Assessment and treatment of bipolar II postpartum depression: A review

Journal of Affective Disorders 125 (2010) 18–26

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Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d

Review

Assessment and treatment of bipolar II postpartum depression: A review Verinder Sharma a,b,⁎, Vivien K. Burt c,d, Hendrica L. Ritchie a a b c d

Department of Psychiatry, University of Western Ontario, London, Ontario, Canada Perinatal Clinic, St. Joseph's Health Care, London, Ontario, Canada Department of Psychiatry, Geffen School of Medicine at UCLA, Los Angeles, California, USA Women's Life Center, Resnick Neuropsychiatric Hospital at UCLA, Los Angeles, California, USA

a r t i c l e

i n f o

Article history: Received 8 July 2009 Received in revised form 23 September 2009 Accepted 23 September 2009 Available online 17 October 2009 Keywords: Bipolar disorder Postpartum hypomania Postpartum depression Assessment Treatment

a b s t r a c t Objective: This paper critically reviews the current literature on the detection, diagnosis, and treatment of bipolar II postpartum depression. Method: A Pub-Med search (1998–2009), using the search terms ‘postpartum depression’, ‘postpartum depression AND screening/detection/diagnosis/treatment’, ‘bipolar I AND postpartum depression’, ‘bipolar II AND postpartum depression’, ‘postpartum hypomania’, and ‘postpartum hypomania AND screening’, was carried out. The reference lists of articles identified were also searched to select other relevant publications. Results: Brief hypomanic symptoms occur in the early puerperium in approximately 15% of women. Despite preliminary evidence that postpartum depression in some patients may be a manifestation of bipolar II disorder or bipolar disorder NOS, there are no screening instruments to differentiate unipolar from bipolar depression arising in pregnancy or the postpartum. Also lacking are evidence-based treatment options specifically targeted to treat bipolar II postpartum depression. Conclusions: Research into postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis, and has largely ignored the study of bipolarity beyond bipolar I disorder. The clinical and research implications of the misdiagnosis of bipolar II depression as major depressive disorder in the postpartum period are discussed. © 2009 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4. 5. 6. 7. 8.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . Bipolar spectrum disorder and postpartum mood disorders . . . . . Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Postpartum hypomania in non-clinical populations . . . . . . . . . Bipolar postpartum depression . . . . . . . . . . . . . . . . . . Screening and monitoring. . . . . . . . . . . . . . . . . . . . . Pharmacological and psychotherapeutic studies . . . . . . . . . . Under-diagnosis of postpartum bipolarity: causes, consequences and 8.1. Common causes . . . . . . . . . . . . . . . . . . . . . . 8.2. Consequences of missed bipolarity . . . . . . . . . . . . . 8.3. Clinical and research implications. . . . . . . . . . . . . .

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⁎ Corresponding author. Specialized Adult Program, Regional Mental Health Care London, 850 Highbury Avenue North, P.O. Box 5532, Station B, London ON, Canada N6A 4H1. Tel.: +1 519 455 5110x47392; fax: +1 519 455 3011. E-mail address: [email protected] (V. Sharma). 0165-0327/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2009.09.014

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9. Recommendations Role of funding source Conflict of interest . . Acknowledgements . . References . . . . . .

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1. Introduction Since bipolar postpartum depression is frequently overlooked and mistaken for unipolar major depression, the goal of this article is to review the literature on the detection, diagnosis, and treatment of bipolar postpartum depression. We will review bipolar spectrum disorder in general and bipolar depression specifically as these relate to postpartum mood disorders. Data suggesting that the prevalence of postpartum hypomania is higher than lifetime prevalence rates for bipolar spectrum disorder will be presented and the relevance of postpartum hypomania to later postnatal depression will be discussed. Evidence will be presented that bipolar II depression in the postpartum is often misdiagnosed as unipolar major depression and that this may result in inadequate treatment and a worsening of mood instability. We suggest that the dearth of screening, monitoring and diagnostic instruments to specifically identify bipolar depression during pregnancy and the postpartum has made it difficult to adequately treat and prevent this condition. Finally, the clinical consequences of missed bipolarity in the setting of the postpartum will be summarized and suggestions will be made for research to improve detection, diagnosis and treatment of postpartum bipolar II depression and bipolar disorder NOS. The main thrust of the article is on the depressed phase of bipolar II disorder and bipolar disorder NOS because 1) a means of detection of this presentation has lacked clarity and consistency, 2) patients with these conditions are more likely to be misdiagnosed as having major depressive disorder, and 3) this patient population is consequently at risk of mismanagement. Because it generally presents with a psychotic mixed mania rather than depression, we have also excluded a discussion of postpartum psychosis. 2. Bipolar spectrum disorder and postpartum mood disorders The term bipolar spectrum disorder has been variously defined (Phelps et al., 2008) but it generally includes bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified (NOS) (Hirschfeld et al., 2000). There have also been proposals to include the following presentations under the rubric of bipolar spectrum disorder: a) hypomania induced by antidepressants and other psychoactive substances; b) recurrent unipolar depression with a family history of bipolar disorder; and c) depression characterized by multiple non-manic symptoms usually associated with a bipolar course (Phelps et al., 2008; Ghaemi et al., 2002). Bipolar I is a disorder marked by recurrent episodes of mania and depression, bipolar II disorder involves recurrent episodes of depression and hypomania, and bipolar NOS is a disorder with a course that is marked by manic and

