Postpartum (Puerperal) Psychosis – Pathophysiology | Diagnosis | Management
The early postpartum period is a time of much greater risk than usual for the development of severe psychiatric disorders. [Kendell et al., 1987]
Postpartum or puerperal psychosis (PPP) is a serious form of postnatal psychiatric disorder with a strong and specific association with bipolar disorder. [Munk-Olsen et al., 2006]
Though its prevalence is rare (1-2 per 1,000 women), it is a key risk indicator for future affective disorders. This has significant public health, mental health and economic implications and contributes broadly to the global burden of disease. [VanderKruik et al., 2017], [Osborne, 2018]
The exact mechanisms involved in postpartum psychosis remain poorly understood. While childbirth appears to be a potent trigger of severe mood disorders, evidence from aetiological studies indicates that most episodes manifest as bipolar disorders, possibly induced by vulnerabilities to certain perinatal triggers. [Perry et al., 2021]
So far, neurobiological factors such as hormones, immunological dysregulation, circadian rhythm disruption and genetics have all been implicated in the pathogenesis of PPP. [Perry et al., 2021]
In this article, we discuss the aetiology, risk factors, diagnosis and management of women with postpartum psychosis.
HISTORY OF POSTPARTUM PSYCHOSIS [Osborne, 2018]
Hippocrates described the first known case in 400 BC with the patient presenting with confusion, hallucinations, and insomnia six days after giving birth to twins.
Hippocrates described PPP as:
A kind of madness caused by excessive blood flow to the brain.
A medieval gynaecologist, Trotula of Salerno, attributed the disorder to
Too much moisture in the womb causing the brain to fill with water which was then involuntarily shed as tears.
Esquirol wrote the first review in 1838, describing 92 women with postpartum psychosis, of which 53% had predominantly manic symptoms, 38% had depressive symptoms, and 9% had non-affective psychosis.
A 23-year-old suffered from nervous disorders from her menarche. At 21 she married a general and promptly became pregnant. Seven days after the birth, there was an adverse event. Her lochia was suppressed and she started to rave, but for only 2 days. She relapsed on the 25th day. Délire furieuse switched to stupor. In the 5th month, her periods returned and she became obese. In spite of the death of her husband, she remained well.
French psychiatrist Louis-Victor Marcé published the first textbook on postpartum disorders in 1858 that included detailed clinical descriptions of women with postpartum disorders called Traité De La Folie Des Femmes Enceintes, Des Nouvelles Accouchées Et Des Nourrices. [Trede at al., 2009]
Some women in whom depression is not strong enough to rob the mind of all lucidity, show a cold-bloodedness in the execution of their plans and cleverness that can’t always be outsmarted. (Marcé)
EPIDEMIOLOGY OF POSTPARTUM PSYCHOSIS (PPP)
PPP typically presents in the first two weeks (1-14 days) after childbirth as either acute mania or depression, with psychosis. [Kendell et al., 1987]
PPP should be distinguished from postnatal depression (PND), which is more common (10-15%). While both can be equally serious, differentiating the two is essential due to treatment implications. Postpartum depression refers to a nonpsychotic depressive episode, while postpartum psychosis refers to a manic or affective psychotic episode linked temporally with childbirth.
- PPP usually occurs in around 1–2 of every 1000 deliveries.
- Onset can be rapid and, in some cases, life-threatening, particularly where a desire to harm an infant is expressed. [VanderKruik et al., 2017]
- The risk of requiring psychiatric admission for postnatal psychosis increases to around 22 times more likely in the first month postnatally.
- The risk for primiparous mothers (those who have given birth to their first baby) was 35 times higher than in the general population. [Kendell et al.,1987]
- Pre-existing mental health diagnoses exist in around 60% of mothers who develop PPP.
- Bipolar disorder is the most common illness associated with PPP, with an estimated 1 in 5 new mothers with bipolar illness experiencing a psychotic or manic postnatal episode. [Munk-olsen et al., 2012]; [Azorin et al, 2012]
- The presence of first-episode postnatal depression in new mothers may precede a new bipolar diagnosis. [Munk-olsen et al., 2012]
- A family history of bipolar illness is also more commonly reported in PPP.
- Postpartum hospital readmission rates are up to 37 times more likely in women with children than non-mothers. [Munk-Olsen et al., 2009]
- A previous diagnosis of bipolar affective disorder was the strongest predictor of readmissions 10 to 19 days postpartum. [Munk-Olsen et al., 2009]
- In women with schizophrenia and other mood disorders, admission risk only marginally increased in the first 3 months postpartum (with a relative risk of 4.6 and 3.0, respectively). [Munk-Olsen et al., 2009]
AETIOLOGY OF POSTPARTUM PSYCHOSIS (PPP)
Amongst the strongest risk factors for PPP are personal or family, history of bipolar disorder or related psychotic disorder (seen in about 40%-50% of PPP cases).
