Postpartum Mood and Anxiety Disorders Minnesota Psychiatric Society October 1, 2016 Michelle Wiersgalla, MD Women s Reproductive Mental Health Program Park Nicollet Health Services PMADs: The Basics PMADs = Perinatal Mood and Anxiety Disorders Baby Blues Mood disorders (depression, bipolar disorder, etc.) Anxiety disorders (panic, generalized anxiety disorder, OCD, PTSD, etc.) Psychosis (schizophrenia, mania, depression, etc.) 1
What percentage of women will experience postpartum depression or anxiety? A) 1-3% B) 6-8% C) 10-25% D) 95% What percentage of women will experience postpartum depression or anxiety? A) 1-3% B) 6-8% C) 10-25% D) 95% About Perinatal Mood and Anxiety Disorders (PMADs) 70-80% of new mothers will experience the baby blues 15-20% will experience postpartum depression 10-25% develop an anxiety disorder 0.1-0.2% develop postpartum psychosis Of all women who will experience depression in their lifetimes, 50% will have their first episode after having a baby. When do symptoms present? Anytime within the first 12 months, often in the first 2-4 months postpartum, sometimes during pregnancy 2
Previous history of psychiatric illness increases risk What is the risk of PMADs? No history of psychiatric illness: 10-20% History of major depression: 25% History of depression during pregnancy: 35+% History of bipolar disorder or postpartum depression: 23+% if meds continued 66+% if off meds 17+% will be severe illness History of postpartum psychosis: 30-90% 29+% will be severe illness Screening JAMA January 2016: US Preventive Services Task Force recommends screening all pregnant and postpartum women for depression Risks: mental health care is in short supply so referral may be difficult Validated screening tools: EPDS, PHQ9, MDQ, others Which of the following are risk factors for PMADs? A) Thyroid disorders B) Discontinuation of psychiatric medications C) Breastfeeding difficulties D) Past history of depression E) All of the above 3
Which of the following are risk factors for PMADs? A) Thyroid disorders B) Discontinuation of psychiatric medications C) Breastfeeding difficulties D) Past history of depression E) All of the above Causes of PMADs The specific cause of PMADs is unknown, but it is likely multifactorial. Physical changes such as a obstetric complications, dramatic drop in progesterone, thyroid dysregulation, changes in immune functioning, use of DMPA contraception, may contribute to mood changes. Emotional factors such as anxiety about caring for the newborn, sleep deprivation, a sense of loss of control, or a struggle with one s sense of individual identity, also may contribute to the onset of depression and anxiety. Physical Changes Environmental factors such as a colicky baby or demanding older child, having a very pre-term infant, financial problems, difficulty with breastfeeding, relationship problems, family history of mental illness, or other stressors may play a causal role. Discontinuation of an antidepressant during or just prior to pregnancy increases the risk of PMADs. Up to 68% of women who stop medication will relapse, many within a few weeks. Environmental Factors Emotional Factors Diagnosis 4
The Baby Blues The baby blues are characterized by mild symptoms of depression with no impairment in functioning. This occurs within the first 2 weeks postpartum and is experienced by 70-80% of women. Symptoms tend to peak around the fourth or fifth day postpartum and gradually remit on their own, but some of women with baby blues will go on to develop postpartum depression. The baby blues do not indicate pathology and no treatment is needed other than reassurance, monitoring, and family support. Severe blues may be difficult to distinguish from early signs of postpartum depression or psychosis. Typical Symptoms: Mood reactivity Irritability Anxiety Tearfulness Trouble sleeping Poor concentration Easily overwhelmed Case example Alyssa is a 32 y.o. woman who is 3 weeks postpartum after having her first child. She has past diagnoses of major depression and generalized anxiety disorder predating her pregnancy, but worsened symptoms since the baby was born. She tearfully says I keep having these flashes of images pop into my head about the baby getting hurt, like what if I dropped him down the stairs and he broke his arm or what if I roll over onto him while we re napping together and he can t breathe? It s so scary, I don t know where these thoughts are coming from. I love him so much, I d never hurt him. Which of the following are in the differential diagnosis? A) Major depressive episode, postpartum onset B) Generalized anxiety disorder C) OCD D) Postpartum psychosis E) All of the above are in the differential Case example Alyssa is a 32 y.o. woman who is 3 weeks postpartum after having her first child. She has had past diagnoses diagnoses of major depression and generalized anxiety disorder predating her pregnancy, but worsened symptoms since the baby was born. She tearfully says I keep having these flashes of images pop into my head about the baby getting hurt, like what if I dropped him down the stairs and he broke his arm or what if I roll over onto him while we re napping together and he can t breathe? It s so scary, I don t know where these thoughts are coming from. I love him so much, I d never hurt him. Which of the following are in the differential diagnosis? A) Major depressive episode, postpartum onset B) Generalized anxiety disorder C) OCD D) Postpartum psychosis E) All of the above are in the differential but this sounds most like GAD exacerbation or OCD 5
