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Table 1 Possible tests if postpartum patient is constantly fatigued

Laboratory test Confirms or rules out Order if patient also presents with: Acetylcholine receptor Myasthenia gravis Double vision, droopy eyelids, muscle weakness or medical problem? Alkaline phosphatase Primary biliary cirrhosis Jaundice, pruritus Antimitochondrial Primary biliary cirrhosis Jaundice, pruritus Watch for fatigue, weight change, other physical signs Antinuclear antibody Systemic lupus ‘Butterfly’ facial rash, joint pain, erythematosus morning stiffness CBC Microcytic anemia, Pallor, low energy, peripheral neuropathy, megaloblastic anemia shortness of breath Andreea L. Seritan, MD Electrolytes Adrenal insufficiency, Low pressure, seizures, Assistant clinical professor renal disease skin pigmentation Department of psychiatry and behavioral sciences ® Dowden Health Media Glucose (fasting or Type 1 or 2 Blurred vision, excessive thirst/hunger, headaches, University of California, Davis Copyright glucose tolerance) diabetes mellitus frequent urination, unexplainable weight loss For personal use onlyHIV HIV infection/AIDS Anorexia, recurrent infections, weight loss Liver function tests Alcohol abuse, hepatitis, Asterixis (flapping tremor), easy bruising, primary biliary cirrhosis jaundice, pruritus, spider telangiectasias Lumbar puncture Multiple sclerosis Bladder dysfunction, gait ataxia, ocular signs, any medical conditions common among sensory loss, spasticity M new mothers can cause depressed mood, fatigue, and other symptoms that suggest post- partum depression. To help you quickly pinpoint the source of a new mother’s depressive symptoms and plan treatment, this article reviews: for her baby and 2-year-old son, and she depends on because Mrs. A has gained 20 lb. A switch to sertra- • new-onset or pre-existing neurologic, cardio- a family member to stay home with her. Financial line, 25 mg/d, has no effect. vascular, , and other conditions that mimic concerns force her back to work 3 months after giv- Eighteen months after symptom onset, Mrs. A postpartum depression ing birth, but she is so despondent that she can bare- still sleeps poorly, even though her daughter—now • risk factors and clinical features that distin- ly function. age 2—sleeps through the night. Her depressed guish postpartum depression from other psychi- Mrs. A’s primary care physician diagnoses prima- mood—undiagnosed by the physician—continues to atric disorders ry insomnia and prescribes mirtazapine and zolpidem, worsen. She sees a psychiatrist after routine blood • laboratory tests that confirm or rule out 15 and 10 mg each night, respectively, but her sleep tests and a sleep study reveal no medical cause for medical problems. disturbance persists after 6 weeks. The physician her insomnia. adds the hypnotic temazepam, 15 mg at night, and CASE: ‘I CAN’T SLEEP’ the sedating anticonvulsant gabapentin, 300 mg at IS IT POSTPARTUM DEPRESSION? Mrs. A, age 40, sleeps 2 hours nightly at most. bedtime. Both are titrated over 6 months to 45 mg Mrs. A’s despondent mood, sleep disturbances, Awakened by her 3-month-old daughter’s overnight and 1,800 mg at bedtime, respectively, but Mrs. A feelings of inadequacy as a parent, and impaired crying, she lies awake and ruminates over the day’s continues to lose sleep. concentration suggest postpartum depression. events. Throughout the day, she fears she cannot care After 6 months, the doctor stops mirtazapine Ego-dystonic obsessive thoughts of harming the © 2006 Jan Stromme, Getty

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Table 2 Possible tests if postpartum patient has lost or gained weight

Laboratory test Confirms or rules out Order if patient also presents with: Antithyroid antibody Postpartum Constipation, dry skin, hair loss, lethargy, memory loss Glucose (fasting or Type 1 or 2 Blurred vision, excessive thirst/hunger, glucose tolerance) diabetes mellitus fatigue, frequent urination, headaches HIV HIV infection/AIDS Anorexia, fatigue, recurrent infections TSH ± thyroid panel Constipation, dry skin, hair loss, lethargy TSH ± thyroid panel Agitation, anxiety, heat intolerance,

