I. What every physician needs to know.

Depression and mania are serious disease states with significant morbidity and mortality. Patients with depressive symptoms should be screened for active suicidality, and if present, should be hospitalized if they are high risk. Mania is a medical emergency. Most patients with a manic episode should be hospitalized and stabilized.

II. Diagnostic Confirmation: Are you sure your patient has depression or a bipolar disorder?

Major depression is defined as a patient having at least five of the following eight symptoms for a significant period of time over at least two weeks: depressed mood, loss of interest or pleasure in most or all activities, insomnia or hypersomnia, change in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration, thoughts of worthlessness or guilt, or recurrent thoughts about death or suicide.

The mnemonic SIG E CAPS is helpful for remembering all of the diagnostic symptoms: sleep, interest, guilt, energy, concentration, appetite, psychomotor retardation and suicidality.

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Patients with bipolar disorder can present with a depressive episode or with mania, so all patients presenting with a depressive episode should also be asked about a family history of mania or previous episodes of mania. Mania is characterized by elevated mood or euphoria, psychomotor agitation, decreased need for sleep, increased optimism, impaired judgement, disinhibition and impulsivity. Mania, in the absence of other explanatory diagnoses, is sufficient for the diagnosis of bipolar disorder I (classical bipolar). Hypomanic patients have a less severe form of mania without serious occupational and social dysfunction. Patients who present only with hypomania have bipolar II.

A. History Part I: Pattern Recognition:

Not applicable

B. History Part 2: Prevalence:

In the US, the lifetime prevalence rate for major depression is between 10% and 25% for women and between 5% and 12% for men. For patients with chronic medical conditions, the prevalence of depression is as high as 20%. For bipolar disorder I, the prevalence in the US is approximately 1%.

C. History Part 3: Competing diagnoses that can mimic disease depression and bipolar disorders.

Several depressive syndromes can mimic major depression. Patients with depressed mood who do not meet criteria in symptom duration or severity could be classified as having minor or subclinical depression. Patients could have secondary depression that is caused as a side effect of a medical condition, or medication or substance use or withdrawal. Depression can also be present as part of bipolar disorder or schizoaffective disorder.

D. Physical Examination Findings.

There are no specific physical exam findings for depression or bipolar disorder.

E. What diagnostic tests should be performed?

Typically no laboratory tests or imaging studies are required as the diagnosis of depression or bipolar disorders can be made on the basis of history alone. In some cases, lab studies may be helpeful to evaluate for alternative or exacerbating diagnsoses. In patients presenting with severe depression with multiple comorbitidies, including old age, thyroid-stimulating hormone (TSH), liver function tests (LFTs), and rapid plasma reagin (RPR) could be considered. In patients with new onset mania, urine toxicology could also be considered. In patients with severe depression, a urine toxicology screen and basic metabolic panel (BMP) may be useful to evaluate for common drugs used in suicide attempts.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Not applicable.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Not applicable.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Not applicable.

III. Default Management.

For a patient in an outpatient or emergency room setting, the first step is determining whether the patient needs hospitalization.

In depression, patients should be screened for suicidality. In addition to asking about thoughts of suicide, providers should ask about specific intent, plans, and actions. Lack of ability for self-care is also an indication for hospitalization. Early in the hospitalization, a severely depressed patient may require a “sitter.”

Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for depressed patients. Studies have not found any particular SSRI to be superior to others in the class. Individual patients may have a better or worse response or tolerance to side effects. In many cases partial efficacy is seen in as few as two weeks. In cases of severe depression, the decision to institute electroconvulsive therapy is done in consultation with a psychiatrist. SSRIs are usually contraindicated as monotherapy in depressed patients with bipolar disorder I because they may precipate mania.

Patients with acute mania are at a particular high risk of harm. They usually require hospitalization (this is often involuntary) for stabilization and treatment. Early in the hospitalization, these patients may also require a sitter.

Initial stabilization for patients with acute mania is with a typical or atypical neuroleptic. Haloperidol is the first generation drug of choice and can be started at 5-15mg given daily or twice a day. Haloperidol is typically given with benadryl or benztropine to minimize extrapyramidal side effects. Apiprazole, olanzapine, quetiapine, risperdone, and zipradone are equally effective for mania. A mood stabilizer such as lithium, valproate, or carbamazepine can be added later. Some also recommend lithium as initial monotherapy. The starting dose is typically 300mg per os (PO) twice a day and must be titrated up every five days to reach therapeutic levels.

A. Immediate management.

For patients requiring hospitalization, psychiatry should be consulted early in the admission. The purpose of the consult is to assist in ongoing management and in developing a plan for follow-up, either as an outpatient or for transfer to the psychiatry service. For patients admitted at night, the psychiatry consult can usually wait until the next morning. Emergency room physicians and hospitalists can acutely treat depression and mania, and can also involuntarily admit a patient if they meet the critieria.

B. Physical Examination Tips to Guide Management.

All patients presenting with a new diagnosis of mania should have a thorough physical examination to rule out organic or pharmacologic causes. The important areas which may help in diagnosis are the vital signs, a head, ears, eyes, nose, and throat (HEENT) examination and a neurological examination. A fever may signal infection, or intoxication with anticholinergics or sympathomimetics. Mild tachycardia may simply indicate agitation; however, extreme tachycardia signals infection, or drug exposure or withdrawal.

