Diagnosing and treating bipolar disorder is not always black-and-white. Dr. Kevin Johns teaches us how to not get tripped up on this tricky diagnosis. (The Ohio State University Wexner Medical Center)
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The term “bipolar” is often incorrectly used outside of the medical field to label mood swings throughout the day. However, changes in mood in response to positive or negative events are normal, and excessive pathological mood lability over the course of a few hours is a characteristic of borderline personality disorder, not bipolar disorder (Biskin and Paris 2012). Bipolar disorder is defined as the presence of a major depressive episode and one manic episode (bipolar I) or hypomanic episode (bipolar II) not better explained by another condition (APA 2022).
A manic episode is defined as at least one week of elevated, expansive, or irritable mood along with pressured speech, hypersexuality, grandiosity, and/or flight of ideas. Hypomanic episodes are distinguished from manic episodes by duration and severity; they last less than a week, but more than 4 days and do not cause a major deficit in function (APA 2023). Dr. Johns reminds us that mania isn’t always euphoric, patients can have irritability and anger and the symptoms are often mixed.
A major depressive episode is a period of anhedonia (the inability to enjoy normally pleasurable things) or a time when the patient is persistently sad, pessimistic, or overwhelmed by negative thoughts. Symptoms of a major depressive episode can include, changes in weight, changes in sleep, agitation or psychomotor retardation, fatigue, difficulty focusing, guilt or feelings of worthlessness, recurrent thoughts of death, and suicidal ideation (APA 2023).
The day before their first manic episode, patients with bipolar disorder could meet the criteria for major depressive disorder. Multiple conditions can cause a major depressive episode (substances, medical conditions, schizoaffective disorder, and bipolar disorder), so it is important to screen for bipolar disorder in patients presenting with depression. Over 3 out of every 30 patients diagnosed with unipolar depression have unrecognized bipolar disorder (Daveney et al 2019). Depressive episodes are the most common and impairing presentation of bipolar disorder (Judd et al 2002).
To screen for bipolar disorder, Dr Johns avoids listing the DSM criteria to avoid leading the patient. He prefers open ended questions like:
If a patient answers yes, he likes to get more information about those times with questions like:
Dr. Johns reminds us that it is important to use collateral in the room and ask if they have ever noticed the patient acting strange.
There are formal screening tools for bipolar disorder. The Mood Disorder Questionnaire (MDQ) has a good negative predictive value, but a low positive predictive value (Hirschfeld 2002). Dr. Johns likes to say that the MDQ is the “d-dimer” of psychiatry; if it is negative, you can be fairly certain that the patient doesn’t have bipolar disorder, but a positive value does not give you a definitive diagnosis (Hirschfeld et al 2005). In the primary care setting, Dr. Johns recommends the WHO Composite International Diagnostic Interview (CIDI) (Kessler et al 2006). THe CIDI bipolar screening tool takes 5-10 minutes to administer and emphasizes that the symptoms need to overlap for an extended period of time to better identify a manic episode. The Young Mania Rating Scale is another tool, but it aims to identify acute mania and is typically less useful in the primary care setting (Young et al 1978).
Family history and substance use history are both particularly important when talking to a patient with suspected bipolar disorder. Bipolar disorder has a strong genetic component (Gordovez and McMahon 2020), with a monozygotic twin concordance rate of nearly 50% (Kieseppa et al 2014). Stimulants, methamphetamines, cocaine, and dissociative substances can cause symptoms that can mimic mania, but important to note, substance use is not always the primary cause of behavioral changes; bipolar disorder and substance use disorder are common comorbid conditions (Cassidy et al 2008). It can be difficult to tease out the primary diagnosis in patients with bipolar and substance use disorders; patients tend to engage in risky behaviors while manic, and it can be hard to tell what came first the drug use or the mania.
There are many mimickers of bipolar disorder. Psychological disorders that can sometimes be confused with bipolar disorder include schizoaffective disorder bipolar type, schizophrenia, borderline personality disorder, PTSD, ADHD, cyclothymic disorder, and substance use disorder. Schizoaffective disorder and schizophrenia are different from bipolar disorder because the psychotic disorder is the primary disorder; unlike patients with bipolar disorder, patients with schizophrenia or schizoaffective disorder can have psychosis outside of periods of disturbed mood (Benabarre et al 2020). Borderline personality disorder also can get confused with bipolar disorder; patients with borderline personality disorder can have rapid mood shifts within a day, whereas bipolar disorder mood changes may last weeks (Fowler et al 2019). ADHD can cause short bursts of impulsivity that may look like mania, but these are lifelong process don’t comprise a concentrated week (Brus et al 2014). Cyclothymic disorder is a psychiatric disorder similar to bipolar II, but the symptoms are subthreshold hypomania symptoms with subthreshold major depressive disorder. Substance use disorder, discussed above, is likely the most common mimicker of bipolar disorder.