The strongest single risk factor for PPP is a personal history of bipolar disorder, with 20-30% of parous women with known bipolar disorder experiencing PPP. [Osborne, 2018]
The aetiology of postpartum psychosis is unique in that it takes place within a specific timeframe. This is invaluable in helping clinicians and researchers accurately predict the complex, yet specific biological, social and psychological triggers, preceding its onset. These triggers include: [Perry et al., 2021]
- Obstetric factors
- Psychological and social stressors, including medication use
- Hormone change sensitivities relating to labour and birth
- Sleep and circadian rhythm disruption in the perinatal period
- Immunological factors
- Genetics
Obstetric Considerations
- Primiparity is a significant risk factor for developing postpartum psychosis. [Munk-Olsen et al., 2014]
- Study data on obstetric factors such as mode of delivery [Nager et al., 2008], infant gender [Agrawal et al., 1990] and complications in pregnancy or birth remain inconclusive, and replication of findings has proven difficult.
- In another study, stillbirth was associated with an increased risk of developing a severe psychiatric disorder, but this relationship was not explored and requires further investigation. [Lewkowitz et al., 2019].
Psychological and Social Factors
- Personality traits, cognitive styles and moods do not correlate precisely with postpartum psychosis, though they have shown to be important in developing postnatal depression and bipolar disorder. [Perry et al., 2019]
- There have also been no consistent relationships found between life stressors, such as history of trauma during pregnancy, childhood [Meltzer-Brody et al., 2018] or in the 12 months before delivery. [Dowlatshahi & Paykel, 1990]
- Some studies cite relationship difficulties or lack of a partner as contributing factors, but it is unclear whether these are causes or consequences of the illness. [Kendell et al., 1987]
- Unmet maternal needs and expectations, as well as feelings of shame and failure, are linked to increased postnatal depression and anxiety [McIntyre et al., 2018]. PPP has been linked more closely with difficult labour and a lack of familial support. [Glover et al., 2014]
- Women with bipolar disorder often have to limit or omit psychotropic medication perinatally if they wish to breastfeed or are anxious about possible teratogenic side effects, which can increase the risk of relapse. [Dolman et al., 2016]
- In one study, the omission of lithium in pregnant women increased relapse rates of bipolar disorder in up to 66% of participants compared to those who kept taking prophylactic mood stabilising medication during pregnancy. [Wesseloo et al., 2016]
- But in others, relapse risk remained high regardless of medication type or duration. [Taylor et al., 2019]
This suggests that aetiological factors other than medication are implicated in the onset of postpartum psychosis.
Hormonal Factors
- Progesterone and oestrogen reduce abruptly after birth, coinciding with peak symptom onset in postpartum psychosis.
- Menstrual cycles have also been linked to mood changes in women with bipolar disorder [McIntyre et al., 2018]; [Kahalon et al., 2022], and some women experience severe mood episodes only around the time of childbirth. [APA, 2013]
- Monoaminergic functioning is known to be impacted by oestrogen and progesterone, with oestrogen facilitating dopaminergic transmission. [Barth et al., 2015]
- Estradiol generally induces excitatory actions, while progesterone induces inhibitory actions on the CNS. [Carta et al., 2012]
- Monoamines also play an intrinsic role in mood and psychosis, so it is assumed that the post-childbirth drop in hormones may account for dopaminergic hypersensitivity, particularly in women who are likely to be triggered during childbirth. [Belmaker, 2008]; [Ashok et al., 2017]
- Prolactin inhibitors (dopamine D2 receptor agonists) may also be implicated as triggers for postpartum psychosis. They are often prescribed for illnesses such as hyperprolactinemia and Parkinson’s disease, and they can prompt or aggravate mania and psychosis outside the postpartum period. [Harris et al., 2012]; [Mohapatra et al., 2017]
- In a sample of women with first-episode psychosis, controlling for the potentially confounding effect of long-term antipsychotic use [Delgado-Alvarado et al., 2019], psychotic symptom severity increases were linked to increased prolactin plasma levels. Though the role of prolactin is yet to be fully established, some systematic reviews showed that prolactin inhibitors, especially Bromocriptine (Dopamine agonist), could increase psychosis risk when used to suppress postnatal lactation. [Snellen et al., 2016]
- The abrupt-withdrawal hormone theory has been criticised for being too simplistic [Appleby, 1990]
- Steroid hormone levels do not appear to differ between women affected by postpartum mood disorders and those who remain well. [Bloch et al., 2000]
- Thus it is postulated that some women may be particularly sensitive to endocrine changes occurring during pregnancy and childbirth. [Elder Schiller et al., 2015]
- In a seminal study of pregnant women with and without a history of postnatal depression, supraphysiologic levels of oestrogen and progesterone were observed. [Bloch et al., 2000]
- Following blind steroid withdrawal, 62% of women with a history of postpartum depression developed significant mood disorder symptoms, compared to none in the control group. Such studies support the theory that abrupt hormone withdrawal may be a vital precursor to postpartum psychosis.
