Prosepctive randomized two armed study to evaluate moderate depression during pregnancy treated with interbnetbased CBT and sertarline or placebo and longterm outcome in the children.Secondary objectives are effects on pregnancy, maternal bleeding, and epigenetic changes inthe mother and child.
Conditions
Interventions
Product Name: Zoloft
Product Code: sertraline
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
None listed
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female > 18 years old 2. Pregnant, gestational week 11-17 . 3. Verified moderate depression according to SCID-I with or without concomitant anxiety disorder. 4. Signed informed consent 5. Able to understand the Swedish language orally and in written and able to use the internet for the ICBT 6. Are willing to participate to all study visits 7. Plans to give birth at the Department of Obstetrics at Karolinska University Hospital, Huddinge Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any of the below mentioned: 1. Known drug or alcohol abuse 2. Serious psychiatric disorder such as psychosis, bipolar disorder, severe personality disorder, ADHD/ADD, autism or mental retardation) and severe melancholic or psychotic depression. 3. Known idiosyncrasy to Zoloft or allergy to one of the Zoloft excipients 4. Ongoing medication with SSRI, SNRI, TCA, mood-stabilizers, antiepileptic drugs ,psychotropic drugs, tramadol, propafenon, tolbutamid, flekainid, psychostimulants and atomoxetine, insulin or steroids 5. Any severe somatic disease that necessitate regular treatment with systemic steroids, severe heart and lung disease, kidney disease, liver disease, diabetes mellitus, or epilepsy with drug treatment. 6. Women who either during screening or treatment on self-assessment forms (MADRS-S: 4 or more points on question about suicidal ideation (question 9)) report symptoms of severe suicidal thoughts or suicide plans will be contacted for structured suicide risk assessment by telephone (by experienced staff from the unit for internet psychiatry according to clinical routine). If judged necessary patients will be booked for psychiatric assessment by study nurse. If acute assessment or care is judged necessary, referral to psychiatric emergency departments will be made according to the same routine as in regular care. Also women, who contact the study personal and report symptoms of suicidal thoughts or suicide plans will receive psychiatric assessment as specified above. Women who according to psychiatric assessment have a high suicidal risk will be excluded from the study. These women will be actively transferred into necessary psychiatric treatment as usual. 7. Other factors that are clinical significant and could jeopardize study results or its intention, as judged by study psychiatrist or study obstetrician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Longterm outcome in children exposed to maternal depression, treated with internetbased CBT and setraline or placebo, during fetal life.;Secondary Objective: The secondary objectives are to evaluate the safety and the efficacy of sertraline in addition to treatment with ICBT. This include: a) to study if the effect of ICBT for pregnant women with moderate depression can be increased by adding sertraline b) to study if add-on treatment with sertraline increases the risk for maternal bleeding and pregnancy complications c) To study associations between antenatal maternal depression and endocrinological, inflammatory, epigenetic and telomere biology changes in relation to treatment effects of SSRI in mother and child ;Primary end point(s): Cognitive development at 2 years evaluated by the standard Bayley Scales of Infant and Toddler Development v 3 (BSID-III) in children exposed to maternal treatment with ICBT and sertraline compared to exposure to I-CBT only.;Timepoint(s) of evaluation of this end point: 2 yeras after birth of the child | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Maternal effects Add-on effect of sertraline measured in difference i) in self-report of depressive symptoms (MADRS-S),ii) in rate of remission from depression (measured by diagnostic psychiatric interview with MADRS at -12weeks, 14 weeks, and 30 weeks (= 3 months postpartum) of treatment. Treatment effect of ICBT calculated as change in self-report of symptoms (MADRS-S) from pre- and post- treatment and including the weekly measures between them. Treatment effect stability of ICBT calculated as change in MADRS-S from 12 to 22 weeks, including the measure at 14 weeks. Differenced in risk of suicidality between sertraline and placebo measured as change from baseline (measured by the suicidal ideation item in MADRS-S (item 9) and MADRS ) Effects on levels of saliva- and plasma cortisol, allopregnanolone, estradiol, progesterone, oxytocin, prolactin, corticotrophin-releasing hormone (CRH), S-hCG, cytokines, EGF, VEGF, BDNF Epigenetic and telomere biology assessments: DNA methylation, telomere length and telomerase activity Pharmacological assessment: sertraline serum concentration, sertraline metabolism, Evaluate the risk for maternal postpartum bleeding in ml and postpartum hemoglobine day 2. APTT /TPK and placenta biopsy for evaluation of 11 beta-hydroxysteroid dehydrogenase type 2 and DNA methylation for telomere length and telomerase activity. Evaluate risk for pregnancy complications preeclampsia, placental abruption and increased cesarean section rate. Neonatal effects: Admission to neonatal care unit Plasma concentrations of sertraline, cortisol, 5-HTAA, S100, brain-derived neurotropic factor (BDNF), genetic variants of metabolizing enzymes/transporters, telomerase activity through the umbilical vein and buccal swabs for analysis of epigenetic variables and telomere biology. Infant motor behavior examined with standardized methods HINE) and neonatal abstinence effects scored with NAS ;Timepoint(s) of evaluation of this end p | — |
Countries
Sweden
Outcome results
None listed