A Review of Post Partum Psychosis

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JOURNAL OF WOMENS HEALTHVolume 15, Number 4, 2006 Mary Ann Liebert, Inc.

A Review of Postpartum Psychosis

DOROTHY SIT, M.D.,1 ANTHONY J. ROTHSCHILD, M.D.,2

and KATHERINE L. WISNER, M.D., M.S.1

ABSTRACT

Objective: The objective is to provide an overview of the clinical features, prognosis, differ-ential diagnosis, evaluation, and treatment of postpartum psychosis.Methods: The authors searched Medline (19662005), PsycInfo (19742005), Toxnet, and

PubMed databases using the key words postpartum psychosis, depression, bipolar disorder,schizophrenia, organic psychosis, pharmacotherapy, psychotherapy, and electroconvulsivetherapy. A clinical case is used to facilitate the discussion.Results: The onset of puerperal psychosis occurs in the first 14 weeks after childbirth. The

data suggest that postpartum psychosis is an overt presentation of bipolar disorder that istimed to coincide with tremendous hormonal shifts after delivery. The patient develops frankpsychosis, cognitive impairment, and grossly disorganized behavior that represent a completechange from previous functioning. These perturbations, in combination with lapsed insightinto her illness and symptoms, can lead to devastating consequences in which the safety and

well-being of the affected mother and her offspring are jeopardized. Therefore, careful andrepeated assessment of the mothers symptoms, safety, and functional capacity is imperative.Treatment is dictated by the underlying diagnosis, bipolar disorder, and guided by the symp-tom acuity, patients response to past treatments, drug tolerability, and breastfeeding prefer-ence. The somatic therapies include antimanic agents, atypical antipsychotic medications, andECT. Estrogen prophylaxis remains purely investigational.Conclusions: The rapid and accurate diagnosis of postpartum psychosis is essential to ex-

pedite appropriate treatment and to allow for quick, full recovery, prevention of futureepisodes, and reduction of risk to the mother and her children and family.

CASE HISTORY

MS. A. IS A 27-YEAR-OLD PHYSICIAN who deliv-ered her baby 7 days before evaluation at

a teaching hospital. She underwent an uncom-plicated delivery, and her baby boy was full term

and healthy. This was a planned pregnancy, andthe family was excited about the birth. Within 2

days of delivery, she told her husband that shethought he was poisoning her food and that the

baby was staring at her strangely. She thoughtshe smelled horses and heard them galloping out-

1University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania.2University of Massachusetts Medical School, Worcester, Massachusetts.D.S. is funded in part by the National Alliance on Research for Schizophrenia and Depression (NARSAD) 2002

Young Investigator Award.

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side her bedroom. She could not fall asleep evenwhen her mother came to the house to care fortheir newborn and allow the patient to rest. Athome, Ms. A. was able to sleep only 23 hoursnightly. Her husband noticed that she wouldgaze out the windows in their apartment forhours without explanation. She had not bathed

for 6 days. She required much help in simpletasks, such as diapering her baby. She expressedguilt about being a terrible mother and felt shedid not deserve to have her family. She told herhusband that she heard voices commanding herto go with her infant son to the subway and jumpin front of the train; these hallucinations terrifiedher and became stronger after she returned homefrom the hospital. The husband became very con-cerned and brought his wife to the emergencyroom.

THE CLINICAL PROBLEM

Postpartum psychosis (PP) occurs in 12/1000childbearing women within the first 24 weeksafter delivery.17 The onset of PP is rapid.8 Asearly as 23 days after childbirth, the patient de-velops paranoid, grandiose, or bizarre delusions,mood swings, confused thinking, and grossly dis-organized behavior that represent a dramaticchange from her previous functioning. PP is farless common than postpartum depression whichaffects 10%13% of new mothers,9 and the ma-ternity blues, which affects 50%75% of postpar-tum women.10 However, the combination offrank psychosis and lapsed insight and judgmentin PP can lead to devastating consequences inwhich the safety and well-being of the affectedmother and her offspring are jeopardized.11

Therefore, it is critical to quickly identify andtreat the symptomatic patient.

Although the Diagnostic and Statistical Manualof Mental Disorders, 4th ed. (DSM-IV),12,13 allowsfor classification of PP as a severe form of majordepression or the onset/recurrence of a primary

psychotic disorder, such as schizophrenia, thepreponderance of data suggests that PP is anovert presentation of bipolar disorder after de-livery.14 Among patients who develop PP imme-diately after childbirth, 72%88% have bipolarillness or schizoaffective disorder, wheras only12% have schizophrenia.15,16 Puerperal hormoneshifts,17 obstetrical complications,18,19 sleep de-privation,20 and increased environmental stress

are possible contributing factors to the onset ofillness.

The intention of this paper is to inform physi-cians and health professionals about PP so theywill be able to recognize the symptoms, medicallyevaluate and appropriately (and expeditiously)refer the patient for psychiatric intervention, and

educate the patient and her family about this ill-ness.

CLINICAL ASPECTS OF PP

Clinical features

Brockington15 described the classic picture of amother with PP: . . . an odd affect, withdrawn,distracted by auditory hallucinations, incompe-tent, confused, catatonic; or alternatively, elated,

labile, rambling in speech, agitated or excessivelyactive.15 The womans strange beliefs may focuson childbirth themes and concern for the babysaltered identity or a sense of persecution from the

baby/changeling.15 Wisner et al.11 reported thatwomen with childbearing-related onset of psy-chosis frequently experienced cognitive disorga-nization and unusual psychotic symptoms. Thesewere often mood-incongruent delusions of refer-ence, persecution, jealousy, and grandiosity,4,6,11

along with visual, tactile, or olfactory hallucina-tions that suggest an organic syndrome.12 Themean age of onset in PP is 26.3 years,21,22 whichis a time when most women are having their firstor second child.23 Compared with women withchronic mental illness, patients with PP usuallyhave attained higher functional levels before theonset of illness.