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depressive symptoms but the presentation does not reach the DSM-IV criteria for bipolar I or bipolar II disorder. Bipolar I disorder is a reliable and relatively stable diagnostic category but bipolar II disorder and bipolar disorder NOS are often under-diagnosed or misdiagnosed as major depressive disorder or a personality disorder (Ghaemi et al., 2001). Despite data supporting high attendant morbidity and mortality, there is a common impression that bipolar II disorder and bipolar disorder NOS are milder forms of illness (Vieta and Suppes, 2008). Furthermore, there is accumulating evidence that most of bipolarity exists beyond the realm of bipolar I disorder. The recently published National Comorbidity Survey Replication (NCS-R) study reported prevalence rates of 1.0% for bipolar I, 1.1% for bipolar II, and 2.4% for bipolar disorder NOS (Merikangas et al., 2007). Angst et al. (2007) however, reported that the total prevalence of the bipolar spectrum was about 11% which is similar to that of major depressive disorder. The significant variability between these cited prevalence rates suggest possible inconsistencies between detection methods and lack of clarity regarding diagnosis. Studies of postpartum mood disorders have historically included the baby blues, postpartum depression, and puerperal psychosis. The baby blues denotes a brief period of mild emotional disturbance characterized by dysphoria, tearfulness, mood lability, insomnia, reduced appetite, irritability, and anxiety. Symptoms occur in up to 85% of women, begin several days after delivery, and usually remit by the tenth day (O'Hara et al., 1990; Stein, 1980). Usually no treatment is required but the blues may herald an episode of postpartum depression in some women. Postpartum depression is a serious public health problem with an estimated prevalence of 13% among mothers (O'Hara and Swain, 1996). Recent Scandinavian studies have reported that the first three months postpartum represent a time of increased risk for new-onset psychiatric disorders, inpatient admission, and outpatient treatment in new mothers (Munk-Olsen et al., 2006, 2009). Postpartum depression was the most common new-onset psychiatric disorder in these new mothers (Munk-Olsen et al., 2006). For women with a previous psychiatric diagnosis and a history of psychiatric admission prior to childbearing, the strongest predictor for readmission in the postpartum period was a diagnosis of bipolar disorder (Munk-Olsen et al., 2009). Thus, research has indicated that the postpartum is a time of increased risk for first onset and serious depression (Kendell et al., 1987; Cox et al., 1993). The etiology of postpartum depression is unknown but the rapid decline in the levels of reproductive hormones and/or neuroreceptor downregulation following delivery is hypothesized to contribute to the development of depression in susceptible women (Bloch et al., 2000; Maguire and Moody, 2008). Women with a history of depression, postpartum depression, or a family history of mood disorders are at an increased risk of experiencing postpartum

