TREATMENT IN PSYCHIATRY

Treatment of Psychosis and Mania in the
Postpartum Period
Veerle Bergink, M.D., Ph.D., Karin M. Burgerhout, M.D., Kathelijne M. Koorengevel, M.D., Ph.D.,
Astrid M. Kamperman, M.Sc., Ph.D., Witte J. Hoogendijk, M.D., Ph.D., Mijke P. Lambregtse-van den Berg, M.D., Ph.D.,
Steven A. Kushner, M.D., Ph.D.

Postpartum psychosis is a severe disorder that warrants psychotic episode fulfilling DSM-IV-TR criteria. Using this
acute clinical intervention. Little is known, however, about treatment algorithm, the authors observed that nearly all
what interventions are most effective. The authors present patients (98.4%) achieved complete remission within the
treatment response and remission outcomes at 9 months first three steps. None of the patients required ECT. At 9
postpartum using a four-step algorithm in patients with first- months postpartum, sustained remission was observed in
onset psychosis or mania in the postpartum period. Treat- 79.7%. Patients treated with lithium had a significantly
ment involved the structured sequential administration of lower rate of relapse compared with those treated with
benzodiazepines, antipsychotics, lithium, and ECT. The out- antipsychotic monotherapy. Multiparity and nonaffective
come of clinical remission was examined in 64 women psychosis were identified as risk factors for relapse. The
consecutively admitted for postpartum psychosis. Remission authors conclude that a structured treatment algorithm
was defined as the absence of psychotic, manic, and se- with the sequential addition of benzodiazepines, antipsy-
vere depressive symptoms for at least 1 week. Women chotics, and lithium may result in high rates of remission in
who remitted on antipsychotic monotherapy were advised patients with first-onset postpartum psychosis and that
to continue this treatment as maintenance therapy, and lithium maintenance may be most beneficial for relapse
women who required both antipsychotics and lithium to prevention.
achieve remission were maintained on lithium monotherapy.
Relapse was defined as the occurrence of any mood or Am J Psychiatry 2015; 172:115–123; doi: 10.1176/appi.ajp.2014.13121652

Postpartum psychosis is a psychiatric emergency that re- thyroiditis (6), and, less frequently, autoimmune encephalitis
quires immediate medical attention and mental health care (7, 8), primary hypoparathyroidism (9), vitamin deficiency,
referral. The prevalence in the general population is esti- stroke, and drug-induced psychosis (10). Case reports have
mated to be 1–2 cases per 1,000 childbirths (1, 2). In the ma- documented misdiagnosis of postpartum psychosis revealing
jority of cases, the onset is rapid and occurs within 2 weeks a late-onset urea cycle disorder (11) and type I citrullinemia
of delivery. Early symptoms often include insomnia, mood (12). Clinicians must ensure the adequate safety of the patient
fluctuation, and obsessive concerns regarding the newborn, and her children, as postpartum psychosis is associated with
followed by more severe symptoms, such as delusions, hal- a highly elevated risk of suicide and infanticide.
lucinations, and disorganized behavior. Severe mood symp- Because of the severity of the symptoms and the un-
toms, such as mania, depression, or a mixed state are a hallmark predictable nature of the illness, pharmacological treatment
of the illness. Because clinical presentation, family history, and is typically initiated immediately. Unfortunately, however,
the longitudinal illness course overlap markedly with those few standardized treatment recommendations are currently
of bipolar disorder, postpartum psychosis is generally consid- available for postpartum psychosis, as research has been
ered a bipolar spectrum illness and not a primary psychotic limited and no randomized trials have been conducted. The
disorder (3–5). effects of lithium (13, 14), antipsychotics (15), ECT (13, 14),
The initial clinical evaluation for postpartum psychosis estrogen (16–18), progesterone (19), and propranolol (20) have
requires a thorough medical and psychiatric history, physical been examined. A total of 21 treatment studies of postpartum
and neurological examinations, and comprehensive labora- psychosis can be found in the literature of the past few dec-
tory analysis to exclude organic causes for acute psychosis. ades, all of them based on small samples; the majority involve
The differential diagnosis should include infectious dis- case reports, and few studies have included more than 10 pa-
eases (e.g., mastitis, endometritis), eclampsia, postpartum tients (21, 22).

