You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Navigating the Depressive Episode: Best Practices in Differentiating Mood Disorders

  • Authors: Leslie Citrome, MD, MPH
  • CME / ABIM MOC / CE Released: 9/28/2022
  • Valid for credit through: 9/28/2023
Start Activity

  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0.25 contact hours are in the area of pharmacology)

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for psychiatrists, primary care physicians, nurse practitioners, physician assistants, nurses, and other healthcare providers who care for patients with bipolar disorder.

The goal of this activity is for learners to be better able to improve clinician understanding of the diagnostic criteria for mood disorders and elevate their ability to differentiate between depressive episodes.

Upon completion of this activity, participants will:

  • Demonstrate improved performance associated with
    • Distinguishing unipolar and bipolar depression
    • Using validated instruments to screen for mood disorders
  • Demonstrate greater confidence in their ability to
    • Incorporate interprofessional strategies into mood disorder screening


Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


  • Leslie Citrome, MD, MPH

    Clinical Professor
    Psychiatry and Behavioral Sciences
    New York Medical College
    Valhalla, New York


    Leslie Citrome, MD, MPH, has the following relevant financial relationships: 
    Consultant or advisor for: AbbVie/Allergan; Acadia; Adamas; Alkermes; Angelini; Astellas; Avanir; Axsome; BioXcel; Boehringer Ingelheim; Cadent Therapeutics; Eisai; Enteris BioPharma; HLS Therapeutics; Impel; Intra-Cellular Therapies; Janssen; Karuna; Lundbeck; Lyndra; Medavante-ProPhase; Merck; Neurocrine; Novartis; Noven; Otsuka; Ovid; Relmada; Reviva; Sage; Sunovion; Supernus; Teva; and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research
    Speaker or member of speakers bureau for: AbbVie/Allergan; Acadia; Alkermes; Angelini; Eisai; Intra-Cellular Therapies; Janssen; Lundbeck; Neurocrine; Noven; Otsuka; Sage; Sunovion; Takeda; Teva
    Stock options from: Reviva
    Owns stock (publicly traded) in: Stocks (small number of shares of common stock): Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased > 10 years ago


  • Clinton W. Wright, PharmD, BCPP

    Medical Education Director, Medscape, LLC


    Clinton W. Wright, PharmD, BCPP, has no relevant financial relationships.

  • Frances McFarland, PhD, MA

    Medical Education Director, WebMD Global, LLC


    Frances McFarland, PhD, MA, has no relevant financial relationships.

Compliance Reviewer/Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

Accreditation Statements

In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

    For Physicians

  • Medscape, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

    Contact This Provider

    For Nurses

  • Awarded 0.25 contact hour(s) of nursing continuing professional development for RNs and APNs; 0.25 contact hours are in the area of pharmacology.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

Follow these steps to earn CME/CE credit*:

  1. Read about the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or print it out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate, but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period, you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.


Navigating the Depressive Episode: Best Practices in Differentiating Mood Disorders

Authors: Leslie Citrome, MD, MPHFaculty and Disclosures

CME / ABIM MOC / CE Released: 9/28/2022

Valid for credit through: 9/28/2023


Activity Transcript

Scene 1 Begins

Scene 1: [Scene begins as Stacey enters the doctor’s office]

Doctor: Good morning, Stacey, what can I do for you today?

Stacey: Well, I wanted to talk to you about the treatment I’m getting for my depression. I’ve been taking the treatment that was prescribed...what was it called again?

Doctor: Let’s see. [looking at computer/tablet screen] So, it looks like your previous doctor started treating you with a serotonin reuptake inhibitor called fluoxetine, but that didn’t seem to have an effect. And then... [scrolling down a bit on the screen] it looks like you started treatment with a different kind of drug, venlafaxine. Is that right?

Stacey: Yes, that’s right. I’ve been taking the new treatment for a few months now, but I’m not feeling any better. I still feel like I did before I started taking the medication, and I haven’t been able to go back to work. Is there anything else we can try?

Doctor: Hmmm. [thinking a moment] Stacey, would you mind if I asked you some questions, first? I'd like to try to get to the bottom of this, since your symptoms should have responded to one of these treatments, and I want you to start feeling better.

Stacey: OK.