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depression (O'Hara and Swain, 1996; Wisner and Stowe, 1997). Stressful life events and poor social support also play a role (Swendsen and Mazure, 2000). Postpartum psychosis is relatively rare and occurs in approximately 1–2 per 1000 women after childbirth. At highest risk are women with a personal or family history of bipolar disorder or postpartum psychosis (Robertson et al., 2005). The nosological status of postpartum psychosis remains a topic of debate, but it is usually a manifestation of bipolar disorder triggered by childbirth (Chaudron and Pies, 2003). The DSM-IV-TR postpartum-onset specifier can be applied to a depressive, manic, or mixed episode if it begins within four weeks after childbirth in women with major depressive disorder, bipolar I disorder, or bipolar II disorder; however, there is no provision for its use to denote a hypomanic episode, nor is there a specifier for bipolar disorder NOS (APA, 1994). The literature on postpartum depression has focused almost exclusively on major depressive disorder and has neglected the study of the depressed phase of bipolar disorder in the postpartum period. Moreover, there is no information on the screening, assessment and treatment of bipolar depression in the postpartum period. This is surprising given a) the prevalent nature of bipolar disorder, b) the greater time spent in the depressed phase than the (hypo) manic phase, and c) the elevated risk for the onset or exacerbation of mood episodes after delivery in women with bipolar disorder. 3. Method On April 6, 2009, a Pub-Med search (1998–2009) using each of the following search terms was completed: ‘postpartum depression’ (n = 2159); ‘postpartum depression AND screening/detection/diagnosis/treatment’ (n = 942/79/1056/1229); ‘bipolar I AND postpartum depression’ (n = 84); ‘bipolar II AND postpartum depression’(n = 12); ‘postpartum hypomania’ (n = 8); and ‘postpartum hypomania AND screening’ (n = 4). The reference lists of articles identified were also searched to select other relevant publications. 4. Postpartum hypomania in non-clinical populations Since 1962, when Robin reported that elation was particularly common on postpartum day one and that it ‘appeared more intense than ordinary happiness’ (Robin, 1962), there have been several reports of hypomanic symptoms occurring immediately after delivery (Glover et al., 1994; Lane et al., 1997; Hasegawa, 2000; Webster et al., 2003; Farías et al., 2007; Heron et al., 2009). Associated symptoms include increased goaldirected activity, over-talkativeness, racing thoughts, decreased sleep requirement, distractibility and irritability (Glover et al., 1994). Even though elation has been reported as a symptom of the baby blues in some studies (Kennerly and Gath, 1989; Stein, 1980), postpartum hypomania can be distinguished by its greater symptom severity and by the onset of these symptoms on day one postpartum rather than day three or four for the blues (Glover et al., 1994). Glover et al. (1994) used the Highs scale, a self-rating instrument based on the Schedule for Affective Disorders and Schizophrenia—Lifetime Version (SADS-L) (Endicott and Spitzer, 1978) to study the phenomenon of postnatal elation. The scale has seven items including feeling elated, more ac-

tive than usual, more talkative than usual, racing of thoughts, feelings of being an especially important person, decreased need of sleep, and trouble concentrating due to attention jumping to unimportant things. A score of ≥8 is indicative of the ‘highs’ (hypomania). The correlation between the Highs score and the blind observer-rated diagnosis by the Comprehensive Psychopathological Rating Scale was 0.62 (P b 0.01) (Asberg et al., 1978). About 10% of women reported features of hypomania in the first five days following delivery in the study by Glover et al. (1994). Women scoring above the cut-off score of seven were at a higher risk of experiencing depression at six weeks than women with no psychopathology soon after childbirth. Another study used a similar methodology and reported that 18.3% of women at postpartum day three and 9% of women at week six had above threshold scores on the Highs scale (Lane et al., 1997). The best predictors of the Edinburgh Postnatal Depression Scale (EPDS) scores of N13 at week six postpartum were the mothers' scores on the EPDS and the Highs scale at postpartum day three. The peak prevalence of hypomanic symptoms is immediately after delivery even though the risk remains elevated for several weeks. As shown in Table 1 (Glover et al., 1994; Lane et al., 1997; Hasegawa, 2000; Webster et al., 2003; Farías et al., 2007; Heron et al., 2009), estimates of the prevalence of postpartum hypomania in nonclinical populations have ranged from 9.6% to 20.4% on day three postpartum. While there are no comparative studies on the prevalence of hypomania during the puerperium versus the non-puerperal periods, the rates reported in these studies are significantly higher than the lifetime prevalence rates for bipolar spectrum disorder. The symptoms of hypomania are not limited to the immediate postpartum period. Interestingly, in Glover's study 28% of women had the symptoms at both study periods (three days and six weeks) (Glover et al., 1994). It is not clear from these studies how many women were on antidepressants that could have played a role in the induction of hypomania. The only study to report on the use of the Highs scale outside the postpartum period showed that hypomania increased from 1.4% during pregnancy to 11.7% in the immediate postpartum period (Heron et al., 2009). In this study the cases of probable depression, as defined by a score of 13 or higher on the EPDS (Cox et al., 1993), did not significantly increase from pregnancy to postpartum indicating that the processes related to childbirth might be playing a specific role

