How do you evaluate for bipolar disorder in depressed patients? 

Olivia is a 19 yo woman who presents to primary care during her first major depressive episode. She feels depressed every day with a deep sense that she will always be a failure. She can’t concentrate well enough to read anymore, though she can follow short TV shows. She has low energy and wakes up every morning at 3am. She has lost 10 lbs over the last 3 months. Her PHQ9 is 18 with no suicidal ideation. She has never felt like this before, and she is open to taking medication for depression.  

Knowing that people with bipolar disorder commonly seek medical care when they are depressed, you ask her, “Have you ever had a manic episode – a time when you felt really good and had a lot more energy than usual.” She is confused by the question, and you think, “How do I evaluate for bipolar disorder in depressed patients in primary care?

Why this diagnostic difference matters.

While antidepressants are first-line treatments for moderate-to-severe major depressive disorder, we treat bipolar depression with mood stabilizers like lithium and lamotrigine, and with some second generation antipsychotic medications like lurasidone and quetiapine. In randomized control trials, antidepressants are no better than placebos for treating bipolar depression (Sachs 2007). Antidepressants are the wrong treatment for bipolar depression because they don’t work. Antidepressants can also worsen the clinical outcomes of people with bipolar disorder by precipitating manic episodes or rapid mood cycling (an increase in the frequency of depressed or manic episodes).  

When patients are currently depressed, how do you evaluate for bipolar disorder?

The diagnosis of bipolar disorder is based on a history of a manic episode (bipolar 1) or a hypomanic episode and a major depressive episode (bipolar 2). When patients present as manic or hypomanic, a new diagnosis of bipolar disorder can be made with some confidence. People who are hypomanic or manic are energized, with moods that are very happy or more irritable. You can feel the energy in the room, and it manifests in different ways. People are unable to sleep and generally sleep less than 6 hours a night, but they don’t crash from exhaustion. They may talk more or faster or over you. Their thoughts come quickly and shift rapidly, leading them to start new projects and do more. They also feel more confident and are less concerned about consequences, leading them to spend too much money, drive too fast, say things they later regret, or do things sexually that they wouldn’t normally do. The depressions of people with major depressive disorder and bipolar disorder are not phenotypically different. 

Bipolar disorder is underdiagnosed in primary care – 1 in 6 primary care patients who are taking antidepressants for major depression actually have bipolar disorder (Singh 2018). Your patients with bipolar disorder are more likely to seek mental health care for depression – they spend 3x (bipolar 1) or 39x (bipolar 2) as much time depressed as manic (Judd 2002, 2003). In the early 2000s, the median delay from symptom onset to initial treatment for bipolar disorder was 6 years (Wang, 2005).   

When you see a patient who is depressed, you’re generally trying to evaluate for a prior history of hypomanic or manic episodes, which is much harder than recognizing current hypomania or mania. Psychiatrists who specialize in mood disorders don’t get this right every time. We move forward with treatment of a mood disorder diagnosis that is supported by a preponderance of evidence, not accurate beyond a reasonable doubt.

There are, unfortunately, no existing screening tools for bipolar disorder that have good enough metrics to be relied on for diagnosing bipolar disorder. The gold standard for diagnosis is a detailed psychiatric history. Here is an example of an interview guide.



Interview Guide for Evaluating for Hypomania & Mania in People Presenting to Primary Care With Depression

The diagnosis of (hypo)mania requires a distinct mood shift along with increased energy or activity. It must last for at least several days (4 days for hypomania, 7 days for mania); be observable by other people (hypomania) or cause “marked impairment in social and occupational functioning” (mania); and have several supporting symptoms (3 supporting symptoms if the mood is elevated, 4 supporting symptoms if the mood is irritable).

Screening questions  

Q1 – Have you ever had a period of time that lasted several days when you were feeling so good, excited or ‘hyper’ that other people thought you were not your normal self?