In women with postpartum depression or anxiety, how many have intrusive thoughts about the baby being harmed or injured? A) 1-2% B) 5-10% C) 10-30% D) 40-90% In women with postpartum depression or anxiety, how many have intrusive thoughts about the baby being harmed or injured? A) 1-2% B) 5-10% C) 10-30% D) 40-90% Postpartum Depression (PPD) Postpartum depression (PPD) is much more serious than the baby blues because it impairs the mother s functioning (her ability to care for herself and the baby). It affects approximately 17% of women. Symptoms typically begin 2 weeks to 4 months after delivery. However, some women have a delayed onset so symptoms may occur any time within the first year. It s common to have anxiety as well as depression. One symptom that can be quite upsetting to a mother is having scary thoughts about the baby s safety, or intrusive thoughts of herself harming the baby. These should be assessed thoroughly, but in most cases, they do not indicate that the baby is unsafe or that the mother is at risk of following through with the thoughts. Studies show 41-89% of mothers with with postpartum depression or anxiety report having these types of thoughts. Typical Symptoms: Intense irritability, anger, or mood swings Sad mood Crying spells (often untriggered) Insomnia Loss of appetite or overeating Overwhelming fatigue Loss of interest Withdrawal from family & friends Guilt & negative thoughts about her mothering Ambivalent or negative thoughts towards the baby Thoughts of harming herself or the baby 6
Depression 50% of women with postpartum depression experienced depression symptoms during pregnancy Treating depression during pregnancy helps to prevent postpartum depression Postpartum Anxiety (PPA) 10-25% of women will experience postpartum anxiety which can manifest as obsessive thinking, excessive worries, panic attacks, severe insomnia, distorted thinking, or intrusive thoughts. It s common to have a combination of depression and anxiety symptoms. Postpartum obsessive compulsive disorder typically occurs within the first 12 weeks after delivery. The most common obsessive thought is accidentally harming the baby. These thoughts are intrusive and produce significant distress in the mother. Women are often ashamed to reveal these thoughts. These obsessive thoughts may be extreme and unlikely to actually happen but they are NOT out of touch with reality and do NOT represent actual plans to harm the baby. Women may present with fears of contaminating the baby or with excessive worries about the baby s health, sometimes accompanied by frequent calls and trips to the pediatrician. Common Themes of Anxious Thoughts: The baby dying in its sleep. Harming the child with a knife or by shaking. Accidents or mistakes leading to injury or death. Sexual misconduct involving the child. Case example Bethany is a 32 y.o. woman who is 1 week postpartum after having her first child she is scheduled to see you for an initial evaluation. She has been diagnosed by a past provider with bipolar 2 disorder and anxiety disorder NOS. Her husband accompanies her and says she doesn t seem like herself. The patient herself is vague about her symptoms, but you notice flat affect, staring eye contact, and according to her husband she has seemed out of it, confused at times. Part way into the interview, she mentions that all baby formula is poison. She later says, without demonstrating any accompanying affect, that she knows the baby will die if she feeds him formula. She has not slept well, even when she has the opportunity to sleep, and she says this is in part because she thinks her mother-in-law will try to give the baby formula while she (the pt) is sleeping. What do you do? A) Hospitalize for safety and further work-up. B) Reassure her and her family that this is simply postpartum depression. C) Start sertraline to treat presumptive postpartum depression. D) Start an antipsychotic medication such as olanzapine to help her sleep. 7
Case example Bethany is a 32 y.o. woman who is 1 week postpartum after having her first child she is scheduled to see you for an initial evaluation. She has been diagnosed by a past provider with bipolar 2 disorder and anxiety disorder NOS. Her husband accompanies her and says she doesn t seem like herself. The patient herself is vague about her symptoms, but you notice flat affect, staring eye contact, and according to her husband she has seemed out of it, confused at times. Part way into the interview, she mentions that all baby formula is poison. She later says, without demonstrating any accompanying affect, that she knows the baby will die if she feeds him formula. She has not slept well, even when she has the opportunity to sleep, and she says this is in part because she thinks her mother-in-law will try to give the baby formula while she (the pt) is sleeping. What do you do? A) Hospitalize for safety and further work-up. B) Reassure her and her family that this is simply postpartum depression. C) Start sertraline to treat presumptive postpartum depression. D) Start an antipsychotic medication such as olanzapine to help her sleep. Postpartum Psychosis Postpartum psychosis (PPP) is an acute, severe illness occurring at a rate of 0.25-2 per 1,000 births. It is notable for its abrupt onset; typically between day 3-10 postpartum. (New onset psychosis is even more rare during pregnancy vs during the postpartum.) Acute episodes may last 1-2 months. Symptoms of postpartum psychosis can be difficult to elicit. Collateral history can be very useful. Thoughts or attempts to harm baby or self are often reported as thoughts that the baby would be better off dead or better off if mom were not around (delusions of altruistic homicide ). These thought may represent religious delusions, the mother s fixed false belief that she is incapable, delusions that the baby is defective, or other thinking that reflects a break with reality. True or False: A woman with symptoms of postpartum psychosis needs mental health assessment immediately, and likely inpatient psychiatric admission. A) True B) False 8