Table 1 Prevalence of postpartum hypomania. Study

Day 3

6 weeks

Glover et al. (1994) a Lane et al. (1997) Hasegawa, M (2000) Webster et al. (2003) Farías et al. (2007) Heron et al. (2009) b

10% 18.3% 13.5% 9.6% 20.4% 11.7%

7% 9% NA NA NA 4.9% (8 weeks)

a b

11% had a score of ≥8 on the Highs scale on day 5 postpartum. 1.4% of cases had hypomanic symptoms at 12 weeks of pregnancy.

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in the evolution to bipolar mood disorders, rather than mood disorders in general. Although postpartum hypomania itself does not cause marked impairment in social or occupational functioning (APA, 1994), the clinical significance lies in its association with later postnatal depression (Lane et al., 1997; Hannah et al., 1993; Brockington et al., 1998) and it has been suggested that postpartum hypomania does not simply reflect happiness at having a baby but is rather a manifestation of bipolar disorder (Glover et al., 1994). Still, more accurate phenomenological understanding, detection methods, and diagnostic tools are required to better enable and predict when a clinically significant course may arise from these presentations. 5. Bipolar postpartum depression There is a dramatic rise in the prevalence of mania and puerperal psychosis in the postpartum period (Kendell et al., 1987; Kadrmas et al., 1980; Hunt and Silverstone, 1995; Valdismarsdottir et al., 2009), but childbirth is also a trigger for episodes of bipolar depression (Freeman et al., 2002; Viguera et al., 2007). According to the DSM-IV, the postpartum-onset specifier can be applied to an episode of depression in patients with bipolar I disorder or bipolar II disorder (APA, 1994). Freeman et al. (2002) reported that 67% of 30 women with bipolar I or II disorder had a postpartum mood episode within one month of delivery. The authors found a 100% recurrence rate of depression following a subsequent delivery in the eight women who had experienced depressive episodes following their first delivery. Notably, 90% of the women were not treated with psychotropic medication despite the fact that all but one of 30 women had reported onset of a mood episode prior to having children. Another study found that approximately 20% of women with bipolar disorder retrospectively reported having postpartum mood episodes, mainly of the depressive type (Payne et al., 2007). Compared to those with major depressive disorder, women with bipolar disorder are more likely to have episodes of postpartum depression (Ghaemi et al., 2002). Hannah et al. (1993) interviewed women with postpartum depression using the SADS-L and noted that about one quarter of them met the criteria for hypomania during the first postpartum week. Glover et al. (1994) found that 19% of women with hypomanic symptoms at three days developed postpartum depression (EPDS ≥ 13) at six weeks postpartum. Using the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1997), Sharma et al. (2008) reported that 54% of patients with postpartum depression had a lifetime diagnosis of bipolar spectrum disorders; however, only a small number (10%) of these patients reported receiving a previous diagnosis of bipolar disorder. Approximately 13% of women in this study scored above the threshold score of seven for the highs immediately after delivery. Of the positive cases on the Highs scale, 83% had a primary diagnosis of bipolar II disorder or bipolar disorder NOS and the remaining had recurrent major depressive disorder. Of the 30% of patients who had a positive screen for bipolar spectrum disorder on the Mood Disorders Questionnaire (MDQ), 86% met the DSM-IV diagnosis of bipolar disorder. Evidence in support of postpartum depression having a bipolar diathesis also comes from literature on antidepres-

