Is a medical illness causing your patient’s depression?

Depressed CS patients often experience poor concentration, early morning waking, and decreased libido. Compared with nondepressed individuals with CS, those with depression tend to be older (average age 37.5) and more likely to be female, have more severe CS-related symptoms, and exhibit higher urine cortisol levels at diagnosis (average 1.694 pmol/L).^14,15

Antidepressants typically will not resolve depression in patients with CS unless you also correct the hypercorticalism.¹⁶

Addison’s disease (AD). Major depressive disorder is >2 times more prevalent in AD patients compared with matched controls.¹⁷

Signs and symptoms. Hyperpigmentation, salt cravings, low blood pressure, nausea, and vomiting are AD hallmarks. AD patients present with fatigue, vegetative symptoms, weight loss, and weakness that mimics a major depressive episode.

AD is caused by damage to the adrenal cortex. These patients do not have enough of the mineralocorticoid aldosterone, which maintains sodium and potassium balance and regulates blood pressure via the renin-angiotensin-aldosterone pathway. Decreased morning serum cortisol level, hyponatremia, and hyperkalemia confirm the diagnosis. AD can be serious—possibly fatal—so prompt referral to an endocrinologist is warranted.

Table 4

Clinical symptoms of hyperparathyroidism

Neurologic disorders

Stroke. Post-stroke depressive symptoms generally do not differ from endogenous depression. Apathy, catastrophic reactions, hyper emotionalism, and diurnal mood variations are more prevalent in stroke patients,¹⁸ although some of these features have been noted in other neurologic conditions.

Signs and symptoms. Look for depression onset or a change in existing depression symptoms that occurs in the context of a clinically apparent stroke.¹⁹ Antidepressants such as serotonin reuptake inhibitors may relieve post-stroke depression.

Seizures. Depressive symptoms could appear before or after a seizure or may be the clinical presentation of a simple or complex partial seizure.¹

Signs and symptoms. Episodic, short-lived depression that resolves rapidly may warrant a seizure evaluation. Prodromal depressive symptoms such as irritability, depression, fear, or anger²⁰ may precede a seizure by 1 to 3 days and could improve after the seizure.

Caused by a simple partial seizure, ictal depression is characterized by guilt, anhedonia, or sudden-onset suicidal ideation without an environmental trigger. Symptoms are fairly short-lived, lasting from a few hours to a few days.⁵

Depressive symptoms also may develop minutes before a complex partial seizure or a secondarily generalized seizure.² Mood changes typically are brief, stereotypical, and associated with other ictal phenomena. Interictal depression involves mild chronic symptoms similar to dysthymia. Postictal depression may last for several days.

Prodromal and ictal depression often improve when antiepileptic therapy reduces seizure frequency.

Huntington’s disease (HD) is a hereditary chorea caused by expanded trinucleotide repeats and characterized by abnormal movements, cognitive impairment, and neuropsychiatric symptoms. The suicide rate among HD patients is 4 times higher than in the general population.²¹

Signs and symptoms. Depression concurrent with neurologic symptoms such as chorea or dystonia may warrant an HD evaluation. Patients may present with psychiatric complaints such as depression, apathy, insomnia, or anxiety that may coincide with or precede other neurologic symptoms.²² Mood-congruent delusions and auditory hallucinations also have been reported.²³ In one study, 98% of HD patients exhibited psychiatric symptoms—including dysphoria, agitation, irritability, apathy, and anxiety—that occurred irrespective of cognitive or motor symptoms.²⁴

Research into the cause of HD’s neuropsychiatric symptoms has focused on abnormalities in frontostriatal brain circuitry.²⁵ Depressive symptoms might respond to any class of antidepressant.

Wilson’s disease—caused by copper accumulation in the liver and basal ganglia—is characterized by degenerative changes in the brain, liver disease, and golden-brown or green Kayser-Fleischer rings in the cornea.

Signs and symptoms. Hepatic symptoms include hepatomegaly, hepatitis, and cirrhosis. Psychiatric symptoms—which include personality changes, depression, irritability, and psychosis—may occur alone or concurrent with neurologic symptoms such as tremor or dystonia.²⁶ Neuropsychiatric symptoms—the initial presentation in up to one-third of Wilson’s disease patients—may respond to anticopper therapies.²⁶

Multiple sclerosis (MS). Up to 50% of MS patients experience depression, although it is unclear if symptoms are caused by the disease or the impact of having a progressive chronic illness.

Signs and symptoms. MS may cause weakness, visual loss, incontinence, paresthesias, and speech disturbances. MS symptoms such as fatigue, insomnia, and poor concentration overlap with DSM-IV-TR criteria for major depression. Depressive symptoms may worsen during disease flare-ups and with advanced neurologic disease.