infant might emerge, although nonpsychotic Include bipolar disorder in the differential patients rarely act upon them.1 diagnosis. Ask new mothers with depressive Finding risk factors for postpartum depres- symptoms if they feel inexplicably happy, irritable, sion can clarify the diagnosis. Ask the patient: or unusually energetic at times. Also screen for • When did you first notice symptoms? DSM- , which can progress to bipo- IV-TR says postpartum depression usually begins lar disorder7 and—worse—greatly increase the within 4 weeks of giving birth,2 but most risk of infanticide. researchers define the as ≤ 6 The Edinburgh Postnatal Depression Scale,8 a months after delivery. 1,3 Mrs. A’s depression and 10-item self-report screening tool that takes about insomnia started 3 months after . 5 minutes to complete, can help identify postpar- • Have you been depressed before? Women tum depression (see Related resources). with past postpartum or other depressive episodes face a high risk of recurrence after subsequent CASE CONTINUED: A POSTPARTUM HEADACHE .1,3 Active eating disorder during preg- During our initial interview, Mrs. A denies thoughts nancy4 and past premenstrual dysphoric disorder of harming herself or her children, and psychotic also are risk factors.1,3 symptoms are not apparent. She reports no past • Has anyone in your family had depression? depressive or anxiety episodes and does not use This increases postpartum depression risk.5 alcohol or illicit drugs. Her sister has a history of • Who is helping you? Psychosocial stress and depression (not postpartum). lack of social support can fuel postpartum depres- During review of systems, Mrs. A complains sion.1,3 Mrs. A gets practical help from family of persistent headaches. Brain MRI reveals a 4.5 members, but life’s pressures are taking their toll. x 5 mm microadenoma in the pituitary gland. We refer her to an endocrinologist, who obtains pro- IS IT ANOTHER MENTAL ILLNESS? lactin readings of 92 and 122.4 ng/mL (normal Screen women with postpartum depressive range, 2.8 to 29.2 ng/mL). symptoms for anxiety, which is highly comorbid Discussion. Mrs. A had few predictive factors for with depression.6 postpartum depression, an atypical presentation continued on page 67

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Table 3 Possible tests if postpartum patient has other physical symptoms

Laboratory test Confirms or rules out Order if patient presents with: Blood urea Renal disease, dehydration Back pain, frequent urination or oliguria, nitrogen/creatinine low blood pressure Brain MRI Brain tumors, Focal deficits, headaches, seizures, white matter disease vision problems, vomiting C-reactive protein Rheumatoid arthritis Joint pain, morning stiffness ECG Cardiomyopathy Extremity swelling, palpitations, shortness of breath at night and with exertion Erythrocyte Rheumatoid arthritis, ‘Butterfly’ facial rash, joint pain sedimentation rate SLE Folate Folate deficiency Ataxia, loss of vibration and position sense, peripheral neuropathy, weakness Prolactin Prolactinoma, Amenorrhea/, headache, hypopituitarism visual field loss Rapid plasma reagin Syphilis Ataxic wide-based gait, loss of position, deep pain and temperature sensation, palmar/plantar rash Rheumatoid factor Rheumatoid arthritis Morning stiffness, symmetric joint pain Urinalysis Urinary infection, diabetes, Burning or difficulty with voiding, renal disease dark-colored urine, frequent urination Urine drug screen Substance abuse disorder Erratic behavior, irritability or aggression; violence, mental status changes Vitamin B12 Anemia, malnutrition, Loss of position or vibratory sensation, inflammatory bowel disease mood and cognitive changes, tingling and numbness in hands and feet

SLE: Systemic lupus erythematosus with insomnia as the main symptom, and incom- sleep). Common causes include sleep depriva- plete response after 18 months of treatment. tion, thyroid disorders, anemia, cardiomyopathy, These findings—plus her elevated prolactin and and infections (Table 1, page 63).9 brain MRI results—suggest a medical cause. • Weight change could signal a medical con- dition whose symptoms resemble postpartum IS IT A MEDICAL PROBLEM? depression—such as diabetes or human immun- Pre-existing or new-onset postpartum medical odeficiency virus (HIV) (Table 2, page 64). conditions can confound the diagnosis. • Other disorders—including neurologic dis- • Fatigue can mimic depression’s neurovege- eases, prolactinomas, systemic lupus erythemato- tative signs (poor energy, decreased appetite, sus, diabetes, and rheumatoid arthritis—can cause