Doctor: In the past months, have you noticed moments when you’ve been very energetic, almost hyper?

Stacey: Ugh, no, not really.

Doctor: Are you sure?

Stacey: [Now pausing and thinking for a moment] Well, OK; before I went to my doctor the first time for my depression, there were a few times when I felt like I had a lot of energy. Which was strange, you know, because I hadn’t been sleeping very well. But I usually drink a lot of coffee in the morning, so I thought that was why. But I felt great -- I got so much done at work, but I kept getting easily distracted.

Doctor: And how long did you feel this way?

Stacey: I don’t know. It was for a while, though. Maybe 4 days? But then I started feeling depressed again, so that was that.

Doctor: Can I ask, Stacey, have you used any kind of recreational drugs in the past few months?

Stacey: No. I mean, I’ll have a drink every once in a while, but no more than 2 or 3 in one evening. But no drugs, nothing like that.

Doctor: OK, that’s good to know. And do you know if anyone else in your family has ever experienced symptoms like you are having?

Stacey: Umm, well, my mother had ADHD and has anxiety disorder, but she’s the only one I know of.

Doctor: And have you ever had a moment where you thought you heard or saw something, but nothing was there?

Stacey: No, nothing like that! I would definitely remember if something like that happened.

Doctor: Ah, OK. I think we’re getting closer to an explanation now, Stacey. I would like to do some further tests and check your blood to make sure there’s nothing else going on that could explain your symptoms.

Stacey: OK, but this is starting to sound serious. Do you have an idea of what might be going on? I thought I just had a stubborn case of depression...

Doctor: It could be that your depression was not diagnosed correctly, Stacey. I think you might actually have bipolar 2 disorder. Depression is certainly a part of that, but that one period of increased energy and your family background suggest that more might be going on.

Stacey: Seriously? [Pausing] But if that’s the case, what can we do? Is there a better treatment that might help me?

Doctor: Well, let’s get these tests done first, and then, if it turns out you do have bipolar disorder, we can discuss treatment steps. How does that sound?

Stacey: That sounds great, thanks.

Leslie Citrome, MD, MPH: Hello. I'm Dr Leslie Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla, New York.

Bipolar depression is defined by having major depressive episodes and a history of manic or hypomanic episodes. Bipolar type 1 exists when there is a history of manic episodes. Bipolar type 2 is when there is a history of hypomanic episodes but no manic episodes. On cross-sectional examination, the symptoms of a major depressive episode are the same for both major depressive disorder and bipolar disorder, so it's easy to misdiagnose bipolar depression for major depressive disorder and the other way around. Up to 69% of people with bipolar disorder are misdiagnosed initially, most often as major depressive disorder. There's an average 3.5 diagnoses made and 4 clinicians encountered before receiving the right diagnosis. About 35% of patients with bipolar disorder may wait for at least 10 years for an accurate diagnosis.

A major concern is the inappropriate use of antidepressant medication for people with bipolar depression. No antidepressant is approved for the treatment of bipolar depression with the exception of fluoxetine in combination with olanzapine. Antidepressant monotherapy can destabilize a person with bipolar depression. It could lead to an induction of mania or hypomania and/or rapid cycling. Antidepressants do not confer a treatment advantage for either acute or enduring response. However, in medicine "never say never", and there may be some instances, particularly in some with bipolar type 2, where antidepressants are used. Increase your index of suspicion for bipolar depression when there's a family history of bipolar disorder, when the course of illness indicates early age of onset, for example, a mood episode in the teenage years or young adulthood. Treatment response can also provide clues regarding that we're dealing with bipolar depression if a person is not responding to a traditional antidepressant medication. Certainly if manic symptoms are evident, then it's clear we're not dealing with major depressive disorder.

There are screening instruments for bipolar disorder. Two of them deserve additional mention. The Mood Disorder Questionnaire consists of several questions that relate to a history of manic or hypomanic symptoms that the person may have experienced in the past. This questionnaire allows the clinician to provide an assessment that is more complete because it is systematic in its approach. An endorsement of items on the Mood Disorder Questionnaire would lead the clinician to ask additional questions and consider bipolar disorder in the differential diagnosis.