Q2 – What about a period of time that lasted several days when you were so irritable and energetic that you found yourself shouting at people or starting fights or arguments?

If a patient answers yes to Q1 or Q2, continue to Q3.

Q3 – During that same period, were you much more active than usual – for example doing lots of different projects at the same time?

If a patient answers yes to Q3, continue with the follow-up questions.  

Follow-up questions 

Open ended question – Tell me about that period of time. It is helpful to identify a date or life phase – like the 1st year of college – so you can reference it later.

Duration – How long did the period last? (hours/days/weeks) A few days or longer is typical of bipolar disorder. Hours are more likely mood lability associated with borderline personality disorder.    

Questions to assess for supporting symptoms 

The open ended question “Tell me about that period of time” may have already elicited some supporting symptoms. If a patient answers “yes” to any of the following questions about supporting symptoms, learn more. I like the phrase “tell me more about that.” 

  • Decreased need for sleep – What was your sleep like during that period? Did you sleep less than usual without it affecting you? 
  • Racing thoughts / Flight of ideas – During this period, did you have so many ideas that you couldn’t catch up with them or keep track of them? 
  • Distractible – During this period, did you find it hard to keep your mind on what you were doing?  
  • More talkative / pressured speech – During this period, did you find it hard to stop talking?  
  • Grandiosity – During this period, did you feel especially self-confident or have any particularly good ideas? 
  • Increase in (goal-directed) activity – During this period, did you start any new projects?
  • Indiscrete – During this period how did you spend your time? Did you do anything that was out of character or unusual for you? Did you talk about things you would normally keep private, or act in ways that you would usually find embarrassing? What about driving too fast, spending too much money, or doing things sexually that you wouldn’t normally do?

“Yes” answers to 3-4 supporting symptom questions during the same time period suggests a hypomanic or manic episode.

Questions to differentiate bipolar disorder from other common comorbidities

How frequently do these (hypo)manic episodes occur?
Daily or weekly episodes do not suggest bipolar disorder and are more likely mood lability. Rapid cycling bipolar disorder is defined by having 4 or more mood episodes a year, and most people with bipolar disorder have fewer mood episodes than that.

Were you taking any drugs like cocaine, methamphetamine, Adderall, or other stimulants when you had these symptoms? Were you taking any medications, like steroids that may have affected your mood? Have you had an experience like this at a time when you were not using the drug? 

Comorbidity is the norm rather than the exception in bipolar disorder. In a group of people with bipolar disorder, 35% have an anxiety disorder, 17% have ADHD, and 20% have borderline personality disorder (Pavlova 2016, Schiweck 2021, Frías, 2016). Half of patients with bipolar disorder will be diagnosed with a substance use disorder at some point in their life (Hunt 2016).

Features that increase the likelihood of bipolar disorder (vs major depressive disorder)

Age on onset – When did you first have problems with mood?
Bipolar disorder generally begins at age 15-25, a younger on average than MDD.

Recurrences – How many depressive episodes have you experienced?
Bipolar disorder is associated with more depression recurrences than MDD.

Family History – Does anyone in your family have bipolar disorder? 
While you’re at it, ask about a family history of depression, suicide, psychosis, and substance use disorders.

Collateral information

 If the interview is challenging or you don’t have enough information, ask the patient for permission to speak with someone who knows them well. While patients are often good at reporting their depressive symptoms, family members or friends may be better at reporting symptoms of hypomania. Patients often experience hypomania as a time when they were not depressed and were feeling well. I routinely talk to a family member or friend of a patient if I am considering a new diagnosis of bipolar disorder.

Getting Permission – To be sure that I am not missing anything, I’d like to talk to one of your friends or family members about their observations of your moods. Is there someone who has known you for years who I could talk with briefly?   

Preserving Confidentiality – I’ll mainly be asking them for information. Is there anything that we talked about today that you would not want me to mention to them?


Returning to the case 

 You say to Olivia, “Have you ever had a period of time that lasted several days when you were feeling so good, excited or ‘hyper’ that other people thought you were not your normal self?”

