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Med/Psych Update

Postpartum depression or medical problem?

Watch for fatigue, weight change, other physical signs.

Vol. 5, No. 9 / September 2006

Many medical conditions common among new mothers can cause depressed mood, fatigue, and other symptoms that suggest postpartum depression. To help you quickly pinpoint the source of a new mother’s depressive symptoms and plan treatment, this article reviews:

  • new-onset or pre-existing neurologic, cardiovascular, thyroid, and other conditions that mimic postpartum depression
  • risk factors and clinical features that distinguish postpartum depression from other psychiatric disorders
  • laboratory tests that confirm or rule out medical problems.

Case: ‘I can’t sleep’

Mrs. A, age 40, sleeps 2 hours nightly at most. Awakened by her 3-month-old daughter’s overnight crying, she lies awake and ruminates over the day’s events. Throughout the day, she fears she cannot care for her baby and 2-year-old son, and she depends on a family member to stay home with her. Financial concerns force her back to work 3 months after giving birth, but she is so despondent that she can barely function.

Mrs. A’s primary care physician diagnoses primary insomnia and prescribes mirtazapine and zolpidem, 15 and 10 mg each night, respectively, but her sleep disturbance persists after 6 weeks. The physician adds the hypnotic temazepam, 15 mg at night, and the sedating anticonvulsant gabapentin, 300 mg at bedtime. Both are titrated over 6 months to 45 mg and 1,800 mg at bedtime, respectively, but Mrs. A continues to lose sleep.

After 6 months, the doctor stops mirtazapine because Mrs. A has gained 20 lb. A switch to sertraline, 25 mg/d, has no effect.

Eighteen months after symptom onset, Mrs. A still sleeps poorly, even though her daughter—now age 2—sleeps through the night. Her depressed mood—undiagnosed by the physician—continues to worsen. She sees a psychiatrist after routine blood tests and a sleep study reveal no medical cause for her insomnia.

Is it postpartum depression?

Mrs. A’s despondent mood, sleep disturbances, feelings of inadequacy as a parent, and impaired concentration suggest postpartum depression. Ego-dystonic obsessive thoughts of harming the infant might emerge, although nonpsychotic patients rarely act upon them.1

Finding risk factors for postpartum depression can clarify the diagnosis. Ask the patient:

  • When did you first notice symptoms? DSMIV-TR says postpartum depression usually begins within 4 weeks of giving birth,2 but most researchers define the postpartum period as ≤6 months after delivery.1,3 Mrs. A’s depression and insomnia started 3 months after childbirth.
  • Have you been depressed before? Women with past postpartum or other depressive episodes face a high risk of recurrence after subsequent pregnancies.1,3 Active eating disorder during pregnancy4 and past premenstrual dysphoric disorder also are risk factors.1,3
  • Has anyone in your family had depression? This increases postpartum depression risk.5
  • Who is helping you? Psychosocial stress and lack of social support can fuel postpartum depression.1,3 Mrs. A gets practical help from family members, but life’s pressures are taking their toll.

Is it another mental illness?

Screen women with postpartum depressive symptoms for anxiety, which is highly comorbid with depression.6

Include bipolar disorder in the differential diagnosis. Ask new mothers with depressive symptoms if they feel inexplicably happy, irritable, or unusually energetic at times. Also screen for postpartum psychosis, which can progress to bipolar disorder7 and—worse—greatly increase the risk of infanticide.

The Edinburgh Postnatal Depression Scale,8 a 10-item self-report screening tool that takes about 5 minutes to complete, can help identify postpartum depression (see Related resources).

Case continued: A postpartum headache

During our initial interview, Mrs. A denies thoughts of harming herself or her children, and psychotic symptoms are not apparent. She reports no past depressive or anxiety episodes and does not use alcohol or illicit drugs. Her sister has a history of depression (not postpartum).

During review of systems, Mrs. A complains of persistent headaches. Brain MRI reveals a 4.5×5 mm microadenoma in the pituitary gland. We refer her to an endocrinologist, who obtains prolactin readings of 92 and 122.4 ng/mL (normal range, 2.8 to 29.2 ng/mL).

Discussion. Mrs. A had few predictive factors for postpartum depression, an atypical presentation with insomnia as the main symptom, and incomplete response after 18 months of treatment. These findings—plus her elevated prolactin and brain MRI results—suggest a medical cause.

Is it a medical problem?

Pre-existing or new-onset postpartum medical conditions can confound the diagnosis.

  • Fatigue can mimic depression’s neurovegetative signs (poor energy, decreased appetite, sleep). Common causes include sleep deprivation, thyroid disorders, anemia, cardiomyopathy, and infections (Table 1).9
  • Weight change could signal a medical condition whose symptoms resemble postpartum depression—such as diabetes or human immunodeficiency virus (HIV) (Table 2).
  • Other disorders—including neurologic diseases, prolactinomas, systemic lupus erythematosus, diabetes, and rheumatoid arthritis—can cause depressive and other psychiatric symptoms (Table 3).