True or False: A woman with symptoms of postpartum psychosis needs mental health assessment immediately, and likely inpatient psychiatric admission. A) True B) False Postpartum Psychosis Many researchers and clinicians believe that postpartum psychosis is a manifestation of bipolar disorder. This is an important clinical point because antidepressants could worsen symptoms if a woman has previously undiagnosed bipolar disorder. Postpartum psychosis is a PSYCHIATRIC EMERGENCY and requires immediate assessment by a mental health professional. In one study, up to 5% of women with postpartum psychosis committed suicide and 4% committed infanticide. Typical Symptoms: Confusion and disorganized thoughts May look like delirium Extreme mood lability, irritability Insomnia Paranoia Delusions often related to the theme of childbirth Thoughts or attempts to harm self or baby Delusions of altruistic homicide Postpartum Psychosis Possible Etiologies Genetics Variations in serotonin transporter gene Hormones Decline in estrogen and/or progesterone levels Cortisol/dopamine interactions Immune/inflammatory Associations with thyroiditis and/or preeclampsia Autoimmune encephalitis (anti-nmda in some, unknown antigen in others) Monocytosis Circadian rhythm disruption 9
Possible Organic Etiologies for PMADs The differential diagnosis of PMADs should include possible organic causes of the symptoms. A medical assessment should be undertaken if indicated, to rule out organic etiologies such as: Postpartum thyroid dysfunction/grave s disease Sheehan s Syndrome (pituitary infarction due to postpartum hemorrhage can lead to fatigue, weight loss, etc) Intoxication/withdrawal states Pregnancy-related autoimmune disorders Postpartum thyroiditis Autoimmune encephalitis (anti-nmda receptor autoantibodies) in postpartum psychosis The diagnosis of anti-nmdar encephalitis is confirmed by the detection of IgG antibodies to the GluN1 (also known as NR1) subunit of the NMDAR in serum or CSF Anti-NMDA receptor encephalitis (UTDOL) Anti-NMDA receptor encephalitis Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with a predictable set of symptoms that combine to make up a characteristic syndrome. Many patients present with prodromal headache, fever, or a viral-like process, followed in a few days by a multistage progression of symptoms that include: Prominent psychiatric manifestations (anxiety, agitation, bizarre behavior, hallucinations, delusions, disorganized thinking); isolated psychiatric episodes may rarely occur at initial onset or at relapse. Insomnia. Memory deficits. Seizures. Decreased level of consciousness, stupor with catatonic features. Frequent dyskinesias: orofacial, choreoathetoid movements, dystonia, rigidity, opisthotonic postures. Autonomic instability: hyperthermia, fluctuations of blood pressure, tachycardia, bradycardia, cardiac pauses, and sometimes hypoventilation requiring mechanical ventilation. Language dysfunction: diminished language output, mutism. Echolalia is often noted in the early stages or in the recovery phase of the disorder. CSF lymphocytic pleocytosis or oligoclonal bands (although CSF can be normal initially). EEG with infrequent epileptic activity, but frequent slow, disorganized activity that does not correlate with most abnormal movements. In one study, 7 of 23 adults had a unique electrographic pattern called extreme delta brush, a finding associated with a more prolonged illness. Brain MRI that is often normal or shows transient FLAIR or contrast enhancing abnormalities in cortical (brain, cerebellum) or subcortical regions (hippocampus, basal ganglia, white matter). While not routinely performed, positron emission tomography reportedly shows a characteristic change of increased fronto-to-occipital gradient of cerebral glucose metabolism which correlates with disease severity. Risks Associated with Untreated PMADs 10
Which of the following have been identified as outcomes of not treating PMADs? A) Increased drug, alcohol, and tobacco use by mothers B) Less success with breastfeeding C) Aggressive behaviors in toddler and school-age offspring D) Increased rates of ADHD in offspring E) All of the above Which of the following have been identified as outcomes of not treating PMADs? A) Increased drug, alcohol, and tobacco use by mothers B) Less success with breastfeeding C) Aggressive behaviors in toddler and school-age offspring D) Increased rates of ADHD in offspring E) All of the above Risks Associated with Untreated PMADs Poor self-care Poor nutrition Poor sleep Depression relapse with med discontinuation (68%) Bipolar relapse with med discontinuation (>70% total may relapse, with 50% relapsing within 2 weeks) Increased risky behaviors in mania Higher rates of drug, alcohol, and tobacco use during pregnancy 11