The baseline risk for PP is 1:500; however, therisk rises to 1:7 for women with even one pastepisode of PP.1 In fact, women with bipolardisorder or schizoaffective disorder have a 50%risk for another episode of PP.15,2427 Jones andCraddock27 found that PP affected 74% of moth-ers with bipolar disorder and a first-degree rela-

tive who had PP, compared with only 30% ofbipolar women without any family history of PP.Patients who stop their mood stabilizer treatment,specifically lithium, are much more likely to ex-perience a recurrence of bipolar disorder or PP af-ter childbirth compared with those who remainon antimanic treatment (70% and 24%, respec-tively).28 The mothers who cease antimanic treat-ment suddenly have an added risk for relapse.

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Sleep loss, such environmental stressors as mari-tal discord, and the precipitous drop in hormonelevels that occurs shortly after childbirth are otherfactors linked to PP.20,29 Primiparity, socioeco-nomic status, and ethnicity are less compellingrisk factors.2,21,3032 Therefore, physicians mustwatch carefully for the emergence of symptoms

suggestive of PP in new mothers with bipolar ill-ness and in those women with a personal or fam-ily history of PP (Tables 1 and 2).

In the first year after childbirth, suicide risk in-creases 70-fold, and suicide is the leading causeof maternal death up to 1 year after delivery.42 Of1000 women with PP, 2 complete suicide.42 Thesewomen often used more irreversible and aggres-sive means (self-incineration, jumping fromheights) compared with most reports that indi-cate women generally complete suicide nonvio-lently (overdose).43 Therefore, it is critical that

physicians and health professionals gauge thesafety of their patient by inquiring about suicidalideationthoughts of dying, feelings of life notworth living, active plans to take her life, accessto weapons, and past suicide attempts. Suicidalideation must be taken seriously, and patientswith recent or active suicidal plans should be re-ferred to an emergency setting.

Homicidal behavior rarely occurs in PP.11,39,44,45

Among women hospitalized for PP, 28%35% de-scribed delusions about their infants, but only 9%had thoughts of harming the infant.7 Women with

PP, however, are more likely to express homici-dal ideation than women with nonpsychoticchildbirth-onset illness, such as postpartum de-pression.11 The cognitive disorganization that oc-curs with PP may result in a mothers neglect ofher infants needs and unsafe practices.7,46 It is im-portant to ask the patient with PP about homici-dal thoughts or plans and to enlist the help of psy-chiatric and social service supports to preventharm to herself or other family members.47,48 In-fanticide and neonaticide are separate and distin-guishable entities. Spinelli49 investigated 16 casesof neonaticide and found the women sufferedfrom dissociative symptoms. These patients de-nied their pregnancy and the pain of childbirth;they often experienced dissociative hallucina-tions, brief amnesia, and depersonalization. Themothers may avoid all antenatal obstetrical visits,deliver at home without any medical attention,and abandon the newborn after giving birth.Neonaticide is more difficult to prevent, as it in-volves denial of pregnancy.

Prognosis

Longitudinal data indicate a good prognosisfor most women who experienced PP arisingfrom bipolar illness; 75%86% remained symp-tom free after a single episode of PP.33,50 For wo-men with schizophrenia, 50% remain well afterone episode of PP, 33% have recurrent PP, and5% have a refractory illness with numerous puer-peral and nonpuerperal recurrences.33 Womenwho sought help within 1 month of delivery hadmore favorable outcomes and were less likely tosuffer long-term disability than women with late-onset PP, that is, after 1 month postpartum (13%and 33%, respectively).25,51 Compared with wo-men with new onset of non-PP, the patients withfirst episode PP had higher levels of confusionand disorientation but required only half the timeto achieve treatment response40 (Table 1).

In summary, the defining characteristic of PP

is an illness that occurs shortly after childbirth.PP is marked by symptoms of mood lability, cog-nitive disorganization, delusional beliefs, andhallucinations that resemble a clinical picture ofdelirium but is most likely an overt presentationof bipolar illness. Predictors of recurrence includea personal or family history of PP, bipolar disor-der, and cessation of antimanic treatment. Allpatients should be asked about the presence ofsuicidal and homicidal symptoms. The overallprognosis is positive, especially when symptomsemerge 1 month postdelivery.

SCREENING FOR PP

The woman with known bipolar disorder anda personal or family history of PP is at sub-stantial risk for PP. She and her family should

be informed of the symptoms to recognize, thatis, mood swings, confusion, strange beliefs, andhallucinations, especially in the first 24 weekspostchildbirth, and to contact her physician ifthese symptoms arise. Even before delivery, theat-risk patient is encouraged to consult with apsychiatrist to help her consider treatment op-tions or treatment prophylaxis at delivery toavoid illness.14 Physicians are strongly urged toask about symptoms of PP in the high-risk pa-tient at her 6-week obstetrical follow-up visit. TheEdinburgh Postnatal Depression Scale (EPDS)52

and the Mood Disorder Questionnaire (MDQ)53

are useful tools to screen for depression and

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TABLE 1. SUMMARY OF FOLLOW-UP STUDIES

