Major depression/depressie, SSRI, fluoxetine, serotonine, development/ontwikkeling
Conditions
Interventions
1. Random assignment to a flexible dose of fluoxetine or placebo drug treatment for 16 weeks, followed by a medication-free wash-out period of three weeks
2. 3.0 Tesla MR imaging including diffusion tensor imaging (DTI), task-related functional MRI (fMRI) and pharmacological MRI (phMRI) following 5-HT challenge with a low dose of the SSRI citalopram (5
3. Assessment of a neuropsychological test battery and short questionnaires
4. Collection of several saliva samples for cortisol measurement and a genetic assay for serotonin transporter gene promoter (5-HTTLPR) polymorphism.
Sponsors
Academic Medical Center (AMC), Amsterdam
Eligibility
Inclusion criteria
Inclusion criteria: 1. Female outpatients, newly diagnosed with moderate to severe MDD and/or anxiety disorder (AD) (but not AD not otherwise specified (NOS) or adjustment disorder) as determined by a structured interview (DISC-IV; Ferdinand et al., 1998) or CIDI lifetime version 2.1 (WHO, 1992) by a (child and adolescent) psychiatrist. Rating scales: Children’s Depression Rating scale-Revised in adolescents: (CDRS-R; Poznanski and Mokros, 1995) > 45, Children’s Global Assessment Scale (CGAS; (Shaffer et al., 1983) 18, Clinical Global Impression scale (CGI, Guy 1976) > 4, and or Hamilton anxiety scale (HAM-A; Hamilton)>20; 2. Subjects must exhibit stable dysphoria/depressed mood and/or anhedonia and/or persistent anxiety symptoms for at least 2 weeks prior to enrolment and mood should be pervasive; 3. Also, already diagnosed MDD and AD adolescents unresponsive to CBT (but without prior pharmacotherapy treatment) will be included; 4. Age range is 12-14 or 23-40 years of age at the time of study entry. Based on the above mentioned criteria, subjects will be enrolled in the study that are suffering from mild-to-severe MDD or AD that are in need of pharmacotherapy with an SSRI (fluoxetine) and therefore are eligible for participation in this ‘acute treatment’ study.
Exclusion criteria
Exclusion criteria: 1. Estimated IQ < 70 (subtests Wechsler Intelligence Scale for Children-Revised (WISC-R); Wechsler, 1981 or National Adult Reading Test (NART); Nelson, 1991); 2. Other current Axis I psychiatric disorders like psychotic disorder, autistic disorder, ADHD and substance abuse, as defined in the DSM-IV; 3. 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); 4. Prenatal use of SSRI by mothers of the patients; 5. Current treatment with CBT in adults; 6. Acute suicidality; 7. 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); 8. Contraindications to MRI scanning (such as any kind of irremovable metal inside the body, claustrophobia, etc); 9. Pregnancy, breastfeeding or sexually active and not using/willing to use medically accepted means of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. phMRI: % change in citalopram induced BOLD signal from baseline; 2. DTI: % change in FA values from baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. fMRI: % change in task related BOLD signal from baseline; 2. Neuropsychological functioning: change in outcome of several well-validated neuropsychological (computer)tasks addressing (verbal) memory, impulse control and emotional processing, compared to baseline measurements; 3. 5-HT-related HPA axis functioning: changes in baseline cortisol level and cortisol response after 5-HT challenge. | — |
Contacts
Public ContactLiesbeth Reneman
Meibergdreef 9
Outcome results
None listed