She says no. 

“What about a period of time when you were so irritable and energetic that you found yourself shouting at people or starting fights or arguments?”

Olivia’s eyes widened. “3 months ago, right before my mood crashed, my boyfriend kept asking me why I was suddenly picking fights with him all the time. I didn’t notice it, but he did.”  

“During that time, right before your mood crashed, were you much more active than usual – for example doing lots of different projects at the same time?”

“Yes.”

Olivia reports having been irritable with increased energy for about a week. She slept 5 hours a day instead of her usual 8-9 hours without really noticing it. Several friends got annoyed with her for calling multiple times in the middle of the night. She joined 3 new clubs that were focused on tutoring children, and developed a plan to become president of all of them and then lead the merger of the clubs. After feeling this energy for about a week, she went to a party alone, accepted a stranger’s offer of cocaine for the first time, and had sex with 2 different people. “I would never do cocaine or have sex with someone I didn’t know. It’s just not me.” The next day her boyfriend of two years broke up with her, and her depressive symptoms started. Her depressive symptoms have worsened and persisted for 3 months. Her maternal grandmother has a history of bipolar disorder and took lithium.  

You think that Olivia is describing a previous hypomanic episode followed by the current episode of major depression. The cocaine use was in the context of hypomania, not the precipitating factor. She likely has bipolar disorder, not major depressive disorder, so you don’t start an antidepressant because antidepressants don’t work for bipolar depression. You connect Olivia with therapy and place an urgent referral for psychiatry. 


Key Points

  1. Antidepressants are not effective for bipolar depression.
  2. An evaluation for bipolar disorder starts with 2 screening questions. By asking these questions of every depressed patient who is going to start a medication for depression, we can identify the 1 in 6 patients in primary care who presents depressed but has bipolar disorder.
  3. If the diagnostic interview is challenging or you don’t have enough information, consider talking to a friend or family member of the patient who can comment on the patient’s moods and behaviors.

References:

Cerimele, Joseph M., et al. “The presentation, recognition and management of bipolar depression in primary care.” Journal of general internal medicine 28 (2013): 1648-1656.

Frías, Álvaro, Itziar Baltasar, and Boris Birmaher. “Comorbidity between bipolar disorder and borderline personality disorder: prevalence, explanatory theories, and clinical impact.” Journal of Affective Disorders 202 (2016): 210-219.

Judd, Lewis L., et al. “The long-term natural history of the weekly symptomatic status of bipolar I disorder.” Archives of general psychiatry 59.6 (2002): 530-537.

Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003 Mar;60(3):261-9. 

Hunt, Glenn E., et al. “Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990–2015: systematic review and meta-analysis.” Journal of affective disorders 206 (2016): 331-349.

McIntyre, Roger S., et al. “Differential diagnosis of major depressive disorder versus bipolar disorder: current status and best clinical practices.” The Journal of Clinical Psychiatry 80.3 (2019): 20884.

Pavlova, B., et al. “Prevalence of current anxiety disorders in people with bipolar disorder during euthymia: a meta-analysis.” Psychological medicine 47.6 (2017): 1107-1115.

Sachs, Gary S., et al. “Effectiveness of adjunctive antidepressant treatment for bipolar depression.” New England Journal of Medicine 356.17 (2007): 1711-1722.

Schiweck, Carmen, et al. “Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis.” Neuroscience & Biobehavioral Reviews 124 (2021): 100-123.

Singh, Sukhmeet, Paul Scouller, and Daniel J. Smith. “Evaluation of the 13-item Hypomania Checklist and a brief 3-item manic features questionnaire in primary care.” Bjpsych Bulletin 41.4 (2017): 187-191.

Wang, Philip S., et al. “Failure and delay in initial treatment contact after first onset of mental disorders in the National Comorbidity Survey Replication.” Archives of general psychiatry 62.6 (2005): 603-613.


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