Psychopharmacology and Pregnancy: Treatment Efficacy, Risks, and Guidelines 2014

10. Postpartum Psychosis

Veerle Bergink  and Steven A. Kushner1

(1)

Department of Psychiatry, Erasmus Medical Center, ‘s Gravendijkwal 230, 3000 CA Rotterdam, The Netherlands

Veerle Bergink

Email: v.bergink@erasmusmc.nl

10.1 Epidemiology, Phenomenology and Diagnosis

10.2 Diagnostic Classification of Postpartum Psychosis: A Brief History

10.3 Postpartum Psychosis and Bipolar Disorder

10.4 Treatment

10.5 Pharmacotherapy

10.6 Mother–Infant Bonding

10.7 Prevention of Subsequent Episodes

References

Abstract

Postpartum psychosis is a severe and potentially life-threatening disorder that warrants acute clinical intervention. The initial clinical evaluation for postpartum psychosis requires a thorough medical and psychiatric history, physical and neurological examination, and comprehensive laboratory analysis to exclude known organic causes for acute psychosis. Unfortunately, little is known about what interventions are most effective, as research has been very limited and no randomized trials have been performed. Antipsychotic medication, lithium, and ECT have been described in case series and are frequently used in clinical practice as treatment options for postpartum psychosis.

Prevention of postpartum psychosis is a major challenge for mental health practitioners and obstetricians. Recently, we have proposed distinct clinical treatment algorithms for women with bipolar disorder versus women with a history of psychosis limited to the postpartum period. In bipolar women, prophylaxis during pregnancy appears critically important for maintaining mood stability during pregnancy and postpartum. In contrast, we recommend initiating prophylactic treatment immediately postpartum in women with a history of psychosis limited to the postpartum period. Considering together the available phenomenological, epidemiological, and treatment outcome data, we believe that postpartum psychosis should not be considered as a primary psychotic disorder as its name might otherwise suggest, but rather as a diagnostically independent entity within the group of bipolar affective disorders.

Keywords

Bipolar disorderMood stabilizersPostpartum psychosisPregnancy

10.1 Epidemiology, Phenomenology and Diagnosis

After childbirth, women are vulnerable to the onset of serious psychiatric symptomatology. Women are approximately 22 times more likely to experience the onset of a manic or psychotic episode in the first month postpartum than at any other time in their lives. Postpartum psychosis is the most severe form of childbirth-related psychiatric illness. The prevalence of postpartum psychosis in the general population is estimated as 1–2 per 1,000 childbirths (Munk-Olsen et al. 2006).

In the majority of cases, the onset is rapid and within 2 weeks postpartum. The early symptoms include insomnia, mood fluctuation, and sometimes obsessive concerns regarding the newborn, followed by more severe symptoms such as delusions, hallucinations, disorganized behavior, and serious mood symptoms. The occurrence of these severe mood symptoms such as mania, depression, or a mixed state is very prominent in postpartum psychosis. Affective phenomenology seems to be a hallmark of the disease and is more prevalent in postpartum psychosis compared to non-postpartum psychosis. Apart from its prominent affective symptoms, postpartum psychosis is also notable for its curious delirium-like appearance. Women with postpartum psychosis sometimes exhibit atypical cognitive symptoms such as disorientation, confusion, perplexity, misrecognition of people, derealization, and depersonalization. Of note, there is a relatively low incidence of schizophrenia-like symptoms, such as “Schneiderian first-rank symptoms” (Spinelli 2009; Sit et al. 2006; Brockington et al. 1981). Together, given that postpartum psychosis is generally considered a mood disorder and not a primary psychotic disorder, the term postpartum psychosis is therefore somewhat misleading.

By far, the most important risk factors of postpartum psychosis are a history of bipolar disorder or a previous episode of postpartum psychosis. In either case, the risk of postpartum psychosis is estimated as 25–50 % following every (subsequent) delivery. A family history of postpartum psychosis or bipolar disorder is also a well-known risk factor. Several family studies have consistently reported familial aggregation of psychiatric (particularly affective) disorders in first-degree relatives of women with postpartum psychosis (Jones and Craddock 2007). Previous studies have suggested a number of demographic and clinical variables that may be associated with postpartum psychosis, such as primiparity and complications during delivery (Blackmore et al. 2006). Indeed, primiparity has been repeatedly observed as a significant covariate in modeling the risk factors for postpartum psychosis. However, a recent large population-based study in primiparous mothers without previous psychiatric hospitalization found no significant influence of delivery complications on the risk of postpartum psychosis (Valdimarsdottir et al. 2009). Furthermore, no significant evidence has ever implicated psychosocial factors.