This article is featured in this month’s AJP Audio and provides Clinical Guidance (in the Table of Contents)

Am J Psychiatry 172:2, February 2015 ajp.psychiatryonline.org 115

B was treated with lorazepam her mother’s suggestion that she discontinue breast. and antidepressants for depressive symp. 32). an antipsychotic. Ms. then adjunctive psychosis were eligible for the study. and lithium was gressively more impulsive. Although the efficacy of antipsychotics five-bed inpatient unit that specializes in the care of patients in the absence of mood stabilizers has been described in only with severe psychopathology in the postpartum period. As postpartum psychosis 116 ajp. The first refractory postpartum psychosis (25. their baby in a fully staffed nursery adjoining the unit (33). Nighttime feedings were performed exclusively the third day postpartum. she and her daughter were discharged home from the hos- exposed her breasts while shouting: “Look at these! pital 7 weeks after delivery. Case reports and case series have described positive bipolar patients. ECT has been described as an effective treatment option the prevention of postpartum psychosis (28–31). in patients with severe catatonic features. Patient Edition (SCID) (34). Axis I Disorders. Over the weeks of treatment with haloperidol. chosis and mania (15). the past 4 years of outpatient follow-up since discharge.org Am J Psychiatry 172:2. with no previous psychiatric history. B Medical Center. and lithium. including thyroid screening. tively manic with psychotic features. to perform daytime bottle feedings under the supervision fed her daughter every 2–3 hours without difficulty. “Ms. the next rec. a ning on day 4 (step 2). and disorganized. Recently. B has remained in full remission. 34). of the Erasmus Medical Center (Rotterdam. her manic and psy- daughter to the Mother-Baby Unit of the Erasmus chotic symptoms remitted over the next 3 weeks. delivered a healthy During periods of clinical stability. haloperidol. antipsychotics and mood stabilizers for psychotic and monotherapy in patients with postpartum psychosis (13. pines and antipsychotics is recommended for 2 weeks. assessed with the Structured Clinical Interview for DSM-IV The step 2 treatment with a combination of benzodiaze. with close outpatient follow- My breasts are great! I want to breastfeed 24 hours up. ECT is recommended algorithm with guidance from the extensive literature on (step 4). B expressed concern that by nursing staff. Over features (Young Mania Rating Scale score. If at Patients 18–45 years of age with a diagnosis of postpartum 2 weeks there is no significant clinical response. studies have demonstrated efficacy of lithium in toms. and here we examine prospectively how treatment outcomes with ECT in women with treatment- this treatment approach might affect outcomes. in patients whose symptoms have not responded even been proposed as a first-line treatment option (23–25). Benzodiazepines are used for insomnia and ium and antipsychotics is more effective than antipsychotic agitation. After 2 violent and kicked her mother in the abdomen. In response to On admission. ECT has Finally. The after 3 days of benzodiazepine monotherapy. partment of Psychiatry at the Erasmus Medical Center. Ms. step in treatment involves benzodiazepines at bedtime for 3 days (step 1). Ms. antipsychotics are frequently used world. monotherapy for 3 days without significant clinical im- feeding to enable better sleep. her husband wanted to kill their newborn. B became pro. antipsychotics are often Every patient admitted to the unit between August 2005 and considered the preferred pharmacological treatment option June 2011 (N5200) was screened for study inclusion and for acute mania outside the postpartum period (27). Find. The purpose of starting with an initial period of METHOD benzodiazepine monotherapy is to evaluate whether resto- ration of sleep results in clinical remission of manic and Participants psychotic symptoms. after which haloperidol was initiated. study was performed at the Mother-Baby Unit of the De- ommended step involves antipsychotic medication begin. B. added to her treatment regimen. B became extremely provement. Ms. She breast.psychiatryonline. Lithium was discontinued after 9 months. irritable.TREATMENT IN PSYCHIATRY A patient develops first-onset postpartum psychosis after the birth of her first child.” a 28-year-old primiparous primigravid woman investigations. 14). Women are given the option for admission together with wide as first-line treatment for patients with postpartum psy. and lithium. treatment in clinical lithium is recommended (step 3). With a combination of On day 7 postpartum. On of a nurse. as sleep loss has been considered an The study was approved by the Institutional Review Board important etiological factor in postpartum psychosis (26). three case reports. All patients provided written informed consent. and mother-child interaction nonstop!” She was diagnosed as manic with psychotic therapy. were normal. B remained ac- next 4 days (postpartum days 4–7). manic symptoms. ings from physical examination and routine laboratory Ms. Ms. B was admitted with her lorazepam. Furthermore. Furthermore. One small open-label study practice is typically based on the most prominent symptom and a case report have suggested that the combination of lith- dimensions. Ms. lithium monotherapy. In the absence of formal guidelines. February 2015 . Ms. During the admission interview. after 12 weeks of combination treatment with a benzodiaz- We have developed a four-step standardized treatment epine. Ms. the Nether- For patients whose manic or psychotic symptoms persist lands). B was encouraged daughter after an unremarkable pregnancy.

Women who remained clinically stable after 9 months chosis or mania outside the postpartum period and therefore were assisted in gradually tapering their medication to were excluded from our analyses. 15 patients had a history of psy. We defined relapse as the occurrence of any mood Step 3. SPSS. logistic regression analysis. Phe- nomenology was quantified using the Bipolar Affective Disor- Nonpharmacological Treatment der Dimension Scale (36). sustained remission was recommended for those patients who did not have a signifi. antipsychotic and the Clinical Global medication was recommended beginning on day 4. February 2015 ajp. with maintenance lithium with psychotic features. brief psychotic disorder. depression. All psy. 83 patients fulfilled the criteria for postpartum monotherapy throughout the first 9 months postpartum. These interventions trum illness.psychiatryonline. In our data analysis. categorical demographic variables were chotropic medications would be tapered to discontinuation compared with Fisher’s exact test. One patient was excluded discontinuation. Armonk.B. a dimensional rating scale intended All women received nonpharmacological interventions to for use in clinical cohorts with a high incidence of bipolar spec- optimize mother-baby interaction (35). than for those using the Edinburgh Postna.3. and an Edinburgh Postnatal Depression Scale score #10 (40). or mania.0. For a polar spectrum disorders (39). Am J Psychiatry 172:2. ECT was recommended. adjunctive lithium was CGI-BP score . initial onset of psychiatric symptoms until remission. Longitudinal assessment of mood episodes was performed using the National Institute Step 4. because of substance abuse.8–1. The specifier “onset for relapse prevention was achieved based on plasma level postpartum” requires that the onset of symptoms occur within (target. manic. taining a CGI-BP score #3. Lithium dosing fied. Women who achieved clinical remission using both interview generated any of the following diagnoses and re. an partum (41). with antipsychotics. 