The Rapid Mood Screener is another instrument that can be used for screening for bipolar disorder. This is somewhat shorter than the Mood Disorder Questionnaire, with only six items. These items focus on a history of depression and episodes of depression, particularly before the age of 18. This can be a very helpful instrument to consider when constructing a differential diagnosis, but additional questions will need to be asked of that individual patient that is being evaluated.

Scene 2 Begins

Scene 2: [The same physician’s office, after the patient has been diagnosed and started receiving quetiapine to treat her bipolar 2 disorder.]

Doctor: Hello Stacey, it’s good to see you again.

Stacey: Hi, Dr Clearwater.

Doctor: So Stacey, it’s been a few months since we diagnosed your bipolar disorder and started you on treatment with quetiapine. How have you been feeling?

Stacey: I’ve definitely noticed some improvements in my mood -- I feel a lot better. I’m not so down all the time, and I’ve even started going back to work for a few days a week.

Doctor: That’s terrific, Stacey, and I’m really glad things are improving for you!

Stacey: Just one thing, though. I’ve been taking this medication for a few months now; I’ve gained a lot of weight, to the point where my clothes don’t really fit me so well anymore.

Doctor: How much weight have you gained?

Stacey: Well, in the 2 months I’ve been on the treatment, I’ve gained about 17 pounds.

Doctor: I see, indeed, I can imagine that might be distressing for you. Treatment with this particular drug, quetiapine, has been known to cause weight gain in some patients. So that might be why you’ve gained some weight in the past 2 months.

Stacey: Ah, OK. So is there anything we can do about that? I mean, I’m glad I’m feeling better and all, but will I keep gaining weight if I stay on this treatment? Is there maybe anything else we can try? I really don’t like the fact that I can’t fit into most of my clothes anymore, and I don’t want to have to buy a new wardrobe just because of this.

Doctor: There is another FDA-approved treatment option we can try, which may not have such an impact on your weight. It’s a treatment approved for both patients with bipolar 1 disorder and bipolar 2 disorder. We can try switching to that and see how things go.

Stacey: But, will I still keep feeling better? Is there a chance my depression will come back if we switch my medication? I’d rather have a few extra pounds than start feeling so awful again.

Doctor: You should still feel better after switching, Stacey, but let’s make an appointment for another visit after you start the treatment, just so we can touch base again and see how your feeling, OK?

Stacey: OK, thank you, Dr Clearwater.

Dr Citrome: There are several FDA-approved medications for bipolar depression and all are efficacious; however, they do differ in terms of their specific indications. All of them are approved for bipolar 1 depression. This includes olanzapine-fluoxetine combination, quetiapine immediate or extended release, lurasidone, cariprazine, and lumateperone. However, only 2 of the 5 are also approved for bipolar type 2 depression. This includes quetiapine and lumateperone. Only 1 of the agents was tested in people with psychotic depression. That's olanzapine-fluoxetine combination. Approved for adjunctive use with lithium or valproate are lurasidone and lumateperone, and approved for pediatric populations include olanzapine-fluoxetine combination and lurasidone.

Although all of these choices are efficacious, they do differ in terms of their tolerability profiles. Some tolerability challenges include weight gain. For example, gaining at least 7% of one's initial body weight in a short-term trial would be problematic. Extrapyramidal symptoms, somnolence, akathisia, nausea, or perhaps discontinuation in the clinical trial due to adverse events.

We can calculate the number needed to harm for each agent vs placebo regarding these outcomes. The higher the number-needed-to-harm value, the less concerned we are about that adverse outcome. However, number-needed-to-harm values less than 10 indicate the high frequency of this event with that particular agent. For example, weight gain of at least 7% when comparing olanzapine-fluoxetine combination with placebo resulted in a number needed to harm of 6. For every 6 people randomly assigned to olanzapine-fluoxetine combination rather than placebo, one would expect to encounter 1 additional patient gaining at least 7% of their initial body weight. This is quite frequent and would be a source of concern.

For quetiapine, the major adverse event that we encounter frequently is somnolence. Number-needed-to-harm value of 3. For every 3 people randomly assigned to quetiapine immediate or extended release -- at either of the doses tested -- for every 3 vs placebo, we would expect 1 additional person with a complaint of somnolence. That is very common.