Postpartum psychosis must be clearly differentiated from postpartum depression (Table 10.1). In particular, postpartum depression refers to a non-psychotic depressive episode that affects approximately 10 % of mothers after childbirth. Women with postpartum depression experience symptoms of misery, apathy, irritability, social isolation, anxiety, failure to cope, and guilt, which are likely to have an impact on a mother’s relationship with her child. Like non-puerperal depression, this disease entity is highly heterogeneous: psychosocial risk factors, such as a poor social background, lack of support, and stressful life events, factor prominently in the risk and clinical manifestations. Postpartum depression has a markedly different onset from postpartum psychosis. The onset of postpartum depression is highly variable: often with symptoms during pregnancy (in almost half of the cases), as well as episodes of depression with their onset throughout the entire first year postpartum.

Table 10.1

Mood symptoms and syndromes during the postpartum period

 

Estimated incidence

Onset

Frequent symptoms

Management

Maternity “blues”

50 %

3–5 days postpartum

Emotional lability, moodswings, anxiety

Self-limited, emotional support

Postpartum depression

10 %

Variable window: during pregnancy up to 1 year postpartum

Low mood, feelings of guilt, impaired feelings of bonding with the child

Psychotherapy, antidepressant medication, mother–baby therapy

Postpartum psychosisa

0.1–0.2 %

Within 4 weeks postpartum (usually within 2 weeks)

Agitation, irritablility, euphoric mood, depression, delusions, hallucinations, confusion, cognitive symptoms

Hospitalization, medical workup, lithium, antipsychotics, ECT

aIncluding postpartum mania and postpartum depression with psychotic features

Although an early postpartum onset is typical for postpartum psychosis, prodromal symptoms of postpartum psychosis are sometimes difficult to distinguish from the normal, physiological maternity blues. About half of recently delivered mothers experience the maternity blues between day 3 and 5 postpartum. This term refers to the brief occurrence of dysphoria, irritability, and mood swings. In contrast to postpartum psychosis, the duration of maternity blues ranges from a few hours to a few days, and for which the more severe symptoms that define postpartum psychosis are entirely absent (Table 10.1).

Understandably, most studies and scientific reviews have focused on postpartum blues and depression. The relatively low incidence, the clinical severity, and diagnostic uncertainty regarding the proper classification of postpartum psychosis have all contributed to the paucity of research.

10.2 Diagnostic Classification of Postpartum Psychosis: A Brief History

One of the initial case reports of postpartum psychosis arose from the autobiographical work of Margery Kempe who delivered her first baby in the UK in 1393 (Staley and Kemp 2000). In brief, she described that she became gravely ill after delivery and called for a priest. The priest began to censure her before she could divulge her sins, and then left. Fearing eternal damnation, she fell into a delusional state, where she described seeing devils around her. Because she tried to throw herself out of the window and tried to bite through the veins in her wrist, her husband chained her in a storeroom. After 6 months, she saw Jesus sitting at her bedside; the effect was miraculous as she was suddenly sane. Later case reports from Germany, France, and the UK describe similar cases: women with an acute onset of severe affective psychosis immediately postpartum. Importantly, some of these case reports described women with multiple postpartum episodes but none outside the postpartum period, which suggested the existence of a specific postpartum disease. Over time, several names have been given to this postpartum disease, such as “mania lacteal”, “amentia”, “puerperal insanity”, “puerperal psychosis”, “puerperal mania”, “dreamlike delirium”, and finally “postpartum psychosis”. Since the eighteenth century, postpartum psychosis has been widely appreciated as a severe disease, requiring acute intervention (Brockington 1996).

The first treatments described were cutting of hair, applying ice packs to the head, and/or application of leeches. In the nineteenth century, physicians focused on the control of excitement, guarding against suicide, and supportive management pending an expected spontaneous remission. Remarkably, current treatments of postpartum psychosis do not have a substantially improved empirical basis than the treatments over the last centuries (Doucet et al. 2010). Furthermore, in the second half of the twentieth century, the diagnostic category of “postpartum psychosis” was abolished: the prevailing view from experts in the field has been that postpartum psychoses are not specific and fall mainly within the bipolar spectrum.

