - IQ < 70 (subtests Wechsler Intelligence Scale for Children-Revised (WISC-R); Wechsler, 1981 or National Adult Reading Test (NART); Nelson, 1991). - Other current Axis I psychiatric disorders like psychotic disorder, autistic disorder, ADHD and substance abuse, as defined in the DSM-IV. - Current or previous treatment with medications that influence the 5-HT system (for adults before 23 years of age): SSRIs, tricyclic antidepressants, triptans, MAO inhibitors. Current or previous (ab)use (for adults before 23 years of age): of MDMA, amphetamine, methamphetamine, cocaine, heroine and LSD). - Prenatal use of SSRI by mothers of the patients. - Current treatment with CBT in adults - Acute suicidality - Contraindications to fluoxetine treatment (known hypersensitivity to one of the contents, use of other SSRIs or pimozide (Orap), thioridazine or monoamine oxidase inhibitors (MAOI) and Saint John’s Wort). - Contraindications to MRI scanning (such as any kind of irremovable metal inside the body, claustrophobia, etc) - Pregnancy, breastfeeding or sexually active and not using/willing to use medically accepted means of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To report on the age-dependency of the effect(s) of the SSRI fluoxetine on the outgrowth of the serotonergic system using Magnetic Resonance Imaging (MRI) techniques;Secondary Objective: - To report on the age-dependency of the effect of fluoxetine on the outgrowth of the serotonergic system using several behavioral outcome measures related to 5-HT (emotional processing, verbal memory and impulsivity) using fMRI and a neuropsychological test battery. - To report on the age-dependency of the effect of fluoxetine on the 5-HT driven hypothalamic-pituitary-adrenal (HPA) axis, using cortisol and prolactine measures (baseline and after 5-HT challenge) - To report on the age-dependency of the effect of fluoxetine on growth, pubertal development and insuline-like growth factor (IGF-1) levels ;Primary end point(s): Main study parameters Difference in functioning of the 5-HT system after treatment, when compared to baseline conditions, as measured by: - phMRI: % change in citalopram induced BOLD signal from baseline - DTI: % change in FA values from baseline ;Timepoint(s) of evaluation of this end point: At week 0 (baseline) and week 19 (3weeks wash out period) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - fMRI: % change in task related BOLD signal from baseline - 1H-MRS: ratio of the 1.28 ppm peak to creatine peak - Neuropsychological functioning: change in outcome of several well-validated neuropsychological (computer)tasks addressing (verbal) memory, impulse control and emotional processing, compared to baseline measurements. - 5-HT-related HPA axis functioning: changes in baseline cortisol levels and cortisol and prolactine response after 5-HT challenge - Growth: % change in length, body weight, Tanner stage and IGF-1 levels from baseline ;Timepoint(s) of evaluation of this end point: At week -2(2 weeks prior to baseline), week 0, week 18 and week 19 | — |
Countries
Netherlands
Contacts
Public ContactDr.L.Reneman
Academical medical Center
Outcome results
None listed