Recognizing the following disorders’ physical signs is key to uncovering a medical cause for postpartum depressive symptoms.

Thyroid disease. Postpartum thyroiditis (PPT) can occur 1 to 3 months after delivery,10 often recurs after subsequent pregnancies,11 and can progress to permanent hypothyroidism within 5 years.10 Hypothyroidism can cause cognitive slowing, depression, and psychosis, and acute mania has been reported with severe hypothyroidism secondary to PPT.12

Find out if the patient tested positive early in gestation for thyroid antibodies, as this may predict postpartum depression.

Multiple sclerosis (MS) can cause anxiety, mania, depression, and cognitive impairment.13 Drugs used to treat MS—such as steroids or interferon—can induce depression.

Relapses are infrequent during pregnancy but increase significantly within 3 months after giving birth14 in about one-third of women with active MS before pregnancy.15 Gait ataxia, sensory loss, numbness, hyperactive reflexes or spasticity, bladder dysfunction, visual impairment, disordered ocular motility, and fatigue are prominent clinical signs of MS.16

Myasthenia gravis (MG). Women who become pregnant within 1 year after diagnosis run a high risk of MG exacerbation.17

Fatigue and muscular weakness caused by MG can mimic depression, and adjusting to this debilitating illness can cause depression. Double vision, droopy eyelids, and muscle weakness alleviated by rest but worsened by activity are pathognomonic signs.16

Other neurologic diseases. Pre-existing seizure disorders can worsen after giving birth and cause depression.14

Subtle presentations of brain tumors include cognitive deficits, mood disturbance, and personality change. A left frontal lobe tumor can cause depression.

Ask the patient if she has had headaches, visual symptoms, vomiting, seizures, or focal neurologic deficits—any of these could signal a primary brain tumor or intracranial hemorrhage.

Prolactinomas, the most common pituitary tumor in pregnant and postpartum women, enlarge during pregnancy and regress after delivery.14 Depression, anxiety, apathy, and personality changes may stem from the pituitary tumor, its treatment, or changes in the hypothalamic-pituitary-end organ axis.18 Typical amenorrhea-galactorrhea syndrome resembles postpartum physiologic changes.

Headaches are common, and compression of the optic chiasm with macrodenomas causes visual field changes.

Systemic lupus erythematosus (SLE), most prevalent in young women, might flare during pregnancy and within 6 weeks after giving birth.11 Headaches, seizures, or cerebrovascular events with comorbid mood disorders, delirium, dementia, psychosis, or anxiety can signal SLE.13

Suspect SLE if the patient presents with fatigue, “butterfly” face rash, or joint pain. Test for renal or cardiopulmonary involvement.

Rheumatoid arthritis (RA). Because inflammatory activity is heightened after childbirth, postpartum women—particularly after bearing a first child—face a five-fold risk of RA compared with other women.11 Breast-feeding might worsen RA, presumably by increasing prolactin production.

Physical limitations caused by RA can cause depression. Symmetric joint pain associated with morning stiffness—especially in the fingers, hands, or knees—might signal RA.

Anemia. Increased need for iron and folic acid during pregnancy can lead to anemia. Neuropsychiatric manifestations of folate deficiency range from mild irritability to severe depression, dementia, psychosis, and confusion.19 Vitamin B12 deficiency can lead to megaloblastic anemia or neurologic problems such as peripheral neuropathy, as well as depression, delirium, or dementia.19

Ask the patient about:

  • alcohol dependence, malnourishment, chronic illness, inflammatory bowel disease, gastric bypass or other gastric surgery, which can impair vitamin B12 absorption
  • use of anticonvulsants such as carbamazepine or valproic acid, which can decrease folate.

Hypotension mimics anergia. Postpartum hypotension can cause partial or total necrosis of the anterior pituitary gland. This leads to panhypopituitarism (Sheehan’s syndrome)—a rare complication characterized by failure to lactate, amenorrhea, hypothyroidism, and adrenal insufficiency.

When not in hypotensive circulatory shock, patients with adrenal insufficiency might present with depression, delirium, or psychosis.13 Ask the patient if she is having lactation problems and irregular periods, which could signal a pituitary problem.

Peripartum cardiomyopathy—an acute dilated cardiomyopathy— appears ≤6 months after delivery and may cause fatigue.10,20 Check for shortness of breath at night and with exertion, palpitations, and extremity swelling.

Gestational diabetes. Pregnancy-induced insulin resistance leads to gestational diabetes mellitus. Women with gestational diabetes can develop type 2 diabetes after giving birth.10

Blood sugar fluctuations can cause depression, irritability, or memory problems. Depression can sabotage adherence to diet and treatment, leading to poor glycemic control.