4 weeks after delivery. video-interaction guid. all participants and their relatives with psychosis or mania limited to the postpartum period were interviewed by a psychiatrist (V. as well as main- on plasma level (target. and continuous demographic before initiation of ECT. Mania Rating Scale (37). Cat- egorical outcomes of relapse risks were examined using Fisher’s Maintenance Treatment exact test. variables were compared with the Mann-Whitney U test. and Kaplan-Meier esti- After complete remission of symptoms.org 117 . Accordingly. we switched to an atypical antipsychotic. and lithium.. Assessments we describe her illness course separately. For patients in whom side effects global illness severity and time course in patients with bi- occurred.05 was considered statistically significant. One patient was lost to follow-up after remission. Our pri. monotherapy until 9 months postpartum. Analyses were performed using vised to taper benzodiazepines to discontinuation. 0. A two-tailed p value ceiving antipsychotic monotherapy were advised to continue . Dur.).The rate of sustained ing hospitalization. All women were encouraged to continue maintenance Overall. we skipped step 1 and continued treat.Y. we this treatment as maintenance therapy until 9 months post- defined eligible subjects as those patients for whom the SCID partum. For patients receiving lorazepam monotherapy who tal Depression Scale (38).6–0. Women re. and ance. There are four identified dimensions: mania. had persistent manic or psychotic symptoms. After 2 weeks of combination treatment with a ben. All patients were initially treated with lorazepam at weekly using the Young monotherapy with lithium bedtime for 3 days.M. version 20. #8. subset of patients (N511) who had already been treated with Clinical remission was defined as the absence of psy- an antipsychotic for more than 2 days before admission (e. version of the CGI scale that allows the clinician to rate the operidol at 2–6 mg/day. chotic. defined as absence of any DSM-IV-TR mood or psychotic cant clinical response.). Impressions–Bipolar Disorder scale (CGI-BP). 64 patients In addition to the SCID. TREATMENT IN PSYCHIATRY is not described as a distinct illness entity in DSM-IV-TR.maintenance monotherapy Step 2. and two patients declined par- ticipation.0 (IBM. or psychotic episode fulfilling DSM-IV-TR criteria or a zodiazepine and an antipsychotic. a modified mary recommendation for antipsychotic treatment was hal. Of these.K. psychotic disorder not otherwise speci. included feedback from nursing staff. mation of the log-rank test. Lithium dosing was achieved based episodes throughout the follow-up period. a Young Mania Rating Scale score ment with the same antipsychotic.2 mmol/L). psychosis. Dura- were evaluated weekly during admission and at 9 months tion of episode was defined as the number of days from the postpartum. with a CGI-BP score #3. N. In total. by acute services).g. and depressive symptoms for at least 1 week. all women were ad. and baby massage. For patients who did not have a response after 12 of Mental Health Life-Chart Method at 8 months post- weeks on combination treatment with a benzodiazepine. clinical remission was higher for Pharmacological Treatment evaluation was performed patients using maintenance Step 1. 0. mood incongruence. or K. antipsychotics and lithium were advised to gradually ta- quired the specifier “onset postpartum”: depressive disorder per off antipsychotic treatment.8 mmol/L). antipsychotic. psychosis or mania.

8 4 30.37 Multiparity 14 21. quartile range [IQR]55–14).90 N % N % N % Treatment Step 1 4 6. 30 days. four with (17.54 Duration of episode (days) 40 26–65 42 23–69 38 29–48 0.8 0 0.6 4.00 Previous postpartum psychosis 10 15.4 4 7.7 0 0.7 8 61. and in the other patient lithium was contraindicated be- cause of psoriasis (median time to remission.01 Step 3 48 75. As expected.1 1. 2 despite persistent symptoms: one declined adjunctive lith- A flowchart of treatment outcomes is presented in Figure 1. RESULTS the 3-day step 1 period.6 14 27.org Am J Psychiatry 172:2. The phenomenological classification a combination of benzodiazepines and antipsychotics (step 2). Categorical variables were tested using Fisher’s exact test.6 9 69. and lithium.3 0. passivity experiences.5 0.0 41 80. and depression with psychotic features (9. although they both ultimately We assessed treatment outcomes for 64 enrolled patients. Only olanzapine. or originating in some part of the body. despite having persistent symptoms at the end of treated with haloperidol.3 28 54. achieved full remission (median time to remission. Antipsychotic treatment was as fol- azepine treatment (median time to complete remission.8 0. Participants’ demographic and clinical characteristics are Twelve patients (18.9 8 61.9 4. or broadcasting.9 8 15. lows: 37 patients were treated with haloperidol.6 0. Two of these patients experienced remission of 47 patients (73. The median onset of initial within 2 weeks of treatment initiation. Of these. Complete Remission Forty-eight patients were treated with a combination of Four of the 64 patients (6.psychiatryonline. included manic-psychotic features (65. 39 days).0 0. and one with quetiapine.8 0.1 0. bizarre delusions.3%) remitted at step 1 of the treatment benzodiazepines.19 Previous depression or anxiety 8 12.6%). and one with quetiapine. The median time to clinical re- IQR521–41).40 N % N % N % Dutch ethnicity 56 87.0 12 92.8 0.0 0. and continuous variables were tested using the Mann-Whitney U test.4 0. Ten of these patients five patients had a postpartum psychosis without prominent experienced full resolution of manic and psychotic symptoms affective symptomatology (7. ium.2 0.6 6 11.2%).6 7 53.2 11 84.34 Depressed or mixed 17 26.2 0. eight were switched to an atypical 118 ajp.05 Psychotic symptoms Mood incongruence 40 62. nine with Two patients declined to advance further in the treatment olanzapine. algorithm. The remaining two patients were limited to step mission was 40 days (IQR526–65).8 4.4 7 53.5 1.9 50 98.66 Education beyond high school 36 56.7 32.5 45 88. c IQR5interquartile range. seven were treated with haloperidol. algorithm (Figure 1).4 0. they had a substantially longer duration of illness. 21 days). Of the 37 patients algorithm.6 35 68.7 31.5 3 23.4%).00 Nonaffective psychosis 5 7.19 Affective psychosis With manic psychotic features 42 65.5 8 15.59 Median IQRc Median IQRc Median IQRc Onset (days postpartum) 8 5–14 7 5–14 10 5–16 0. withdrawal. insertion. b First-rank symptoms include thought echo. discussing subject in third person.8%) remitted during treatment with summarized in Table 1. February 2015 .TREATMENT IN PSYCHIATRY TABLE 1.3 4 7.2 1.57 Step 2 12 18.76 Married or living with partner 62 96.8 2 3.9 37 72. despite a more per- psychiatric symptoms occurred at 8 days postpartum (inter- sistent affective instability (median time to remission.8 2 15. hallucinatory voices giving running commentary.03 Psychiatric history No psychiatric history 46 71.8%). or catatonia.7 6 46. antipsychotics.8 6 11. Demographic and Clinical Characteristics of Women With Sustained Remission or Relapse After Postpartum Psychosis Women With Women Without All Women Sustained Remission Sustained Remission Characteristic (N564) (N551) (N513) pa Mean SD Mean SD Mean SD Mean age (years) 31.4%) remitted under step 3 of the treatment manic and psychotic symptoms after only 3 days of benzodi.5 32 62.9 3 23.07 a Women with sustained remission were compared with women without sustained remission. mixed episode Of these.8 6 46. 161 days).00 First-rank symptomsb 6 9.