Anabolic steroids and corticosteroids have both been shown to cause mania and psychosis which can be confused with bipolar disorder (Franey et al 2018 and Brown and Chandler 2001). Other medical conditions can cause symptoms that look like depression or mania. Additional bipolar disorder mimickers are physiologic conditions like hypo or hyperthyroidism or less common conditions like paraneoplastic encephalitis and limbic encephalitis.
If a patient presents to your clinic with a diagnosis of bipolar disorder, it is important to learn the circumstances leading to their diagnosis and who made the diagnosis; a bipolar diagnosis made by a psychiatrist is more likely to be accurate than one made by a professional without specialized training. Dr. Johns reminds us that even highly trained and specialized psychiatrists struggle with making this diagnosis, and a correct diagnosis often requires establishing a long term relationship with the patient. Bipolar is challenging to diagnose unless you directly observe the patient during a manic episode.
It is imperative to evaluate for suicidality at every visit. Patients with bipolar disorder are 20-30 times more likely to lose their lives to suicide than the general population (Plans et al 2019).
First line monotherapy for bipolar disorder can be lithium, valproate, or antipsychotics. The different treatments for bipolar disorder have different efficacies in treating the manic and depressive symptoms of bipolar disorder.
While lithium is a lifesaving medicine, due to its narrow therapeutic window and drug-drug interactions, prescribing lithium is challenging. If you have a patient on lithium, it is important to closely monitor thyroid function with TSH and kidney function with urinary protein and eGFR (Shah et al 2017).
Atypical antipsychotics (second generation antipsycotics) are the mainstay of treating bipolar disorder. They treat manic symptoms well but, they are not as effective for the depressive phase of the illness. Lurasidone and quetiapine are two exceptions in this class and have been shown to also be effective against depressive symptoms (Loebel et al 2014 and Young et al 2013), Dr. Johns recommends starting with Quetiapine 25-50 mg at bedtime and gradually increase in 50 mg increments to 300mg/day. The main downsides for lurasidone or quetiapine are their metabolic side-effects (Vancampfort et al 2012). Neuroleptic malignant syndrome (NMS) is an extremely rare complication, and extrapyramidal side effects along with tardive dyskinesia can occur with long term use.
Valproic acid is useful for the management of acute manic episodes, but less effective for treating depression. Valproate can be stated at a low dose of 250 mg twice a day and titrated upwards while monitoring serum levels (goal 70-90 ug/mL) and side effects. Patients on valproic acid should have a CBC and LFTs checked every 6 months to monitor for hepatic or hematologic dysfunction (Shah et al 2017).
Lamotrigine has been shown to be useful in the management of bipolar depression. However, it is not useful in the acute setting due to the need for slow titration to avoid Stevens- Johnson syndrome. Lamotrigine is started at a dose of 25 mg/day for 2 weeks, then 50 mg/day for two more weeks, and subsequently the dose can be increased an additional 50 mg/day per week until therapeutic response (Shah et al 2017).
Bipolar disorder is a biosocial disease so it is important to counsel patients and family on how to address the disease. Encourage them to look out for changes in mood. It is also recommended to have an overall healthy lifestyle with a good diet and exercise; disrupted sleep can set off a manic episode (Wehr et al 1987). Cognitive behavioral therapy (CBT) is also an important component of treating bipolar disorder (Miklowitz et al 2021).
Antidepressants are not a monotherapy for bipolar disorder and can trigger manic episodes, but occasionally antidepressants can be used if a patient is on top of an adequate dose of a mood stabilizing medication (Yatham et al 2023).
Cannabis use is not recommended for patients with bipolar disorder; there is little to no evidence for benefit, but there is evidence for an association between use and negative outcomes (Pinto et al 2019). With a patient who is using cannabis, it is important to acknowledge that the patient is using cannabis for a reason. Try to address those reasons with a more appropriate therapy.
Listeners will learn to diagnose and manage bipolar disorder
After listening to this episode listeners will…
Dr. Kevin Johns and The Curbsiders report no relevant financial disclosures.
Gorth, DJ, Johns, K, Heublein M, Williams PN, Watto MF. “#415 Bipolar Disorder”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast November 13, 2023
Written and Produced by: Deborah Gorth MD, PhD
Infographic and Cover Art: Deborah Gorth MD, PhD and Meryl Gorth MPH, RD
Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP; Deborah Gorth MD, PhD
Reviewer: Molly Heublein MD
Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP
Technical Production: PodPaste
Guest: Kevin Johns MD
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