Sample size and Follow-upAuthor description period (years) Findings

Protheroe, 196933 134 35 Average age at admission, 28.3 yearsPrimiparous, 63%Incidence:

Affective psychosis, 68%Schizophrenia, 28%Organic, 4/5%

Recurrence:Affective psychosis, 33%Schizophrenia, 50%Organic, 4.5%

PPa recurrence frequency, 33%Both PP and non-PP recurrence, 5%

Kadrmas et al., 157, with age- 3.45.9 PP associated with greater frequency197934 matched controls of psychosis; less non-PP

recurrences than controlsPlatz and Kendell, 72 matched pairs, 9 PP, fewer relapses, fewer suicides,

198835 women with less hospitalizations, shorternonpuerperal inpatient staysillness

Benvenuti et al., 30, no controls 418 63% relapse rate of PP199236 76% affective disorder (DSM III-R)

24% brief reactive psychosis orschizoaffective disorderNo schizophrenia

Videbech and 50 714 Bipolar illness: incidence40% of allGouliaev, PP cases (50% had depression)199532 Non-PP recurrences in 50%

60% readmission rateSchizophreniform disorder: incidence

12%Functional outcomes:

Early onset PP (1 month), 13% ondisability insurance

Late onset PP (1 month), 33% ondisability

Hunt and 36 bipolar 2 Rate of affective episodes at 3Silverstone, women with PP; months after childbirth: 28%199537 22 bipolar women, 14% men

women non-PP First episode bipolar disorder inacute episode; puerperium: 33% women, 0% men28 bipolar men Rate of PP in primiparous, 65%with acute Rate of PP in multiparous, 37%episode Relapse rate of bipolar disorder in

puerperium: 25%40%Pfuhlmann et al., 39 12 Unipolar psychotic depression, 28%

199938 Acute transient psychosis, 21%Cycloid psychosis (bipolar illness),

54%Pregnancy or puerperal relapse

rate, 50%Nonpuerperal relapse rate, 11%Suicide rate, 4%

Robling et al., 64 23 Unipolar psychotic depression, 55%200025 Bipolar disorder, 30%

Schizophrenia/schizoaffective/otherprimary psychosis, 11%

Recurrence rate of PP, 75%: 38% 3relapses; 29% puerperal onsetrelapses

Lower relapse rates associated withprimiparity, PP onset 1 monthafter delivery, unipolar depression

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mania/hypomania. The EPDS is a self-ratinginstrument that uncovers the presence of persis-tent low mood, anhedonia, guilt, anxiety, andthoughts of self-harm. The MDQ explores for pastand current symptoms of high, hyper or irritablemood, excess energy, racing thoughts, pressuredspeech, and symptoms that are linked with ma-nia/hypomania. When the patient reports confu-sion, threats to harm herself or others, difficultycaring for her children, or poor self-care, thephysician must consider these as red flags andarrange a psychiatric referral quickly.

EVALUATION AND DIFFERENTIALDIAGNOSIS

PP is considered an emergency that necessitatesan urgent evaluation, psychiatric referral, and pos-sible hospitalization.54 The initial evaluation re-quires a thorough history, physical examination,and laboratory investigations to exclude an or-ganic cause for acute psychosis (Table 3). Impor-tant tests include a complete blood count (CBC),electrolytes, blood urea nitrogen (BUN), creati-

nine, glucose, vitamin B12, folate, thyroid functiontests, calcium, urinalysis and urine culture in thepatient with fever, and a urine drug screen. A care-ful neurological assessment is essential; this in-cludes a head CT or MRI scan to rule out the pres-ence of a stroke related to ischemia (vascularocclusion) or hemorrhage (uncontrolled hyperten-sion, ruptured arteriovenous malformation, oraneurysm).55 The stroke patient is differentiated

from the patient with PP by a history of hyper-tension or preeclampsia, evidence of fluid/elec-trolyte imbalance, and complaints of severeheadache, unilateral weakness, sensory deficits,and even seizures with the neurological event.56

The primary psychiatric diagnosis to considerwith the case of early-onset PP is bipolar disorder.Wisner et al.16 found that 95% of PP cases fulfilledResearch Diagnostic Criteria (RDC) for cyclicmood disorders at 5-year follow-up. Of thesecases, 50% were misdiagnosed at first presenta-tion. Other studies replicated this finding and in-dicated a high likelihood of a primary cyclic moodillness (43%66%).3,8,21,57 This is not surprising, asPP and bipolar psychosis or mixed episodes sharecommon symptoms of elation, dysphoria, moodlability, confusion, and heightened sensitivity tosleep deprivation.4,6,8,11,20,31,5861 Women with apast or family history of bipolar illness are morelikely to have BD that precipitates an episode ofPP. These patients require antimanic drug treat-ment. Choices include lithium, such antiepilepticdrugs as valproate or carbamazepine, and atypi-cal antipsychotic medication, such as olanzapine,quetiapine, ziprasidone and the newer agent,

aripiprazole.Patients with PP are differentiated from those

with unipolar major depression by the presence ofcognitive disturbance, delusional beliefs, and dis-organized behavior. However, women with a pasthistory of unipolar psychotic depression can re-lapse shortly after delivery with an episode ofPP.4,30,31,62 These patients often report low mood,distraught feelings about their inability to enjoy

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TABLE 1. SUMMARY OF FOLLOW-UP STUDIES (CONTINUED)


Davidson and 82 11.7 Unipolar psychotic depression, 52%Robertson, Bipolar disorder, 18%198539 Schizophrenia, 16%