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sant-induced mood instability and the family history of bipolar disorder (Sharma et al., 2008). Sharma (2006) reported three cases of early onset postpartum depression in which bipolarity manifested following antidepressant treatment. While there was no past history of psychiatric disturbance, each case involved a family history of bipolar disorder. Treatment with antidepressants resulted in a highly unstable illness course but discontinuation of antidepressants and initiation of mood stabilizers and atypical neuroleptics resulted in sustained improvement. Family history is perhaps the most important external validator of psychiatric diagnoses (Ghaemi et al., 2002; Akiskal, 2002; Winokur and Tsuang, 1996; Angst and Gamma, 2002; Coryell, 1999; Robins and Guze, 1987; Kendler, 1990). Family history of mental disorders was not a risk factor for postpartum mental disorders in a meta-analysis by O'Hara and Swain (1996), but more recent studies have shown an excess of familial psychopathology in women with postpartum disorders including bipolar illness (Jones and Craddock, 2001; Forty et al., 2006; Murphy-Eberenz et al., 2006). Familial factors are known to play a triggering role in postpartum depression especially in women with early onset episodes (Murphy-Eberenz et al., 2006). A recent study reported a 24-fold increase in the risk of postpartum psychiatric admissions for women with a first-degree relative with bipolar disorder compared to the reference group (Munk-Olsen et al., 2007). The clinical picture of bipolar postpartum depression requires further clarification. While Brockington et al. (1998) has reported that an early onset of depression (within two weeks of delivery) and a characteristic clinical profile (less anger, less self-rated emotion and more animation) represent a clinical entity related to bipolar disorder, there are no studies that have systematically compared the symptom profiles of postpartum depression in women with major depressive disorder to those with bipolar disorder (Sharma, 2005).

6. Screening and monitoring Early and accurate diagnosis of bipolar spectrum disorder is essential in order to avoid its misdiagnosis as major depressive disorder and to provide safe and effective care during pregnancy and after delivery. While there are a large number of formal rating scales for the assessment of various clinical aspects of bipolar spectrum disorder and unipolar postpartum depression, there are currently no validated instruments for screening, diagnosing, or monitoring during pregnancy and postpartum in patients with bipolar disorder. Unlike some of the commonly used depression rating scales, the screening tools for postpartum depression are not sufficiently sensitive to capture the symptoms commonly associated with bipolar depression such as hypersomnia, hyperphagia, and psychomotor retardation. For example, both the EPDS and the Postpartum Depression Screening Scale (PDSS) (Beck and Gable, 2000) have items to assess insomnia but not hypersomnia. On the PDSS there are two items on reduced appetite but none on increased appetite. Interestingly, there are two items on this scale that assess emotional lability including irritability and ‘emotions being on a roller coaster’.

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The Highs scale is the only scale that was designed specifically to assess hypomanic symptoms after delivery but it has not been validated as a diagnostic instrument (Glover et al., 1994). The Highs scale assesses recently occurring symptoms of hypomania in contrast to the lifetime occurrence of hypomania assessed by the MDQ (Hirschfeld et al., 2000). Moreover, unlike the MDQ, the Highs scale assesses cognitive and affective symptoms of hypomania independently of those symptoms having produced substantial dysfunction in social/occupational activities. This means that the Highs scale is more pertinent to daily life in which the woman has neither gone back to work nor had the opportunity to engage in regular social activities. The MDQ is a widely used screening tool for bipolar disorder but it has not been validated during pregnancy or postpartum. In summary, with the exception of the Highs scale, there are no clinically validated and easy to use screening tools to facilitate the early detection and treatment of patients with postpartum bipolar spectrum disorder. 7. Pharmacological and psychotherapeutic studies The current literature on pharmacological treatment of postpartum depression consists of three randomized controlled trials (Appleby et al., 1997; Wisner et al., 2004; Wisner et al., 2001) and five open-label studies (Stowe and Nemeroff, 1995; Misri et al., 2004; Nonacs et al., 2005; Cohen et al., 2001; Suri et al., 2001). These studies showed that serotonin reuptake inhibitors (fluoxetine, sertraline, fluvoxamine, and paroxetine), bupropion and venlafaxine are effective in the acute treatment of postpartum depression. Due to the limited nature of the data and the lack of clear evidence about the effectiveness, it is not possible to draw any clear conclusions about their role in the prevention of postpartum depression (Howard et al., 2005). As in trials of antidepressants in nonpuerperal major depressive disorder, patients with bipolar disorder are routinely excluded from clinical trials in postpartum depression. However, in spite of the lack of efficacy and safety data, antidepressants are routinely used as first line drugs in the management of bipolar postpartum depression. The impact of prophylactic treatment on postpartum mood episodes has been evaluated in at least three studies. Viguera et al. (2001) retrospectively compared recurrence rates and survival functions for 101 women with bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum or during equivalent periods (weeks 1–40 and 41–64) for age-matched non-pregnant subjects after discontinuation of lithium. Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women. Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in non-pregnant women during weeks 41–64. Depressive or dysphoric-mixed episodes were more prevalent in pregnant than non-pregnant women and the recurrence risk was greater for patients with more prior affective episodes, but was similar for diagnostic types I and II. Cohen et al. (1995) retrospectively compared the risk of postpartum recurrences in 27 women with bipolar disorder who were medicated prophylactically with women who were not receiving any