- Women with hypothyroxinemia during early gestation are at risk for poor cognitive function throughout gestation, adjusted for depression and sleeping problems. [Pop et al., 2019]
Role of Neurosteroids:
- Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. [Carta et al., 2012]
- During pregnancy, neurosteroids such as AlloP increase dramatically and rapidly decline following the baby’s birth. This change in AlloP levels can affect GABA-A receptor plasticity resulting in an imbalance between excitatory and inhibitory GABAergic circuits. [Gilbert Evans et al. 2005]
- This dysregulation of GABA circuits can lead to monoaminergic dysregulation, which is associated with psychosis.
- Progesterone (PROG) and its reduced metabolite, Allopregnanolone (AlloP), are neuroactive steroids with sedative-hypnotic, anxiolytic, anticonvulsant, and anti-stress properties via positive allosteric modulation of the GABA-A receptor. [Rege, 2021]
- Allopregnanolone reduces basal dopamine content (by a maximum of 65 to 75%) in the prefrontal cortex and nucleus accumbens in a dose-dependent manner but does not affect dopamine output in the striatum.[Motzo et al., 1996].
- Brexanolone, an intravenous stabilised form of AlloP, produces a stable level of AlloP, thus potentially mitigating the steep postnatal decline postulated to cause postnatal depression. It has recently been FDA approved to treat postpartum depression. [Faden & Citrome, 2020]
- An open-label, proof of concept trial is ongoing to investigate the efficacy, safety and tolerability of Zulresso (brexanolone) in PPP.
- Olanzapine, clozapine and lithium increase neurosteroids. [Carta et al., 2012]
- Neurosteroids may act as endogenous mood stabilisers, as supported by the evidence from case reports of recovery from postpartum refractory mania. They may specifically target the mixed-aggressive component of bipolar symptomatology. [Carta et al., 2012]
Sleep and Circadian Rhythm Disruption
- Acute sleep disruption is common during the initial postpartum period. [Yang et al., 2020]
- Sleep loss is a commonly reported precursor to mania in non-pregnant women [Lewis et al., 2017]. In mood disorders, it is well evidenced that the neurotransmitters dopamine, noradrenaline and serotonin, are responsible for regulating sleep cycles, circadian rhythms and hormone emission. [Rosenwasser & Turek, 2015]; [Radwan et al., 2019]
- Large retrospective studies have shown that parous women who reported sleep loss as lifetime triggers to manic episodes were at double the risk of developing postpartum psychosis as those who did not. [Lewis et al., 2018]
- However, in an earlier prospective study of high-risk women with histories of bipolar disorder or postpartum psychosis, sleep patterns mimicked healthy controls. Only three women went on to develop postpartum psychosis making successful comparison impossible. [Bilszta et al., 2010]
- Though there is a paucity of studies directly linking sleep disturbance to the onset of postpartum psychosis, current evidence suggests that a neurobiological explanation is credible.
Immunology
- Immune dysregulation is a possible trigger of postpartum psychosis.
