Postpartum Depression with Comorbid Anxiety: Optimizing Treatment
Postpartum anxiety is a common and often under-recognized condition that affects a substantial proportion of new mothers. Recent studies estimate that between 20% and 34% of women experience significant anxiety symptoms in the weeks and months following childbirth. While some degree of worry is normal for new parents, postpartum anxiety is characterized by persistent, excessive worry, intrusive thoughts, and physical symptoms such as restlessness, sleep disturbance that interfere with daily functioning and maternal well-being. Importantly, postpartum anxiety can occur on its own or alongside postpartum depression, and many women experience both conditions simultaneously.
The clinical presentation of postpartum anxiety is diverse. Symptoms may include constant or near-constant worry about the baby’s health and safety, racing thoughts, a sense of dread, irritability, and difficulty sleeping—even when the baby is resting. Some women may experience panic attacks or develop postpartum obsessive-compulsive disorder, marked by intrusive, distressing thoughts about harm coming to their infant.
Listen to the latest episode of So Glad You Asked with Dr. Ruta Nonacs:
We’re Here To Help You Answer: Do I Have Postpartum Depression or Anxiety?”
Multiple studies have demonstrated the effectiveness of antidepressant medications for the treatment of postpartum depression (PPD). Most of these studies focused on the impact of these medications on depressive symptoms; however, it is clear that many, or maybe most, women with PPD also have significant anxiety symptoms. Thus, we can hypothesize that medications which have both antidepressant and anxiolytic effects would be the most beneficial for the treatment of PPD.
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are widely recognized as first-line pharmacologic agents for moderate-to-severe postpartum depression (PPD), and their use extends to the management of postpartum anxiety.
Clinical studies support the effectiveness of SSRIs for treating both depressive and anxiety symptoms in the postpartum period. Notably, a 12-week clinical trial from Misri and colleagues evaluated paroxetine monotherapy and paroxetine combined with cognitive behavioral therapy (CBT) in women with postpartum depression and comorbid anxiety symptoms. Both treatment arms demonstrated significant improvement in depressive and anxiety symptoms, with high response rates (87.5% for paroxetine alone and 78.9% for combination therapy).
While women with generalized anxiety and panic disorder may respond to typical doses of SSRIs, those with OCD symptoms may require higher doses of an SSRI and longer duration of treatment to achieve remission.
Serotonin-Norepinephrine Reuptake Inhibitors
Serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine, desvenlafaxine, and duloxetine are increasingly considered in the pharmacologic management of postpartum depression. While SSRIs remain the first-line agents, SNRIs offer an alternative for women who do not respond to or tolerate SSRIs, and it is believed that their dual mechanism of action may be advantageous in cases where both depressive and anxiety symptoms are significant
This hypothesis is supported by the finding that venlafaxine (Effexor) is highly effective for the treatment of PPD. In this study, despite very high levels of depressive symptoms at baseline, 12 out of 15 subjects experienced remission of major depression (HAM-D score
In another study from Misri and colleagues, 25 women with PPD and comorbid anxiety were treated in an open trial with flexible dosing of desvenlafaxine (50–100 mg). The majority of women responded to medication (88.2%) and experienced a remission of depression (82.4%) and anxiety symptoms (82.4%).
Benzodiazepines
Benzodiazepines may play a valuable adjunctive role in the management of postpartum depression with comorbid anxiety, particularly when accompanied by severe sleep disturbance. While antidepressants such as SSRIs and SNRIs are the mainstay of pharmacologic treatment for PPD, their therapeutic effects can take several weeks to become fully apparent. During this period, women suffering from severe anxiety and insomnia may benefit from the short-term, adjunctive use of a benzodiazepine, which can offer rapid symptom relief and help stabilize sleep patterns.
The acute relief provided by benzodiazepines can be particularly helpful for women experiencing debilitating insomnia, which is both a risk factor for and a symptom of PPD. In clinical practice, low-dose benzodiazepines are sometimes prescribed at the initiation of antidepressant therapy, with the intention of tapering and discontinuing them once the antidepressant becomes effective (typically after 2–3 weeks). This approach can help bridge the gap for women who are struggling with overwhelming anxiety or sleep loss, improving their overall functioning and potentially enhancing adherence to longer-term treatment.
Zuranolone
Zuranolone, a neuroactive steroid and positive allosteric modulator of GABA-A receptors, has emerged as a novel, rapid-acting oral treatment for postpartum depression. Recent clinical trials and post-hoc analyses have demonstrated the efficacy of zuranolone not only in alleviating depressive symptoms but also in addressing co-occurring anxiety symptoms and insomnia.
In a phase 3, double-blind, randomized, placebo-controlled study, zuranolone demonstrated significant and rapid improvements in both depressive and anxiety symptoms compared to placebo. In this study, women diagnosed with PPD received oral zuranolone 30 mg daily for 14 days. Anxiety was assessed using validated scales, including the Hamilton Anxiety Rating Scale (HARS), the HDRS-17 Anxiety/Somatization subscale, and the Edinburgh Postnatal Depression Scale anxiety subscale.
Anxiety symptoms improved to a greater degree with zuranolone than with placebo as early as day 3, with sustained benefits through day 45. Importantly, zuranolone was also associated with improvements in insomnia symptoms and overall functioning.
Clinical Guidelines
Routine and systematic screening for postpartum depression and anxiety is essential for early identification and intervention. Validated instruments such as the Edinburgh Postnatal Depression Scale (EPDS) can identify anxiety symptoms; however, screening can be supplemented with anxiety-specific screening instruments, such as the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Perinatal Anxiety Screening Scale (PASS).
Screening should occur at key time points: initial prenatal visit, later in pregnancy, and at postpartum visits, as well as during well-child visits at 1, 2, 4, and 6 months postpartum. When screening results are positive, further diagnostic evaluation is necessary to confirm the diagnosis and determine the appropriate treatment plan.
Non-pharmacological interventions, such as cognitive-behavioral therapy (CBT), are a cornerstone of treatment for mild to moderate PPD and anxiety, and are often recommended as first-line or adjunctive therapies.
Medication should be considered If anxiety or depressive symptoms are severe or are compromising the mother’s ability to care for her. SSRIs and SNRIs should be considered for the management of postpartum anxiety symptoms, whether they co-occur with depression or not. Adjunctive benzodiazepines may be helpful for the short-term management of severe anxiety and insomnia.
For women with PPD and comorbid anxiety, zuranolone represents a significant advance, offering rapid and concurrent improvements in depressive, anxiety, and insomnia symptoms.
Ruta Nonacs, MD PhD
References:
Cohen LS, Viguera AC, Bouffard SM, Nonacs RM, Morabito C, Collins MH, Ablon JS. Venlafaxine in the treatment of postpartum depression. J Clin Psychiatry. 2001 Aug; 62(8):592-6.
Deligiannidis KM, Citrome L, Huang MY, Acaster S, Fridman M, Bonthapally V, Lasser R, Kanes SJ. Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression. J Clin Psychiatry. 2023 Jan 30; 84(1):22m14475.
Misri S, Reebye P, Corral M, Milis L. The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial. J Clin Psychiatry. 2004 Sep;65(9):1236-41.
Misri S, Swift E, Abizadeh J, Shankar R. Overcoming functional impairment in postpartum depressed or anxious women: a pilot trial of desvenlafaxine with flexible dosing. Ther Adv Psychopharmacol. 2016 Aug;6(4):269-76.