There are some number-needed-to-harm values that indicate intermediate risk, so these are values between 10 and 19. Finally, a number-needed-to-harm value of 20 or greater indicates lower risk. We can see that the options that are more recently approved, specifically lurasidone, cariprazine, and lumateperone are less likely to cause problematic adverse effects than the older agents of olanzapine-fluoxetine combination and quetiapine. The lower doses of lurasidone and cariprazine seem to be better tolerated than the higher doses of lurasidone or cariprazine.

Scene 3 Begins

Scene 3: [Stacey has switched to treatment with lumateperone, and is now coming for her follow-up appointment with Dr Clearwater, 2 months after switching treatments.]

Doctor: Welcome back, Stacey.

Stacey: Thanks Dr Clearwater, it’s good to see you again.

Doctor: So, tell me, Stacey, how are you doing?

Stacey: So much better. I started taking that new treatment, and I’m feeling much better. I’m so glad my symptoms didn’t come back after I switched!

Doctor: And did you gain any more weight gain?

Stacey: No, no more weight gain. I’ve started getting more exercise and trying to eat healthy, and I’ve actually lost some of the weight I gained when I was taking the other medication. I’ve also started going back to work full time, and so far it’s going really well!

Doctor: That’s wonderful to hear, I’m glad you are feeling better. Have you noticed any drowsiness or dizziness, or noticed any signs of low mood or other mood changes? Have you had a fever or any muscle stiffness?

Stacey: Hmmm.. [thinks for a moment] I was a little drowsy when I first started taking it, like we discussed on the phone last month, but that went away after a few days. I haven’t noticed any other effects since then.

Doctor: OK, that’s fine. Please let me know, though, if you start experiencing any of these side effects, though, OK?

Stacey: Of course. [Pauses] I also wanted to tell you, Doctor, that I’ve started seeing a therapist, and even though I’ve only been to see her a few times, I feel like she’s helping me. We’ve been discussing effective coping strategies for managing stress, and talking about certain situations that might trigger emotions associated with my bipolar disorder. It’s hard work, but I think it will be pretty effective, in the long run. I do have one question, though.

Doctor: Of course.

Stacey: Will this ever go away? Or is bipolar disorder a lifelong condition?

Doctor: It is a lifelong condition, but I feel like you are on the right path now, and will be able to manage very well going forward.

Stacey: I feel that way, too.

Doctor: It would be good for us to keep in regular contact, just to monitor how things are going, and to make any adjustments in your treatment, if needed. You’ve been in contact with Anna, the nurse practitioner, right? She can also help you with any questions you might have about your treatment going forward.

Stacey: Of course, I’ve spoken with her a few times, and she always has good advice for me! And thank you for everything -- I’m so glad we finally found the reason for my depression and have been able to find a treatment for it.

Doctor: You’re very welcome, Stacey.

Dr Citrome: Collaboration with other clinicians is key. This includes other healthcare professionals involved in the care of the patient: primary care, perhaps also specialty care. Clinical pharmacists are often involved in the care of individuals as well as nurse practitioners and physician assistants. Nurses perform a key function in the care of individuals. Accurate diagnosis is based on the history as provided by all of the participants in a person's care.

Major depressive episodes in unipolar and bipolar disorder appear the same in cross-section, at least as per the DSM-5 text revision criteria. Thus, the diagnosis is made by past history, history you get from all sources, and any hints of bipolarity can be found using clues in addition, such as family history, age of onset, the characteristics of the depressive episodes and comorbidities and so on. So for example, a family history of bipolar disorder would increase our index of suspicion. A young age of onset would also increase our likelihood of us dealing with bipolar disorder. If the depressive episodes start and stop abruptly, we also consider this more likely to be a bipolar depressive episode.

The distinction between unipolar and bipolar disorder has implications for treatment selection and prognosis. If we provide a SSRI or SNRI treatment to someone with bipolar depression, they may not get better. They may become worse, and this worsens their overall prognosis over time. It appears that as many as one in five primary care patients who have clinically significant depressive episodes and who are receiving antidepressant treatment actually have bipolar 1 or bipolar 2 disorder.

Thank you for participating in this activity. Check out the right side of the program page for helpful tools and resources for both you and/or your patients.

This transcript has not been copyedited.

« Return to: Navigating the Depressive Episode: Best Practices in Differentiating Mood Disorders
  • Print