medications. Only one of the 14 women taking prophylactic medication (lithium and/or carbamazepine) relapsed during the three months after delivery, while eight of the 13 unmedicated women had a relapse. In a study of 26 participants including 16 women with bipolar I disorder and 10 with bipolar II disorder, Wisner et al. (2004) evaluated the efficacy of valproate (valproate plus symptom monitoring versus monitoring without medication) in the prevention of postpartum recurrences in women with bipolar disorder. Results of this single-blind, non-randomized clinical trial showed no significant differences between groups in the proportion of women who developed hypomania/mania, depression or mixed states. A prospective cohort study of women with bipolar I (n = 8) and bipolar II (n = 28) disorder found that olanzapine alone or in combination with an antidepressant or mood stabilizer was associated with a lower risk of postpartum mood episodes (18% versus 57%) than treatment with antidepressants, mood stabilizers, or no medication for a minimum of four weeks after delivery (Sharma et al., 2006). Still, there are no studies specifically on the prevention of postpartum depression in women with bipolar II disorder and bipolar disorder NOS. 8. Under-diagnosis of postpartum bipolarity: causes, consequences and implications 8.1. Common causes Due to their dramatic presentations, diagnosing postpartum mania or psychosis is not difficult. However, recognizing hypomania can be particularly challenging due to the rather unique circumstances accompanying childbirth. Diminished sleep, a common symptom of hypomania, is ubiquitous after childbirth. The feelings of elation over having given birth may be difficult to distinguish from the euphoria experienced as part of hypomania (Sharma et al., 2008; Sharma, 2005). Another common reason for failure to diagnose postpartum hypomania may be that the DSM-IV does not permit the use of the postpartum-onset specifier to capture symptoms of hypomania (Sharma, 2005). Meanwhile, the under-reporting of a history of hypomania may be due to the “statedependent” effects in which individuals currently in a state of postpartum depression remember only previous depressions. Due to the general lack of awareness, clinicians may not inquire about episodes of mood elevation and unless asked specifically, women may fail to report hypomanic symptoms and focus instead on symptoms of depression. 8.2. Consequences of missed bipolarity The NCS-R reported that only about 16% of patients with bipolar II disorder and 8% of patients with bipolar disorder NOS received appropriate medication, while 46% and 68% of patients with these disorders received no medication. Failure to identify hypomania frequently results in bipolar disorder being misdiagnosed as major depressive disorder and causes a delay in the initiation of appropriate treatment interventions. The consequences of this misdiagnosis can be particularly serious in the postpartum period as treatment with antidepressants may precipitate mania or rapid cycling and thereby increase the risk for hospitalization. The injudicious

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use of antidepressants in patients with a bipolar diathesis has also been linked to polypharmacy and treatment refractoriness (Sharma et al., 2005; Sharma, 2001). Patients with bipolar disorder, particularly those with type II disorder, are at high risk for suicide attempts and completion (73). There is also a concern that antidepressants may cause mixed episodes that in turn may increase the risk for suicide (Akiskal et al., 2005; Balazs et al., 2006). Antidepressant medications have not been studied in the acute or prophylactic treatment of bipolar postpartum depression; but, in general, these drugs are not considered as effective in bipolar depression as in major depressive disorder (Ghaemi et al., 2004). Studies have reported that children of depressed mothers are at risk for cognitive and developmental delay and are more likely to develop behavioral problems (Murray, 1997; Weinberg and Tronick, 1998; Pilowsky et al., 2006). Postpartum depression is also associated with disruption in marital relationships, impaired occupational and social functioning, poor quality of life, and low self-esteem (Da Costa et al., 2006); however, the data on the consequences of bipolar postpartum depression for women, their offspring, and their families are lacking.