Risks Associated with Untreated PMADs Babies with more difficult temperaments Less success with breastfeeding Difficulty with bonding/attachment Poorer adherence to sound safety and discipline practices (back sleeping, baby gates, TV time, spanking, etc.) Higher rate of developmental delays by 18 mos Higher rates of later psychiatric illness in the child Risks Associated with Untreated PMADs (by developmental age) Infants: colic, less vocalizing, less exploration Toddlers: insecure attachment, lower self-esteem, aggression, motor delays Preschoolers: anxiety, aggression, behavioral problems, deficits in cognitive development School age: aggression, anger, poorer cognitive processing, sleep problems, anxiety, ADHD Teens: conflicts with family/peers, depression, school problems, anxiety Risks Associated with Untreated PMADs Suicide Lifetime suicide risk for women with major depressive disorder is ~1%. Wisner 2013: Suicide accounts for about 20 percent of postpartum deaths and is the second most common cause of mortality in postpartum women. Infanticide The rate of homicide of infants up to 1 year of age is 8 per 100,000 in the United States More commonly associated with postpartum psychosis than with depression or anxiety 12
Treatment: Overview Treatment: The Baby Blues This condition usually resolves within a few days to weeks without medical intervention. Reassurance, support, and education are enough in most cases. Women should be monitored to ensure that their symptoms do not persist or evolve into more severe illness. Women with the baby blues should be encouraged to: Get as much rest as possible Get help with the baby and with household tasks from family and friends Avoid alcohol Exercise when medically cleared Try to leave the house every day Eat a healthy, balance diet Spend occasional time away from the baby to get a break 13
Treatment: Postpartum Depression & Anxiety Most successful treatment strategies are multifactorial and interdisciplinary. Strategies may include education, individual psychotherapy, group support, couples counseling, medications. Interpersonal Psychotherapy, Cognitive Behavioral Therapy, and support groups all have extensive empirical support for the treatment of PMADs. The patient should be encouraged to get as much rest as possible, reduce her other responsibilities, and obtain support from family and friends for infant care and household tasks. Medications are effective in the treatment of PMADs. The decision to treat with medications should consider the patient s comfort with medication if she is breastfeeding, given that a very small amount will be present in the breast milk. Treatment: Postpartum Psychosis This condition requires immediate assessment of risk and safety issues. Because patients with Postpartum Psychosis are at higher risk for child neglect, child abuse, infanticide, and suicide, psychiatric hospitalization is usually indicated. Hospitalization can challenge a mother s ability to breastfeed and is difficult because it imposes separation on the family. However, it can provide a safe environment for the new mother and allows for completion of a thorough psychiatric and medical work-up. Hospitalization also allows the patient to be assessed regularly by staff so that medication changes can be made quickly leading to more rapid stabilization. Although antidepressants are beneficial for patients with depression and anxiety, they should be used with caution in patients with postpartum psychosis given the strong association of bipolar disorder with this condition. Antidepressants can precipitate or worsen manic or mixed states in bipolar patients. Good discharge planning from the hospital is essential, including setting up aftercare with a psychiatrist and a therapist. Treatment: Psychotherapy 14
Psychotherapy Cognitive Behavioral Therapy (CBT) and Interpersonal Therapy (IPT) are empirically supported treatments for PMADs CBT: challenging negative and irrational thinking IPT: improving interpersonal relationships, role transitions, communication Key themes that often arise in therapy: Feeling overwhelmed and incapable Changing identity and role transitions Frustration and anger towards a partner who isn t helping as much as she needs Feeling guilty about asking for help Social isolation Worries about making the wrong decisions for the baby Anxieties about a chaotic or traumatic birth experience Psychotherapy and Self-Care Strategies Sleep, sleep, sleep! Psychoeducation about sleep hygiene Asking for help overnight sleep when the baby sleeps?? Negotiating a new schedule and expectations Cleaning, laundry, other chores Making mom the priority at times Importance of time away from the baby Asking for help & communicating with social supports Delegating tasks, avoiding gatekeeping Dealing with disputes and disagreements 15
Psychotherapy and Self-Care Strategies Diet/nutrition and exercise Psychoeducation about importance of nutrition and mood Staying active is can reduce depression and anxiety symptoms Social connections Getting out of the house In-person or online groups Helping the partner understand PMADs Psychoeducation about PMADs Teaching the partner what is and is not helpful Treatment: Medications Treatment: Medication Fundamentals People with mental illnesses deserve high-quality treatment Every baby deserves a healthy mother Mental illnesses AND/OR medications used to treat them may each pose risks to mother and child We need to provide a balanced view of risks and benefits The relative importance of various risks and benefits will be different for each patient Treatment decisions may be very different for each individual Trust and a good working relationship between patient and provider are critical for this decision-making 16