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depressive and other psychiatric symptoms (Table Subtle presentations of brain tumors include 3, page 67). cognitive deficits, mood disturbance, and person- Recognizing the following disorders’ physical ality change. A left frontal lobe tumor can cause signs is key to uncovering a medical cause for post- depression. partum depressive symptoms. Ask the patient if she has had headaches, . Postpartum thyroiditis (PPT) can visual symptoms, vomiting, seizures, or focal occur 1 to 3 months after delivery,10 often recurs neurologic deficits—any of these could signal a after subsequent pregnancies,11 and can progress primary brain tumor or intracranial hemorrhage. to permanent hypothyroidism within 5 years.10 Prolactinomas, the most common pituitary Hypothyroidism can cause cognitive slowing, tumor in pregnant and postpartum women, depression, and psychosis, and acute mania has enlarge during and regress after been reported with severe hypothyroidism sec- delivery.14 Depression, anxiety, apathy, and per- ondary to PPT.12 sonality changes may stem from the pituitary Find out if the patient tested positive early in tumor, its treatment, or changes in the hypo- gestation for thyroid antibodies, as this may pre- thalamic-pituitary-end organ axis.18 Typical dict postpartum depression. amenorrhea-galactorrhea Multiple sclerosis (MS) can cause anxiety, syndrome resembles post- mania, depression, and cognitive partum physiologic changes. impairment.13 Drugs used to treat Headaches are common, and Did the patient MS—such as steroids or interfer- compression of the optic chiasm with on—can induce depression. test positive macrodenomas causes visual field Relapses are infrequent dur- early in gestation changes. ing pregnancy but increase signif- for thyroid Systemic lupus erythematosus (SLE), most icantly within 3 months after giv- antibodies? prevalent in young women, might flare ing birth14 in about one-third of during pregnancy and within 6 weeks women with active MS before preg- after giving birth.11 Headaches, nancy.15 Gait ataxia, sensory loss, numbness, seizures, or cerebrovascular events hyperactive reflexes or spasticity, bladder dysfunc- with comorbid mood disorders, delirium, demen- tion, visual impairment, disordered ocular motili- tia, psychosis, or anxiety can signal SLE.13 ty, and fatigue are prominent clinical signs of MS.16 Suspect SLE if the patient presents with Myasthenia gravis (MG). Women who become fatigue, “butterfly” face rash, or joint pain. Test pregnant within 1 year after diagnosis run a high for renal or cardiopulmonary involvement. risk of MG exacerbation.17 Rheumatoid arthritis (RA). Because inflammatory Fatigue and muscular weakness caused by activity is heightened after childbirth, postpartum MG can mimic depression, and adjusting to this women—particularly after bearing a first child— debilitating illness can cause depression. Double face a five-fold risk of RA compared with other vision, droopy eyelids, and muscle weakness alle- women.11 Breast-feeding might worsen RA, pre- viated by rest but worsened by activity are pathog- sumably by increasing prolactin production. nomonic signs.16 Physical limitations caused by RA can cause Other neurologic diseases. Pre-existing seizure depression. Symmetric joint pain associated with disorders can worsen after giving birth and cause morning stiffness—especially in the fingers, depression.14 hands, or knees—might signal RA. continued on page 71

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Table 4 Findings that signal a possible postpartum medical problem

Laboratory finding Could signal … Low hemoglobin, hematocrit and Microcytic anemia mean cell volume (MCV) values MCV > 100 mm3 Megaloblastic anemia Positive anticardiolipin or Systemic lupus erythematosus antinuclear antibody Blood urea nitrogen > 20 mg/dL, Acute or chronic renal failure creatinine > 1.5 mg/dL Low specific gravity on urinalysis Diabetes insipidus or renal tubular abnormalities with glycosuria Diabetes mellitus Proteinuria with protein or cellular casts Systemic lupus erythematosus Hyponatremia and hyperkalemia Adrenocortical insufficiency Hypo/hypernatremia Seizures Albumin < 3 g/dL Malnutrition SGOT/SGPT > 35 u/L (each) Alcohol abuse disorder, hepatitis, hepatic encephalopathy Alkaline phosphatase > 120 u/L, Primary biliary cirrhosis positive antimitochondrial antibody Erythrocyte sedimentation Systemic lupus erythematosus, rheumatoid arthritis rate > 20 mm/hr Positive rheumatoid factor Rheumatoid arthritis Prolactin > 24 ng/mL Prolactinoma TSH > 5 µu/mL Hypothyroidism TSH < 0.35 µu/mL Hyperthyroidism IgG > 1.4 mg/dL, oligoclonal bands, Multiple sclerosis myelin basic protein in CSF White matter hyperintensities Multiple sclerosis, CNS vasculitis, tumors in brain MRI