- Women with postpartum psychosis have altered cytokine levels of pro-inflammatory type 1 and 17 T-helper cells and regulatory T-cells, as well as abnormal levels of cytotoxic natural killer cells in some instances. [Bergink et al., 2013]
- Inflammatory cytokines are significantly raised in acute psychosis [Bergink et al., 2014], particularly during acute bipolar episodes. [de Melo et al., 2017]
- Immune disorders such as postpartum thyroiditis and rheumatoid arthritis are worse than postpartum. They also share similar courses to postpartum psychosis. [Bergink et al., 2013]
- Tentative studies show that in some immunological conditions, such as pre-eclampsia and anti-N-methyl-D-aspartate receptor encephalitis, psychiatric symptoms closely mimic those seen in postpartum psychosis. [Reddy et al., 2018]; [Brockington, 2017]
- Neuroinflammation affects serotonin and melatonin pathways by diverting the conversion of tryptophan to kynurenine rather than serotonin which can increase the risk of postpartum mood disorders. [Duan et al., 2018]
Inflammation and Depression – A Simplified Guide
Genetics
- Mood disorders (both childbirth and non-childbirth related) have been shown to have a strong genetic association. In one study of patients with a history of postpartum psychosis, approximately 40-50% of first- and second-degree relatives screened positive for mood disorders, significantly higher than the general population. [Benvenuti et al., 1992], [Robertson et al., 2005]
- Findings suggest that the vulnerabilities specific to postpartum depression may also be used to predict certain genetically heterogeneous subtypes of bipolar illnesses accurately. In a pivotal 2001 study of women with bipolar disorder and a family history of postpartum psychosis in a first-degree relative, 74% experienced severe childbirth-triggered episodes, compared to only 30% of women with bipolar with no family history. [Jones et al., 2001]
Specific Genes:
- 16p13 and 8q24 in a genome-wide study of 54 sibling pairs with bipolar disorder and at least one family member with a history of postpartum psychosis [Jones et al., 2007]
- Other possible target genes include those implicated in hormonal [Thippeswamy et al., 2017], neurotransmitter [Coyle et al., 2000], immunological [Weigelt et al., 2013] and circadian rhythm functioning. [Dallaspezia et al., 2011]
- Methyltransferase like 13 [Thippeswamy et al., 2017]
- The serotonin transporter (5-HTT ) gene, known to be influenced by hormones, is linked with PPP in women with bipolar disorder. [Coyle et al., 2000]
- The STin2.12 allele was specifically associated with a four-fold increased risk of postpartum recurrence. This effect size was further increased when the analysis was confined to only multiparous women with a history of recurrent postnatal psychosis. In an independent sample of women with bipolar disorder, findings have been replicated, with several polymorphisms of serotonergic genes associated with postpartum psychosis. [Kumar et al., 2007]
- Steroid sulfatase (STS), encoded by the X-linked STS gene: The STS enzyme cleaves sulfate groups from a variety of steroid hormones, notably dehydroepiandrosterone sulfate (DHEAS), thus allowing them to be used as precursors for a variety of androgens and oestrogens; hence it is a key modulator of the steroid hormone axis. In STS-deficient women, abnormally low levels of postpartum DHEA may result in hyperactivation of the immune system. Moreover, a positive correlation exists between serum levels of DHEAS and psychoticism (anxiety, paranoia, psychosis) in healthy women and women exhibiting postpartum psychiatric distress. [Davies, 2017]
- Cellular communication network genes (CCN). Genetic risk variants in the CCN family member gene may result in abnormal expression in the developing maternal brain, maternal placenta and adrenal glands. In the future, this may affect neurodevelopment, myelination, and immunological function and increase the risk for hypertension and preeclampsia. Neurodevelopmental vulnerability increases the risk of psychiatric disorders, which may be triggered by the interaction between a dysfunctional CCN axis and hormonal changes in the postpartum state. On the other hand, hypertension and preeclampsia increase maternal stress and affect cerebral perfusion, which may trigger postpartum psychosis. [Davies, 2019]
CLINICAL PRESENTATIONS - CASE STUDIES
Below are some descriptors from patients and clinicians. [Osborne, 2018], [Bergink et al., 2016]
CASE 1: [Article]
I had started experiencing delusional thoughts only days after giving birth.
Confused, my family dismissed my increasingly odd behaviour as being a side effect of lack of sleep. But, while my son behaved like the ‘perfect’ newborn, sleeping in five-hour blocks, I had lost the need to sleep.
However, in contrast to what you may expect, I was euphoric.
I floated around with limitless energy tending to our son’s every need without difficulty, the whole time feeling like the epitome of superwoman.
My entire sensory experience of the world was heightened; colours were more intense, smells deeper, nature more beautiful.
I saw everything as an all-encompassing pattern.
It was as if I had unlocked a hidden area of my mind and now all I had ever learnt was accessible.
I believed I had discovered the secrets of the universe and that with that I would end poverty and solve climate change.
Rapidly, my world descended into the depths of more sinister delusions that were so vivid and so real that I have difficulty distinguishing some of my memories of this time from reality.
I believed that it was up to me to stop an imminent terrorist attack targeting those I loved most, all while being hunted by corrupt government agents.
Words cannot accurately describe the extreme terror I felt in those moments.
CASE 2:
My thoughts are unstoppable and fly around. My brain is in a centrifuge and is connected to the nearest electric outlet. My right hand makes circling movements, which I cannot control.
The environment feels strange. Something I have never felt before, an almighty feeling. I feel connected with all people in the world via invisible wires. Something terrible is going on, but I cannot figure out what this is. I am pacing up and down not knowing what to do. Everything feels strange, and yet apparently nothing changed. I tell my husband, “I will find you another wife.” He is shocked. I see the panic in his eyes. I say to him, “I became God.”
