Initiate an atypical antipsychotic such as olanzapine for acute psychotic symptom management and a mood stabilizer such as lithium given the presentation's resemblance to bipolar disorder with psychotic features and the strong family history, with temporary discontinuation of breastfeeding during acute treatment and a plan to reassess lactation compatibility once stabilized

Breastfeeding should be temporarily discontinued during acute treatment with plans to reassess once the patient is stabilized, as the immediate priority is treating the psychotic episode. Lithium is particularly important given the high recurrence risk of postpartum psychosis and its role in relapse prevention. Plan for close monitoring of lithium levels and renal and thyroid function. Postpartum psychosis is most closely related to bipolar disorder and treatment follows bipolar psychosis guidelines. The combination of an atypical antipsychotic for acute symptom management plus lithium as a mood stabilizer addresses both immediate psychosis and the high recurrence risk. Lithium has specific evidence for preventing recurrence of postpartum psychosis in subsequent pregnancies.

Start a low dose of an SSRI such as sertraline

Since it is the safest antidepressant during breastfeeding, combined with a low-dose atypical antipsychotic such as quetiapine 25 mg at bedtime for sleep restoration. The psychotic symptoms likely reflect severe postpartum depression with psychotic features, and the SSRI will address the underlying mood disorder while the low-dose antipsychotic targets insomnia and acute psychosis. Sertraline has extensive safety data for breastfeeding mothers and allows the patient to continue nursing, which promotes maternal-infant bonding critical in the postpartum period. This presentation is consistent with postpartum psychosis related to bipolar disorder, not psychotic depression.

Begin valproic acid as a mood stabilizer with antimanic properties and add haloperidol for rapid control of the acute psychotic symptoms

Valproic acid has robust evidence for acute mania treatment and can be loaded for rapid therapeutic levels. Haloperidol provides potent dopamine blockade for hallucinations and disorganized thinking. Both medications are compatible with breastfeeding at appropriate monitoring levels. This combination provides the most aggressive acute treatment for a psychiatric emergency with risk for harm to self and infant. While valproic acid treats acute mania, it lacks the specific evidence lithium has for postpartum psychosis recurrence prevention, which is a critical consideration given the high relapse rate. Valproic acid also has significant teratogenic risk if subsequent pregnancies occur, making it less desirable in reproductive-age women.

Initiate brexanolone infusion as it is the only FDA-approved treatment specifically for postpartum mood disorders and addresses the neurosteroid changes underlying the postpartum psychiatric presentation

Supplement with lorazepam for acute agitation and psychotic symptom management while the brexanolone takes effect over the 60-hour infusion. This targeted neurosteroid approach addresses the specific pathophysiology of postpartum psychiatric illness rather than applying generic psychiatric treatments to a condition with a unique neuroendocrine etiology. Brexanolone is FDA-approved for postpartum depression, not postpartum psychosis, which is a distinct and more severe condition. Postpartum psychosis is a psychiatric emergency most closely related to bipolar disorder and requires treatment with mood stabilizers and antipsychotics. Lorazepam does not treat psychosis and benzodiazepine monotherapy is inadequate for managing hallucinations, delusions, and mania.