Source: Reference 5

Anemia. Increased need for iron and folic acid anemia or neurologic problems such as peripher- during pregnancy can lead to anemia. al neuropathy, as well as depression, delirium, or Neuropsychiatric manifestations of folate defi- dementia.19 ciency range from mild irritability to severe Ask the patient about: depression, dementia, psychosis, and confusion.19 • alcohol dependence, malnourishment, Vitamin B12 deficiency can lead to megaloblastic chronic illness, inflammatory bowel disease, gas-

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tric bypass or other gastric surgery, which can HIV infection often leads to cognitive loss and impair vitamin B12 absorption depression with suicidal thoughts.13 Highly active • use of anticonvulsants such as carbamazepine antiretroviral medications commonly cause agita- or valproic acid, which can decrease folate. tion, pain, mood changes, and insomnia. Hypotension mimics anergia. Postpartum hypoten- Ask the patient is she is HIV positive. Watch sion can cause partial or total necrosis of the ante- for weight loss, fever, anorexia, and recurrent rior pituitary gland. This leads to panhypopitu- infections. itarism (Sheehan’s syndrome)—a rare complica- Substance abuse. Intoxication, withdrawal, or tion characterized by failure to lactate, amenor- long-term alcohol or drug use can contribute to rhea, hypothyroidism, and adrenal insufficiency. depression. Women at high risk for substance When not in hypotensive circulatory shock, abuse disorder might not adhere to psychiatric patients with adrenal insufficiency might present treatment and may be prone to sexually transmit- with depression, delirium, or psychosis.13 Ask the ted diseases. If possible, see the patient every 3 to 4 patient if she is having lactation problems and weeks during the postpartum period. irregular periods, which could signal a pituitary Pain—if not adequately con- problem. trolled—can fuel depression. Peripartum cardiomyopathy—an Ask the patient if she has chronic acute dilated cardiomyopathy— pain or suffered a severe injury. Has the patient lost appears ≤ 6 months after delivery weight? Does she and may cause fatigue.10,20 Check DETERMINING A MEDICAL CAUSE for shortness of breath at night have recurrent Laboratory and neuroimaging findings— and with exertion, palpitations, infections? She obtained in concert with the patient’s pri- and extremity swelling. could be HIV positive mary care physician—will help confirm or . Pregnancy- rule out a medical problem (Table 4, page induced insulin resistance leads to ges- 71). Consult with a neurologist, endocri- tational diabetes mellitus. Women with gestation- nologist or rheumatologist if indicated. al diabetes can develop type 2 diabetes after giving birth.10 CASE: WILL THE TUMOR RESOLVE? Blood sugar fluctuations can cause depres- Mrs. A’s endocrinologist prescribes bromocriptine to sion, irritability, or memory problems. Depression manage her hyperprolactinemia, but she refuses to can sabotage adherence to diet and treatment, start the dopamine agonist after the doctor explains leading to poor glycemic control. that it might cause psychosis. Ask the patient if she was diagnosed with ges- Working closely, the psychiatrist and endocrinolo- tational diabetes and if she is experiencing gist postpone bromocriptine therapy to see if the pro- fatigue, excessive thirst, frequent urination, lactinoma will resolve without treatment. They order blurred vision, headaches, excessive hunger, or brain MRIs every 6 months to track the tumor. unexplainable weight loss. Mrs. A starts weekly psychodynamic therapy, Primary biliary cirrhosis is most prevalent in during which she explores her fear of failure as a women ages 35 to 60 and may cause depression.20 mother. Within 2 months, she recognizes that she Pruritus, fatigue, jaundice, and liver abnormali- has set unrealistically high expectations for herself. ties point to this autoimmune disease, and post- Adopting a supportive approach, the therapist partum exacerbations have been reported.21 encourages her to go on dates with her husband continued on page 75

