Earlier this year as Christmas dinners were digested and New Year’s resolutions planned, many people were glued to their screens watching the latest EastEnders storyline unfold. EastEnders resident Stacey, who has bipolar disorder, developed postpartum psychosis.

Postpartum psychosis is more common in women with bipolar disorder and even more so in those who were medication free during pregnancy (Wesseloo et al, 2016). Patients who suffer from schizophrenia also report worsening mental health following pregnancy (Jones et al, 2014).

There is a severe lack of evidence on the risks and benefits of psychotropic medication in pregnancy. No randomised controlled trials have been conducted that establish whether the benefits of taking antipsychotic drugs outweigh the risks for pregnant or postpartum women (Webb et al 2004, 2009). Some psychotropic medications are known to have teratogenic and adverse neurodevelopmental effects (Epstein et al, 2015; Tomson et al 2012) and currently no psychotropic medication is licensed for use in pregnancy. This creates a dilemma for healthcare professionals and patients; protect the woman’s mental health or protect the unborn child from the potentially damaging effects of psychotropic medication?

The National Institute for Health Research has commissioned research to address the question: What are the risks and benefits of psychotropic drugs in women treated for psychosis who become pregnant? (Peterson et al, 2016).

Methods

The researchers used data from two existing electronic health records sources: The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD). These databases provide anonymised general practice data and include data from more than 10% of the population and are representative of the UK population (Blak et al 2011; Williams et al, 2012).

Using data from 1 January 1995 to 31 December 2012 researchers identified a cohort of women who had a diagnosis of psychosis (bipolar disorder, schizophrenia or overlap syndromes) who were in receipt of antipsychotics, lithium and anticonvulsant mood stabilisers and who became pregnant.

The researchers divided the project into two parts:

1. The first part consisted of five descriptive studies with a focus on psychotropic drug utilisation, discontinuation and restarting of treatment.
2. The second part consisted of a series of cohort studies that examined the absolute and relative risks of adverse maternal and child outcomes associated with psychotropic medication.

Results

During the time period of the study overall antipsychotic treatment increased by more than 50% before and during pregnancy and prescriptions of anticonvulsant mood stabilisers to women with a record of psychosis or depression almost doubled. In contrast, lithium prescribing after delivery almost halved, in fact so few women were prescribed lithium no further analyses could be conducted.

Descriptive studies

• Prescribing of psychotropic medication decreased in early pregnancy and then increased after delivery to equal or above pre-pregnancy levels.
• Rates of recorded suicide attempts, overdose or deliberate self-harm declined during pregnancy, rates rose after pregnancy but to only half of pre-pregnancy levels.
• Instances of mental health hospital admission or invoking the Mental Health Act more than tripled just after delivery and the recording of psychosis, mania and hypomania doubled just after delivery.
• Pregnant women discontinue psychotropic medication at a higher rate compared to non-pregnant women.

Cohort studies

• Antipsychotic medication in pregnancy did not increase the risk giving birth to a child with major congenital malformation.
• Women prescribed antipsychotics were at a higher risk of delivering by caesarean section, giving birth to a child with poor birth outcomes and neurodevelopmental and behavioural disorders. However, after controlling for confounding factors these associations were not significant.
• Women prescribed anticonvulsant mood stabilisers during pregnancy experienced higher risks of all poor child outcomes. The increased risk persisted after adjustment for health and lifestyle factors. Valproate was associated with a higher risk compared to other anticonvulsant mood stabilisers.

Conclusions

The results show that the majority of women discontinue psychotropic medication either before or early in pregnancy.

In this cohort, women prescribed anticonvulsant mood stabilisers, in particular valproate, were at increased risk of giving birth to a child with major congenital malformation, neurodevelopmental and behavioural disorders.

This is in contrast to those prescribed antipsychotics where, after controlling for confounding factors such as obesity, alcohol problems, smoking, concomitant medications and illegal drug use, there was no increased risk of major congenital malformations, confirming previous research (Tomson et al 2012; Coughlin et al, 2015; Wide et al, 2004) and Guidelines (NICE, 2014).

Strengths and limitations

This is the largest and most comprehensive study of its kind to date. The use of primary care databases is a notable strength of this study, it is also a weakness as primary care electronic health records are designed for clinical management not research. Electronic health records do not record discussions that detail clinical judgements and it may actually be difficult to identify all the relevant data based on the coding systems used. Thus the question about benefits of psychotropic medication in pregnancy could not be fully explored with the data available. The inability of electronic databases to fully capture the social aspects that surround the difficult decisions under scrutiny here is a major limitation of this study.

As mentioned before, some associations between adverse outcomes and psychotropic medications were negated by confounding factors. While this was perhaps beyond the scope of the current study, I feel that further discussion around this topic would be of value when interpreting the results. Indeed this was explored using a lived experience advisor panel although the authors themselves admitted that this resource was under-utilised. Managing pregnancy in women taking psychotropic medication is multifactorial and neglect of other influencing factors has implications for the clinical application and changes that this research is able to drive forward.

Summary

For each individual women the decision to continue or discontinue psychotropic treatment encompasses a range of factors and for some this could be the hardest decision of their lives. Healthcare professionals need to be better equipped to advise women making these decisions and can only do so with high quality research such as the study discussed here.

Further studies should investigate how to avoid the problems encountered here using primary care databases, including the potential use of RCTs to examine if the use of antipsychotics in pregnancy can reduce the risk of relapse. Further research is urgently required to investigate the use of valproate and how this can be reduced in pregnancy.

This study also emphasises the need for healthcare professionals to be alert to the heightened risk of poor maternal and child outcomes associated with psychotropic medication and risky lifestyle factors associated with this patient population.

Links

Primary paper

Petersen I, McCrea RL, Sammon CJ, Osborn DPJ, Evans SJ, Cowen PJ, et al. Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records. Health Technol Assess 2016;20(23) dx.doi.org/10.3310/hta20230

Other references

Blak BT, Thompson M, Dattani H, et al (2011) Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2011;19:251–5. (PubMed Abstract)

Coughlin CG, Blackwell KA, Bartley C, et al (2015) Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy. Obstet Gynecol 2015;125:1224–35.

Epstein RA, Moore KM, Bobo WV (2015) Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges. Drug Healthc Patient Saf 2015;7:7–29

Jones I, Chandra PS, Dazzan P, et al (2014) Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet 2014;384:1789–99. (PubMed Abstract)

NICE (2014) Antenatal and Postnatal Mental Health: Clinical Management and Service Guidance. NICE CG 192, 2014.

NICE (2014) Bipolar Disorder: The Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care. NICE CG 185, 2014.

Tomson T, Battino D. (2012) Teratogenic effects of antiepileptic drugs. Lancet Neurol 2012;11:803–13. (PubMed Abstract)

Webb RT, Howard L, Abel KM. (2004 and 2009) Antipsychotic drugs for non-affective psychosis during pregnancy and postpartum. Cochrane Database Syst Rev 2004;2:CD00441.

Wesseloo R, Kamperman AM, Munk-Olsen T, et al. (2015) Risk of Postpartum Relapse in Bipolar Disorder and Postpartum Psychosis: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2016 Feb 1;173(2):117-27 (PubMed Abstract)

Williams T, van Staa T, Puri S, et al. (2012) Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource. Ther Adv Drug Saf 2012;3:89–99.

Photo credits

• Thomas Van Der Weerd CC BY 2.0
• Torsten Mangner CC BY 2.0
• Kai Schreiber CC BY 2.0
• Jay Reed CC BY 2.0