Personality disorder and depression,

8%Organic disorder, 2%

Rohde and 86 26 Schizoaffective disorder, 49%Marneros, Schizophrenia, 28%199321 Affective disorder, 13%

Functional disability in 33% of studypopulation

Kirpinar et al., 64 matched pairs 11 Schizophrenia, 40%199940 Schizoaffective disorder, 11%

Bipolar illness, 20%Unipolar depression, 20%

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TABLE 2. SUMMARY OF FAMILY STUDIES


Protheroe, 196933 134 35 Morbidity risks for PPa:both siblings and parents, 11.7%;

98 probands siblings, 8.9%; parents, 14.7%with family

Morbidity risk for family of bipolarpatients, 10%15%

119 parents andsiblings enrolled Morbidity risk for schizophrenia in

siblings and parents of PPprobands, 10.4% (similar to risk forfirst-degree relatives ofschizophrenia patients)

Reich and 35 females, 1317 Morbidity risk for affective disorderWinokur, 29 first-degree in first-degree relatives, 23.5%197041 relatives Morbidity risk for affective disorder

in first-degree relatives, 34.7%PP recurrence in proband, 50%PP recurrence in first-degree

relatives, 30%

Kadrmas et al., 157 relatives of 3.45.9 Affectively ill first-degree relatives:197934 bipolar PP women, 19%women with Matched controls, 38%PP, 136 age- Female manic group, 36%matchedcontrolrelatives ofpatients withnonpuerperal

bipolar maniaPlatz and Kendell, 72, with matched 9 Morbidity risk for unipolar

198835 controls depression in first-degree relatives:PP, 7.7%; control, 12.2%

Morbidity risk for bipolar disorderin first-degree relatives: PP, 1.6%;

control, 3.4%Morbidity risk for puerperal disorderin first-degree relatives: PP, 4.9%;control, 4.2%

Morbidity risk for admission in first-degree relatives: PP, 9.3%; control,15.9%

Dean et al., 198924 51 puerperal-only 8.9 Mood disorder in 60% first-degree33 puerperal and relatives

non-PP episodes Significantly more first-degree19 bipolar and relatives of PP-only and both PP

only non-PP and non-PP groups receivedepisodes psychiatric treatment than bipolar

group10-fold risk for PP in first-degree

relatives of PP-only group

Jones and 152 women with Not PP occurred in 26% women with BD ICraddock, BD I or S-affective stated or schizoaffective disorder bipolar200127 disorder bipolar type

type (313 births)PP occurred in 57% women with

BD I and family history of PP

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their new baby, psychomotor slowing or pacingbehaviors, anxiety, fatigue, poor concentration,and preoccupations with strange ideas and suspi-cions.6365 Without intervention, they are at risk for

worsening symptoms, treatment resistance, andmortality.63,65,66 These patients respond best to acombination of antidepressant and antipsychoticdrug treatment or electroconvulsive therapy.

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TABLE 3. SUMMARY OF DIFFERENTIAL DIAGNOSIS AND EVALUATION OF PP

Differential diagnosis Evaluation and laboratory tests

Psychiatric disordersBipolar I disorder (BD I): Manic or mixed or Careful exploration of present and past: mood

depressed episode with psychotic features, symptoms, low mood and high or irritable moods;postpartum onset unusual beliefs, suspiciousness, grandiosity;

obsessive-compulsive symptoms; suicidality and

Unipolar major depression with psychotic features thoughts to harm others

Schizophrenia, single episode or schizophreniform Past treatment response and recent history ofdisorder (first episode psychosis) stopping medications

Family history of mood disorder or PPa

Obsessive-compulsive disorder (unlikely)Medical or organic causes

Cerebrovascular Careful medical history, with history of severeIschemic stroke (arterial or venous) secondary headache, preeclampsia during pregnancy,

to preeclampsia or eclampsia, severe unilateral weakness, new onset sensory deficits,hemorrhage during delivery seizurelike behaviors; check blood pressure;

Hemorrhagic stroke secondary to uncontrolled consider head CT or MRI; consult neurologisthypertension, arteriovenous malformation, urgentlyaneurysm, disseminated intravascularcoagulation

Normal pressure hydrocephalusMetabolic or nutritional Serum electrolytes

Hyponatremia or hypernatremiaHypoglycemia or diabetic ketoacidosis Fasting blood glucose, HbA1C in patient with insulin-

dependent diabetes, type II diabetes, glucoseintolerance during pregnancy

Uremic encephalopathy BUN, creatinine in patients with history of renaldysfunction

Hepatic failure Liver function tests in patients with history of hepatitisor known liver disease; AST, ALT, alkalinephosphatase, LDH, bilirubin (direct and indirect),lipase

Graves disease (hyperthyroidism) or myxedema Thyroid function tests, total T4, T3, thyroid reuptake,(hypothyroidism) TSH

Parathyroid disease (hypercalcemia/hypocalcemia) Serum calcium levels

Vitamin B12, folate deficiency Serum B12, RBC folate levelsThiamine deficiency Thiamine levelsMedications Medical history; consider urine drug screen

CorticosteroidsNarcotics: meperidine (Demerol)Sympathomimetics: amphetamine, theophylline,

ephedrine, phenylephrineAntibiotics: gentamicin, sulfonamides, isoniazid,

metronidazole, vancomycinAnticholinergics: atropine, benztropine,

diphenhydramine, eye/nose dropsAntivirals: acyclovir, interferonBenzodiazepines and barbiturates

