Med/Psych Update

Is a medical illness causing your patient’s depression?

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Endocrine, neurologic, infectious, or malignant processes could cause mood symptoms



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Ms. G, age 56, presents with the chief complaint of “depression.” Review of symptoms reveals 6 months of depressed mood, anhedonia, tearfulness, 30-pound weight gain, low energy, and bilateral ankle edema. Her psychiatrist orders a thyroid stimulating hormone (TSH) level, which shows 9.51 mU/L (normal range 0.35 to 4.94 mU/L), indicating hypothyroidism. After 1 month of treatment with levothyroxine, Ms. G’s mood symptoms and edema resolve and her weight stabilizes.

A patient who comes to you for treatment of depression might also present with physical symptoms (such as, fatigue, nausea, balance problems, etc.) that could point to a medical illness. Endocrine, neurologic, infectious, and malignant processes (Table 1) and vitamin deficiencies (Table 2) could be causing your patient’s depression. To help differentiate various etiologies of depressive symptoms, we review common medical causes of depression, their distinguishing characteristics, and pertinent treatment issues.

DSM-IV-TR considers major depression secondary to a general medical condition to be diagnostically separate from a major depressive episode. When considering nonpsychiatric causes of depression, begin with a thorough medical history including current and past medications (Table 3),1-7 illicit substance use, review of systems, and a detailed neurologic exam.

Table 1

Medical conditions with evidence of causing depression

Cushing’s syndrome
Addison’s disease
Huntington’s disease
Wilson’s disease
Multiple sclerosis
Parkinson’s disease
Traumatic brain injury
Human immunodeficiency virus
West Nile virus
Creutzfeldt-Jakob disease
Lyme disease
Hepatitis C
Paraneoplastic syndromes
Pancreatic cancer

Table 2

Vitamin deficiencies that can lead to depression

B12Megaloblastic anemia
Decreased appetite
Unexplained pancytopenia
Depressed mood
Depressed mood
Impaired vibratory sensation
Hyper- or hyporeflexia
Macrocytic anemia

Table 3

Medications that may be linked to depressive symptoms

Antiepileptic drugs
Primidone, tiagabine, vigabatrin, felbamate, levetiracetam, topiramate, and phenytoin may cause depression,1 and phenobarbital may cause depression associated with suicidal ideation2
Recent randomized studies indicate these drugs do not carry a higher risk of depression, contrary to earlier accepted wisdom
Depressive symptoms may occur after initial corticosteroid administration, with long-term use, or with drug discontinuation3
Interferon alfa
Depression rates of nearly 50% have been reported.4 Depressive symptoms seem to be related to dose and duration of treatment and may take several weeks to develop
Interferon beta
Initial studies raised concern about an increased risk of depression and suicide, but a review of 16 studies did not detect an increased risk of depression5
Although initial studies did not show an association between isotretinoin and depression and suicide, 24 reports of depression and more than 170 cases of isotretinoin-associated suicide have been reported.6 In many patients, depressive symptoms resolved when the medication was discontinued, and several case studies reported depression recurrence with medication rechallenge
Varenicline and bupropion
Postmarketing cases have described neuropsychiatric symptoms including depression and suicidal ideation with these antismoking agents, prompting changes in the drugs’ prescribing information. Many of the cases reflect new-onset depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating treatment. Patients with pre-existing psychiatric illness may experience worsening of symptoms7

Endocrine disorders

Hypothyroidism increases a patient’s risk of a mood disorder 7-fold, compared with the general population.8

Signs and symptoms. Patients with hypothyroidism may complain of constipation, thinning hair, dry skin, edema, sensitivity to cold, goiter, thyroid nodule, or hoarse voice. Symptoms such as fatigue, weight gain, and sleep disturbance overlap with depressive symptoms. A TSH value >4.94 mU/L indicates hypothyroidism and warrants referral to a primary care provider or endocrinologist.

Although the pathophysiology is unclear, 1 study found elevated thyroid peroxide antibodies in depressed postmenopausal women who had abnormal thyroid function tests, suggesting an autoimmune link between depression and hypothyroidism.9 In another study, 2.5% of depressed patients had abnormal serum TSH or thyroxine levels indicating hypothyroidism.10 Thyroid hormones have been used to augment treatment of refractory depression.11

Hyperparathyroidism. “Moans, groans, stones, and psychiatric overtones” describes the constellation of hyperparathyroidism symptoms. As serum calcium levels rise, mood and physical symptoms worsen (Table 4).

Signs and symptoms. Elevated serum calcium (normal range 8.7 to 10.7 mg/dL) and parathyroid hormone (PTH) levels support the diagnosis. Depressive symptoms may diminish or even resolve when calcium levels return to normal after parathyroidectomy.12

Cushing’s syndrome (CS). As many as 80% of patients exhibit depressive symptoms when CS is active.13

Signs and symptoms. Distinguishing CS symptoms include:

  • hirsutism
  • truncal obesity
  • acne
  • hypertension
  • facial flushing
  • purple striae.

Elevated serum cortisol, the condition’s hallmark, may be caused by pituitary adenomas, adrenal tumors or hyperplasia, or ectopic adrenocorticotropic hormone secretion. The most common cause is exogenous administration of glucocorticoids. A dexamethasone suppression test or 24-hour urine cortisol confirms CS diagnosis.


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