Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.

BACKGROUND: Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant. OBJECTIVE(S): (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy. DESIGN: Retrospective cohort studies. SETTING: Primary care. PARTICIPANTS: Women treated for psychosis who became pregnant, and their children. INTERVENTIONS: Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME MEASURES: Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES: Clinical Practice Research Datalink database and The Health Improvement Network primary care database. RESULTS: Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy. LIMITATIONS: A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage. CONCLUSIONS: Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics. FUTURE WORK: Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

Vulnerability to depression is associated with a failure to acquire implicit social appraisals

Major depressive disorder is frequently associated with disrupted relationships with spouses, partners, family and peers. These problems can precipitate the onset of clinical illness, influence severity and the prospects for treatment and recovery. Here, we investigated whether individuals who have recovered from depression use interpersonal signals to form favourable appraisals of others as social partners. Twenty recovered-depressed adults (with at least two adult episodes of major depressive disorder but euthymic and medication-free for six months) and twenty three healthy, never-depressed adults completed a reaction time task in which the gaze direction of some faces reliably cued the location a target (valid faces), whereas the gaze direction of other faces cued the opposite spatial location (invalid faces). None of the participants were aware of this contingency. Following this task, participants judged the trustworthiness of the faces. Both the recovered-depressed and healthy never-depressed participants were significantly faster to categorise targets following valid compared with invalid gaze cueing faces. Whereas the healthy never-depressed participants judged the valid faces to be significantly more trustworthy than the invalid faces; this implicit social appraisal was absent in the recovered-depressed participants. Individuals who have recovered from major depressive disorder are able to respond appropriately to joint attention with other people but appear to not use joint attention to form implicit trust appraisals of others as potential social partners

Risks associated with antipsychotic treatment in pregnancy: Comparative cohort studies based on electronic health records.

BACKGROUND: Limited information is available on whether antipsychotics prescribed in pregnancy are associated with increased risks of adverse outcomes. METHODS: We used electronic health records from pregnant women and their children to examine risks of adverse maternal and child outcomes in three cohorts of women who: (A) received antipsychotic treatment in pregnancy (n=416) (B) discontinued antipsychotic treatment before pregnancy (n=670), and (C) had no records of antipsychotic treatment before or during pregnancy (n=318,434). Absolute and risk ratios were estimated and adjusted for health and lifestyle and concomitant medications. RESULTS: Caesarean section was more common in cohort A (25%) than C (18%), but non-significant after adjustment for health and lifestyle factors (Risk Ratio (adj.) 1.09 (95% CI: 0.92, 1.30). Proportion of gestational diabetes was similar in cohort A (2.6%) and B (2.7%), but lower in A than B after adjustments (RRadj: 0.43 (0.20, 0.93). Premature birth/low birthweight were more common in cohort A (10%) than B (4.3%) and C (3.9%), A versus B (RRadj: 2.04 (1.13, 3.67), A versus C (RRadj: 1.43 (0.99, 2.05). Major congenital malformations were more common in A (3.4%), than B (2.2%) and C (2%). However no significant difference was observed (A versus B: RRadj: 1.79 (0.72, 4.47) A versus C RRadj: 1.59 (0.84, 3.00)). Risks estimates were similar for women prescribed atypical and typical antipsychotics. CONCLUSIONS: Antipsychotic treatment in pregnancy carries limited risks of adverse pregnancy and birth outcomes once adjustments have been made for health and lifestyle factors

A leaky umbrella has little value:evidence clearly indicates the serotonin system is implicated in depression

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this

Developing a Series of AI Challenges for the United States Department of the Air Force

Through a series of federal initiatives and orders, the U.S. Government has been making a concerted effort to ensure American leadership in AI. These broad strategy documents have influenced organizations such as the United States Department of the Air Force (DAF). The DAF-MIT AI Accelerator is an initiative between the DAF and MIT to bridge the gap between AI researchers and DAF mission requirements. Several projects supported by the DAF-MIT AI Accelerator are developing public challenge problems that address numerous Federal AI research priorities. These challenges target priorities by making large, AI-ready datasets publicly available, incentivizing open-source solutions, and creating a demand signal for dual use technologies that can stimulate further research. In this article, we describe these public challenges being developed and how their application contributes to scientific advances

Serotonergic activity influences the cognitive appraisal of close intimate relationships in healthy adults

Our results suggest that central serotonin activity influences the appraisal of close intimate partnerships, raising the possibility that serotonergic dysfunction contributes to altered cognitions about relationships in psychiatric illnesses