In the HEENT examination, dilated pupils suggests anticholinergic, hallucinogents or sympathomimetic agents. Nystagmus suggests serotonin syndrome, ketamine, toxic alcohols, or phencyclidine. Dry mucous membranes, though non-specific, could indicate anti-cholinergic toxicity.

A non-focal neurological examination is consistent with psychiatric illness; any focal symptoms suggests a primary central nervous system (CNS) cause.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Lithium levels should be monitored approximately five days after intiation or dose increase. Target serum level for acute phase management is between 0.8-1.2meq/L, and levels should not exceed 1.2meq/L. The trough value is typically drawn prior to AM dose.

D. Long-term management.

For depression, patients are typically maintained on antidepressant therapy for 6-9 months. Patients with bipolar disease need to remain on lifelong maintenence therapy with a mood stabilizer alone or in conjunction with an atypical antipsychotic.

E. Common Pitfalls and Side-Effects of Management


IV. Management with Co-Morbidities

A. Renal Insufficiency.

Many patients with a diagnosis of bipolar disorder are maintained on lithium which is renally excreted and has a narrow therapeutic range. SSRIs should be used with caution in patients with severe renal disease

B. Liver Insufficiency.

SSRIs should be used with caution in patients with severe hepatic impairment. In addition, they may be associated with hyponatremia. Divalproex is also not for use with patients with severe hepatic impairment.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

Depression is associated with increased mortality in post-myocardial infarction patients. Buproprion is cautioned against in patients with recent myocardial infarction.

E. Diabetes or other Endocrine issues

Depression is associated with worse outcomes in diabetes self-care. In addition, many antidepressants are associated with weight gain, which can worsen diabetes control. In general SSRIs are preferred over tricyclic antidepressants because of less weight gain. Venlaxfine, buproprion, and duloxetine are associated with improvement in neuropathic pain symptoms. They may be useful in diabetic patients with both depression and peripheral neuropathy.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

No change in standard management.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

Sign-out considerations should include the patient’s list of PRN medications for acute agitation as well as the patient’s current mental status. It should also include whether the patient is considered competent and is able to consent for medical procedures or sign-out against medical advice. If the patient is not deemed able to consent for themselves, then the patient designated medical decision-maker or court appointed designee should also be listed on the sign-out.

B. Anticipated Length of Stay.

Patients may have a short stay in a medical facility to rule out underlying medical cause and to stabilize concomittant medical conditions prior to transfer to an acute psychiatric facility.

C. When is the Patient Ready for Discharge.

Depressed patients are ready for discharge if they are able to contract for safety and can manage self-care activities. Patients with bipolar disorder are safe for discharge once the acute episode has been stabilized.

D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom.

Patients with depression can be followed-up as an outpatient by their primary care physician. They should be seen within two weeks of discharge to monitor symptoms, medication adherence, and side effects. Patients with bipolar disorder should be transferred to a psychiatry service or seen by a psychiatrist within a week of discharge for symptoms monitoring and medication titration.

2. What tests should be conducted prior to discharge to enable best clinic first visit.


3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit


E. Placement Considerations.

Not applicable.

F. Prognosis and Patient Counseling.

Not applicable.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

Not applicable.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Patients should understand the importance of continuing medication therapy even after they feel better. Warning about potential side effects and their expected duration can also increase medication adherence. Outside of an acute episode, patients may minimize the severity of their illness or the need for medication or treatement. Therefore, an important consideration is asking patients if you can inform family members or friends about their diagnosis and treatment plan. Having family support can increase adherance to medication and follow-up mental health care.

VII. What's the evidence?

“Diagnostic and Statistical Manual of Mental Disorders”. 2000.

Benazzi, F. “Bipolar disorder-focus on bipolar II disorder and mixed depression”. Lancet. vol. 369. 2007. pp. 935-45.

Benazzi, F. “Bipolar II disorder: epidemiology, diagnosis and management”. CNS Drugs. vol. 21. 2007. pp. 727-40.

Blazer, DG, Kessler, RC, McGonagle KA & Swartz, MS. “The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey”. Am J Psychiatry. vol. 151. 1994. pp. 979-86.

Ciechanowski P & Katon, W. Initial Treatment of Depression in Adults.. 2012.

Fountoulakis, KN, Vieta, E, Sanchez-Moreno, J, Kaprinis, SG, Goikolea JM & Kaprinis, GS. “Treatment guidelines for bipolar disorder: A critical review”. Journal of affective disorders. vol. 86. 2005. pp. 1-10.

Rodin G & Voshart, K. “Depression in the medically ill: an overview”. Am J Psychiatry. vol. 143. 1986. pp. 696-705.

“Initial antidepressant choice in primary care: Effectiveness and cost of fluoxetine vs tricyclic antidepressants”. JAMA: The Journal of the American Medical Association. vol. 275. 1996. pp. 1897-1902.

“Whooley, MA & Simon, GE: Managing Depression in Medical Outpatients”. New England Journal of Medicine. vol. 343. 2000. pp. 1942-1950.

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