CASE 3: [Article]
4 weeks after birth
I started not trusting my husband. I started to believe that I was being kept under surveillance, that there was a camera behind the clock in my living room.
I actually started to believe that there was literally a court case, and I literally believed that my darling husband, Andrew, and I were being investigated for planning to plot and murder my son. I started seeing police cars everywhere, hearing sirens, seeing the flashing lights. Basically, I was starting to get engulfed in this story…well, it was my reality at the time that we were being investigated. And at this stage, obviously, it wasn’t the case. And I couldn’t communicate this to anyone at the time, this was just what I was living inside my own head.
Case 4:
5 days after delivery
She moved very slowly and seemed confused; she had poor appetite, did not seem to understand how to hold or care for the baby, and spent much of the day lying in bed but did not seem able to sleep.
“I’m not here” and “I didn’t have a baby.”
The patient was oriented to her name only; she could not name the season, nor what type of building she was in; she clung to her sister’s hand and was unable to find the door of the room she was in.
CLINICAL FEATURES AND DIAGNOSIS OF POSTPARTUM PSYCHOSIS
The symptoms of postpartum psychosis are distinctive and unique.
The onset is typically sudden, and symptoms usually begin within the first 2 weeks after delivery, with approximately 65% of episodes occurring in the first three days postpartum. [Osborne, 2018]
Recently, researchers have argued for the designation of postpartum psychosis as a separate diagnostic entity. However, there are arguments that characterising the illness as a distinct entity does not encourage a nuanced approach to treatment. [Sharma et al., 2022]
The symptoms are most commonly of affective psychosis, with perplexity common, and often are rapidly and constantly changing, leading to the term “kaleidoscopic” presentation. [Sharma et al., 2022]
Distinctive clinical features of PPP:
- Delirium-like presentation (disorientation, disorganisation, confusion, derealisation, and depersonalisation.)
-
Insomnia
-
Irritability
-
Abnormal thought content (delusions and/or hallucinations)
-
Abnormal mood (mania or agitation; depression; mixed)
- Kaleidoscopic presentation
Latent class analysis has described cases with 3 distinct symptom profiles: [Kamperman et al., 2017]
- Depression and/or anxiety (41%)
- Mania and/or agitation, with irritability much more common than elevated mood (34%)
- Atypical or mixed profile (25%)
The most prevalent symptoms of PPP were irritability (73%), abnormal thought content (72%), and anxiety (71%).
Across all cases, 25% of patients were disorganised, 20% disoriented, 10% had disturbed consciousness, and 5% developed catatonia. The abnormal thought content most often consisted of persecutory delusions, and a minority had frank hallucinations. Though hallucinations and delusions can occur, the most common symptoms are delusions of reference or persecution. [Kamperman et al., 2017]
These usually focus on the infant, but thoughts of self-harm are also common. This puts mothers with postnatal psychosis at a very high risk of suicide compared to those with other psychiatric disorders. [Kamperman et al., 2017]; [Johannsen et al., 2016]
In the UK, maternal deaths by suicide are a leading cause of mortality. [Knight, 2019]
The depressive profile was most common but can easily remain undetected, leading to treatment delay and risk of suicide/infanticide.
Affective symptoms such as anxiety, irritability and agitation are particularly prevalent in postpartum psychiatric episodes compared to non-postpartum episodes and may be linked to endocrine changes postpartum. [Kamperman et al., 2017]
Considering the nature of the illness based on past history is essential to avoid underdiagnosis or misdiagnosis of underlying psychopathology, particularly depression or obsessive-compulsive disorder as postpartum psychosis.
Bergink et al. classified the clinical presentations as [Bergink et al., 2016],
- Mania or mixed episodes (with or without psychotic features): Symptoms may be atypical than in patients with bipolar disorder.
- Depressive episodes with psychotic features
- Non-affective psychotic episodes (occurring in 10% of cases).
Differential diagnoses in PPP:
Obsessive thoughts:
There is evidence of an increased risk of onset and flare of OCD during times of reproductive transition. It is important to distinguish between the frightening intrusive thoughts common in OCD (obsessions) and the delusions characterising PPP. [Osborne, 2018]
Homicidal thoughts and filicide:
- Obsessive thoughts about harming the baby can occur, which should be differentiated from homicidal thoughts.