Immunological Medical and family history, ESR; rheumatologySystemic lupus erythematosus consultation

Infectious Complete blood count and differential, electrolytes,Sepsis BUN, creatinineMeningitis or encephalitis Possible lumbar puncture or CT of headHIV Serum HIV test

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PP must be distinguished from obsessive-com-pulsive (OC) symptoms and obsessive-compulsivedisorder (OCD). OC symptoms and OCD are char-acterized by intrusive thoughts and compulsive, ir-resistible behaviors. Intrusive thoughts often cen-ter on themes of contamination, causing harm totheir children, offensive violent or sexual images,

religious preoccupations, and urges for symme-try.67 The compulsions include urges to clean,check, repeat, order, and hoard and such mentalrituals as counting. Women with postpartum de-pression commonly experience comorbid OC cog-nitions (41%57%).6769 OC or OCD is differenti-ated from PP by the preservation of rational

judgment and reality testing; patients typically donot act on their aggressive thoughts. Rather, theyavoid objects or places that provoke anxiety andsuffer discomfort from their unwanted cognitions.This contrasts with patients with florid psychosis,

who are unable to discern reality, feel compelledto act on their delusional beliefs, and cannot assessthe consequences of their actions.70 First-line treat-ment for OCD includes serotonin reuptake in-hibitors (SRIs), with such agents as sertraline, flu-oxetine, and fluvoxamine; the gold-standard drugis clomipramine (which is both an SRI and a nor-epinephrine inhibitor). Most patients require phar-macotherapy in combination with cognitive be-havioral therapy. Patients with refractory illnessmay require augmentation with an atypical an-tipsychotic drug.

PP could be a presentation of a primary psy-chotic disorder, such as schizophrenia. Althoughwomen with known schizophrenia have a 25%risk for puerperal exacerbations,46,71 many stud-ies have indicated a low prevalence of schizo-phrenia in early-onset PP (3.4%4.5%).1 These pa-tients respond best to pharmacotherapy withatypical antipsychotic drugs; if the physician sus-pects the presence of comorbid depression, theaddition of an antidepressant medication ishighly recommended. Mothers with schizophre-nia also may suffer cognitive impairment. Thesewomen could benefit greatly by referral to in-home services for additional support and en-hancement of parenting skills.

TREATMENT OF PP

Psychoeducation and psychotherapy

Once the diagnosis has been established, thephysician should (1) educate the patient and herfamily about the illness, (2) rule out organic

causes, (3) initiate pharmacotherapy and sup-portive therapy, and (4) repeatedly assess the pa-tients function and safety status.72 Physicianswill contribute greatly by informing patients andtheir families about the symptoms, treatments,expected outcomes, and strategies to prevent re-currence of PP. The process of psychoeducation

is essential. It will enhance the therapeutic al-liance; furthermore, it will strengthen the pa-tients decision-making process about treatmentand her feelings of self-efficacy and mastery overillness.73,74

After stabilizing the patient and starting acutepharmacotherapy for PP, a careful discharge planmust be developed before the patient leaves thehospital. Referral to intensive outpatient therapy(or day program), along with closely spaced out-patient follow-up visits, is advisable for the firstseveral weeks after discharge. These measures

will facilitate the patients return home and allowthe physician or health professional to closelymonitor treatment response, address problemswith drug intolerance, and spot clinical worsen-ing early. Treatment plans work best when theyare individualized for each patient and includeinterventions that provided good response in thepast. Sleep loss is a major precipitant of maniaand PP. Physicians could encourage patients andtheir partners to enlist the help of other family orfriends or doula services to reduce the affectedmothers burden and allow her to regain sleep

and recover from illness. Patients and their fam-ilies should be advised to contact their physiciansquickly when symptoms recur.7577 At this point,the physician should explore the patients adher-ence to treatment and evidence of problematicside effects and consider a dose adjustment ormedication switch if necessary.

Supportive psychotherapy that begins priorto hospital discharge may incorporate parentingskills and early infant interventions to addressmaternal-infant bonding and infant develop-ment. In-home services could optimize bothmother and infant outcomes. Other psychother-apy options, such as family-focused therapy,cognitive behavioral therapy, or interpersonalpsychotherapy (IPT), are effective adjunctivetreatments for postpartum mood disorders.78 IPT,specifically, was adapted for women dealing withchildbearing-related events and is structured tohelp women who are facing losses, role changes,or relationship tensions. These advanced forms ofpsychotherapy are recommended once patientshave regained an organized level of thinking.



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Pharmacotherapy overview

Acute pharmacotherapy is essential to managethe psychotic and mood-related symptoms of PP.The medication options include atypical antipsy-chotic agents and mood stabilizer or antimanicagents, such as lithium or antiepileptic drugs(AED).51 Although monotherapy is preferable,certain women require more than one drug toachieve a desirable level of symptom control andillness remission.12,79 Women often reach higherserum levels and prolonged adverse effects fromfat-soluble drugs that have a high volume of dis-tribution and a long half-life. For better treatmentadherence, side effects can be minimized withlower starting doses that are titrated slowly to theresponse dose.