Ask the patient if she was diagnosed with gestational diabetes and if she is experiencing fatigue, excessive thirst, frequent urination, blurred vision, headaches, excessive hunger, or unexplainable weight loss.

Primary biliary cirrhosis is most prevalent in women ages 35 to 60 and may cause depression.20 Pruritus, fatigue, jaundice, and liver abnormalities point to this autoimmune disease, and postpartum exacerbations have been reported.21

HIV infection often leads to cognitive loss and depression with suicidal thoughts.13 Highly active antiretroviral medications commonly cause agitation, pain, mood changes, and insomnia.

Ask the patient is she is HIV positive. Watch for weight loss, fever, anorexia, and recurrent infections.

Substance abuse. Intoxication, withdrawal, or long-term alcohol or drug use can contribute to depression. Women at high risk for substance abuse disorder might not adhere to psychiatric treatment and may be prone to sexually transmitted diseases. If possible, see the patient every 3 to 4 weeks during the postpartum period.

Pain—if not adequately controlled—can fuel depression. Ask the patient if she has chronic pain or suffered a severe injury.

Table 1

Possible tests if postpartum patient is constantly fatigued

Laboratory test

Confirms or rules out

Order if patient also presents with:

Acetylcholine receptor antibodies

Myasthenia gravis

Double vision, droopy eyelids, muscle weakness

Alkaline phosphatase

Primary biliary cirrhosis

Jaundice, pruritus

Antimitochondrial antibody

Primary biliary cirrhosis

Jaundice, pruritus

Antinuclear antibody

Systemic lupus erythematosus

‘Butterfly’ facial rash, joint pain, morning stiffness


Microcytic anemia, megaloblastic anemia

Pallor, low energy, peripheral neuropathy, shortness of breath


Adrenal insufficiency, renal disease

Low blood pressure, seizures, skin pigmentation

Glucose (fasting or glucose tolerance)

Type 1 or 2 diabetes mellitus

Blurred vision, excessive thirst/hunger, headaches, frequent urination, unexplainable weight loss


HIV infection/AIDS

Anorexia, recurrent infections, weight loss

Liver function tests

Alcohol abuse, hepatitis, primary biliary cirrhosis

Asterixis (flapping tremor), easy bruising, jaundice, pruritus, spider telangiectasias

Lumbar puncture

Multiple sclerosis

Bladder dysfunction, gait ataxia, ocular signs, sensory loss, spasticity

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 thyroiditis

Constipation, dry skin, hair loss, lethargy, memory loss

Glucose (fasting or glucose tolerance)

Type 1 or 2 diabetes mellitus

Blurred vision, excessive thirst/hunger, fatigue, frequent urination, headaches


HIV infection/AIDS

Anorexia, fatigue, recurrent infections

TSH±thyroid panel


Constipation, dry skin, hair loss, lethargy

TSH±thyroid panel


Agitation, anxiety, heat intolerance, palpitations

Table 3

Possible tests if postpartum patient has other physical symptoms

Laboratory test

Confirms or rules out

Order if patient presents with:

Blood urea nitrogen/creatinine

Renal disease, dehydration

Back pain, frequent urination or oliguria, low blood pressure

Brain MRI

Brain tumors, white matter disease

Focal deficits, headaches, seizures, vision problems, vomiting

C-reactive protein

Rheumatoid arthritis

Joint pain, morning stiffness



Extremity swelling, palpitations, shortness of breath at night and with exertion

Erythrocyte sedimentation rate

Rheumatoid arthritis, SLE

‘Butterfly’ facial rash, joint pain


Folate deficiency

Ataxia, loss of vibration and position sense, peripheral neuropathy, weakness


Prolactinoma, hypopituitarism

Amenorrhea/galactorrhea, headache, visual field loss

Rapid plasma reagin


Ataxic wide-based gait, loss of position, deep pain and temperature sensation, palmar/plantar rash

Rheumatoid factor

Rheumatoid arthritis

Morning stiffness, symmetric joint pain


Urinary infection, diabetes, renal disease

Burning or difficulty with voiding, dark-colored urine, frequent urination

Urine drug screen

Substance abuse disorder

Erratic behavior, irritability or aggression; violence, mental status changes

Vitamin B12

Anemia, malnutrition, inflammatory bowel disease

Loss of position or vibratory sensation, mood and cognitive changes, tingling and numbness in hands and feet

SLE: Systemic lupus erythematosus

Determining a medical cause

Laboratory and neuroimaging findings—obtained in concert with the patient’s primary care physician—will help confirm or rule out a medical problem (Table 4). Consult with a neurologist, endocrinologist or rheumatologist if indicated.

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