In This article

• Postpartum psychosis is a medical emergency requiring rapid assessment, psychiatric hospitalization, safety planning, and initiation of treatment.
  
• Evidence supports a treatment algorithm using benzodiazepines, antipsychotics, and lithium, with most women achieving remission only with the addition of lithium.
  
• Antipsychotic monotherapy may lead to higher relapse rates; lithium has the strongest evidence for relapse prevention in the first postpartum year.
  
• ECT is a highly effective option, particularly for cases with catatonia, severe suicidality, or psychotic depression, and may be considered early.
• Long-term mood stabilizer treatment is recommended for women with bipolar disorder. Preconception counseling is recommended prior to future pregnancies.

We have relatively few studies to guide our treatment decisions when it comes to postpartum psychosis (PPP), and many published studies predate the widespread use of atypical antipsychotic agents, which are now first-line medications for psychotic symptoms and are commonly used in individuals with mood disorders.

Because postpartum psychosis is a psychotic illness, most women will receive treatment with an antipsychotic medication. However, given the strong association between postpartum psychosis and bipolar disorder, the use of mood stabilizers, particularly lithium, is also important to consider. In addition, electroconvulsive therapy (ECT) is a rapidly effective treatment option in severe or treatment-resistant cases.

Hospitalization: Postpartum Psychosis Is a Psychiatric Emergency

Before considering specific medications, it must be emphasized that PPP is a medical emergency, and inpatient psychiatric admission is recommended for individuals with postpartum psychosis. Inpatient treatment allows for diagnostic evaluation and initiation of treatment. Moreover, inpatient care ensures the safety of both mother and child and facilitates close monitoring during the acute phase of illness.

Treatment focuses on rapid symptom stabilization, prevention of suicide and harm to the infant, restoration of sleep, and management of medication safety during breastfeeding. If needed, ECT can be used in an inpatient setting for severe, rapidly deteriorating, or treatment-resistant cases.

While the ideal treatment setting is a mother–baby unit where the mother and her child are hospitalized together, mother–baby units are not widely available in the United States. In addition, mothers with PPP may present with agitation, delusional thinking, and impaired judgment, symptoms that may limit their ability to safely and consistently participate in the care of their infant.

So What Is the Best Medication for Postpartum Psychosis?

In the absence of formal, widely adopted guidelines for postpartum psychosis, clinical practice is typically based on addressing the most prominent symptoms. Benzodiazepines are used for insomnia and agitation, antipsychotics and mood stabilizers for psychotic and manic symptoms, and antidepressants for depressive symptoms. Often, multiple medications are used concurrently to achieve remission.

Based on clinical observations and data from naturalistic studies, the best approach to PPP resembles the treatment of acute mania with psychotic features in non-perinatal populations. In this setting, the primary goal is to treat the current episode while choosing a regimen that is also effective for preventing recurrence of both postpartum and non-postpartum mood episodes.

Treatment recommendations are largely based on naturalistic cohort studies and expert consensus. The largest study to date, including 64 patients with postpartum psychosis, supports the efficacy of a structured, sequential approach involving benzodiazepines, antipsychotics, lithium, and ECT. Using this algorithm, 98% of hospitalized patients with PPP achieved remission.

Bergink and colleagues developed a four-step standardized treatment algorithm; this is the only study that has prospectively assessed effectiveness.

Step 1: Benzodiazepines at bedtime for 3 days. 

Starting with benzodiazepines allows the clinician to evaluate whether restoration of sleep results in clinical remission of manic and psychotic symptoms.

Step 2: Addition of an antipsychotic.
For patients with persistent manic or psychotic symptoms, the next step involves adding an antipsychotic medication. Treatment with a combination of benzodiazepines and antipsychotics is recommended for approximately 2 weeks.

Step 3: Addition of lithium.
If at 2 weeks there is no significant clinical response, adjunctive lithium is recommended. This recommendation is based on a small open-label study and case reports suggesting that the combination of lithium and antipsychotics is more effective than antipsychotic monotherapy and that lithium is effective in preventing recurrent mood episodes and postpartum psychosis

Step 4: Consideration of ECT.
At 12 weeks, ECT should be considered in patients whose symptoms have not responded to combination treatment with benzodiazepines, antipsychotics, and lithium. Case reports and case series have described positive treatment outcomes with ECT in women with PPP, including those with treatment-refractory symptoms.

In this stepwise treatment study, 6.3% of women achieved remission with a benzodiazepine alone, 18.8% with a combination of benzodiazepine and antipsychotic, and 73.4% with a combination of benzodiazepine, antipsychotic, and lithium. Notably, in this cohort, all participants remitted by the stage at which lithium was added.pmc.ncbi.nlm.nih+1

Taking a Multi-Pronged Approach

While the four-step algorithm is a thoughtful and carefully researched approach with proven efficacy, several practical issues arise in acute clinical settings.

The efficiency of treatment is critical in PPP, given the severity and rapid onset of symptoms.

• Psychotic symptoms may compromise the patient’s capacity to adhere to a prolonged stepwise regimen.
  Agitation is common, and delaying treatment with antipsychotics may put the patient, staff, and infant at risk.

A later iteration of this algorithm from Jairaj and colleagues did not specify a specific timeline for each step but instead argued for tailoring the pace of treatment escalation to illness severity and clinical response.

