The quality of lactation studies including antipsychotics.

THE AIM OF THE STUDY: The aim of this study is to determine the quality of lactation studies that investigated antipsychotics in breast milk according to the Food and Drug Administration (FDA) and International Lactation Consultant Association (ILCA) draft guidelines. MATERIALS AND METHODS: We used the draft FDA and ILCA guidelines to review the quality of articles including antipsychotic use during breastfeeding. We used PubMed and Lactmed for the literature search. Furthermore, cross references were searched for additional studies. RESULTS: Of the 51 studies, only one olanzapine and one quetiapine study calculated the milk to plasma ratio (M:P ratio), the Absolute Infant Dose (AID), and the Relative Infant Dose (RID) correctly. In the remaining studies, at least one of the three endpoints was not determined properly. No correct endpoints were calculated in studies containing chlorpromazine, chlorprothixene, clozapine, haloperidol, sulpiride, trifluoperazine, ziprasidone, zonisamide, and zuclopenthixol. This review investigated that there was a lack of information on the sampling methods of breast milk. Furthermore, the concentrations needed for the calculations of the three endpoints were mainly based on single measurements instead of at least five measurements during one dose interval. In many studies, the RID was not calculated correctly due to the fact that the RID was not normalized by the maternal weight or an average maternal weight of 70 kg was used as a standard. CONCLUSION: Except for two studies, most studies about the safety of antipsychotic use during lactation did not meet the criteria of the draft FDA and ILCA guidelines. Further research is mandatory to assess the safety of using antipsychotics while breastfeeding.

Adherence of antidepressants during pregnancy: MEMS compared with three other methods.

BACKGROUND: Data about adherence of antidepressants during pregnancy are lacking. However, it is important to gain insight into adherence in this population to reduce perinatal risks for relapse of depression. OBJECTIVE: The objective of this study was to search for an inexpensive and easy method to implement daily for assessing medication adherence during pregnancy. METHODS: An observational study was conducted to measure adherence by comparing pill count, Beliefs about Medicine questionnaire (BMQ) and blood level monitoring against the standard, the Medication Event Monitoring System (MEMS). We used a logistic regression model to determine potential predictors for poor adherence (age, marital class, highest level of education, monthly net income, employment, smoking, alcohol use and type of antidepressant). RESULTS: From January 2010 until January 2012, 41 women were included within the first trimester of pregnancy; data could be evaluated in 29 women. Using MEMS, 86% of the women took in more than 80% of all prescribed doses on time and could be classified as adherent. Pill counts showed good agreement with MEMS. We did not find predictors for poor adherence in our study population. CONCLUSION: Adherence of antidepressants during pregnancy using MEMS is 86%. There was a good agreement between MEMS and pill counts. This method may serve as a good alternative that can be easily implemented into daily practice.

[Life-threatening psychosis caused by using sibutramine-contaminated weight-loss coffee]. / Levensbedreigende psychose na gebruik van afslankkoffie verontreinigd met sibutramine.

BACKGROUND: Weight-loss products, which are freely available in some other countries and on the Internet, may be contaminated with ingredients not mentioned on the label. CASE DESCRIPTION: We describe a 43-year-old woman who presented to the emergency ward of our hospital after stabbing herself in the stomach with a knife, because of severe psychosis. A few days after admission her symptoms were completely gone and there were no longer signs of psychosis. The most likely explanation for the psychosis was the use of sibutramine-contaminated weight-loss coffee (Brazil Potent Slimming Coffee). CONCLUSION: Brazil Potent Slimming Coffee and possibly also other weight-loss products may be contaminated with sibutramine and as a result cause severe adverse reactions. It is always important to consider intoxication due to the use of herbal supplements and other OTC products in the differential diagnosis.

Clomipramine concentration and withdrawal symptoms in 10 neonates.

AIM: After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODS: Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTS: We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min(-1). Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONS: In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.

Pharmacological aspects of neonatal antidepressant withdrawal.

UNLABELLED: Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to explain the importance of antidepressant therapy during pregnancy and postpartum, summarize the important neonatal effects of antidepressants, and describe the potential teratogenic effects of antidepressants.