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Day # 47: Medical Workup for Mania

Welcome back to our current theme of bipolar disorder. Today we will round out some additional clinical pearls to include what medical work-up should be pursued in a patient with new manic symptoms.

Today's Content Level: Intermediate; Advanced


•If you remember back to the psychotic disorders theme you may remember that we stressed the importance of medical workup for psychosis before attributing it to a psychiatric diagnosis. We discussed the importance of determining if these symptoms are caused primarily by a medical or neurological condition or induced by medications or other substances.

•We did something similar for the medical workup for depression.

•Today we will do the same for new-onset mania.

•Bipolar disorder can occur at any age. The average age of onset is 18-21 years old. A bimodal distribution of the incidence of bipolar has been suggested and studies have found two peaks in age of onset at 15–24 years and at 45–54 years. If manic symptoms present for the first time far outside of these age ranges a thorough medical workup becomes that much more important.

•Review the vital signs and perform a complete physical exam. If they are normal they don't tell you much but they can be the first clue that something other than purely psychiatric may be going on.

•Clinical interview -> should address all current and significant past general medical illness, medications, substance use, review of systems, and family medical and psychiatric history in order to identify potential medical contributors of the manic condition.

•Several types of general medical disorders (example: endocrine or neurologic) can cause bipolar disorder. Any additional testing should be guided by abnormal findings in the history and examination.

Known examples of medical causes of mania include: 1

  • Hypercortisolism

  • Hyperthyroidism

  • Multiple sclerosis

  • Stroke (right-sided subcortical or cortical lesion with links to limbic system)

  • Traumatic brain injury

  • Systemic lupus erythematosus

Known examples of substance causes of mania include amphetamines, cocaine, and phencyclidine (PCP). Known medication causes include stimulants, corticosteroids, fluoroquinolones, and "switching" with antidepressants. This term is used to described a patient developing mania after being treated with an antidepressant.


Obtaining select laboratory testing plays a role in the following ways:

  1. Rule out medical causes for their symptoms.

  2. Medications used to treat bipolar disorder have important effects on the body, so you must ensure adequate function prior to treating (example: kidney function for lithium).

  3. Bipolar disorder is a lifelong illness and establishing baseline studies is important prior to treatment.

•Labs are commonly performed in the following scenarios: new onset mania, treatment-resistant mania, those with known or suspected substance use, monitoring throughout treatment, and in patients who have or are at risk for chronic medical conditions.

Commonly performed screening laboratory tests include:

  • CBC (complete blood count): rule out infectious causes (WBC count). Anemia may also contribute to the depressive periods of the illness. Treatment with certain mood stabilizers / anticonvulsants suppresses bone marrow, so monitor RBC and WBC counts. Lithium may increase WBC count.

  • CMP (complete metabolic): rule out electrolyte disturbances, paying attention to low sodium for depression and high calcium for mania or depression. Also note glucose (hypoglycemia or diabetic ketoacidosis), and renal failure (creatinine and BUN).

  • TSH (thyroid stimulating hormone): rule out hyperthyroidism (mania) and hypothyroidism (depression). Treatment with lithium can cause hypothyroidism, and hypothyroidism may cause rapid cycling of mood. In one study patients with bipolar disorder were 2.55 times more commonly associated with thyroid dysfunction than individuals without bipolar disorder. 2

  • BAL (blood alcohol) and Urine toxicology: alcohol abuse and abuse of a wide variety of drugs can present as either mania or depression. Stimulants (amphetamine, cocaine, etc) are known to cause a manic-like presentation. Also, individuals with bipolar disorder have a disproportionately high rate of comorbid substance use disorders. 3

  • Prior to starting treatment/medications -> check for pregnancy (Beta hCG), liver function panel (LFT's), fasting blood glucose, lipid panel, and EKG because medications used to treat mania affect these levels long-term (antipsychotics, mood stabilizers).

  • Brain CT or MRI (computed tomography or magnetic resonance imaging): like we discussed in the psychotic disorders section, obtaining brain imaging for psychiatric presentations is controversial. Some routinely order at the first episode of mania, whereas others reserve for patient's whose presentation and history suggests an increased likelihood of structural brain disease such as those with focal neurologic signs on physical exam. Evaluate for space-occupying lesions (tumors, AVM's, abscess, etc...), demyelinating disorders, stroke, or hemorrhage.

Other diagnostic tests that are less commonly indicated, but should still be considered in certain patients. These additional tests should be pursued as guided by the medical history, review of symptoms, and physical examination. Consider the following:

  • ESR (erythrocyte sedimentation rate): marker of inflammation. In later lessons we will explore the relationship of inflammation and mental disorders, however for now know that high ESR is associated with increased risk for mania.

  • ANA (antinuclear antibody): several large-scale studies have found positive associations between autoimmune diseases and mania. Particularly, autoimmune diseases as multiple sclerosis and lupus are known to have higher frequencies of neuropsychiatric symptoms, including psychosis and mania, compared to healthy controls.

  • Serum cortisol: adrenal insufficiency has been shown to display a wealth of possible psychiatric presentations including psychosis, depression, anxiety, mania, and cognitive impairment, alongside the known vague physical symptoms.

  • HIV: Now commonly diagnosed with an HIV viral load. Three technologies measure HIV viral load in the blood: reverse transcription polymerase chain reaction (RT-PCR), branched DNA (bDNA) and nucleic acid sequence-based amplification assay (NASBA). Can present as a variety of psychiatric symptoms.

  • FTA-ABS (fluorescent treponemal antibody absorption) or RPR (rapid plasma reagin): testing for syphilis. If not treated, 30% of patients may develop tertiary syphilis, where neurosyphilis is included. Neurosyphilis can present a variety of psychiatry symptoms, including mania, depression, psychosis and dementia.

  • Copper/ceruloplasmin: Wilson's disease (disorder of copper metabolism) is very rare, however can have neuropsychiatric manifestations to include mania, depression, and psychosis.

  • LP (lumbar puncture): a lumbar puncture is indicated to rule out meningitis or other evidence of infection if there is evidence of delirium, fever, leukocytosis, or change in level of consciousness.

  • EEG (electroencephalogram): generally not necessary. Used to rule out seizure disorder if there is a history consistent with possible seizure activity.

  • Neuropsychiatric testing: you may opt to send the patient for thorough neuropsychiatric testing to gain a more in-depth understanding of the effects on their cognition and personality.


Good work today. Next lesson will cover non-pharmacological treatment interventions for those with bipolar disorder.

Resources today include the articles linked in the body of the article, Pocket Psychiatry, and an article on Medscape.

Bullet Psych is an Amazon Associate and we receive a small commission if you use our links for the purchase of our recommended resources.

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