- Brockington found that the filicide rate was more than 5-fold higher in women with psychotic depression compared to those with psychosis alone. The filicide rate is high in depressive psychoses (4.5 %) but lower in episodes without overt depression (less than 1 %), and some of these appear accidental, without intent to kill. [Brockington, 2017]
- Significant risk factors for filicide included postpartum-onset depression, psychotic symptoms, “powerlessness, poverty and alienation”, and non-altruistic motivation for filicide. [Sharma et al., 2022], [Friedman & Sorrentino, 2012]
- The use of antidepressants without concomitant mood stabiliser therapy can increase the risk of filicidal acts by mothers with latent or misdiagnosed bipolar disorder. [Sharma et al., 2022]
- All mothers should be asked about thoughts of harming the baby in a non-judgmental way.
Suicide:
- Suicide is rare during the acute episode, but the rate is high later in the mother’s life and first-degree relatives. [Brockington, 2017]
- Women with the onset of bipolar disorder in the form of a depressive episode postpartum have fewer lifetime depressive episodes and fewer suicide attempts than women with a non-postpartum onset. [Tebeka et al., 2021]
The article by Brockington describes several cases of filicide and suicide.
Medical causes should be ruled out.
- Neurological symptoms, including seizures, decreased consciousness, dyskinesia, overt motor symptoms, and extrapyramidal symptoms, raise the index of suspicion for anti-NMDAR encephalitis or flares of autoimmune conditions such as Lupus. [Read more on neuropsychiatric manifestations of autoimmune disorders]
- Thyroid autoimmune diseases occur in up to 20% of women with postpartum psychosis. Women with thyroid peroxidase antibodies (TPOAb) positivity are at the highest risk of thyroid dysfunction and should be monitored. As there is a well-known postpartum rebound of TPOAb during the first months postpartum, an initial negative screen immediately postpartum does not rule out thyroid disease. Hence, measuring thyroid-stimulating hormone, free T4, and thyroid peroxidase antibodies both at the time of diagnosis and a few months later is recommended. [Bergink et al., 2016]
- Late-onset inborn errors of metabolism can present with clinical features similar to postpartum psychosis. Serum ammonia will help in identifying urea cycle disorder.
NOSOLOGY - DSM AND ICD CLASSIFICATION
Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium”, “with onset in the first six months of delivery,” and only episodes “not classified elsewhere. [WHO, 2012]
DSM-5 definition:
Episodes are usually severe episodes of mood illness, denoted with a peripartum specifier if onset occurs in pregnancy or within 4 weeks of delivery. [APA, 2013]
SUGGESTED DIAGNOSTIC ALGORITHM
MANAGEMENT OF POSTPARTUM PSYCHOSIS
Postpartum psychosis is a psychiatric emergency and preferably requires inpatient hospitalisation. The ideal setting is a mother-baby unit.
This may not be possible in many places; thus, the clinician must create a setting that ensures close monitoring of the patient and involves the family.
Pharmacological treatment:
- The choice of the medication should depend on the underlying psychiatric disorder, response to past trials of drugs, safety issues and side effect profile.
- Identifying the underlying nature of the illness based on psychopathology provides a nuanced approach to treatment. e.g. use of a typical neuroleptic such as haloperidol might worsen depression in patients with a mood disorder. Similarly, lithium may not be effective in patients with mixed episodes or a rapid cycling variant of bipolar disorder. [Sharma et al., 2022]
- Antidepressants should be avoided in women with psychotic depression. However, they may be effective in women with obsessive-compulsive disorder with delusional beliefs. [Bergink et al., 2015]
- The main pharmacological agents used are benzodiazepines, antipsychotics and lithium. [Bergink et al., 2015]
Benzodiazepines:
- The initial period of benzodiazepine monotherapy evaluates whether sleep restoration results in the clinical remission of manic and psychotic symptoms, as insomnia is strongly associated with postpartum psychosis.
- Lorazepam 0.5 – 1.5 mg nocte for 3 days
- Limited use of short half-life benzodiazepine agents to promote sleep is preferred during the postpartum period, while chronic use of benzodiazepines during breastfeeding may result in infant sedation.
Antipsychotics:
- Antipsychotics are recommended for the acute treatment of manic and psychotic symptoms.
- In one study, antipsychotic monotherapy was efficacious in 20% of women within 2 weeks, after which non-remitted women were treated with lithium. [Bergink et al., 2015]
- Lithium is highly beneficial for acute treatment when given together with antipsychotics.
- Infant doses of olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole received through breast milk have been estimated to be less than 5% of the maternal dose. [Wisner et al., 2016]
Lithium:
- Lithium is highly efficacious for the acute and maintenance treatment of postpartum psychosis.