history. 12 relapsed (18. 2.org 119 . postpartum. Sustained Remission and Relapse Rates After 9 Months In total. This patient suffered from depression with psychotic time to remission for patients treated under step 3 was 44 features and was without manic symptoms. Of the remaining clinical algorithm (Figure 1). psychiatric three patients were thyroperoxidase antibody positive. anti- after declining antipsychotic treatment and was therefore psychotics. Nota. 63 of the 64 enrolled patients (98.0. The median ment. were identified in demographic characteristics. Among the 12 patients who achieve remission during the 9-month follow-up period. and (N=4) (N=12) lithiuma (N=48) Never achieved remission (N=1) Fully remitted. All patients with clinical thyroid dysfunction or 3. phenomenological characteristics. Admission or no medication and antipsychotics antipsychotics. with lithium. four were di. No other differences dysfunction. the one patient who was lost to follow-up did not remaining patient advanced from step 1 directly to step 3 respond to the sequential addition of benzodiazepines.3%). for which no treatment was needed. p.psychiatryonline. We compared the demographic and clinical character- ical thyroid dysfunction among the 16 who were not treated istics of patients who achieved clinical remission at step 1. There were no other adverse consequences of lithium treatment. the duration of illness Of the 48 patients treated with lithium. The However. TREATMENT IN PSYCHIATRY FIGURE 1. none of the lithium-treated patients without autoimmune tency to onset of symptoms. or postpartum la- bly. was 186 days. and lithium and remitted only after ECT treat- treated with only benzodiazepines and lithium.7%) (Figure 1). symptoms began at postpartum day 4. two to quetiapine. Fully remitted. Women who received a combination of benzodiaze- were specifically diagnosed with autoimmune thyroid disease.01). and one to risperidone). Am J Psychiatry 172:2.4%) achieved Sustained remission at 9 months postpartum was observed a full clinical remission within the first three steps of the in 51 of the 64 patients (79. thyroid disease developed clinical thyroid dysfunction. The remaining patient was 13 patients.6%). 10 had a depressive episode (83. Flowchart of Treatment Outcomes in 64 Women With Postpartum Psychosis Women followed through 9 months postpartum (N=64) STEP 1 STEP 2 STEP 3 Acute treatment with Acute treatment Acute treatment benzodiazepines only. Her psychiatric days (IQR526–69). olanzapine. February 2015 ajp. Five of average than those who received adjunctive lithium treatment the lithium-treated patients had transient subclinical thyroid in step 3 (Fisher’s exact test. after which the patient was discharged home agnosed as having clinical thyroid dysfunction at 9 months and subsequently lost to follow-up. compared with two patients found to have clin. pines and antipsychotics (step 2) were significantly older on as evidenced by thyroperoxidase antibody positivity. Fully remitted. b Three patients were maintained on both lithium and an antipsychotic. None experienced relapse. tapered off tapered off tapered off benzodiazepines benzodiazepines benzodiazepines (N=4) (N=12) and antipsychotics (N=47) Discontinued Maintained Discontinued Maintained Discontinued 9 months benzodiazepines on antipsychotics antipsychotics on lithiumb lithium (N=7) postpartum (N=4) (N=8) (N=4) (N=40) Sustained Sustained Relapse Sustained Relapse Sustained Relapse Sustained Relapse remission remission (N=4) remission (N=2) remission (N=4) remission (N=2) (N=4) (N=4) (N=2) (N=36) (N=5) a One patient declined antipsychotic medication.8%) and one had not remitted by discharged against medical advice during step 3 and did not 9 months postpartum (1. with benzodiazepines with benzodiazepines. antipsychotic because of side effects (five were switched to of the 64 enrolled patients were treated with ECT (step 4). Of these.