Given that 73.4% of women in Bergink’s study required a regimen combining benzodiazepines, an antipsychotic, and lithium, one could argue for a more “kitchen sink” approach during the acute phase of treatment. Rather than waiting to see if a single medication strategy works, acute treatment would involve early and concurrent initiation of benzodiazepines, an antipsychotic, and lithium. 

At our site, we usually recommend the following approach to postpartum psychosis:

• Lorazepam: For managing agitation, sleep disruption, and catatonic symptoms. Key advantages include its relatively short half-life and flexible routes of administration (oral, intravenous, or intramuscular). Typical doses of lorazepam start at 0.5 to 1 mg three times daily, titrated as needed to manage symptoms. Dose may be reduced if excessive sedation occurs.
• Antipsychotic Medications: We typically use second-generation antipsychotics. While olanzapine may not be an ideal long-term choice due to weight gain and sedation, it is an excellent short-term option for managing psychotic symptoms, agitation, sleep disruption, and mood instability. Second-generation antipsychotics are preferred over first-generation agents when catatonia is present because they exert lower dopamine antagonism and are therefore less likely to worsen catatonic symptoms. Aripiprazole may also be considered given its partial agonist activity at dopamine receptors.
• Lithium: Although underutilized, lithium should be considered a first-line treatment for PPP. In the study by Bergink and colleagues described above, 73.4% of patients did not achieve remission until lithium was added to the regimen. In this setting, lithium dosing is comparable to that used to treat acute mania in patients with non-puerperal bipolar disorder, with a target serum level of approximately 0.8 to 1.0 mmol/L.

ECT: ECT is highly effective and should be considered early in cases of PPP associated with catatonia, high suicidal risk, or severe psychotic depression. Overall, postpartum episodes respond well to ECT, and response appears to be more robust during the postpartum period compared to episodes occurring outside the postpartum window. Although ECT is typically not considered a first-line intervention, its rapid onset of action may make it an attractive option in situations where there is imminent risk or poor response to pharmacotherapy.sciencedirect+2

Maintenance Treatment and Relapse Prevention

While remission with antipsychotic monotherapy has been described in case reports of postpartum psychosis, antipsychotics alone have been associated with higher relapse risk within the first postpartum year. Bergink and colleagues demonstrated that lithium is protective against relapse during the first postpartum year, especially when used as maintenance after combination treatment in the acute phase.

The optimal duration of maintenance treatment after remission is not well established. In the Bergink algorithm, maintenance treatment consisted of gradual discontinuation of benzodiazepines once symptoms had resolved. Women treated with antipsychotics and lithium were advised to taper off antipsychotics and continue lithium monotherapy for 9 months postpartum. Women treated with antipsychotic monotherapy were also advised to continue therapy for 9 months, but this group had higher relapse rates during the first postpartum year compared to those continuing lithium.

If there is a clear diagnosis of bipolar disorder preceding the episode of postpartum psychosis, we recommend long-term treatment with a mood stabilizer to reduce the risk of relapse. 

Preconception counseling is essential prior to subsequent pregnancies, as women who have had one episode of postpartum psychosis are at significantly increased risk for recurrence in future postpartum periods.

MGH P3 Support Line

In addition to the MGH P3 Support Line, which offers free brief consultations to medical providers caring for patients with postpartum psychosis via MGHP3.org, there are other resources available for clinicians seeking real-time guidance. 

Postpartum Support International (PSI) operates a national Perinatal Psychiatric Consult Line (1-877-499-4773) that allows clinicians to discuss diagnostic questions and treatment options with perinatal mental health specialists, and also coordinates a growing network of state-based perinatal psychiatry access programs that provide provider-to-provider consultation across the United States. These access lines can be particularly helpful for clinicians in settings without local perinatal psychiatry expertise who are managing complex cases such as postpartum psychosis and need support with medication selection, risk–benefit discussions, and care coordination.

Where to Find Information on the Treatment of Postpartum Psychosis?

Most clinicians do not have familiarity with the treatment and management of postpartum psychosis. We recommend seeking the input of providers with expertise in the treatment of perinatal mood and anxiety disorders; however, it may be difficult to access a perinatal psychiatrist in a timely fashion. Several resources are available for clinicians, patients and families so that they can obtain evidence-backed information on postpartum psychosis and its treatment. 

For clinicians:

The Mass General Hospital MGH P3 Support Line provides free brief consultations for medical providers caring for patients with postpartum psychosis. Website: MGHP3.org.

PSI Perinatal Psychiatric Consult Line: Postpartum Support International offers Phone consultation with perinatal mental health specialists about diagnosis and treatment, including complex cases of postpartum psychosis. Phone: 1-877-499-4773.

Perinatal Psychiatry Access Programs are a network of state-based programs that provide provider-to-provider consultation across the United States. These access lines can be particularly helpful for clinicians in settings without local perinatal psychiatry expertise. For a current listing of perinatal psychiatry access programs by state, clinicians can visit the Postpartum Support International directory of state perinatal psychiatry access lines.

For Patients and Families:

Postpartum Support International (PSI) HelpLine provides emotional support, information, and help connecting to local resources. Call or text: 1-800-944-4773.

National Maternal Mental Health Hotline provides 24/7 support for pregnant and postpartum individuals and their families. Call or text: 1-833-TLC-MAMA (1-833-943-5746). 

—Ruta Nonacs, MD PhD