Breastfeeding

The mothers breastfeeding preference and theassociated benefits and risks must be considered

by the patient and her physician.80,81 The Amer-ican Academy of Pediatrics (AAP)82 has providedhelpful recommendations on breastfeeding andthe use of lithium or AED. It is imperative to in-form the pediatrician of the mothers choice to

breastfeed; this permits the pediatrician to ap-propriately monitor the clinical state of the breast-fed infant. Likewise, mothers must be instructedto observe for behavioral changes indicative of in-fant toxicity, such as poor hydration, sedation,

poor feeding, and weight gain, as well as signs ofhepatic and hematological impairment. Mothersshould be instructed to contact their pediatriciansimmediately when they notice these symptoms.80

Infant drug serum levels are not obtained rou-tinely in clinical practice, but breast milk expo-sure can be limited by (1) the use of the lowesteffective dose, (2) the use of fewer drugs toachieve response, and (3) dividing daily doses toavoid high peak serum concentrations.

Lithium treatment and prophylaxis

Lithium is an important treatment option forthe prevention and treatment of PP and a stan-dard treatment for bipolar disorder. Results fromsmall open trials suggest that women with pastPP have better outcomes when lithium treatment

begins immediately postdelivery.83 Lithium thatis started in the third trimester is more contro-versial. Retrospective reports and small case se-ries indicate a lower likelihood for early postpar-

tum relapse when treatment is resumed in thethird trimester.83,84 Unfortunately, one mothersuffered a stillbirth after agreeing to lithium pro-phylaxis before delivery.85 Among patients with

bipolar disorder, the recurrence risk is substan-tially higher for women who stop lithium com-pared with those who continue prophylactic

treatment (52%58% vs. 21%).28 If patients aretaking lithium, they should be discouraged fromabruptly discontinuing their medication. Toavoid the high relapse risk after delivery, bipolarpatients should be encouraged to resume treat-ment immediately after childbirth.

Physicians and health professionals are advisedto assess the renal and thyroid functions of patientswho require lithium treatment for symptoms ofPP. Drug levels and renal tests should berechecked after 5 days of starting treatment. Thetarget level of lithium is 0.41.0 mEq/L at 12 hours

postdose; drug levels should be tested every 612months after stabilization.82 Physicians shouldmonitor their patients for side effects, such as se-dation, tremor, renal dysfunction, weight gain,and nausea and vomiting. The window betweentherapeutic and toxic serum levels is narrow. Pa-tients must be instructed to avoid thiazides, non-steroidal anti-inflammatory agents, and angio-tensin-converting enzyme inhibitors that alterfluid balance and interfere with the renal excretionof lithium.86 Women with dehydration or sodium-depleting conditions are at particularly high risk

of lithium toxicity. Physicians must watch care-fully for symptoms of toxicity in women onlithium: excessive sedation, severe tremors, acuterenal dysfunction, and intractable vomiting. Toxi-city is confirmed by elevated drug levels. Lithiumtoxicity must be managed immediately by stop-ping the drug, fluid rehydration, and close moni-toring of electrolyte balance and renal function.

Although lithium is not commonly prescribedfor breastfeeding women, investigators havenoted that the avoidance is based on minimaldata from over two decades ago.80,87 The drugconcentrations in breastfed infants of mothers onlithium rise quickly to a toxic range in newbornsand young infants with feeding problems, fever,or other fluid-depleting conditions. Because thelithium levels of breastfeeding infants reach onethird to one half of the therapeutic blood con-centration, the AAP advises strict caution in

breastfeeding when taking lithium.87,88 If a pa-tient demands to breastfeed while on lithium, theprimary care physician is advised to seek con-

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sultation with a psychiatrist who is experiencedin managing perinatal psychiatric illnesses.

Antiepileptic drugs (AED)

Valproic acid (VPA) is an FDA-indicated drugfor bipolar illness. The starting dose is 500750

mg/day, and the dose is titrated according tosymptom response and serum drug levels. It isadvised to check levels within 1 week of initiat-ing VPA. Periodic monitoring of serum concen-tration, liver function, platelet count, glucose, andlipid profile is suggested with worsened side ef-fects, any dose adjustment, and at least onceyearly while maintained on a stable regimen.Therapeutic levels range from 50 to 125 g/mL;patients with higher levels have more side effects.Valproate levels are affected by enzyme-inducingAEDs, such as carbamazepine. Patients must be

observed closely to ensure therapeutic efficacy.Side effects include nausea, weight gain, tremor,ataxia, diarrhea, abdominal pain, alopecia, he-patitis, thrombocytopenia, and, rarely, pancreati-tis. Menstrual irregularity, anovulation, polycys-tic ovarian syndrome, and insulin resistance may

be associated with VPA.89

Carbamazepine (CBZ) is an FDA-indicateddrug for the treatment of mania. It is protein-

bound and induces hepatic cytochrome P450 3A4enzyme activity to triple its own clearance rate(and the metabolism of such drugs as oral con-traceptives) within 24 weeks of initiation. Ther-apeutic doses range between 400 and 1600mg/day. After starting CBZ, a blood test is nec-essary to verify a therapeutic level (412 g/mL)has been reached. Serum levels, liver functiontests, and a CBC are indicated two or three timesper year in symptomatic patients and at least onceyearly for patients on maintenance therapy. Sideeffects may include hepatitis, leukopenia, throm-

bocytopenia, rash, sedation, and ataxia. Treat-ment with CBZ and clozapine together is con-traindicated because bone marrow suppressionhas been reported with this combination.