p50.58 mmol/L.03. substantial recovery might occur as a result of the spontaneous resolution of these transient changes in post- Effect of Medication on Relapse Rates partum physiology. and four All but one patient achieved full clinical remission.4%). remission and two relapsed (37. p5 0. Among the 12 patients who remitted with benzodia- Percent in Remission zepines and antipsychotics under step 2. Moreover. we observed high remission rates in the acute phase psychiatric history. 86.5%) (Fisher’s exact test. patients with affective until remission) was 40 days. rithm. Using a four-step clinical treatment algo- There were no differences in age. in the present study. ethnicity. The majority of patients re- who did not (N513) (Table 1). a substantially longer duration of illness until clinical remission Patients treated with the combination of benzodiazepines and (8 months on average) (44). odds ratio54. even in the absence with the mood congruence of psychotic symptoms. Antipsychotic or Lithium Maintenance Monotherapya odds ratio56.8%) (Fisher’s exact test. 43). nor endocrine alterations (42. maintenance treatment with lithium (N=47) that of patients who had sustained remission (0. absence of pharmacological treatment. Eight patients discontinued lithium treatment a during the follow-up period. 83. of treatment. the prognosis is 73). Kaplan-Meier Curve of Relapse After Full Remission of (N56/12.0%) compared with those receiving adjunctive Symptoms in Women With Postpartum Psychosis Using Either lithium in step 3 (N56/47. Therefore.2–17. 40. four relapsed (10. relapse was not associated with antipsychotic discontinuation during the follow-up period. median duration of illness (from onset of postpartum psychosis With regard to phenomenology. the postpartum period.0%). 57.41) was similar to and lithium. Step 2: Initial treatment with benzodiazepines and antipsychot- ics. one never achieved Log-rank test. antipsychotics. Relapse occurred a median of 54 days after full remission (IQR=23–101). antipsychotics (step 2) were significantly more likely to relapse the two patients who declined antipsychotic and lithium 120 ajp. and four of these patients relapsed (N54/8. 0 0 50 100 150 the majority (N540/48. We and ratio57. of the four patients who discontinued antipsychotic treatment. p50. The had two previous episodes of postpartum psychosis. their mean lithium level Step 3: Initial treatment with benzodiazepines. However. Similarly. associated with parity. In the mission (log-rank test. We also evaluated whether noncompliance or medication 100 discontinuation might have influenced the significantly higher rate of sustained remission in patients treated with adjunctive lithium. February 2015 . including transient immunological and ated with manic. free patients do not support this alternative hypothesis.0%). maintenance treatment with antipsychotics (N=12) SD50. previous studies of medication- Treatment received was highly predictive of sustained re.4. the rate of sustained remission was higher for pared with multiparous patients (N58/14. p50. SD50. p50.3%).002) (Figure 2). 95% CI51. and a considerable proportion of patients achieved patients who had a sustained remission (N551) and those sustained remission (79. quired combination treatment with a benzodiazepine. or onset or duration of episode between (98. Among patients with affective others have described a higher biological vulnerability during postpartum psychosis. mixed. eight were continu- ously maintained on antipsychotics throughout the follow-up 50 period. 50.0%) com.002. 50. an ever. primiparous women were more antipsychotic. Among than for those using maintenance monotherapy with an the six multiparous patients who experienced relapse.6.6). potentially life- median duration of the relapse episode was 61 days (IQR530– threatening disorder during the acute phase. how. 50. or depressed symptomatology.3%) were continuously main- Days of Remission Until Relapse tained on lithium throughout the follow-up period. patients experience tients treated with benzodiazepine monotherapy relapsed (N54). Sustained remission was. The Given that postpartum psychosis is a severe.3). 83.8). of these.1%) (Fisher’s patients using maintenance monotherapy with lithium exact test.4. This finding might suggest that psychosis were more likely to achieve sustained remission the four-step treatment algorithm was highly effective. On the (N549/59.7–28. The N listed for step 3 is 47 because one of the 48 patients never achieved remission. p50. sustained remission was not associ. Of these 40 patients.psychiatryonline. two antipsychotic. odds ratio55. likely to achieve sustained remission (N543/50.0%).1%) compared with those with nonaffective other hand. and lithium to achieve clinical remission. had a single previous episode of postpartum psychosis.08.TREATMENT IN PSYCHIATRY FIGURE 2.0%) (Fisher’s exact test.org Am J Psychiatry 172:2. one had manic symptoms without psychosis (8.7%).1–49.01. during follow-up (0. remarkably good.57 mmol/L. it might also be attributed to a spontaneously re- psychosis (N52/5. 95% CI51.9–31. Therefore.27). two relapsed (N52/4. Moreover. odds mitting illness course of relatively short duration. None of the pa.4). and one DISCUSSION had a nonaffective psychotic episode (8. 95% CI50. 12.8.05.3%). education. Among patients who received adjunctive lithium (step 3). 95% CI51.

