Bipolar disorder is not well-understood. Symptoms vary widely, across depressed and manic states, and are often masked or exacerbated by self-medicating. A depressed episode may appear similar in cases of unipolar and bipolar depression, making history-taking and an assessment of cycling key to reaching an adequate diagnosis.

In my outpatient psychiatric nursing experience, those with bipolar disorder are most often seen during periods of remission of mania.  Patients do not show up for a therapeutic visit because they have too much energy, feel too good, are too happy, or are accomplishing too much. At the same time, when depressed and feeling hopeless, individuals may not have the energy, motivation, or determination to seek treatment.

When in the depths of a depressed episode, the subject of euphoric mood swings is rarely mentioned. It is up to the provider to ask the right questions in order to differentiate (more on this below).  When in a hypomanic or manic state, the patient often does not recognize their behavior as a problem or may feel so relieved after a depressed episode that they refuse treatment.

Major depressive disorder (MDD) without bipolarity is also referred to as unipolar major depression. A person can have unipolar MDD or bipolar MDD. With bipolar depression, there is often a patient history of hypomania or mania. Thus, bipolar depression is treated differently.(See “DSM criteria” at the end of this article for descriptions of each.)1,2

Depression and the Consequences of a Misdiagnosis

When a patient presents with depression, a skillful interview – such as that proposed below – can prevent the misdiagnosis of a bipolar depressive episode as unipolar depression. In such cases, incorrect treatment with an antidepressant can wreak havoc on the patient by triggering a hypomanic, manic, or mixed episode.

A misdiagnosis may also lead to or worsen rapid cycling where a person has 4 or more distinct episodes of mania/hypomania or depression over a 1-year-period as defined by the DSM.1 Poor outcomes of misdiagnosis and treatment may also include active suicidal ideations and a host of other devastating consequences due to poor judgment on the part of the patient that is often associated with mania.3,4

The literature shows that at least 50% of depressed patients are misdiagnosed in primary care.5,6

A Patient’s History May Help Distinguish Unipolar from Bipolar Depression

When taking a history to determine a patient’s state of depression, medical causes of symptoms, such as hypothyroidism or hyperthyroidism, have to be ruled out. In my experience, this is done by a PCP before the patient is referred to my practice, however, it’s worth noting that basic ER labs are usually not comprehensive enough and additional tests should be ordered as part of an initial assessment.

Relationship, employment, financial, legal, physical, and mental safety can be consequences at stake when misdiagnosing unipolar and bipolar depression. It is extremely important to take the extra time to get an adequate history in order to do the least harm.

Personal History

In terms of questions, the first thing I tend to ask patients is about their sleep.

  • Do they feel the need to sleep during the day, do they feel tired or well-rested?

I also ask about their daily activities.

  • Do they engage in goal-directed activities such as cleaning, painting, or playing video games? Do these activities go on for days?

In this context, it is vital to ask about cycling.

  • What happens after a period of days when they have high activity levels? For example, do they “crash” and sleep for more than 12 hours?

Then, we get into behavioral questions.

  • Has a trusted friend or family member remarked that their behavior is odd, risky, or unlike them?
  • Has a mood swing occurred during a time of extreme stress?
  • Has their routine been disrupted by staying up late or not eating properly?
  • Was there a stressful event, and if so, was there heavy use of drugs or alcohol at the time?
  • Is there a seasonal component to their moods (mania tends to be more prevalent after the sudden increase of spring sunshine which is thought to affect the pineal gland where melatonin is secreted)?7,8
  • Do they wake up feeling down, irritable, or “on the wrong side of the bed”? Do they feel irritable and pick fights?
  • How long has their depression been going on and are there any known triggers? 

As noted, patients are not likely to spontaneously talk about when they feel depressed. If urged, they may describe bipolar depression as a low period followed by a euphoric mood episode.

Of note, I have seen many patients previously misdiagnosed with MDD (instead of the correct bipolar disorder) who have shared that taking an SSRI or SSNI made them feel “worse,” impulsive, suicidal, angry, or unable to sleep. This reaction to one or more antidepressants is often a gift in alerting me to probe more into hypomanic or manic symptoms. (More on medication management below.)

Family History

A family history of bipolar disorder can be very helpful. Adults who have relatives with bipolar have up to a 10-fold or more increased risk of developing bipolar according to many sources. The risk further increases the closer the relation.9-11 A history of brain injury such as concussions have been implicated in bipolar as well.12

It is important to also take a family history of any other mental health issues, drug abuse, alcoholism, suicide, or incarceration – any of which could be a sign of maladaptive coping mechanisms of a mood disorder. 

Depression Assessment Scales: Add-On Questions

It’s important to incorporate formal assessments into history taking for a complete picture and accurate diagnosis. Along with the PHQ-9 depression scale, I like to use the Mood Questionnaire (MDQ). The MDQ is easy to understand and usually takes 5 minutes or less to fill out, especially when there are more positive than negative answers. In my experience, if the diagnosis is bipolar, the patient readily and quickly finishes the questionnaire with the majority being positive answers. In fact, it is not unusual for a patient to mark “yes” to all the MDQ questions. (More on depression screening and gaps in the US)

Before giving a patient the MDQ to fill out, I emphasize that the questions should relate to any time in the person’s life, as far back as middle or high school, and importantly when they were not under the influence of alcohol or drugs. I also ask them to let me help clarify any question they do not understand. I have the patient fill out the form in front of me and, often, I see heads shaking “yes” or statements, such as “Wow, how does this know me so well?”

Many times, patients report to me that they have never been asked these types of questions.  I use this as a jumpstart to further conversation. Asking about each positive answer specifically will improve reliability.