Risk/Benefit Balance There is no 100% risk-free zone We weigh the risks of untreated illness against the risks of medical treatment Medication use in the Postpartum No medications have been FDA-approved for use in PPD, but most antidepressants appear effective for PPD For mild-moderate depression and/or anxiety: Supportive self-care Psychotherapy Address/improve psychosocial concerns For moderate-severe depression and/or anxiety: All of the above Consider medication With treatment, PPD and PPA will usually resolve within a few to several weeks. In general, patients should remain on medication for 6-12 months after symptoms have remitted. Breastfeeding and Psychotropic Medications The data on the use of psychotropic medications in breastfeeding women are reassuring. The baby s pediatrician may be part of the decision-making about breastfeeding while taking a psychotropic medication. Other factors to consider when prescribing psychotropic medication during breastfeeding: the use of short-acting rather than long-acting medications use of medications without active metabolites 17
Medications for Depression SSRIs fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine SNRIs venlafaxine, desvenlafaxine, duloxetine, levomilnacipran TCAs amitripyline, nortriptyline, clomipramine, doxepin MAOIs phenelzine, isocarboxazid, tranylcypromine, selegiline patch Others bupropion, mirtazepine, vilazodone, vortioxetine Which antidepressants have been described as having the best evidence base to support their use in breastfeeding? A) Sertraline B) Paroxetine C) Nortriptyline D) A and C E) All of the above Which antidepressants have been described as having the best evidence base to support their use in breastfeeding? A) Sertraline B) Paroxetine C) Nortriptyline D) A and C E) All of the above 18
Antidepressants and Breastfeeding Infant is exposed to <10% of maternal dose for most medications 10% or less is considered compatible with breastfeeding Psychotropic drugs (excluding lithium) are excreted in small amounts in the breast milk which a normal, full-term infant can handle with no adverse effects. Thomas Hale s Medications and Mother s Milk Lanza di Scalea 2009: Breastfeeding and antidepressant treatments are not mutually exclusive. Sertraline, paroxetine, nortriptyline and imipramine are the most evidence-based medications for use during breastfeeding. Untreated maternal mental illness is clearly detrimental to infants' development. Antidepressants and Breastfeeding University of Adelaide 2014 Women on antidepressant medication are more successful at breastfeeding their babies if taking medication, compared with women who quit antidepressants because of concerns about their babies health. Nothing should trump restoration of euthymia in postpartum women. Lee Cohen MD, Director of Massachusetts General Hospital Center for Women s Mental Health Case example Cara is a 29 y.o. woman who had her second child 6 weeks ago. She has had symptoms of major depressive disorder. She is struggling with breastfeeding. Supply is low and it s been very painful. She s seen a lactation consultant and has gone to lactation support groups. She has good support from her husband and extended family. She has started to dread every feeding, is tearful and anxious almost all the time, and says she feels very guilty because she knows breast is best and that one celebrity tweeted that it should be a crime to feed babies formula in the first 6 months. She says she always envisioned breastfeeding her child for a year. She had a similar experience with her first child she ended up breastfeeding for 3 months with her first. She looks embarrassed as she says But I felt so much better once I stopped breastfeeding, isn t that just terrible? How can I be a good mother if I can t even do this? 19
Breastfeeding considerations Burt V et al, Washington Post, 3/2016: we see far too many tearful new mothers for whom breastfeeding is a source of self-recrimination As physicians we too bought into the dogma that breast is best at all costs. We would never have taken our own advice: when it comes to breastfeeding, your health and happiness matter as much as your baby s. Let s not forget that the mother-baby bond is comprised of healthy mothers and babies and we can t overlook that half of the equation. The professional guidelines [from AAP and ACOG about breastfeeding] are based on good science. But for many new mothers, the recommendations carry the force of a threat: if I don t breastfeed I m not a good mother. Breastfeeding can be a wonderful way to bond with a baby, but it s not the only way. It certainly is not synonymous with good mothering. A good mother? One who is calm, well-rested, and emotionally engaged with her baby in whatever way works. Medications for Anxiety SSRIs SNRIs Benzodiazepines lorazepam, alprazolam, clonazepam, diazepam Antihistamines hydroxyzine, doxylamine Atypical antipsychotics quetiapine, olanzapine Others gabapentin, buspirone, propranolol Benzodiazepines in pregnancy and lactation Lorazepam shows least accumulation in breast milk Use lower doses Use less frequent, intermittent dosing 20
