What is bipolar disorder and why is it so difficult to diagnose?

Takeaways

• Bipolar disorder (BD) frequently is misdiagnosed as depression.
• Indicators of BD include hypomanic symptoms, family history of BD, age of symptom onset, and poor response to antidepressants in the past.

Bipolar disorder (BD) is characterized by extreme mood swings—from emotional highs (mania) to lows (depression). (See BD facts and figures.) Unfortunately, BD frequently is misdiagnosed, which can lead to delays in treatment with mood stabilizers and harmful exposure to antidepressants as monotherapy. Before initiating antidepressant monotherapy, which can induce rapid cycling in people with undiagnosed BD (suggesting the presence of the disorder), patients should be screened to determine if they’re at risk for BD.

A retrospective study by McCormick and colleagues found that over 60% of depressed patients were incorrectly diagnosed and treated for depression rather than BD. In a survey of 600 patients diagnosed with BD by Hirschfeld and colleagues (2003), 69% reported they were misdiagnosed. Among misdiagnosed patients, 70% said they were misdiagnosed three times or less and 30% were misdiagnosed four times or more. Given these daunting statistics, one might wonder why BD is so difficult to recognize and diagnose. Part of the problem is that the same criteria are used to define the depressive episodes of BD and major depressive disorder (MDD). Clinicians need to know that what distinguishes BD from MDD is the presence or history of manic or hypomanic symptoms. A clearly cyclical pattern of episodes is more diagnostic of BD than MDD.

Differences between BD and depression

After ruling out organic causes when assessing a patient with acute depressive symptoms, determine whether a history of mania or hypomania exists. If the patient has no history of either, they most likely have depression. Other factors that suggest BD include family history, course of illness, treatment response, associated features, and manic/hypomanic symptoms.

Mood disorder screening tools, such as the Mood Disorder Questionnaire (MDQ), are effectively used in primary care and psychiatric settings to identify patients likely to have BD. The MDQ, a 13-item self-report questionnaire that takes about 5 minutes to complete, can be downloaded for free here. Most psychiatrists and psychiatric nurse practitioners use the MDQ before prescribing antidepressant medication. (See Ask the right questions.)

To meet the Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria for BD, the patient must have three or more (four if the mood is only irritable, as irritability presents in many psychiatric conditions) symptoms of mania for more than 1 week and symptoms of hypomania for more than 4 days (less than 1 week). Symptoms of mania typically are more severe than hypomania and may require hospitalization. (See Mania symptoms.)

Your ability to recognize BD will improve when you understand the symptoms and diagnostic criteria for BD I, BD II, and MDD; obtain the patient’s history of mania or hypomania and family history of BD; and can identify a manic switch, rapid cycling, or suboptimal outcome in a patient receiving antidepressant medication.

Managing BD

A combination of pharmacologic therapies and psychosocial interventions are recommended to successfully manage BD.

Pharmacologic therapies

Medications used to manage BD include mood stabilizers, second-generation atypical antipsychotics, antidepressants, benzodiaze­pines, and anticonvulsants. Patients with BD typically will require therapy with at least two medications. (See Pharmacologic treatment of bipolar disorder.)

Mood stabilizers (for example, lithium, lamotrigine, and carbamazepine) are the mainstay of bipolar treatment, and lithium remains the gold standard 6 decades after its discovery. It’s the most effective and widely studied medication in BD treatment. Many providers are reluctant to prescribe lithium because of its high toxicity potential, risk of renal failure, and need for periodic blood lithium levels, but studies have shown the drug to be safe when used judiciously. Lithium also lowers suicide risk among patients with BD and depression. Lithium decreases the level of thyroid hormone, so thyroid replacement medication may sometimes be needed.

Several second-generation atypical antipsychotics (for example, aripiprazole, cariprazine, quetiapine, ziprasidone, and aripiprazole) are effective at treating acute BD, but they have several metabolic (weight gain, hyperglycemia, and dyslipidemia) and extrapyramidal side effects. Some newer agents, such as lurasidone, claim to have fewer metabolic side effects. Long-acting injectable antipsychotics frequently are used for BD I maintenance therapy.

Antidepressants (for example, sertraline, fluoxetine, venlafaxine, escitalopram, and duloxetine) aren’t approved for treating BD and should be used only in combination with a mood stabilizer or atypical antipsychotic. Antidepressants can induce rapid cycling and cause a manic or hypomanic episode in some patients. Some debate exists about whether they should be used at all because of concern that some patients may become suicidal when taking them. Antidepressants carry a Black Box warning for children and adolescents up to age 25 years.

Venlafaxine is the most likely antidepressant to induce mania. Do not use tricyclic antidepressants or monoamine oxidase inhibitors (MAOI).

Sometimes benzodiazepines (for example, lorazepam and alprazolam) are used to treat insomnia and anxiety in patients with BD. However, they’re highly addictive and should be used only for short-term treatment. In addition, anticonvulsants (for example, valproic acid, divalproex, and topiramate) may be used to treat manic episodes. They work by calming hyperactivity in the brain.

Psychosocial interventions

BD management is most successful when medications are combined with psychosocial interventions. Individual psychotherapy, cognitive behavioral therapy, and interpersonal and social rhythm therapy (IPSRT) explore psychological issues that may be preventing treatment adherence and focus on self-care. IPSRT also views BD as a circadian rhythm disturbance and uses sleep/wake regulation and daily activities as a treatment strategy. Peer support and education that includes family members and significant others also have been shown to significantly reduce relapse rates. (See Patient education and self-care.)

Barriers to BD treatment

Medication nonadherence is one of the significant barriers to effective BD management. Many patients may be in denial about their diagnosis, especially when they’re experiencing manic symptoms. Patients frequently stop taking BD medications during a manic episode. Also, some patients taking mood stabilizers report “missing” the highs and excitement they experienced during the beginning phase of a manic episode. Other reasons for nonadherence include concerns about real or imagined side effects and financial restraints.

Many patients with BD have comorbid psychiatric disorders, such as substance use disorder (SUD) and generalized anxiety disorder. Alcohol use disorder rates can be as high as 43% in patients with BD. SUD can mask the signs and symptoms of BD. Comorbid disorders in combination with self-medicating behaviors can complicate treatment adherence and lead to poor outcomes. These patients may need referrals to other specialists (for example, an addiction treatment program) before BD treatment can begin.

According to McCormick and colleagues, suicide risk in patients with BD is 20% to 30% greater than the general population, with suicide completion rates between 14% and 60%. Suicidal behaviors increase with alcohol use. Clinicians should regularly monitor all BD patients for suicidal thoughts and behaviors. Lithium treatment decreases suicidal behavior in many BD patients.

Be alert

BD frequently is misdiagnosed. However, when you’re alert to BD signs and symptoms, you can help connect patients with the care they need and encourage referrals as appropriate. For patients diagnosed with the disorder, you can provide education, monitor for adverse events, and encourage self-care.

To learn about how to manage BD during the COVID-19 pandemic, click here.

Cynthia Taylor Handrup is a clinical assistant professor in the psychiatric mental health nurse practitioner program and director of the primary care mental health concentration at the University of Illinois at Chicago College of Nursing.

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