this multiparous group included patients with a pre- abled us to carefully evaluate the influence of sleep hygiene vious history of postpartum psychosis (N510/14.3%). affective symptoms were present in . symptoms (mania). with patients with depressed-psychotic or mixed-psychotic quired. 46–48). More- outcomes. the relapse rate of 50% among been falsely attributed to the use of antipsychotics. Notably. According to both DSM-IV- lithium has not been described previously as a first-line op. February 2015 ajp. in par. these findings contribute novel and compelling evi- treatment of women with postpartum psychosis who have pro. As for antipsychotic options. In our study. Allowing a 3-day period of benzodiazepine treatment for relapse. the naturalistic design of our study warrants a cant covariate of postpartum psychosis (33. participants. a distinct diagnostic category of “postpartum mania. with previous studies describing primiparity as a signifi- Overall. B should be diagnosed as having tion for maintenance therapy after postpartum psychosis. Our results pro. Indeed.5 An overwhelming majority of our patients with post- months). Remarkably. dence to a broadening consensus that postpartum psychosis minent manic or psychotic symptoms. the recovery of these two patients may well have disorders” (49). but this is undoubtedly another important tients with postpartum psychosis. compared with only 15% for patients with depressive or a mixed episode without severe manic or psychotic affective psychosis. compared with the median duration of illness in the partum psychosis were primiparous. Naturally. treatment and achieved clinical remission. However. and a prolonged ill. Am J Psychiatry 172:2. with ticular for women with postpartum psychosis and either a a 60% relapse rate. and those multiparous patients who had no previous postpartum maintenance antipsychotic treatment would likely have been episodes is not explained by this hypothesis. we identified multiparity as a significant risk factor step. There was no difference in relapse risk for fit would be fully realized with lithium monotherapy. our The illustrative case vignette we present serves to make study was not designed to compare conventional and atypical additional points about the diagnostic classification for pa- antipsychotics. given the proven benefits should be classified as an affective disorder and not a pri- of antipsychotics over lithium monotherarpy for the treatment of mary psychotic disorder (31. However. had no psychiatric history. whereas in fact maintenance treatment in bipolar patients (45). Ms. we suggest that Ms. as six of 14 multiparous women relapsed. the diagnostic criteria outside the postpartum period. and psychosis Therefore.psychiatryonline.90% of our However. note. If antipsychotic treatment had been initiated a phenomenon known as the “kindling hypothesis of mood sooner. We previously some patients may have a biological vulnerability to severe af- reported evidence that rebound activation of the immune fective psychosis that is limited to the postpartum period. it remains an open question whether this bene. over. Unex- cautious interpretation of the effectiveness of each treatment pectedly. After remission. Of (step 1) before the initiation of antipsychotics (step 2) en. To- lithium and an antipsychotic is the optimal strategy for the acute gether. Re. only one patient with depression with psychotic currently unknown. system during the postpartum period may be central to the The postpartum period is well established as having a pathogenesis of postpartum psychosis (43). she has remained stable lapse compared with antipsychotic monotherapy. question that should be addressed in future studies. mania. Psychotic symptoms in the absence of affective symptoms vide strong evidence that lithium is highly beneficial for were also identified as a significant risk factor for relapse. a consequence of past episodes of postpartum psychosis. TREATMENT IN PSYCHIATRY treatment experienced a much longer duration of illness (. Although throughout 4 years of follow-up. B was primiparous. it is dramatically elevated risk for affective instability and psy- tempting to speculate that the immune suppressive action chosis. of mania or psychosis outside the postpartum period (4). Accordingly. patients with nonaffective benefits of initiating lithium earlier in the algorithm. the threshold for manifesting might lead to recovery in a subgroup of patients. B’s diagnosis features was refractory to pharmacotherapy and required should be converted to bipolar disorder should she ever meet ECT treatment. bipolar I disorder. TR and DSM-5 criteria.” for ness course was mostly due to affective instability. a sizable proportion of women show no evidence symptoms in postpartum psychosis (23–25). and had prominent affective Lithium monotherapy was highly protective against re. numbers are too small (two of four patients) to establish firm The majority of patients responded to adjunctive lithium conclusions. 47). it appears likely that the combination of present in 12 of the 13 patients who relapsed (92. which the need for lifelong mood stabilization treatment is markably. affective symptoms were features. Future studies should also consider the potential symptoms (N517). psychosis (N55) had a significantly poorer prognosis. which is consistent full cohort (40 days).org 121 . severe symptoms such as agitation. Ms. clinical mood symptoms might be lower in these patients as two patients responded promptly to benzodiazepine mono. or patients with manic-psychotic symptoms (N542) compared whether combination treatment with an antipsychotic is re. therapy. Accordingly. although the recommended. Ms. acute mania or psychosis. In contrast. B would be better served by responded well to pharmacotherapy. this diagnosis suggests a lifelong there is extensive evidence of the benefits of lithium for vulnerability to manic and depressive episodes. however. of whom on the severity of symptoms. several studies have demonstrated that over long follow- ECT has been reported to accomplish a swift reduction of up periods. the risk during the postpartum period is estimated to of lithium may have contributed to our positive treatment be 20–25 times higher than during other periods (1). acute treatment when given together with antipsychotics. given that restoration of sleep four relapsed). However.