The AAP Committee on Drugs88 views CBZand VPA as drugs that are compatible with

breastfeeding. Transient hepatic toxicity andcholestatic hepatitis90,91 may occur in neonatesexposed throughout pregnancy and breastfeed-ing. The infant of a woman who was treated dur-ing breastfeeding only developed a CBZ level15% and 20% of the total and free maternal lev-els, respectively.92 In a separate study of 6 moth-

ers who took VPA during breastfeeding only, themothers attained levels from 39 to 79 g/mL, andtheir infants serum levels were 0.71.5 g/mL.93

No adverse effects were described in the infants.The indicators of infant toxicity may include in-creased sedation, poor feeding, and signs of he-patic and hematological impairment.80

Other AEDs that are FDA approved for bipo-lar illness include oxcarbazepine for bipolar ma-nia and lamotrigine for maintenance therapy of

bipolar depression. The importance of a slowtitration of lamotrigine to avoid potentially toxicdermatological side effects implies that lamotrig-ine is less likely to be a first-line agent for man-aging PP. However, patients with an establisheddiagnosis of bipolar illness and good response tothese drugs could choose to continue or resumeeither drug if their symptoms recur or as pro-phylactic treatment in pregnancy or after deliv-

ery.Oxcarbazepine is prescribed in divided doses,with a dose range of 6001200 mg/day. In the liver,it inhibits the enzymes, CYP2C19 and inducesCYP3A4. The parent compound is rapidly and al-most completely metabolized to the active metabo-lite (10 OH-CBZ), which undergoes hepatic glu-curonidation and renal excretion. Adverse effectsmay include hyponatremia, hypersensitivity reac-tions, and lowered oral contraceptive efficacy;other common side effects are headache, dizziness,gait imbalance, fatigue, poor concentration, and

memory changes. The breastfeeding data are lim-ited, but one case report indicated that the amountof drug dropped rapidly in a breastfeeding infant.At 5 days after birth, the infant drug concentra-tions for parent drug and metabolite were only12% and 7%, respectively, of the levels drawnshortly after birth.94

Lamotrigine is indicated for maintenance ther-apy in bipolar depression.95 The importance of agradual titration precludes the use of this drugfor management of acute psychosis. It induces anonserious rash in 7%10% of patients andStevens-Johnson syndrome, a potentially life-threatening condition, in 3 of 1000 patients. A se-rious rash is more likely with rapid dose escala-tions, in combination with valproate, and amongadolescents.86 At the onset of a rash, patientsmust stop this drug immediately and seek med-ical attention. Although the lamotrigine-associ-ated rash is potentially life threatening in rare in-stances, the risk must be weighed against the

benefit of preventing the recurrence of major



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puerperal illness.96 Lamotrigine undergoes he-patic glucuronidation and renal excretion. Thisdrug is transferred to breast milk readily, and theserum drug level decline is noticeably slow inneonates and infants. Therefore, this drug is notadvised for breastfeeding mothers shortly afterdelivery, as are other drugs metabolized by glu-

curonidation, such as oxazepam, lorazepam,aspirin, acetaminophen, VPA, and olanzapine(OLZ).97

Atypical antipsychotic medications

The atypical antipsychotic agents, such as OLZ,risperidone, quetiapine, and ziprasidone, are in-dicated for treatment of acute psychosis, bipolarmania, and schizophrenia. The dose ranges are2.520 mg/day OLZ, 26 mg/day risperidone,25700 mg/day quetiapine, 2080 mg bid ziprasi-

done. The side effects commonly include somno-lence, dry mouth, akathisia (internal sense of rest-lessness), and increased liver transaminases.Hyperprolactinemia occurs commonly withrisperidone (88%) compared with conventionalantipsychotics, such as haloperidol (48%) or OLZ(minimal if any).98 The metabolic effects of atyp-ical agents are considerable. Patients risk signifi-cant weight gain (above 7% baseline weight), el-evated triglycerides, and new onset of metabolicsyndrome or insulin intolerance.99 Vigilant mon-itoring of the glucose and lipid profiles is rec-ommended. Patients on atypical antipsychoticagents must be encouraged to follow healthy eat-ing patterns, diet modification, regular exercise,and dietary counseling to minimize the adversemetabolic effects. Although extrapyramidal sideeffects (EPS), such as tremors, rigidity, akathisia,

bradykinesia, tardive dyskinesia, and dystonia,are reported infrequently with atypical antipsy-chotics, the risk for EPS is elevated in women, theelderly, and patients with affective disorders.

Women who were exposed to atypical an-tipsychotic drugs during pregnancy (60 womenon OLZ, 49 on risperidone, 36 on quetiapine, and

6 on clozapine) delivered babies with low birthweight (LBW) at a rate that significantly exceededthe rate of LBW among nonexposed babies (10%and 2%, respectively).100 Goldstein et al.s follow-up of 20 cases of OLZ exposure in pregnancy in-dicated 4 adverse birth outcomes101: 1 stillbirth at37 weeks gestation to a mother with polysub-stance abuse, premature ruptured membranes,gestational diabetes (GDM), thrombocytopenia,

and hepatitis who took OLZ in the second andthird trimesters; 1 cesarean section delivery at30 weeks gestation to a mother with GDM,preeclampsia, elevated liver transaminases, hy-pothyroidism, who took OLZ in all threetrimesters, the baby survived but required 2weeks of NICU care; 1 postterm baby born with

fetal distress to a mother on OLZ for all threetrimesters; and 1 postterm infant who aspiratedmeconium after a cesarean birth and was born toa mother who took OLZ only in the first trimester.In summary, patients with preexisting psychosisare at elevated risk in the puerperium. They must

be referred and managed by the high-risk ob-stetrical team throughout the antepartum andpostpartum periods. Both the mother and infantmust be treated as high-risk patients after deliv-ery.