8.3. Clinical and research implications The lack of data on postpartum bipolar II and bipolar disorder NOS is surprising given the high prevalence of hypomanic symptoms immediately after delivery, the unique pharmacological challenges posed by bipolar depression, and the heightened risk of suicide associated with bipolar spectrum disorder. The recognition that the postpartum period is also a high-risk period for the occurrence of subtle bipolarity in addition to other mood disorders generally subsumed under the rubric of postpartum disorder has profound clinical and research implications. Accurate differentiation of postpartum bipolar depression from postpartum unipolar depression is crucial for appropriate treatment planning. Untreated postpartum depression is associated with high rates of death from natural and unnatural causes, particularly suicide (Appleby et al., 1998). According to the Confidential Enquiries into Maternal Deaths, suicide is the leading cause of maternal mortality in the UK and it accounts for 28% of maternal deaths. Unfortunately, none of the women reported in the Confidential Enquiry was under the care of a mother and baby unit or perinatal psychiatric service (Oates, 2003). Patients with a positive screen for bipolar disorder are more likely to report worse health-related quality of life as well as more social and family life impairment compared with those with a negative screen (Das et al., 2005). Given the prevalent nature of bipolar disorder and the potentially serious consequences of its misdiagnosis and inappropriate treatment, all women receiving antenatal care should be screened for bipolar disorder and its known risk factors (such as family history of bipolar disorder). This will permit early identification of women at risk and application of formal risk assessment and management plan including close follow-up during the period of risk (Appleby et al., 1998; Oates, 2003). It may also provide an opportunity to address avoidable risk factors such as high levels of stress and sleep disruption in

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late pregnancy and early postpartum (Jones and Craddock, 2005). Childbirth is a potent trigger of mood episodes in women with bipolar disorder and therefore constitutes a window of opportunity for early detection and initiation of appropriate treatment interventions. Moreover, the heightened risk of onset or recurrences of mood episodes during the early postpartum period makes it feasible to mount prospective studies aimed at clarifying the role of putative causal factors such as hormonal changes and sleep loss. Unfortunately, the dominant focus on depression in perinatal research has not clarified the etiological relationship between childbirth and mental illness and the study of bipolar spectrum disorders may provide new leads (28). With the exception of a single study (Heron et al., 2009), all the studies on postpartum hypomania have focused on a limited period after childbirth and there is no information as to whether patients with these symptoms have non-childbirth related mood episodes. There are no data on the incidence, symptom profile, and duration of postpartum hypomanic episodes as defined by contemporary diagnostic systems. Similarly, there is no information on the incidence, prevalence and duration of depression that follows postpartum hypomania. There are no comparative studies on the phenomenology of depression with or without postpartum hypomania. Also lacking are studies of clinical validators such as family history, phenomenology, comorbidity, and illness course that are commonly used to establish the bipolar diathesis of a clinical condition. 9. Recommendations for detections and management Given potentially serious consequences of the underdiagnosis of bipolar disorder or its misdiagnosis as major depressive disorder, it is necessary that currently available research be utilized to guide assessments of women with postpartum mood presentations. Thus, women with histories of major depressive episodes should be routinely screened for (hypo) mania during pregnancy and after delivery. Moreover, the Canadian Network for Mood and Anxiety Treatments and International Society for Bipolar Disorders guidelines for bipolar disorder (2009) recommend universal screening of all pregnant women for bipolar disorder (Yatham et al., 2009). Screening should also include questions about the family history of bipolar disorder. The presence of other clinical features such as diurnal mood variation and hypersomnia during a depressive episode should serve as a clue to the bipolar nature of depression (Forty et al., 2008).

Table 2 Clues to the bipolar nature of postpartum depression. • Subsyndromal elevated mood during pregnancy and after delivery, particularly in women with past histories of mood disorders. • Atypical symptoms in the context of depression (e.g., diurnal mood variation, hypersomnia). • Elevated mood and behavior in response to antidepressant. • Mixed depression, elation, and behavioral agitation. • Disorganization of thought and behavior without apparent awareness of impact on mothering and other responsibilities. • Psychosis (often not full blown, as in classic postpartum bipolar I psychosis) in the context of postpartum depression. • Family history of bipolar disorder.