Case example Darlene is a 25 y.o. woman who is 2 months postpartum with her first child. She is sleeping poorly, even when she has the opportunity. Her husband is happy to share duties for nighttime feedings so she can get some rest. She lies awake worrying about the next day s to-do-list. What might help? A) CBTi Cognitive Behavioral Therapy for insomnia B) Exploration of current sleep hygiene habits C) A night nanny or postpartum doula to help with nighttime feedings D) Medications such as doxylamine, lorazepam, amitriptyline E) A, B, or C F) Any or all of the above Case example Darlene is a 25 y.o. woman who is 2 months postpartum with her first child. She is sleeping poorly, even when she has the opportunity. Her husband is happy to share duties for nighttime feedings so she can get some rest. She lies awake worrying about the next day s to-do-list. What might help? A) CBTi Cognitive Behavioral Therapy for insomnia B) Exploration of current sleep hygiene habits C) A night nanny or postpartum doula to help with nighttime feedings D) Medications such as doxylamine, lorazepam, amitriptyline E) A, B, or C F) Any or all of the above Sleep/Insomnia in Pregnancy and Postpartum Address sleep hygiene (may be a challenge with a newborn) CBTi Medications Doxylamine, diphenhydramine (minimal data on effects on milk supply) Zolpidem (limited data probably compatible with breastfeeding) Benzodiazepines Sedating tricyclic antidepressants Trazodone 21
Mood Stabilizers and Antipsychotics Lithium Valproic acid/divalproex Other AEDs - lamotrigine, carbamazepine, oxcarbazepine, topiramate, gabapentin Antipsychotics aripiprazole, olanzapine, quetiapine, ziprasodone, lurasidone, risperidone, haloperidol, clozapine Case example Ellie is a 30 y.o. woman with bipolar disorder. She was maintained on divalproex with excellent results for several years. She took lamotrigine before and during pregnancy and did ok, but never felt as well as she did when taking divalproex. She had her first child 1 month ago. She is breastfeeding. She d really like to transition back to the divalproex. How do you advise her? A) Stay on the lamotrigine even if she doesn t feel her best. B) Start a cross taper back to divalproex. C) Start a cross taper back to divalproex, but only if she has a very reliable form of birth control planned. D) Avoid any mood stabilizer while breastfeeding, or advise her not to breastfeed. Case example Ellie is a 30 y.o. woman with bipolar disorder. She was maintained on divalproex with excellent results for several years. She took lamotrigine before and during pregnancy and did ok, but never felt as well as she did when taking divalproex. She had her first child 1 month ago. She is breastfeeding. She d really like to transition back to the divalproex. How do you advise her? A) Stay on the lamotrigine even if she doesn t feel her best. B) Start a cross taper back to divalproex. C) Start a cross taper back to divalproex, but only if she has a very reliable form of birth control planned. D) Avoid any mood stabilizer while breastfeeding, or advise her not to breastfeed. 22
Divalproex in Breastfeeding Divalproex monotherapy has not been associated with adverse effects in breastfeeding infants Infants exposed to 4% of mother s dose <10% is considered compatible with breastfeeding Managing Lithium in Breastfeeding Consider not breastfeeding (lithium is the unusual med that has a better established safety record in pregnancy than in lactation) Monitor infant for body fluid volume changes (watch for dehydration due to fever, vomiting, diarrhea) risk of lithium toxicity with volume contraction Check infant levels, TSH, renal function often Tightly coordinate care with pediatrician Lamotrigine in Breastfeeding Theoretical risk of Stevens-Johnson Syndrome in the newborn There have been no reported cases of SJS in a breastfeeding newborn 23
Carbamazepine Postpartum Limited data about breastfeeding no significantly concerning case reports Remember that carbamazepine can induce the metabolism of OCPs Risk for unintended pregnancy with unintended exposure to carbamazepine Antipsychotics and Breastfeeding Monitor mother for excess sedation Data about breastfeeding safety is limited they have not been associated with negative outcomes with breastfeeding infants Prevention of postpartum psychosis In women with h/o postpartum psychosis, begin prophylactic treatment with lithium or an antipsychotic at delivery Continue medications for bipolar disorder through pregnancy Case example Freya is a 27 y.o. woman who is still hospitalized on the OB postpartum unit after having her second child 2 days ago you are called to consult because she seems confused and she has history of bipolar disorder. She had been off medications during pregnancy. You evaluate her she has delusions about the baby being better off without her and admits to thoughts of suicide with a plan to overdose on her home medications, which include lithium. She is guarded when asked about infanticide, and shows no emotional reaction when asked about it. After thorough evaluation, you diagnose postpartum psychosis. She also had postpartum psychosis and was hospitalized after her first child was born. She did respond to lithium and olanzapine then, and addressing sleep hygiene seemed to help as well. 24
