Commentary on RANZCP clinical practice guidelines for the management of schizophrenia and related disorders

The impact of both gender- and sex-based influences on the course and treatment of schizophrenia is clear with influences across onset and course of illness, phenomenology, pharmacokinetics of treatment and the deleterious social and institutional influences on outcomes such as raised by Kulkarni and Galletly. While recognition of the importance of crucial differences between men and women with schizophrenia has been slow to gain traction in clinical care, it is heartening to see this recognized within the latest clinical practice guidelines (Galletly et al., 2016) and associated commentaries.

Reflected in these guidelines is also the considerable research interest, not only in developing effective treatments but equally a focus on prevention of schizophrenia. Fundamental to this is our understanding of the mechanisms of transmission of risk of mental disorders to offspring and crucially modifiable risk factors. While for schizophrenia, genetic heritability is strongly implicated, it is clear there are pathways that are likely to include “neurodevelopmental insults” (Galletly et al., 2016), and these start in pregnancy where neurological development is most vulnerable. For a range of other non-communicable diseases, we can now trace back modifiable risk factors to fetal programming processes that impact long-term offspring health. Understanding the role of fetal programming in schizophrenia is likely to be central to the goal of prevention (Debnath et al., 2015).

Research has made it clear that women with schizophrenia face higher risk pregnancies with increased risk of stillbirth, antepartum hemorrhage, gestational diabetes, hypertension, prematurity, low and high birth weight, and these risks are associated with both illness and treatments (Nguyen et al., 2013). In addition, women with schizophrenia are more likely to be using substances, smoke, abuse alcohol, have inadequate nutrition, vitamin deficiency, a raised body mass index (BMI) and experience domestic violence. Many of these complications and co-morbidities impact both mothers and offspring, but also provide opportunities to improve outcomes through intervention.

In this context, the development of “comprehensive, integrated care for pregnant women with schizophrenia” (Galletly et al., 2016) such as currently exists in Victoria (Galbally et al., 2010) and Western Australia (Nguyen et al., 2013) should be a high priority for perinatal mental health and maternity services. There are well-established services and models of care within most tertiary maternity hospitals for medical disorders that impact pregnancy risk, and it is clear that women with schizophrenia deserve no less in the quality of obstetric expertise and antenatal care accessible to them.

To date, the main focus for psychopharmacological treatment, including antipsychotics in pregnancy, has centered on risk to offspring, however, there is now an interest in the potential for these treatments to confer benefit through protection and buffering of offspring from the effects of maternal mental disorders. However, balancing these are data that suggest associated higher rates of pregnancy complications such as gestational diabetes mellitus, which in turn increases risk for maternal morbidity and offspring health. While registries are helpful, without prospective studies that include treated and untreated women untangling risk from illness, and risk from treatment is impossible.

When examining the often confusing and conflicting findings currently being published for psychotropic medication exposure in pregnancy, it is crucial not to confuse limited or lack of evidence with safety. Much of our comfort in prescribing antipsychotics in pregnancy comes from the lack of negative data rather than the presence of positive data. Prescribing treatments in pregnancy is a balancing act where multiple considerations must be simultaneously considered including the following: maintaining optimal mental health for a woman, the limits of current knowledge of risks and benefits in pregnancy of treatments and consideration of child outcomes.

There are now sufficient studies of early parenting and schizophrenia to suggest there are crucial differences from parenting in the context of other mental disorders such as depression. However, the lack of research into understanding the unique interplay between symptoms, vulnerabilities and parenting holds back the development of evidence-based interventions specific for new parents with schizophrenia. A focus on parenting for women with schizophrenia should be considered as central to a recovery paradigm. In addition, consideration should be given to monitoring a child’s developmental progress given the higher risk of early developmental concerns.

Beyond schizophrenia, the guidelines also include postpartum psychosis, and it is unclear whether this disorder, specific to women, best sits within guidelines for schizophrenia or rather in guidelines for bipolar disorder. What is clear is that timely management is crucial and evidence suggests that treatment algorithms differ from managing either schizophrenia or bipolar disorder in the perinatal period (Bergink and Kushner, 2014).

Understanding how better to manage women with schizophrenia across the life span has the potential to pay dividends not just for improving outcomes for individual women, but may also help us better understand the risk pathways from one generation to the next. However, the challenge to researchers is to design and undertake studies of sufficient sophistication to do justice to the complexity of this area of examination.

See Guideline by Galletly et al., 50: 410–472.