Childbirth is considered a general stressor, which can trigger an attack of any kind of psychiatric illness. Accordingly, the widely used American psychiatric classification system (DSM-IV and DSM-V: Diagnostic Statistic Manual of Disease) does not have a specific category for postpartum psychosis.

Meanwhile in the UK, the British psychiatric classification system ICD-10 (International Classification of Disease) contains a specific section entitled “mental and behavioral disorders associated with the puerperium”. Notably, however, the addendum to this section encourages a very cautious use of this category:

Most experts in this field are of the opinion that a clinical picture of puerperal psychosis is so rarely (if ever) reliably distinguishable from affective disorder or schizophrenia that a special category is not justified. Any psychiatrist who is of the minority opinion that special postpartum psychoses do indeed exist may use this category, but should be aware of its real purpose.

Despite these serious warnings, and while the term “postpartum psychosis” is officially excommunicated, there is an undiminished interest from researchers to understand this phenomenon. In particular, over the last decades clinical research has focused intensely on the strong link with bipolar disorder.

10.3 Postpartum Psychosis and Bipolar Disorder

Women with a diagnosed bipolar disorder are at very high risk (25–50 %) for affective psychosis in the weeks following delivery (Viguera et al. 2011). Cross-sectional symptomatology, family history, and the longitudinal illness course all support the notion of a strong link to bipolar disorder. First, most studies have shown a preponderance of manic symptoms in postpartum psychosis. Further, family studies of patients with postpartum psychosis have consistently found the risk for bipolar disorder to be higher than the risk within the general population. Lastly, a widely held estimate is that after an incipient postpartum affective psychosis, a woman has between 35 and 65 % chance of developing a bipolar disorder (Chaudron and Pies 2003).

Although bipolar disorder is certainly an important risk factor for postpartum psychosis, a large proportion of postpartum psychosis patients have no history of prior manic or psychotic episodes (Oates 2003; Boyce and Barriball 2010). In our research, we have particularly focused on this group: patients with first-onset psychosis postpartum. First-onset postpartum psychosis has markedly different characteristics compared to postpartum psychosis in bipolar patients. Postpartum psychosis patients demonstrate a significantly delayed postpartum onset compared to postpartum relapses in bipolar patients. Further, and in contrast to bipolar patients, obstetric complications are not a risk factor for patients with psychosis limited to the postpartum period. Finally, with clinical treatment an overwhelming majority of patients experience a complete symptom remission within 3 months postpartum. Together, our data contribute to the emerging consensus that women with a history of psychosis limited to the postpartum period might have a distinct variant of bipolar disorder (Bergink et al. 2011b).

10.4 Treatment

Postpartum psychosis is a psychiatric emergency that requires immediate medical attention and psychiatric referral. Inpatient psychiatric treatment is essential to ensure the safety of mother and baby. Within the UK, national guidelines (NICE) recommend that all women requiring postpartum admission are admitted with their infants to specialist Mother and Baby Units (MBU). There is some evidence that admission to an MBU is associated with improved satisfaction with care and reduced time to recovery.

The initial clinical evaluation for postpartum psychosis requires a thorough history, physical and neurological examination, and laboratory analysis to exclude known organic causes for acute psychosis. There are case reports on misdiagnosis of postpartum psychosis revealing a late-onset urea cycle disorder, paraneoplastic encephalitis, citrullinemia type I, and primary hypoparathyroidism. Differential diagnosis should further include infectious diseases, eclampsia, autoimmune diseases, metabolic diseases, vitamin deficiencies, stroke, and drug-induced psychosis (Sit et al. 2006). Therefore, tests should include a complete blood count, electrolytes, blood urea nitrogen, creatinine, calcium, liver function tests, thyroid function, and glucose. With proper indication, head CT or MRI, vitamins B1, B12, and folate, urinalysis, and urine drug screen should also be performed.

We showed that autoimmune thyroid disease is much more prevalent in women with first-onset postpartum psychosis (19 %) than in postpartum women from the general population (5 %). Furthermore, clinical thyroid failure occurs significantly faster and in a greater percentage of patients with postpartum psychosis. Therefore, screening for TPO antibodies, TSH, and fT4 is warranted in patients with postpartum psychosis (Bergink et al. 2011a).