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Psychotic symptoms may not be immediately apparent or prominent and should be identified after careful questioning and observation. Repeated assessments are preferable over single assessments to avoid the under-reporting or overreporting of mood episodes (Akiskal et al., 2000) (Table 2). Clinical assessment should include monitoring of the sleep–wake cycle and pharmacotherapy should be directed towards reducing sleep disruption (Sharma and Mazmanian, 2003; Sharma et al., 2004). While women with postpartum unipolar depression tend to feel guilty because they feel that they are neglecting their infants, women with a bipolar diathesis are more likely to be disorganized and less able to appreciate their inability to care appropriately for their infants. For women who are already receiving antidepressants the need for their continued use in the maintenance treatment of depression should be evaluated and there should be close monitoring for cycle acceleration or a mood switch to hypomania or mania (Table 3). In general, the treatment of bipolar postpartum depression should follow the same guidelines as for the treatment of non-puerperal bipolar depression (Yatham et al., 2009) and compatibility of selected drugs with lactation should be ascertained (Burt et al., 2001). It should be noted that breastfeeding almost always ensures serious sleep deprivation, particularly in the early postpartum period. Thus consideration should be given to formula feeding or supplementation of breast milk with formula in order to maximize consecutive hours of sleep. For the acute treatment of bipolar II depression, treatment options include lithium, lamotrigine, divalproex, lithium or divalproex plus antidepressant, lithium plus divalproex, and antidepressant plus atypical neuroleptic (Yatham et al., 2009). For prophylactic treatment, options include lithium, lamotrigine, lithium or divalproex or atypical antipsychotic plus antidepressant or combination of two of lithium, lamotrigine, divalproex or atypical antipsychotic is included (Yatham et al., 2009). Antidepressant monotherapy should be avoided for the prophylactic or acute treatment (Sharma, 2006). For women who appear to have significant

bipolar illness in the postpartum setting, consideration should be given to continued use of stabilizing medication after the first postpartum year. If medication is discontinued, it is advisable to continue psychiatric monitoring beyond the first postpartum year in order to ensure ongoing maternal emotional stability. Women should be carefully monitored for ongoing mood stability during subsequent pregnancies and postpartum periods. Consideration should be given to prophylactic management with previously effective medications versus careful monitoring and prompt implementation of medications that have been effective in the past (Table 4).

Table 3 Treatment considerations for bipolar II depression in the postpartum period.

Role of funding source Supported by a grant from Ontario Mental Health Foundation.

• Consider mood stabilizer both acutely and to maintain stability. • Address acute management: e.g., initial use of antipsychotics, benzodiazepines in addition to mood stabilizers. • Caution before implementing antidepressant treatment. • In setting of antidepressant administration, consider tapering and discontinuing antidepressant. • Comprehensively assess home situation and support system in order to enhance and maximize opportunity for uninterrupted sleep. • Review risks and benefits of breastfeeding with mother, pediatrician: ○ Assess compatibility of medications with breastfeeding. ○ Balance reduction of mother's opportunity for uninterrupted sleep and advantages of breastfeeding. ○ Consider full-time breastfeeding vs. breastfeeding with supplementation vs. full formula feeding. • Evaluate need for ongoing psychiatric treatment for bipolar disorder beyond the postpartum period: ○ If a decision is made to taper and discontinue mood stabilizer in the setting of complete maternal wellbeing, continue to monitor to ensure continued mood stability. • For subsequent pregnancy and postpartum periods: ○ Preemptively shore up supports. ○ Consider prophylactic treatment versus prompt management with previously effective treatment regimen.

Table 4 Areas for further research. Detection

· Comparison of the symptom profiles of postpartum depression in women with major depressive disorder versus those with bipolar II disorder · Assessment of validity of commonly used clinical markers to establish bipolar diathesis in postpartum setting · Phenomenological clarification of postpartum hypomanic presentations and the indicators predictive of a clinically significant course · Comparison of the symptom profiles of postpartum depression in women with versus without prior postpartum hypomania · Development of validated screening instruments for diagnosis and monitoring of symptom severity of bipolar depression during pregnancy and the postpartum period Diagnosis · Data on the incidence, prevalence, and duration of postpartum hypomanic episodes · Data on the incidence, prevalence, and duration of postpartum bipolar depressive episodes Treatment · Pharmacological and psychotherapeutic studies to ascertain optimum treatment of bipolar postpartum depression and provide algorithms to guide clinical decision making · Studies on the prevention of bipolar II postpartum depression · Development of comprehensive treatment protocols to minimize negative psychological and social consequences of bipolar postpartum depression for mothers, their offspring, and their families

Conflict of interest All authors declare that they have no conflicts of interest.

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