Case example One month later, you see her in follow up in your office. She was hospitalized on the psychiatric inpatient service and restarted lithium and olanzapine. She elected not to breastfeed for 2 reasons she was concerned about lithium s effect on the baby, and she wanted to preserve her sleep schedule. Her husband has been supportive and her in-laws have also helped with nighttime feedings. She reports feeling much better. She no longer voices any suicidal ideation, nor any violent ideation. There is no evidence of persistent psychosis or delusional thinking. She still reports some irritability, some trouble sleeping, poor appetite, and low mood at times. You elect to increase olanzapine to her previous effective dose. Six months later, after several intervening follow up visits, she feels well, with stable mood, good sleep habits. The baby is healthy and she is enjoying being a parent of 2. She plans to continue current medications for at least a few more months before considering changes. She has decided this will be her last pregnancy and has scheduled a tubal ligation. She says she always hoped she could have 2 children, so she is happy with how things have turned out. Postpartum psychosis treatment Bergink 2015, 2016: Hospitalize Labs: CBC, CMP, urine tox, TSH/free T4, UA Consider if indicated: TPO antibodies, CT/MRI, CSF, B12, folate, encephalitis antibody screening, ammonia to eval for late-onset urea cycle disorders Focus on sleep hygiene and structured schedules Trial of BZD x 36-72 hours to improve sleep hygiene may be adequate treatment in small number of pts Avoid antidepressants BZD plus lithium plus antipsychotic required for remission in the majority of patients Lithium was associated with more sustained remission than antipsychotics Lithium plus antipsychotic appeared to be optimal acute treatment Lithium monotherapy appeared to be optimal preventive/maintenance measure (x9 months postpartum) Consider ECT Medications in Pregnancy and Lactation Keep mom healthy Use the medication that works Most antidepressants appear to be equally effective at a population level the effectiveness of each medication can vary from patient to patient First ask yourself: What treatment would help this patient? Then ask yourself: Is that a reasonable choice in pregnancy/lactation? Use the dose that works There is little evidence that higher doses pose greater risk (except lithium) 25
Other Treatments for PMADs Psychotherapy ECT TMS? Light box Omega-3 acids? SAMe? Folate may improve response to SSRIs Acupuncture (may be effective in pregnancy, no clear benefit otherwise) Exercise Strengthening social support networks Best Practices Share information/educate patient, family, concerned others Decrease the sense of black or white Create a sense of options and of working together, continuously weighing risks and benefits to mom and baby A mother s health is a critically important factor in her baby s health and well-being. 26
Resources and References Resources www.womensmentalhealth.org www.postpartum.net www.ppsupportmn.com www.motherisk.org www.reprotox.org www.mothertobaby.org www.lactmed.nlm.nih.gov michelle.wiersgalla@parknicollet.com References Aarskog D. Association between maternal intake of diazepam and oral clefts. Lancet 1975. Andrade C. The safety of Duloxetine during pregnancy and lactation. J Clin Psych 2014. Andrade SE et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiology and Drug Safety 2009. Ansara D et al. Predictors of women s physical health problems after childbirth. Journal of Psychosocial Obstetrics and Gynecology 2005. Banhidy et al. Maternal panic disorder and congenital abnormalities: A population-based case-control study. Clinical and Molecular teratology 2006. Berard, A et al. The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: A systematic review and meta-anlysis. Br J Clin Pharmacol 2015. Bergink V et al. Treatment of psychosis and mania in the postpartum period. Am J Psych 2015. Bergink V et al. Postpartum psychosis: Madness, mania, and melancholia in motherhood. Am J Psych 2016. Blair-West, GW et al. Lifetime suicide risk in major depression: sex and age determinants. J Affect Disord 1999. Boukhris, T et al. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr 12/14/15. Brogan K. Perinatal depression and anxiety: beyond psychopharmacology. Psychiatr Clin N Am 2013. Brown A et al. Understanding the relationship between breastfeeding and postnatal depression: the role of pain and physical difficulties. J Adv Nurs 2015. Casper RC et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003. 27
References Centers for Disease Control and Prevention. Update on Overall Prevalence of Major Birth Defects--Atlanta, Georgia, 1978-2005. MMWR Morb Mortal Wkly Rep. 2008. Chambers CD et al. Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn. NEJM 2006. Clark CT et al. Lamotrigine Dosing for Pregnant Patients With Bipolar Disorder. Am J Psych 2013. Clements, C et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 6/2015. Cohen, LS et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006. Cohen LS, et al. Reproductive safety of second-generation antipsychotics. Am J Psych 2015. Cripe SM et al. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal comorbid mood and migraine disorders during pregnancy. Pediatric and Perinatal Epidemiology 2011. Croen LA et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011. References Davis RL et al. Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiology and drug safety 2007. Earls MF. Incorporating recognition and management of perinatal and postpartum depression into pediatric practice. Pediatrics 2010. Einarson A et al. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 2008. Einarson A et al. Rates of spontaneous and therapeutic abortions following use of antidepressants in pregnancy: results from a large prospective database. J Obstet Gynaecol Can 2009. Fitelson E et al. Treatment of postpartum depression: clinical, psychological and pharmacological options. Int J Womens Health 2011. Friedman SH, et al. Child murder by mothers: a critical analysis of the current state of knowledge and a research agenda. Am J Psychiatry 2005. Furu K et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ 2015. Grzeskowisk LE et al. Antidepressant use in late gestation and risk of postpartum hemorrhage: a retrospective cohort study. BJOG 2015. References Hollins, K. Consequences of antenatal mental health problems for child health and development. Current Opinion in Obstetrics & Gynecology 2007. Hviid, A et al. Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. NEJM 2013. Jennings KD et al. Thoughts of harming infants in depressed and nondepressed mothers.. J Affect Disord July 1999. Khan SJ et al. Bipolar disorder in pregnancy and postpartum: principles of management. Women s Mental Health 1/2016. Kallen BA et al. Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations. Birth Defects Res A Clin Mol Teratol 2007. Kallen B et al. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf 2008. Kaneko S. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999. Kinsella, MT et al. Impact of Maternal Stress, Depression & Anxiety on Fetal Neurobehavioral Development. Clin Obstet Gynecol 7/2013. LaRusso, Elizabeth. Counterpoint: Don t be misled by autism-drug reporting. Minneapolis StarTribune OpEd 12/21/2015. Lassen D et al. First-trimester pregnancy exposure to venlafaxine or duloxetine and risk of major congenital malformations. Basic Clin Pharmacol Toxicol 2015. Lebel C et al. Pre- and post-partum maternal depressive symptoms are related to children s brain structure in preschool. Biol Psychiatry 2016. Li D et al. Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study. Human Reproduction 2009. 28
References Malm H et al. Pregnancy complications following prenatal exposure to SSRIs or maternal psychiatric disorders. Am J Psych 2015. Manber R et al. Acupuncture for Depression During Pregnancy: A Randomized Controlled Trial. Obstetrics & Gynecology 2010. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol 1994. Molgaard-Nielsen D et al. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 2011. Moses-Kolko EL et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. Am J Psych 2005. Nulman I et al. Neurodevelopment of children exposed in utero to antidepressant drugs. NEJM 1997. Nulman I et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psych 2002. Nulman I et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psych 2012. O Brien et al. Does Paroxetine cause cardiac malformations. J Obstet Gynaecol Can 2008. Oberlander TF et al. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 2006. Oberlander TF et al. Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy. Arch Pediatr Adol Med 2007. Occhiogrosso M et al. Persistent pulmonary hypertension of the newborn and selective serotonin reuptake inhibitors: lessons from clinical and translational studies. Am J Psych 2012. Pac CC et al. Depression in parents of very pre-term infants. LAMA Pediatr 2016. Palmsten K et al. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States. BMJ 2013. Peng M et al. Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study. Psychopharmacology 2013. Peterson, I et al. J Clin Psych 2/2016. Qiu C eta l. Associations of depression and depressive symptoms with preeclampsia: results from a Peruvian case-control study. BMC Women s Health 2007. References Rai, D et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population-based case control study. BMJ 2013. Rahman A. Association between antenatal depression and low birthweight in a developing country. Acta Psychiatr Scand 2007. Reefhuis J et al. Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ 2015. Rosenberg L et al. Lack of relation of oral clefts to diazepam use during pregnancy. NEJM 1983. Safra MJ et al. Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet 1975. Salisbury, AL et al. The roles of maternal depression, serotonin reuptake inhibitor treatment, and concomitant benzodiazepine use on infant neurobehavioral functioning over the first postnatal month. AM J Psych 2015. Saxen I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemol 1975. Shiono PH et al. Oral clefts and diazepam use during pregnancy. NEJM 1984. Singata-MadlikiM et al. Injectable contraception may raise risks for postpartum depression. J Fam Plann Reprod Health Care 2016. Spong CY. Defining "term" pregnancy: recommendations from the Defining "Term" Pregnancy Workgroup JAMA 2013. Viguera AC. Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psych 2000. References Warburton W. A register study of the impact of stopping third trimester selective serotonin reuptake inhibitor exposure on neonatal health. Acta Psychiatr Scand 2010. Way CM. Safety of newer antidepressants in pregnancy. Pharmacotherapy 2007. Weinberg MK et al. Emotional Characteristics of Infants Associated With Maternal Depression and Anxiety. Pediatrics 1998. Weinstock M. Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 2001. Weissman MM. Remissions in Maternal Depression and Child Psychopathology. JAMA 2006. Wemakor A et al. Selective serotonin reuptake inhibitor use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study. Eur J Epidemiol 2015. Wesseloo R et al. Risk of postpartum relapse in bipolar disorder and postpartum psychosis. Am J Psych 2016. Wilson KL et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol 2011. Wirz-Justice A et al. A randomized, double-blind, placebo-controlled study of light therapy for antepartum depression. J Clin Psychiatry 2011. Wisner KL et al. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psych 2009. Wisner, KL et al. Onset Timing, Thoughts of Self-harm, and Diagnoses in Postpartum Women With Screen- Positive Depression Findings. JAMA Psychiatry 5/2013. 29
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