To date, only 28 cases of atypical antipsychotic

exposure in breastfeeding infants have been re-ported.80 Kirchheiner et al.102 described one wo-man with schizophrenia who took OLZ 10mg/day throughout the second and thirdtrimesters and continued treatment while breast-feeding. Mother-infant levels were obtained at 2and 6 weeks after birth. At both times, the infantlevels were undetectable (2 ng/mL), and ma-ternal trough levels measured 39.5 and 32.8ng/mL, respectively. The babys growth dimen-sions, for example, head circumference, height,and weight, remained normal up to 11-months

follow-up. Although the child had difficultyrolling over at 7 months, the delay had resolvedby the 11-month evaluation. Infant risks dependnot only on the breast milk-transmitted drug(from the passive diffusion of unbound drug) butalso on neonatal intestinal absorption, distribu-tion, and elimination characteristics. Therefore,the practice of tracking infant drug levels may bevery appropriate for estimating the extent of drugexposure and disposition in breastfed infants.

Regarding breast milk exposure to risperidone,Hill et al.103 described one bipolar patient whostopped all treatment in pregnancy and devel-oped a postpartum psychotic depression within2 months of delivery. She resumed taking ris-peridone and stopped breastfeeding, andplasma/breast milk samples were obtained tomeasure drug and metabolite (9-hydroxyrisperi-done) levels. The infant drug exposure was cal-culated as a product of the average drug concen-tration in breast milk and the quantity of dailymilk intake. They estimated the infant received

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efit from treatment with an antimanic agent, suchas lithium, an AED, or an atypical antipsychoticdrug. Women who have a primary diagnosis ofschizophrenia and recurrent puerperal illnesswill benefit from a medication chosen within theclass of atypical antipsychotic drugs. The choiceof treatment also should be governed by the pa-

tients history of past treatment response, the sideeffects profile, and the acuity of illness. For ex-ample, the postpartum patient with insulin-de-pendent diabetes, an acute onset of paranoiddelusions, inconsolable crying and fitful bursts ofunexplained laughter, and a twin sister withmixed episodes would require antimanic drugtreatment with the fewest metabolic effects. Inthis case, initiation of 20 mg ziprasidone bid,which is an FDA-indicated drug treatment forpsychosis and mania and the least likely to in-duce glucose intolerance, is an acceptable treat-

ment option. A quick titration to a therapeuticdose range of 6080 mg ziprasidone bid may benecessary to achieve symptom relief. If the pa-tient fails to reach a timely response and displaysdeteriorating self-care or becomes desperatelysuicidal, she may require a more aggressive formof treatment, such as ECT. Once she has com-pleted the course of 79 treatments of ECT overa 23-week period, she will need to continue onmaintenance antimanic pharmacotherapy to pre-vent recurrence. Before release from hospital, thetreatment team must work with the patient and

her family to devise a discharge plan that willbolster her supports, incorporate close follow-up,and reduce stressors that contribute to relapserisk. For future pregnancies, her primary carephysician is advised to collaborate with the ob-stetrician, endocrinologist, and other specialistsproviding her care in consideration of antimanicprophylaxis during pregnancy or after childbirth.

CONCLUSIONS

The core features of PP are an early and rapid

onset, accompanied by profound confusion, delu-sional beliefs, mood swings, and inability to func-tion that represent a major change from baseline.Patients with PP usually experience a brief illness,rapid treatment response, and the absence oflong-term impairment. These are clinical cluesthat suggest an underlying affective disorder,most likely a bipolar illness.1,3,4,8,11,21,22,32,113115

The prognosis is optimistic in the setting of acute

onset and lack of premorbid debility.6 PP andpuerperal-onset bipolar illness are distinct frommore severe forms of BD that manifest with re-current bouts of bipolar psychosis, mixed mania,and treatment-refractory bipolar depression andare associated with less promising outcomes.65,116

To move forward with our understanding of

bipolar illness presentations and treatments forreproductive-aged women, we require data fromprospective studies on the treatment responseand outcomes of women with PP and compar-isons with their healthy counterparts. The phys-ical and neurodevelopmental outcomes of anti-manic and antipsychotic drug exposure in

breastfed infants remain critical areas of research.Persistent mental illness has been linked with im-pairments in mother-infant bonding. The impactof untreated vs. treated maternal bipolar disorderon infant and childhood development is essential

in our appreciation of risk for mental disordersin the progeny and how interpersonal relation-ships develop in children of parents with majormental illness. These remain highly significant

but tremendously understudied topics.Correlations among the symptoms of PP, go-

nadal hormone states, and neurotransmitter ac-tivity are also major areas of investigation that arenecessary to explain the pathophysiology of PPand explore novel, efficacious treatments. Func-tional imaging of the frontal and mesolimbicstructures with treatment holds promise for en-

hancing the understanding of the neurobiologythat underlies PP. Ongoing investigations intothe neurobiology, diagnosis, and long-term out-comes of PP will lead to better illness recognitionand effective interventions and will be essentialto unravel the mystery of this fascinating buttragic disorder. This will improve our under-standing and treatment of mothers and familieswho suffer this highly debilitating yet treatabledisorder.

ACKNOWLEDGMENTWe thank Diana Gannon for her help in prepar-

ing the manuscript for submission.

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Address reprint requests to:Dorothy Sit, M.D.

Assistant ProfessorUniversity of PittsburghWestern Psychiatric Institute and Clinic

3811 OHara Street, Oxford 410Pittsburgh, PA 15213

E-mail: [email protected]

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A Review of Post Partum Psychosis