Study setting and procedure
The study was approved by the International Review Board of the Erasmus Medical Centre (Rotterdam, The Netherlands). All patients provided written informed consent. The study was performed on the Mother-Baby Unit (MBU), a five-bed inpatient unit that specializes in the care of patients with severe psychopathology in the postpartum period, located in the Department of Psychiatry in the Erasmus Medical Centre (Erasmus MC) in Rotterdam, The Netherlands. On the MBU, women are admitted with their babies, who stay in a fully staffed nursery adjoining the unit [1]. Every patient admitted to the MBU between May 2005 and December 2016 was screened for study inclusion (N=315).
Participants
We included patients with a diagnosis of first-onset mania or psychosis during the postpartum period, who were aged between 18 and 45 years. ‘Postpartum psychosis’ was operationalized as any of the following DSM-IV diagnoses and requiring the specifier ‘onset postpartum’: manic episode, mixed episode, depressive disorder with psychotic features, psychotic disorder not otherwise specified (NOS) or brief psychotic disorder, as assessed with the SCID interview. Patients were excluded if they had a chronic psychotic disorder, mania or psychosis with onset during pregnancy or > 12 weeks postpartum, a history of psychosis or mania outside the postpartum period, or drug abuse.
A total of 315 women were admitted to the MBU between May 2005 and December 2016. One hundred thirty-seven of these patients received a diagnosis of postpartum psychosis. Of these, 14 women had a prior postpartum psychiatric episode but no episodes of mania or psychosis at other times. Of the 137 women, four patients declined participation. In addition, 21 women were excluded: 18 women were excluded because they had a history of mania or psychosis outside the postpartum period, one woman was excluded because of postpartum drug abuse, one woman was excluded because her symptom onset was > 12 weeks postpartum, one woman was excluded because her symptoms started during pregnancy. Accordingly, 112 patients fulfilled the criteria for first-onset postpartum psychosis. Five patients were lost to follow-up (4.5%) and one patient (0.9%) was lost to suicide (baseline and clinical characteristics of these women can be found in Appendix A, Table A1). In this study, we therefore included 106 women admitted to the MBU between 2005 and 2016.
Symptomatology and clinical course of the initial episode
Patients were diagnosed by a clinician using the Structured Clinical Interview (SCID-1/P research version) [23]. The SCID is a semi-structured interview guide for making diagnoses according to the diagnostic criteria published in the American Psychiatric Association’s Diagnostic and Statistical Manual for Mental Disorders (DSM). Previous hypomanic and manic episodes were also registered using the SCID. We further assessed demographics, psychiatric history, and family history of psychiatric illness (Table 1) (for more detail, see 12).
Phenomenology of the initial episode was assessed using the Bipolar Affective Disorder Dimension Scale (BADDS) [24]. The BADDS comprises four dimensions which provide a quantitative measure of psychopathology in each of four domains: 1) Manic-like episodes (the Mania dimension, M), 2) Depression-like episodes (the Depression dimension, D), 3) Psychotic symptomatology (the Psychosis dimension, P) and 4) the relationship (congruence of content and timing) between psychotic features (if present) and mood episodes (the Incongruence dimension, I). Each dimension provides a composite measure that takes both severity and frequency of relevant psychopathology into account. The dimensions are rated using integers in the range 0 to 100, with higher scores indicating more clinically important psychopathology – typically a mix of severity and frequency/duration.
Treatment regimen
During admission, women with a first-onset postpartum psychosis were treated according to a standardized treatment algorithm [12]. All patients were initially treated with lorazepam at bedtime for three days. For patients receiving lorazepam monotherapy, who had persistent manic or psychotic symptoms, antipsychotic medication was recommended beginning on day four. Our primary recommendation for antipsychotic treatment was haloperidol at 2–6 mg/day. Patients who experienced side effects were switched to an atypical antipsychotic. A subset of patients who had already been treated with an antipsychotic for more than two days before admission (e.g., by acute services) were continued on the same antipsychotic they received before admission. After two weeks of combination treatment with a benzodiazepine and an antipsychotic, adjunctive lithium was recommended for those patients who did not have a significant clinical response. Lithium dosing was achieved based on plasma level (target, 0.8–1.2 mmol/L). After complete remission of symptoms, all women were advised to taper benzodiazepines to discontinuation. Women receiving antipsychotic monotherapy were advised to continue this treatment as maintenance therapy until nine months postpartum. Women who achieved clinical remission using both antipsychotics and lithium were advised to gradually taper off antipsychotic treatment, with maintenance lithium monotherapy until nine months postpartum. Lithium dosing for relapse prevention was achieved based on plasma level (target, 0.6–0.8 mmol/L).
Longitudinal course of the illness
Four years postpartum, women were re-evaluated using the SCID [23]. Women were not seen in between hospital discharge and follow-up for the purposes of this study. Recurrence was defined as the occurrence of any depression, (hypo)mania, psychosis or mixed state episode fulfilling DSM-IV criteria, admission to hospital or a restart of medication. All women with a recurrence were asked retrospectively about the timing of their episode, including whether this was in relation to a subsequent pregnancy. Additionally, we collected information on the timing of tapering or stopping medication if applicable. The patient’s medical records were consulted to validate the information.
Based on information collected at follow-up, women were categorized into one of two groups: 1) women with recurrence of non-postpartum mood or psychotic episodes within the follow-up period, or 2) women with mania/psychosis in the postpartum period and no mood or psychotic episodes outside the postpartum period during follow-up (vulnerability to affective psychosis only after childbirth).
Statistical analysis
We summarize the longitudinal course of the illness per in Table 1. Differences between the two groups in terms of baseline demographic and clinical characteristics were assessed using Chi-squared and t-tests were appropriate (Table 1). A Kaplan-Meier Survival Curve of recurrence rates within the four-year follow-up period after first-onset postpartum psychosis was plotted. Additionally, we used a binomial logistic regression model to identify clinical predictors of postpartum psychosis group (recurrence of non-postpartum mood or psychotic episodes vs. mania/psychosis in the postpartum period only). Potential predictors of recurrence were based on the literature included admission length, maternal age, phenomenology of the index episode, and family history of psychiatric illness [2, 21, 22]. To improve power in the family history variable, depression and anxiety were combined into the category ‘depression or anxiety’ and postpartum depression and postpartum psychosis were combined into the category ‘postpartum psychiatric episode’. Mania/psychosis in the postpartum period only and psychiatric disorder with non-postpartum episodes were coded as 0 and 1 respectively. Results are presented in the form of odds ratios. All statistical analyses were performed using Stata/MP 15 [25]. Lastly, we explored whether the set of psychotic symptoms recognized as having special weight in the diagnosis of schizophrenia and schizoaffective disorder (thought echo, insertion, withdrawal or broadcasting; passivity experiences; hallucinatory voices giving running commentary, discussing subject in third person or originating in some part of the body; bizarre delusions; catatonia) was a precursor for a diagnosis within the psychotic disorder spectrum.