Serum Concentrations of Antidepressant Drugs in Pregnant Women - a Naturalistic Study (PAPA)

The study was a prospective naturalistic PK study of five frequently used antidepressant drugs in pregnant women; citalopram (CIT), escitalopram (ECIT), sertraline (SERT), mirtazapine (MIRT) and venlafaxine VEN) and their major metabolites (Table 1). After signing informed consent pregnant women with ongoing antidepressant treatment, regardless of indication, were recruited at nine antenatal care centers in mid- and small cities and villages in the Southeast Sweden between April 2011 and September 2013.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Pharmacokinetics; Antidepressive Agents
• Intervention / Treatment: Drug: sertraline, mirtazapine, venlafaxine, citalopram, escitalopram

Detailed Description

Serum samples for the antidepressant drug and metabolite(s) concentrations, albumin and creatinine were collected at the first prenatal appointment and at gestational week 15, 20, 25, 35 and at partus. The time interval between drug intake and sampling was registered in all cases. At partus, a serum samples from the umbilical cord was collected drug concentration was assessed. At the first prenatal appointment a blood sample for analyzing the CYP2D6 and CYP2C19 genotype was also collected. All drug concentration analysis were executed post hoc, after last partus, whereas physiological parameters were part of normal routine sampling. Concomitant medication, weight changes and smoking habits were registered throughout the pregnancies.

Our main findings were that dose corrected serum concentrations of neither sertralin nor citalopram changed during the pregnancy. In addition, concentrations of escitalopram and venlafaxine and their metabolites appeared to be stable throughout pregnancy, even though a linear mixed models statistic calculation could not be done due small number of samples.

Results from previous research on sertraline PK during pregnancy are inconclusive. Two studies suggested decreased levels (Freeman, Sit 2), while one study indicated increased levels (Westin). Previous studies, except for Westin's are, however, limited by small sample sizes (six and eight) and a substantial inter-individual variance.

• Study Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• Sweden
  • Linköping, Sweden
    • Linköping University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

At inclusion, median age (min-max) was 31 years (21-42) and median BMI was 25.6 (18.9-47.0)

Description

Inclusion Criteria:

• Pregnancy
• Ongoing treatment with one of the five studied antidepressants.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observed	Drug: sertraline, mirtazapine, venlafaxine, citalopram, escitalopram; Naturalistic treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentrations of drugs and metabolites	levels of parent compound and metabolites in serum	9 months

Collaborators and Investigators

• Sponsor: Linkoeping University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): September 30, 2013
• Study Completion (Actual): September 30, 2013

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; pregnancy; antidepressants
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Sertraline; Citalopram; Venlafaxine Hydrochloride; Mirtazapine
• Other Study ID Numbers: PAPA123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No