How to distinguish Major Depressive Disorder from Bipolar II Disorder

One of the hardest diagnoses to make as a nurse practitioner treating individuals with mental health needs is differentiating Major Depressive Disorder from Bipolar II disorder. 

Some of the most challenging patients I’ve encountered have been those who struggle with depression but have these periods which kinda sorta sound like hypomania but not really. They might have tried a few medications to treat their depression and still. no. relief.  They come to me with very clear signs of depression. Low mood. Lack of interest in things. Little hope. Sleep and appetite disturbances. No energy. But patients don’t always have the best insight into patterns of their moods. 

Is it a major depressive disorder? Bipolar depression? If so, what kind of bipolar depression – type I or type II bipolar disorder?

It leaves you wondering if you’re really treating the right disorder and maybe even questioning your ability to correctly diagnose these disorders. 


Why misdiagnosis of bipolar II disorder occurs

First, know that diagnosing bipolar depression is not an easy task. In fact, up to 60% of clinicians also struggle to diagnose bipolar depression. 

There are several reasons why bipolar disorder is often misdiagnosed. 

    • DSM-5 criteria for the depressive phase of bipolar II disorder is identical to the criteria required for a major depressive episode. In other words, Bipolar II Disorder and Major Depressive Disorder, at periods of time, look exactly the same as one another. So, diagnosing bipolar depression can be like trying to distinguish Katy Perry from Zoey Deschanel when you’ve been spun around 30 times, nearly impossible to do!

    • Another reason why bipolar disorder is misdiagnosed is that hypomania can be really tough for patients to distinguish from a “normal” mood state when they’re just experiencing extra energy and good mood.
    • Also, patients very rarely present to see us providers for treatment while they’re in the middle of a hypomanic episode (I mean, would you seek assistance when you’re feeling great and getting lots of things done?). This mood state is often enjoyable for our patients and not something they would present to us during. So, much of the time when we’re seeing patients, its during a depressive episode that looks a heck of a lot like Major Depressive Disorder.

    Why misdiagnosis of Bipolar disorder is a problem

    Patients who are incorrectly diagnosed with unipolar depression instead of bipolar depression have a greater number of psychiatric hospitalizations and more psychiatric emergency room visits. 

    Adding fuel to the fire, on average, it takes 5 to 10 years after illness onset to reach a correct diagnosis. As previously discussed, it’s not always easy to realize a patient’s symptoms aren’t unipolar depression, but, in fact, bipolar disorder. 

    Other consequences of misdiagnosis include: inappropriate use of antidepressants, increased risk for hypomanic/manic activation, and delay of proper treatment. 

    So, what do we do?


    How to distinguish Major Depressive Disorder from Bipolar II Disorder

    One of the best ways to differentiate unipolar depression from bipolar depression (specifically bipolar II disorder) is to systematically screen all patients with Major Depressive Disorder for bipolar disorder and ask careful questions about prior episodes of hypomania. 

    It can also help to get a sense of how your patients have responded to medications in the past, particularly SSRI response as well as mood stabilizers if they’ve been prescribed them as well to help tease apart the diagnoses. 



    Other factors that are suggestive of bipolar disorder versus unipolar depression include:

        • early-onset depression

        • frequent depressive episodes

        • family history of serious mental illness

        • hypomania/mania symptoms within the depressive episode

        • nonresponse to antidepressants 

      Family history

      Individuals with bipolar depression are likely to have family histories with higher rates of psychiatric illness, and specifically bipolar disorder. Make sure not to skip over assessing family history during a psychiatric evaluation. 

      Course of illness

      Assess for the age of first manic and depressive episode as well as the duration and frequency of episodes. Also check for any seasonality associated with episodes.

      Treatment response

      Look for a pattern of multiple treatment failures – ie, patients not responding to the 4 other antidepressants they have been prescribed at optimized doses. Along the same lines, check for non-response or erratic response to antidepressants. 

      Mania symptoms

      You’ll want to dig fast with this one. I mean this literally. Use DIGFAST to help you recall the assessment components for mania. Distractibility. Insomnia. Grandiosity. Flight of ideas. Activity increase. Pressured speech. Thoughtlessness. 

      Associated features

      It can be also helpful to check for some associated features.  Things like unevenness in intimate relationships, frequent career changes, and/or substance use disorders. 

      This sounds like a lot but shouldn’t take a ton of time. You’re briefly running through these assessments and creating a working diagnosis for your patient. At the end, you may come away feeling confident that your patient is not meeting criteria for bipolar depression, and more likely fits a unipolar depression diagnosis. Perfect. 

      You should still create a differential diagnosis of bipolar disorder, knowing that this may be a possibility for you to consider. 

      You don’t always have to get the diagnosis right at the first visit, or even know the correct diagnosis immediately. But keeping an eye out for bipolar depression will help make sure your patient reaches the appropriate diagnosis as soon as possible. 

      Screening tools to consider

      Although nothing can really replace careful clinical assessment, screen tools can be helpful additions to identify bipolar disorder or rule out an incorrect diagnosis. 

      The MDQ (Mood Disorder Questionnaire) is a simple self-report instrument including 13 questions that assess clustering symptoms and functional impairment in bipolar disorder. Using a combination of the MDQ and follow up questioning can really help with diagnosing bipolar disorder. 

      The bottom line is that diagnosis of bipolar depression is not an easy task. But with an understanding of what to look out for, you can more quickly and appropriately diagnose your patients. And ideally, your patients with bipolar disorder won’t have to wait on average 5 to 10 years to receive appropriate treatment. Cherry on top is that you’ll be able to be that brilliant provider who was able to correctly provide the right treatment in a timely manner. 

      Now I don’t want to minimize how simple this all is, diagnosing and treating mental disorders isn’t always easy. If you want to learn a bit more about a framework for how to diagnose and treat mental disorders, you can sign up for my free Mental Disorders Training

      If you want my most detailed, step-by-step support, you can sign up for my Mental Disorders Crash Course

      Stay the course, you’re on the right path!

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