Lastly, and perhaps most importantly, for any mother who presents with a postpartum mood disorder, the clinician must inquire about thoughts of harming herself or the infant. Delusional thoughts about harm to the infant or herself in postpartum psychosis are ego-syntonic and associated with psychotic belief. The urge to act on psychotic beliefs, combined with loss of reality testing, can quickly and easily lead to dangerous life-threatening situations.

10.5 Pharmacotherapy

Little is known about what interventions are most effective for patients with postpartum psychosis, as research has been very limited and no randomized trials have been performed. In total, only 21 treatment studies of postpartum psychosis can be found in the recent literature (Doucet et al. 2010). Sample sizes are very small: the majority is case reports describing a single patient and very few studies included more than ten patients.

The effects of hormones, propranolol, antipsychotics, lithium, and ECT were examined. Three studies conducted by the same group have found beneficial effects of estrogen (Ahokas et al. 2000). The potential beneficial use of progesterone and hormonal replacement therapy has been described through case reports (Boyce and Barriball 2010). Other case reports have provided support for propranolol (a beta-adrenergic blocker used to treat hypertension) as a treatment option for postpartum psychosis (Steiner et al. 1973).

Lithium and antipsychotic medication are commonly used in the treatment of postpartum psychosis. In our prospective cohort study, we report on the duration of episode while 51 patients received naturalistic treatment using the sequential addition of benzodiazepines, antipsychotics, and finally lithium. Our treatment algorithm was based on our clinical experience, guided by the larger literature for treatment of bipolar patients. Specifically, all patients were initially treated with benzodiazepines. For those patients without a marked improvement on benzodiazepine monotherapy, antipsychotic medication was initiated within the first week of admission. After 2 weeks of combination antipsychotic/benzodiazepine treatment, adjunctive lithium was initiated in those patients without a significant clinical response.

In our cohort, 47 of 51 patients achieved full remission prior to discharge. The median duration of episode, defined as onset (median day 8) until full remission of all affective, cognitive, and psychotic symptoms, was 40 days (Bergink et al. 2011b).

In earlier studies, lithium was found to be effective in one case study where it was used as monotherapy (Lichtenberg et al. 1988), and in two studies where it was used as adjunctive therapy (Silbermann et al. 1975; Targum et al. 1979). The effects of antipsychotics have been described in four case reports, for which treatment was reportedly successful on chlorpromazine, clozapine, and pimozide (Doucet et al. 2010).

A few studies have explored the influence of ECT in the treatment of PP (Focht and Kellner 2012). In one case study, treatment with chlorpromazine was ineffective, while ECT treatment led to remission (Stanworth 1982). Similarly, a case series of five women with treatment refractory PP described positive treatment outcomes with ECT (Forray and Ostroff 2007). Furthermore, a retrospective study compared the clinical responses to ECT of women with postpartum psychosis versus non-postpartum psychosis. Notably, the postpartum group was found to have greater clinical improvement following ECT compared to the non-postpartum group (Reed et al. 1999). Finally in a recent study, 34 women received successful ECT treatment and ECT was proposed as first-line treatment option (Babu et al. 2013).

Unfortunately, few treatment recommendations are available in the literature regarding the treatment of postpartum depression with psychotic features. According to DSM-IV criteria, postpartum depression with psychotic features does not constitute a bipolar depression. However, based on our clinical experience, we have followed the view that early-onset postpartum depression is likely to have a bipolar diathesis, particularly if psychotic features are present. Therefore, we followed the guidelines for treatment of bipolar II depression in patients with the acute onset of depression with psychotic features during the postpartum period, even in the absence of hypomanic symptoms immediately postpartum or of a history of hypomania (Bergink, Koorengevel 2010).

Of our patients (n = 7) diagnosed with a major depressive episode with psychotic features and an onset of symptoms within 4 weeks of the postpartum period, six women were treated with lithium and antipsychotics and one woman refused treatment. Except for one woman, all patients with depression had a complete remission with the combination of lithium and antipsychotics. The one patient who did not respond to treatment with lithium and antipsychotics received ECT, and her depression subsequently remitted (Bergink, Koorengevel 2010).