- Some recommend lithium as the first choice in the acute phase of illness at a target level of 0.8-1.2 (unless there are specific contraindications). [Bergink et al., 2016]
- Lithium maintenance treatment during the first 6–9 months postpartum is recommended (target blood level 0.6–0.8). Gradually tapering off lithium can be considered in women who have only postpartum episodes and who remain in complete clinical remission during a time of low psychosocial stress.
- The Lithium infant to maternal concentrations ranges from 5% to 65%, with the infant level typically about 25% of the maternal level. [Viguera et al., 2007], [Chaudron & Jefferson, 2000]
- Highly effective treatment option in patients with severe catatonic features.
- It is indicated for treating postpartum depression with psychotic features due to the relatively longer median duration of illness compared with postpartum mania.
- The choice between pharmacotherapy and ECT should be made in consultation with the patient, particularly about their preference for breastfeeding.
The 4 step Approach:
The 4 step approach was used in a study for acute and maintenance treatment of patients hospitalised four weeks after delivery for the first onset of psychosis. [Bergink et al., 2015]
Results:
- 98.4% of patients achieved complete remission within the first three steps.
- None of the patients required ECT.
- At 9 months postpartum, sustained remission was observed in 79.7%.
- Patients treated with lithium had a significantly lower relapse rate than those treated with antipsychotic monotherapy.
However, it is important to recognise that this was a naturalistic study, and none of the patients had a previous history of psychiatric illness.
Principles in Breastfeeding:
- Provide breastfeeding support
- Monitor the infant for signs of toxicity (poor suck intensity, decreased feeding, lethargy)
- Be aware of situations that elevate the risk for infant dehydration (reduced feeding/oral intake, excessive fluid loss, or fever)
- Have access to a neonatologist or paediatrician who can monitor the infant.
Non-pharmacological approaches: [Osborne, 2018]
- Blue-light-blocking glasses. [Henriksen et al., 2016]
- Sleep hygiene interventions
- Support for the other parent, if any.
- Specific feedback is designed to improve the mother-baby interaction.
- Video feedback, individual interventions by nursing staff, or baby massage.
PREVENTION AND MONITORING OF HIGH RISK PATIENTS
A meta-analysis demonstrated that patients with either a history of affective psychosis in the postpartum period or bipolar disorder are at high risk for postpartum relapse. [Wesseloo et al., 2016]
- Overall relapse risk of 35%.
- Overall relapse risk of 37% in women with bipolar disorder, with 17% presenting with affective psychosis, mania, mixed episodes, or relapses requiring hospitalisation.
- The overall relapse rate in women with a history of postpartum psychosis was 31%
- Patients with a history of postpartum psychosis were more likely to have severe postpartum relapse episodes than patients with bipolar disorder.
- In women with bipolar disorder, postpartum relapse rates were significantly higher among those who were medication-free during pregnancy (66%) than those who used prophylactic medication (23%).
Women with postpartum psychosis usually have one of two disease courses:
- Isolated postpartum psychosis (vulnerability to affective psychosis only after birth)
- Postpartum psychosis as an expression of bipolar mood disorder with non-perinatal episodes.
- First-onset nonpsychotic postpartum affective disorder can be a marker of underlying bipolarity. [Liu et al., 2017]
- One study showed that 54% of patients diagnosed with postpartum depression were rediagnosed as having a lifetime diagnosis of bipolar disorder. [Sharma et al., 2008]
-
Additionally, 14% of depressed women who had initial psychiatric contact during the first postpartum month converted to a bipolar diagnosis within 15 years, compared with 4% with a first psychiatric contact unrelated to childbirth. [Munk-Olsen et al., 2012]
- Recognition of bipolar disorder postpartum is important to avoid misdiagnosis of bipolar disorder or mixed affective states as a unipolar disorder.
- Missing bipolar disorder can have severe consequences, such as ineffective treatment strategies, delayed referral to specialised psychiatric care, and underestimation of relapse risks after subsequent pregnancies.
- Women with mixed symptoms in the postpartum period are also at greater risk of developing thoughts of self-harm.
- The strongest predictor for developing severe manic and psychotic episodes during the postpartum period, both considered psychiatric emergencies, is a history of bipolar I or II disorder. [Sharma et al., 2017]
Risk of antidepressant use in Bipolar disorder/ diathesis: [Sharma et al., 2017]
- The emergence of mixed states
- Increased cycling
- Risk of Postpartum psychosis
Clinical features that point to a mixed state or bipolar diathesis in women with postnatal depression: [Sharma et al., 2017],[Sharma et al., 2009],[Pope et al., 2014]
- Early onset of depression (within 2 weeks of delivery)
- Characteristic clinical profile—less anger, less self-rated emotion, and more animation.