12:177–180 treatment before initiation of antipsychotics enables the 4. given the relatively might have of harming herself or her children. Chaudron LH. blood urea nitro. With proper clinical indication. From the Department of Psychiatry and the Department of Child and gen. creatinine. Sensakovic JW: Anti-NMDA-receptor en- (53. and glucose. postpartum. Timmermans. Pies RW: The relationship between postpartum clinician to carefully evaluate the influence of sleep hygiene psychosis and bipolar disorder: a review. should also be performed. plasma level. portant aspect of successful treatment from the perspective 296:2582–2589 of the family unit. • Mother-baby interaction deserves particular attention REFERENCES (35. 5. et al: New parents and mental disorders: a population-based register study. After remission. 2014. safety of mother and baby. et al: Primary hypoparathyroid- the illness. on the severity of symptoms while also screening for so. because of the risk of exacerbating mood instability 8. J Assoc Physicians India 2010. and Siska Verploegh for their manage- ment and database assistance. we found that patients with postpartum psychosis or mania achieved favorable treatment outcomes using a • We recommend maintenance treatment using lithium structured treatment algorithm during the acute phase of the monotherapy during the first 9 months postpartum (target illness.g. Chalmers JC. Rothschild AJ. treated with rituximab. support for the father is also an im. because ism: psychosis in postpartum period. Rotterdam. Sit D.TREATMENT IN PSYCHIATRY SUMMARY AND CONCLUSIONS • Antipsychotics are recommended for the acute treatment of manic and psychotic symptoms. brain CT or The authors are grateful to Annemarie van Hulst and Monique Raats for MRI. Bergink (v. partum psychosis. Admission to a mother-baby • ECT has been described as a highly effective treat- unit is associated with improved patient satisfaction and ment option in patients with severe catatonic features may help reduce time to recovery (50). 16.. Patil NJ. 51. ECT • The choice between pharmacotherapy and ECT should be General Strategies made in consultation with the patient. Kushner SA. feeding. who remain in full clinical remission.6–0. Kendell RE. A urine drug screen Adolescent Psychiatry/Psychology. Bergink and Burgerhout contributed equally to this study. Br J Psychiatry 2011. Wisner KL: A review of postpartum psy- chosis. Moreover. Address correspondence to Dr. isting literature. Pedersen CB. Received Dec. Shaaban HS. this often means cessation of breast. February 2015 . thyroid-stimulating hormone.nl). and levels of electrolytes. Munk-Olsen T. et al: Prevalence of autoimmune • We discourage the use of antidepressants for the acute thyroid dysfunction in postpartum psychosis. 58:506–508 122 ajp. limbic encephalitis antibody screening. In clinical practice. unless otherwise contraindicated (e. 6. Bergink V. Erasmus Medical Center. 2013. Jeroen Vervoort. treatment of postpartum depression with psychotic features. Laursen TM. at the time of diagnosis as well as 6 months Drs. 52:568–570 zation.psychiatryonline. Psychosomatics 2011. Use of lactation inhibitors should be avoided. cephalitis presenting as postpartum psychosis in a young woman. 54). accepted July 14. 64:1284–1292 matic comorbidities. maintenance with lithium mono.8 mmol/L). After 9 months. Ann Saudi Med 2012. • ECT should be considered for treatment of postpartum • The clinician must inquire about any thoughts the patient depression with psychotic features. Gokhale YA. and thyroid peroxi. liver AUTHOR AND ARTICLE INFORMATION function tests. Br J Psychiatry 1987. in- cluding physical and neurological examinations. tapering off of lithium should be considered in patients Based on observations from our case series and the ex. Labora- tory testing should include a complete blood count. 198:264–268 7. dase antibodies. Yu AY. Psychiatr Genet 2002. 2. 52). CSF analysis. free T4. B12. Pop V. We also suggest measuring the Netherlands. requires a thorough medical and psychiatric history. and urinalysis should also be performed. of impaired thyroid or kidney function). 150:662–673 Pharmacotherapy 3.bergink@erasmusmc. Jones I. The authors report no financial relationships with commercial interests. 1. a gradual therapy appears to be highly protective against relapse. • Focus on sleep hygiene and a structured rhythm of feedings. 15:352–368 covery in a subgroup of patients.org Am J Psychiatry 172:2. guidance in developing a standardized treatment algorithm and Mirjam measurement of serum vitamin B1. 2014. In this study. Choo HF. calcium. 32:421–423 • Lithium is highly recommended during the acute phase of 9. Moore FG: Paraneoplastic encephalitis presenting as post- particularly in the absence of appropriate mood stabili. revisions received March 22 and July 3. particularly with • Inpatient psychiatric treatment is essential to ensure the regard to their preference for breastfeeding. and folate levels. Yadav SS. Platz C: Epidemiology of puerperal psychoses. (23–25). we propose the recommendations below for the treatment of patients with postpartum psychosis. 0. J Clin Psychiatry 2003. J Womens Health (Larchmt) 2006. Restoration of sleep may lead to re. Craddock N: Do puerperal psychotic episodes identify a more familial subtype of bipolar disorder? Results of a family • Allowing a short period (36–72 hours) of benzodiazepine history study. JAMA 2006. longer median duration of illness compared with post- • The initial clinical evaluation for postpartum psychosis partum mania (33).

