Underestimating the complexity of managing mood disorders in pregnancy: Commentary on the 2020 RANZCP Clinical Practice Guidelines for mood disorders

Mood disorders, the most common co-morbidity associated with the perinatal period, have the capacity to influence the wellbeing not only of the woman but also of her unborn child or infant. We believe that the recent and otherwise comprehensive RANZCP Clinical Practice Guidelines (Mahli et al., 2021) fail to adequately reflect two key areas of perinatal psychiatric practice, namely, the inherent complexity of risk–benefit analysis for treatment selection and the central importance of informed decision-making by the woman herself. We agree with the authors’ statement in the introduction that guidelines must assume an active engaged patient and shared decision-making; however, in our opinion, this could be more strongly reflected in the advice on managing women in the perinatal period. There are also some points of guidance that we believe do not align fully with the current state of evidence.

The recommendation that ‘antidepressant medication should be reserved for those women with more severe depression or where psychological treatment has been ineffective or is not appropriate’ is problematic for two reasons. First, it conflates antenatal and postnatal depression, thereby failing to take into account the different considerations that apply to these two time periods. Second, the potential detrimental impact of untreated mental illness for mother and child leads to a lower, not higher, threshold to treat more assertively (Gentile, 2017). Adverse effects of untreated maternal antenatal depression have been clearly documented and include an increased risk of poorer offspring’s socio-emotional, cognitive and language development (Rogers et al., 2020). While for many women evidence-supported psychological interventions may be sufficient, this current recommendation underplays the need for many women with moderate depressive disorders to also be potentially managed with antidepressant treatment. Women may not respond to psychosocial interventions; they may face difficulty accessing these interventions, and the impact of illness on functioning, including in their caregiving capacity, may be profound, or there may be a clinical risk of deterioration or a history of risk or relapse that would support the use of antidepressant medication in moderate and severe depression. In the general population, antidepressants are commonly prescribed to individuals with moderate to severe depression. Denial of treatment options to women could be considered a denial of access to basic health care and is not reflected in other areas of medical care in pregnancy where choices of agent for treatment of medical illness reflect both the woman’s health needs and balancing the safety of the unborn child.

We recommend that following careful consideration of the benefits and risks of prescribing an antidepressant to a pregnant woman, if appropriate, antidepressants should be used in a similar way to any adult presenting with depression.

We also raise concerns regarding the recommendations for use of lithium in the perinatal period. While we support the recommendations for both monotherapy and lithium as first-line treatment for treatment of bipolar disorder as the agent with the strongest evidence base across the perinatal period, this may underestimate the complexity of individual patient perspectives in terms of risks and options. To provide two examples, one woman who wishes to attempt breastfeeding may be willing to accept the risks of possible lesser efficacy by switching from lithium to an alternative mood stabiliser (such as an atypical antipsychotic) in order to achieve this, or another woman who has a family history of congenital cardiac malformation may feel a higher imperative than most to avoid the small risk associated with lithium.

Second, we are concerned about the unreferenced dosing recommendation of 500 mg/day for lithium in the first trimester. Therapeutic drug monitoring aiming for a serum level within the known therapeutic range is a gold standard treatment. Changes in renal clearance, fluid volume, competing conditions and medications that can influence renal function may make achieving therapeutic levels more difficult during pregnancy. To prescribe a dose without regard for the serum level, and one that is likely to see most patients achieve a subtherapeutic level, confers on the pregnant woman a risk of relapse while continuing to incur any risks related to gestational lithium exposure.

Finally, the Guidelines state, ‘Before birth, lithium dosage can be reduced 2 weeks prior and reintroduced soon after’. This recommendation is also not supported by recent evidence which suggests great variation in lithium levels leading up to birth, during the intra-partum period and over the first 2 weeks postpartum (Wesseloo et al., 2017). In a review of lithium in pregnancy and after delivery, Poels et al. (2018) highlight the high risk of relapse after childbirth and outline clear evidence-based recommendations for the management of lithium in the peripartum period. They, like Wesseloo et al. (2017), do not advise discontinuation in all cases. Rather, they advise, and we support, close monitoring of serum levels weekly across the third trimester of pregnancy, a level before delivery and 24 hours after delivery, and twice weekly for the first 2 weeks postpartum and to adjust the dose accordingly.

Prescribing antidepressant and lithium treatment in pregnancy illustrates the complexity of managing mental illness in pregnancy. This requires consideration of changing pregnancy physiology and metabolism as well as common complications of pregnancy, our evolving evidence base on efficacy, risks and benefits for treatments and for untreated illness for both mother and child, and finally, but most importantly, the individual circumstances and preferences of women managing their mental health across pregnancy. Given the ever-changing state of evidence, we encourage practitioners to not only consult published guidelines but also access regularly updated online databases and, where needed, secondary consultations with specialist perinatal psychiatrists to support women in selecting the treatment that best suits their circumstances.