- Symptoms such as racing thoughts, hypersomnia, mixed features, psychotic symptoms and atypical depressive features
- Younger age at illness onset
- First onset of depression after childbirth
- Mixed features
- History of Bipolar Disorder in first-degree family members.
- History of an antidepressant rapid response
- History of antidepressant loss of response
- Antidepressant-induced hypomania, mania or depressive mixed episodes
- Treatment resistance to antidepressants
Recommendations:
1. Preconception counselling and regular psychiatric care should be recommended for women with or at risk of developing bipolar disorder or postpartum psychosis.
2. Antenatal assessment should include questions about personal and family history of bipolar disorder and postpartum psychosis.
3. An obstetric birth plan, including preference regarding the mode of delivery
4. Collateral information from a family member
- Helpful in the detection of symptoms of an impending mood or psychotic episode. Clinicians should be particularly vigilant about recognising the prepartum/prodromal onset of PPP in the form of euphoria, decreased sleep requirement or inability to sleep, feeling active or energetic, and talkativeness and worsening of these symptoms postpartum.
5. Screening of all women with current depressive symptoms for bipolar disorder in pregnancy and the postpartum period. [Yatham et al., 2018]
- Edinburgh Postnatal Depression Scale (EPDS) cannot distinguish between unipolar and bipolar depression and cannot assess for symptoms of psychosis.
- The Mood Disorder Questionnaire is a valid screening tool for bipolar disorder during and after pregnancy.
- Bipolar at-risk (BAR) criteria or the Bipolar Prodrome Symptom Interview and Scale-Prospective can identify women at risk of transitioning to bipolar disorder after childbirth. [Not validated in perinatal population]
6. Inform women receiving antidepressants for major depressive disorder with the postpartum onset of the risk of mood instability, even when there is no prior history of antidepressant-induced hypomania. A trial of quetiapine in a low dose should be considered in women presenting with mixed depression in the postpartum period. [Sharma, 2018]
7. Close monitoring: [Sharma et al., 2022]
- Women with a history of first-onset of depression in the postpartum period, early psychiatric contact (within the first 4 weeks of delivery), mixed depression, frequent mood episode or a history of bipolar disorder or postpartum psychosis in a first-degree family member should be monitored closely for emerging symptoms of hypo/mania or psychosis.
- Women with bipolar I disorder and schizoaffective disorder, bipolar type are at a particularly high risk of having a psychotic episode after delivery.
8. Medication Prophylaxis: [Bergink et al., 2016]
- Risk-benefit analysis
Women with bipolar disorder: Consider continuation of medication as prophylaxis during pregnancy increases the likelihood of maintaining mood stability during pregnancy and preventing postpartum relapse.
- Lithium shows the best evidence for prophylaxis.
- Data on lamotrigine, olanzapine, quetiapine, and risperidone are scarce.
Women with isolated postpartum psychosis episode:
- Begin prophylactic treatment immediately after birth, limited to the postpartum period.
9. Neonatal medical evaluation for children with in utero medication exposure
10. Discuss preferences for baby feeding
11. Support for mother:
- Strategies to obtain adequate sleep and maintain a stable circadian rhythm
- Strategies to limit their stress
- Involve family support
- Facilitate mother-infant bonding
SUMMARY
Postpartum psychosis (PPP) is a psychiatric emergency associated with risks to mother and baby.
PPP is a critical marker for the risk of developing future affective disorders. This poses significant global public health, mental health and economic risks.
Childbirth is known to be a powerful trigger for many mood disorders. Those with a history of bipolar disorder or postpartum psychosis are at particularly high risk. However, postpartum psychosis can occur in up to 40% of women with no previous psychiatric diagnosis.
Postpartum psychosis usually begins during the first two weeks after childbirth and is characterised by bizarre thoughts and behaviour, alterations of consciousness, and mood fluctuation.
Management includes pharmacological and non-pharmacological strategies. The article covers a 4 step approach with a high response rate.
Though significant progress has been made in identifying pathogenic factors in postnatal psychosis, including hormones, immune dysregulation, circadian rhythm disruption and genetics, key points for future research include:
- Further examination of the nosology (classification) of postpartum psychosis to ensure accurate recording and correct clinical classifications such as those found in diagnostic manuals.
- Future genome-wide studies (GWAS) with cohorts of women with a history of narrowly defined postpartum psychosis (i.e., those with a history of mania or psychosis with onset soon after childbirth).
- Prospective studies of pregnant women at high risk should be conducted to pinpoint the exact aetiological and triggering factors for postpartum psychosis. Different and novel methodological approaches should be considered, and international collaboration may mitigate small sample sizes.
- All available data should be comprehensively combined to develop effective predictive risk models for postpartum psychosis.