For example, if a patient has answered “yes” to having “racing thoughts,” I ask if they are creative, have acted on any worrisome thoughts, second-guessed themselves, etc. Often, the patient will share that, during this time, they are more creative (eg, they may write music, paint, or uncharacteristically go for a run).

When feeling energized, I ask if they tend to start projects and experience a feeling of being very goal-directed? If they report fast speech due to anxiety or nervousness, I ask if it occurs in a certain setting or during an elevated mood? (Reports of slurring words as they cannot get their thoughts out fast enough are not uncommon.)

I also try to distinguish between feelings of confidence and those of invincibility by asking about risk-taking behavior. Such behavior is important to delve into because a positive answer is not always reliable. I have had a patient describe unusual or risky behavior as something quite benign, for instance. More often, I hear risky behavior described as impulsively leaving town without notifying family, running up large amounts on credit cards (extreme financial ruin can occur very quickly during a manic episode), shoplifting, acting on a dare, speeding, or trying to outrun the police. With students, they may report walking across campus late at night unaccompanied or doing something that later makes them question, “What was I thinking?”

To determine if the behavior associated with bipolar is truly risky, I ask patients whether they have ever done anything out of character, such as dance on a tabletop or have a one-night stand. Suggesting an act with a high degree of risk, illegal, outside general social norms, or very out of character for them can provide the patient with a safe and nonjudgmental environment in which to reveal details of manic episodes. It is not unusual for an individual to report staying up for days and then crashing for a 12- to 16-hour night.

How to Deliver – and Follow Up – a Bipolar Diagnosis

In an initial outpatient visit where a mood disorder is suspected, the patient is not suicidal, and the patient is minimizing or voicing resistance to medication, it may be best to educate them about mood swings and mood disorders, including bipolar disorder and its states of depression and mania. I always explain to clients that, unfortunately, people with bipolar disorder often go years before they get a proper diagnosis.

Reactions to this discussion may vary from denial to minimizing and guardedness, to relief. In my experience, far more relief is expressed. Because a bipolar diagnosis usually means taking one or more medications for the rest of one’s life, however, it is not an easy acceptance.

If a patient is in denial about having bipolar disorder and refuses treatment, but is not a danger to themselves or others, it may be best to have them return after allowing time to absorb the information and gather history from close friends and family members, which can be invaluable. Ask them to look for patterns as they report mood swings. For instance, do mood changes occur during increased stress, poor self-care, or even when traveling to another time zone, which can trigger mania.

If there is any doubt in the diagnosis, it is best to ask a patient to return or at least have a nurse call the patient 4 to 7 days after initiating an antidepressant without a mood stabilizer to see how the patient is doing.

Follow-up is of huge importance. In my experience, patients tend to go on and off medications as they either feel better and no longer feel the need to take the prescription, or, they experience intolerable side effects and stop taking the medication, sometimes without reporting these effects to the clinician. Medication adherence is, however, crucial to keep bipolar episodes from occurring as frequently and as intensely.

Medication Options for Bipolar Depression

Should antidepressants be prescribed for a depressed mood episode when bipolar is suspected? This is debatable. Antidepressants have not been proven effective for treating bipolar depression and, therefore, none are FDA-approved for that indication. Yet, it is not unusual for an antidepressant and mood stabilizer to be prescribed simultaneously in a depressed episode of bipolar.

The following atypical antipsychotic drugs are FDA-approved for the treatment of bipolar disorder:

  • aripiprazole (for acute/mixed mania, bipolar maintenance, can be used as monotherapy or adjunct)
  • olanzapine (for acute or mixed episodes, and as maintenance therapy, can be used alone or as an adjunct to lithium or valproate)
  • lurasidone (for bipolar depression, can be used alone or as an adjunct to lithium or valproate).
  • quetiapine (for acute mania, bipolar depression, bipolar maintenance, can be used as monotherapy or adjunct to lithium or valproate)
  • risperidone (used alone, or in combination with lithium or valproate, for treatment of acute/mixed mania)
  • ziprasidone (for treatment of acute/mixed mania and bipolar maintenance)

In addition, the anticonvulsant lamotrigine is FDA approved specifically for bipolar I disorder maintenance therapy but is most often used for patients with bipolar depression.

In my experience, the goal regarding treatment should be to stabilize a patient’s mood first. Some first options include valproate, carbamazepine, oxcarbazepine, cariprazine, and topiramate. When choosing a mood stabilizer or antipsychotic, however, the metabolic side effects (ie, weight gain) should be part of the decision and shared with the patient.

Anecdotally, valproate has been effective when anger, irritability, and aggression are present (note: valproate should be avoided in females of child-producing age due to teratogenicity).

Of note, a patient’s use of certain medications, such as prednisone, can trigger an elevated mood swing. It is important to be aware of all their medications and comorbidities.

See an antipsychotic primer.

Psychotherapy as an Adjunct Treatment for Bipolar Disorder

I have found that psychotherapy can be a valuable adjunct to psychopharmacology as well. Starting an effective medication can help increase the patient’s receptiveness to talk therapy and other behavioral strategies. I usually tell my patients to try to stick with a healthy sleep, nutritional, and exercise routine.  For example, I might recommend avoiding late hours and skipping meals. (A break in routine is often a trigger for mood swings.)

I also suggest choosing a person they trust, often a family member, who is willing to tell them if they “haven’t been themselves lately” in as nonprovocative manner as possible, as opposed to “Have you had your meds today?”

Overall, making a bipolar or unipolar depression diagnosis is not always clear and may, in fact, change over time. Thus, the importance of taking time during a patient’s initial presentation to distinguish between the typical family history, symptoms, and course of their depression to make the best treatment decisions.


See our full Clinician’s Guide to treating bipolar disorder including diagnostic criteria and treatment guidelines.


Last Updated: Jun 1, 2021