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continued from page 72 and run errands or relax alone for 2 hours each Related resources weekend. u Edinburgh Postnatal Depression Scale. The psychiatrist discusses sleep hygiene and http://www.drgrelling.com/Downloads.htm (click on “Edinburgh adds quetiapine, 25 mg at bedtime; reduces Postnatal Depression Scale” under “Resources for professionals”). gabapentin over 3 months to 300 mg nightly; and u Postpartum Support International. www.postpartum.net. titrates sertraline to 100 mg/d. The psychiatrist also DRUG BRAND NAMES weans Mrs. A off temazepam over 3 months, Bromocriptine • Parlodel Sertraline • Zoloft Carbamazepine • Tegretol, others Temazepam • Restoril watching closely for withdrawal symptoms. Gabapentin • Neurontin Valproic acid • Depakene At the psychiatrist’s suggestion, Mrs. A. Mirtazapine • Remeron Zolpidem • Ambien Quetiapine • Seroquel resumes exercising at a gym four to five times a DISCLOSURES week. Mrs. A reduces zolpidem use—taking it only Dr. Seritan reports no financial relationship with any company whose products as needed for insomnia—then tapers off gabapentin. are mentioned in this article, or with manufacturers of competing products. Quetiapine is discontinued. After 4 months, psychotherapy sessions are 12. Stowell CP, Barnhill JW. Acute mania in the setting of severe hypothyroidism. Psychosomatics 2005;46:259-61. decreased to biweekly. Prolactin is 66.6 ng/mL at 3 13. Sadock BJ, Sadock VA. Consultation-liaison psychiatry (Chapter months, then normalizes to 23.4 ng/mL at 6 28.4). In: Synopsis of psychiatry, 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2003:844-7. months. Six months later, brain MRI shows no 14. Karnad DR, Guntupalli KK. Neurologic disorders in pregnancy. change in baseline tumor size. The endocrinologist Crit Care Med 2005;33:S362-S371. continues semiannual brain MRI and prolactin test- 15. Vukusic S, Confavreux C. Multiple sclerosis and pregnancy. Rev Neurol 2006;162:299-309. ing to see if the tumor will shrink without surgery. 16. Kaufman DM. Clinical Neurology for Psychiatrists. Philadelphia: Nearly 1 year after presentation, Mrs. A’s WB Saunders; 2001. 17. Ramirez C, de Seze J, Delrieu O, et al. [Myasthenia gravis and depression is in remission. pregnancy: clinical course and management of delivery and the postpartum phase.] Rev Neurol (Paris) 2006;162:330-8 (French). References 18. Weitzner MA, Kanfer S, Booth-Jones M. Apathy and pituitary 1. Miller LJ. Postpartum depression. JAMA 2002;287:762-5. disease: it has nothing to do with depression. J Neuropsychiatry Clin Neurosci 2005;17:159-66. 2. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000:204. 19. Peselow E. Other pharmacological and biological therapies. In: Sadock BJ, Sadock VA, eds. Comprehensive textbook of psychiatry, 3. Burt V, Hendrick V. Clinical manual of women’s mental health. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. Arlington, VA: American Psychiatric Publishing; 2005:79-100. 20. Kasper DL, Braunwald E, Fauci A, et al. Harrison’s principles of 4. Franko DL, Blais MA, Becker AE, et al. Pregnancy complications internal medicine, 16th ed. New York: McGraw-Hill; 2004. and neonatal outcomes in women with eating disorders. Am J Psychiatry 2001;158:1461-6. 21. Ohba K, Omagari K, Kusakari C, et al. Flare-up of autoimmune hepatitis after delivery in a patient with primary biliary cirrhosis: 5. Berga SL, Parry BL, Cyranowski JL. Psychiatry and reproductive postpartum overlap syndrome of primary biliary cirrhosis and medicine. In: Sadock BJ, Sadock VA, eds. Comprehensive textbook of autoimmune hepatitis. Dig Dis Sci 2005;50:201-6. psychiatry, 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. 6. Altshuler LL, Hendrick V, Cohen L. An update on mood and anxiety disorders during pregnancy and the postpartum period. Many medical conditions common Prim Care Companion J Clin Psychiatry 2000;2:217-22. among new mothers can mimic 7. Chaudron LH, Pies RW: The relationship between postpartum psychosis and bipolar disorder: A review. J Clin Psychiatry 2003; postpartum depression. Look for weight 64:1284-92. changes and other physical signs of a 8. Cox JL, Holden JM, Sagvosky R. Detection of postnatal depression: Development of the 10-item Edinburgh Postnatal Depression Scale. medical problem. Order laboratory and Br J Psychiatry 1987;150:782-6. neuroimaging tests based on clinical 9. Atkinson LS, Baxley EG. Postpartum fatigue. Am Fam Physician 1994;50:113-18. suspicion; watch for findings that warrant 10. Kaaja RJ, Greer IA. Manifestations of chronic disease during referral for further treatment. pregnancy. JAMA 2005;294:2751-7. 11. Stagnaro-Green A. Postpartum thyroiditis. Best Pract Res Clin Endocrinol Metab 2004;18:303-16. Bottom Line

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