Antipsychotic Agents, Breastfeeding, Drug Exposure in Utero, Drug Exposure Via Breast Milk, Mania, Pregnancy, Psychosis, Schizophrenia
Conditions
Keywords
mental ill health, pregnancy, postpartum, long-acting injectable antipsychotics, Risperidone, Paliperidone palmitate, Fluphenazine decanoate, Flupentixol decanoate, Zuclopenthixol decanoate
Brief summary
The goal of this observational study is to learn about how long-acting injectable antipsychotic (LAIA) medications are affected by the changes that take place in the body during pregnancy, and how much an unborn baby is exposed to. The investigators are also interested in the amount of these drugs that enters into breastmilk and taken by babies during breastfeeding. In addition to their regular clinic visits to receive long-acting mental health medicine injection, participants will be invited for up to four study visits between day 2 and 14 after the injection. This will happen only once during pregnancy, and once during the breastfeeding period to collect a few drops of blood on special filter paper card from the finger using safety lancet. A few drops of breastmilk will also be collected. Immediately after delivery, a few drops of blood will be collected from the mother, umbilical cord and the baby heel. The investigators will use these samples to determine the amount of the drug in the body during pregnancy and compare this to the amount during the breastfeeding period. Additionally, every month during the third trimester, and during the first 3 months postpartum, participants will complete a questionnaire (using the Liverpool University Neuroleptic Side Effect Scale) to document how they are feeling. Clinical improvement will be documented by the primary care provider using the Clinical Global Impressions Scale. Findings from this study are expected to help healthcare providers to understand these drugs better so that they can make informed decisions about if and how to use these drugs in women who become pregnant or are breastfeeding.
Detailed description
Primary Objectives 1. To determine the magnitude of changes (if any) in the pharmacokinetics of selected LAIAs during pregnancy and assess the extent of fetal exposure at delivery. 2. To describe breastmilk pharmacokinetics of selected LAIAs and the extent of breastfed infant exposure. Secondary Objectives 1. To assess safety and clinical outcomes following LAIA use during pregnancy and postpartum. 2. To explore sources of variability in maternal and fetal/breastfed infant LAIA exposure.
Interventions
None listed
Sponsors
University of Liverpool
Federal Neuropsychiatric Hospital, Yaba
Federal Neuropsychiatric Hospital, Kaduna
Neuropsychiatric Hospital, Abeokuta
Neuropsychiatric Specialist Hospital, Akure
Federal Medical Centre, Makurdi
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
* Currently pregnant or breastfeeding. * If pregnant, plans to deliver within the facility. * Diagnosis of schizophrenia, mania or other psychoses. * Prescription of long-acting injectable antipsychotic (Risperidone, Paliperidone palmitate, Fluphenazine decanoate, Flupenthixol decanoate and Zuclopenthixol decanoate) as maintenance therapy started before study entry. * Scheduled to receive at least one injection before delivery (if pregnant) or before week 12 postpartum (if breastfeeding). * At least 18 of age at study entry.
Exclusion criteria
* Unable to understand study information. * Unable to provide written informed consent. * Known hypersensitivity to study medication. * Record of poor medication adherence. * Personal circumstances will not allow completion of the schedule of study activities. * Concurrent use of agents with known or uncertain interaction with study drug. * Currently experiencing severe pregnancy related complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimum plasma drug concentration (Cmin) during pregnancy and postpartum | During gestation weeks 33-36 and weeks 9-12 weeks postpartum | Determined from sampling at the end of a dosing interval during pregnancy, and postpartum |
| Minimum breastmilk drug concentration (Cmin) | During weeks 9-12 weeks postpartum | Determined from sampling at the end of a postpartum dosing interval |
| Maximum plasma drug concentration (Cmin) during pregnancy and postpartum | During gestation weeks 33-36 and weeks 9-12 weeks postpartum | Highest concentration during a dosing interval during pregnancy, and postpartum |
| Maximum breastmilk drug concentration (Cmin) | During weeks 9-12 weeks postpartum | Highest concentration during a postpartum dosing interval |
| Area under the plasma concentration-time curve (AUC) | During gestation weeks 33-36 and weeks 9-12 weeks postpartum | For assessment of overall drug exposure in plasma |
| Area under the breastmilk concentration-time curve (AUC) | During weeks 9-12 weeks postpartum | For assessment of overall drug exposure in breastmilk |
| Breastfed infant to maternal plasma LAIA concentration ratio | During weeks 9-12 weeks postpartum | To determine the level of breastfed infant LAIA exposure and elimination |
| Newborn to maternal plasma LAIA concentration ratio | As soon as possible after delivery | To determine the extent of in utero fetal drug exposure and elimination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LAIA associated symptoms | From gestation week 28 to postpartum week 12 | To monitor LAIA side effects during and postpartum using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) |
| Clinical improvement | From gestation week 28 to postpartum week 12 | To monitor illness severity, improvement and LAIA efficacy during pregnancy and postpartum using the Clinical Global Impressions Scale. |
| Single nucleotide polymorphisms in drug disposition genes | From gestation week 28 to postpartum week 12 | To explore genetic sources of interindividual variability in maternal and fetal/breastfed infant drug exposure |
Countries
Nigeria
Contacts
STUDY_CHAIRAdeniyi Olagunju, PhD
University of Liverpool
Outcome results
None listed