Fassier T. et al: Interventions for the 2013. First MB Spitzer RL. 73:1000–1007 prevention and treatment of postpartum psychosis: a systematic 44. 23:188–193 48. Holden JM. validity. 37. 73:159–171 in postpartum psychosis: a pilot study. 14:89–98 J Psychiatry 1969. Klompenhouwer JL. Am J Psy. Häberle J. Weigelt K. Brandon AR. Nederland. 61: 40. Compr Psychiatry 2003. 188:32–36 treatment of postpartum psychosis. Blackmore ER. Am J Psychiatry 2012. Mazmanian D: Sleep loss and postpartum psychosis. Raghunandan VN. Bloch M. 28:31–33 47. Guffon N. 167:572–574 reliability. Salanti G. Rubinow DR: Endocrine factors in the etiology 20. et al: Postpartum prophylaxis related to infant and their association with mother-infant inter- for women with bipolar disorder. part 1: through a husband’s eyes. et al: Immune system Psychiatr Neurol Neurochir 1973. Barbui C. 317:1–34 eyes. Acquaviva C. Laursen TM: Birth order and postpartum 26. Eur J Obstet Gynecol Reprod Biol 2010. of postpartum depression. Ahokas A. Post RM. Cox JL. Bergink V. et al: First manifestation of cit. Am J Psychiatry 1995. Meltzer-Brody S. J Nerv Ment Dis 1979. relapse.psychiatryonline. recurrent affective illness: life chart data from research patients at ence. 133:429–435 15. Ostroff RB: The use of electroconvulsive therapy in ford University Press. Turiainen S: Association between oestradiol and and roughening. Bergink V. terview for DSM-IV Axis I Disorders. Biol Psychiatry 21. Lancet 2011. part 2: through a patient’s the NIMH. Gibbon M. 43. et al: Comparative efficacy and ac. et al: Delusions 29. Brockington I: Motherhood and Mental Health. 54. et al: Obstetric variables asso- study. Spearing MK. Am J Psychiatry 2009. Forray A.org 123 . Trautmann-Villalba P. 166:405–408 1537 11. Hong JS: Microglia and inflammation-mediated neu- Pharmacother 2003. Latz A. Pharmacopsychiatry 1990. Dimension Scale (BADDS): a dimensional scale for rating lifetime chiatr Clin (Basel) 1975. Targum SD. recurrence. Cohen LS. 1999 12. Roy-Byrne P. J Clin Psychiatry 2000. affective illness: toward a new treatment with the anticonvulsant ceptability of antimanic drugs in acute mania: a multiple-treatments carbamazepine. Psy. Acta Psychiatr Scand Suppl 1985. Burgerhout KM. Chandra PS. 78:922–925 1217–1221 33. a prospective cohort study. Stanworth HM: After-care of puerperal psychosis in the commu. Br J Psychiatry 1987. Sharma V. Doshi M. et al: [Interactional ium prophylaxis? Br J Psychiatry 1992. Expert Opin 45. 76:77–98 therapy (ECT) in postpartum psychosis: a naturalistic prospective 46. Austin MP: Puerperal affective psychosis: is there a case for lith. Sharma V. Patient Edition (Neder- chiatry 2011. et al: Misdiagnosed postpartum 34. Bhargavaraman RP. Robertson LM. Hornstein C. Jones I. Focht A. Swets & Zeitlinger. Bergink V. Ahokas A. (German) 169:609–615 53. et al: A rating scale for mania: bonate. Uhde TW. Calabrese JR. 16:300–307 Bipolar Disord 2003. Chandra PS: Use of electroconvulsive Neurobiol 2005. Daly RC. Sichel DA. Silbermann RM. 115:9–30 22. Spinelli MG: Postpartum psychosis: detection of risk and man. et al: Evaluating the 28. Koorengevel KM: Postpartum depression with psy- et al: First-onset psychosis occurring in the postpartum period: chotic features (letter). 17:107–113 J Psychiatry 1991. Br unit. Br J Psychiatry 24. Burt VK. UK. Arch Women Ment Health 2011. Vervoort JS. Steiner M. Meli C. Letourneau N. 378:1306–1315 50. 16:247–251 ciated with bipolar affective puerperal psychosis. et al: Prophylactic clinical effectiveness of a specialized perinatal psychiatry inpatient lithium in puerperal psychosis: the experience of three centres. 18. Nurs Times 1982. 150:782–786 16. Arch Women Ment 1645 Health 2006. TREATMENT IN PSYCHIATRY 10. 161:692–694 therapy program for mothers with postpartum mental disorders: 31. and treatment. Kirov G. 35. Am J Psychiatry 2010. diagnosis. lease in postpartum depression and psychosis. Webster MJ: Postpartum mania in 2004. 9:285–288 30. Vilaseca MA. 14:89–98 Scale. Psychiatry Res 1997. 23:3–17 meta-analysis. Ahokas A. Psy. Ziegler VE. Bergink V. Br J Psychiatry 1978. et al: The longitudinal course of 19. Hirschfeld RM. 56:17–19 42. 44:234–246 zine in the treatment of psychoses associated with childbearing. 158:393–397 51. Post RM. Lisse. Thippeswamy H. Protheroe C: Puerperal psychoses: a long term study. et al: Propranolol versus chlorproma. Atkinson S. Biggs JT. et al: Modification of the chopharmacology (Berl) 1999. de Jong H: Clinical treatment of post 36. Jones I. Hohm E. et al: Defining the clinical 166–169 course of bipolar disorder: response. Munk-Olsen T. and sensitivity. Ox- 25. 152:1641– actions in postpartum psychotic disorders. 40:7–14 puerperal psychosis. Lambregtse-van den Berg MP. Arch Women Ment Health 2013. Oxford. Aito M: Role of estradiol in puerperal psychosis. Young RC. 4:19 bipolar manic-depressive patients withdrawn from lithium car. Doucet S. Kellner CH: Electroconvulsive therapy (ECT) in the 2006. Sharma V: Pharmacotherapy of postpartum psychosis. remission. 166: nity. J Clin Psychiatry 2011. 5:98–105 49. Bipolar Disord 2014. Stewart DE. 168:576–580 landse Versie). 76:421–426 dysregulation in first-onset postpartum psychosis. Atkinson T: Puerperal psychosis: a personal experi. Letourneau N. 72:1531– agement. Bergink V. Sagovsky R: Detection of postnatal depres- prevention and treatment of postpartum psychosis: a systematic sion: development of the 10-item Edinburgh Postnatal Depression review Arch Womens Ment Health 2010. Frye MA. Leverich GS. Psychopharmacol Bull 2007. 1996 postpartum affective disorders. Arch Womens Ment Health 2013. 101:167–169 41. 78:679–684 psychosis and mania in women at high risk. Nervenarzt 2007. 1927–1961. Noorlander Y. Craddock N. Kendell RE. Babu GN. et al: Structured Clinical In- psychosis revealing a late-onset urea cycle disorder. Aito M. February 2015 ajp. Am J Psychiatry 2009. BV. Jones I. Doucet S. Jones I. Aito M. 147:108–110 Clinical Global Impressions (CGI) Scale for use in bipolar illness 17. van den Berg MP: Perceived and ob- rullinemia type I as differential diagnosis to postpartum psychosis served mother-child interaction at time of hospitalization and re- in the puerperal period. Beenen F. 8:314–326 psychopathology in bipolar spectrum disorders. Post RM: Sensitization and kindling perspectives for the course of 27. Acta Psychiatr Scand 2000. 52. Cipriani A. Arch Women Ment 149:228–229 Health 2008. Davenport YB. psychiatric disorders. Health Visit 1983. 39. Block ML. Ritchie HL: Bipolar II postpartum depression: 32. Jones I. Bouvy PF. Rimón R: Positive treatment effect of estradiol (BP): the CGI-BP. et al: The Bipolar Affective Disorder partum delirium with perfenazine and lithium carbonate. detection. 11:49–56 13. Blum I. 167:476–477 Am J Psychiatry 172:2. et al: Prevention of postpartum first results of a pilot project]. BMC Psychiatry 14. Koorengevel KM. J ECT 2012. et al: Interventions for the 38. Br review. Prog 23. 4:1651–1658 rodegeneration: multiple triggers with a common mechanism. J ECT 2007. Pearson B.