We do not know what would have happened if we had treated these seven women with antidepressants, but in our opinion antidepressant treatment could have put these patients at an unacceptable risk for exacerbation of symptoms. Similar to Sharma et al. (Sharma 2006); Sharma et al. 2009), we also have the clinical experience that antidepressants should be used cautiously in the postpartum period. Over the last 4 years, eight postpartum patients were referred to our clinic as a result of a very unstable illness course (manic and psychotic symptoms) after treatment with antidepressants in the absence of mood stabilization.

10.6 Mother–Infant Bonding

Interrupted development of a secure mother–infant bond can lead to long-term problems in a child’s emotional, cognitive, and behavioral development (Murray et al. 2010). Importantly, severe postpartum psychiatric disorders, such as postpartum psychosis, represent a major challenge to maintaining the integrity of mother–infant bonding while symptoms persist. Two small studies have confirmed a deleterious influence of postpartum psychosis on mother–child bonding during the acute phase of the illness (Chandra et al. 2006; Hornstein et al. 2007). Remarkably, however, a recent study from our group demonstrated that women with a postpartum psychosis, in contrast to postpartum depression, experience few difficulties in establishing a healthy bond with their child after discharge from the hospital (Noorlander et al. 2008). Therefore, a more comprehensive series of studies is required to define optimal treatment algorithms for specific postpartum psychiatric disorders based upon empirical evidence and long-term outcomes.

10.7 Prevention of Subsequent Episodes

The strongest predictors for postpartum psychosis are a history of bipolar disorder and/or postpartum psychosis (Munk-Olsen et al. 2009; Doucet et al. 2010; Chaudron and Pies 2003). Consequently, guiding women at high risk for psychosis through pregnancy and the postpartum period is a major challenge for mental health practitioners and obstetricians (Cohen 2007; Viguera et al. 2002; Yonkers et al. 2004; Galbally et al. 2010), for which safe and effective relapse prevention would be the optimal strategy.

Six studies have assessed the efficacy of various prophylactic treatments for prevention of postpartum psychosis in bipolar patients: lithium (three studies) (Stewart et al. 1991; Cohen et al. 1995; Austin 1992), estrogen, valproate, and olanzapine (Kumar et al. 2003; Wisner et al. 2004; Sharma et al. 2006). In all 3 studies using lithium, bipolar women receiving prophylactic treatment had significantly lower rates of postpartum psychosis. In contrast, both estrogen and valproate failed to demonstrate significant prophylactic benefits. Olanzapine prophylaxis was equivocal and therefore warrants further investigation. Notably, a major limitation of these studies was that they included both women who initiated prophylaxis during pregnancy and postpartum, without differentiating between these groups. However, the timing of onset for pharmacological prophylaxis is of paramount clinical importance given that the benefits of prophylaxis during pregnancy need to be carefully weighed against the risks for the fetus (Burt, et al. 2010).

In our recent work, we evaluated the outcome of lithium prophylaxis during pregnancy, compared to immediately postpartum, in 70 women at high risk for postpartum psychosis using standardized clinical guidelines (Bergink et al. 2012). Specifically, we have investigated relapse rates both during pregnancy and in the postpartum period for 41 women with bipolar disorder and 29 women with a history of postpartum psychosis. Women with postpartum psychosis, compared to those with bipolar disorder, had a substantial difference in their clinical outcomes and prophylaxis requirements.

Notably, all women with a history of psychosis limited to the postpartum period were stable throughout their entire pregnancy despite using no prophylactic medication. In contrast, women with bipolar disorder had high rates of relapse during pregnancy. Furthermore, initiation of prophylaxis using either lithium or antipsychotics immediately postpartum in women with a history of psychosis limited to the postpartum period was highly effective for preventing postpartum relapse. In contrast, the efficacy of postpartum prophylaxis in women with bipolar disorder was much lower. During the postpartum period, relapse was highest in women with bipolar disorder who experienced mood episodes during pregnancy.

Therefore, we have proposed distinct clinical treatment algorithms for women with bipolar disorder versus women with a history of psychosis limited to the postpartum period. In bipolar women, prophylaxis during pregnancy appears critically important for maintaining mood stability during pregnancy and to minimize the high risk of postpartum relapse. In contrast, we recommend initiating prophylactic treatment immediately postpartum in women with a history of psychosis limited to the postpartum period, offering an important clinical advantage by avoiding in utero fetal exposure to prophylactic medication.

Disclosure

None of the authors report a competing interest.

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