The Rapid Mood Screener: A Novel and Pragmatic Screener Tool for Bipolar I DisorderPrakash S. Masand,1 Roger S. McIntyre,2 Mehul Patel,3 Amanda Harrington,4 Patrick Gillard,4 Susan L. McElroy,5 Kate Sullivan,⁶ C. Brendan Montano,7 T. Michelle Brown,8 Lauren Nelson,8 Rakesh Jain9

1Global Medical Education, New York, NY, USA; 2University Health Network, Toronto, ON, Canada; 3AbbVie, Madison, NJ, USA; 4 AbbVie, Irvine, CA, USA; 5 Lindner Center of HOPE, Mason, OH, USA; 6Knoxville Behavioral & Mental Health Services, Knoxville, TN, USA; 7Montano Wellness, Cromwell, CT, USA; 8RTI Health Solutions, Triangle Park, NC, USA; 9Texas Tech University School of Medicine – Permian Basin, Midland, TX, USA

Observational Study Participants• Among 160 interview participants, 139 patients had a confirmed

diagnosis of bipolar I disorder or MDD based on the Mini International Neuropsychiatric Interview (MINI) and were included in the final dataset; most cases were consistent with the patients’ self-reported condition at the time of screening and the diagnosis (Figure 1)

Figure 1. Study Participants

Interview participants

with self-reported

diagnosis (N=160)

Final dataset(n=139)

MINI-confirmedbipolar I disorder

(n=67)

MINI-confirmedMDD

(n=72)

Self-reportedbipolar I disorder

(n=61)

Self-reporteddepression/MDD

at screeninga

(n=6)

Bipolar II n=4Other bipolar n=8Unreliable respondent n=4Other medical condition n=2Psychotic disorder n=2Subthreshold MDD n=1

Did not meet diagnostic criteria n=21

Self-reportedMDD

(n=70)

Self-reportedbipolar depression/manic-depression

at screeningb

(n=2)

aPatients who self-reported depression/MDD at screening but had a MINI-confirmed diagnosis of bipolar I disorder.bPatients who self-reported bipolar depression/manic-depression at screening but had a MINI-confirmed diagnosis of MDD.MDD, major depressive disorder; MINI, Mini International Neuropsychiatric Interview.

RES

ULT

S ① The pragmatic new RMS identifies patients with depressive symptoms who are likely to have bipolar I disorder, providing practitioners with a brief and valid tool that may ultimately reduce misdiagnosis and improve treatment selection

 ② When 4 or more items were endorsed, the new 6-item RMS had better estimated sensitivity (.88), specificity (.80), and predictive validity (PPV=.80; NPV=.88) than the MDQ while reducing the number of items by 60%

 ③ The RMS can be completed by patients in less than 2 minutes, in or out of the clinician’s office, to provide real-world guidance for when a more comprehensive assessment for bipolar I disorder is warranted

 ④ To our knowledge, no prior studies evaluating bipolar disorder screening tools have yielded better specificity AND sensitivity than the rates estimated for the RMS in our study

 ⑤ RMS sensitivity and specificity will be further evaluated in subsequent studies and in different patient populations CO

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• The mean age of participants was 46 years old, and most were female and white (Table 1)

– Slightly more than a quarter of the overall patient population had a current depressive mood episode; all patients had depressive symptoms, with Center for Epidemiologic Studies Depression Scale (CES-D) scores suggesting mild-to-moderate severity on average

Table 1. Demographic and Mood Episode Characteristics

Participant Characteristic

Overall (n=139)

Bipolar I Disorder

(n=67)MDD

(n=72)Age, mean (SD) 46 (13) 44 (12) 47 (14)Female, n (%) 90 (65) 41 (61) 49 (68)Race and Ethnicity, n (%) White 89 (64) 48 (72) 41 (57) Black/African American 23 (17) 7 (10) 16 (22) Hispanic or Latino 16 (12) 6 (9) 10 (14) Asian 3 (2) 1 (1) 2 (3) Other 8 (6) 5 (7) 3 (4)Mood Episode (MINI), n (%) Patients with lifetime MDE 136 (98) 64 (96) 72 (100) Patients with current MDE 39 (28) 18 (28) 21 (28) Patients with lifetime mood disorder with psychotic features

43 (31) 37 (55) 6 (8)

Current Depressive Symptoms (CES-D) CES-D score, mean (SD)a 25 (15) 23 (16) 26 (14)aScores range from 0 to 60, with higher scores indicating greater depressive symptoms. CES-D, Center for Epidemiologic Studies Depression Scale; MDD, major depressive disorder; MDE, major depressive episode; MINI, Mini International Neuropsychiatric Interview.

RMS Item Selection• Ten draft items were administered to participants along with additional

questions designed to evaluate various item permutations (Table 2); responses to the additional questions (items 1, 2, 3, 5, 6, 8) were used to further inform comparisons among potential solutions

Table 2. Draft Screener Items With Threshold Values and Concept Variations

Screening Tool ItemsAdditional Questions To Elicit Threshold or Concept Variations

1. Have there been at least 3 different periods of time (at least 2 weeks) when you felt deeply depressed?

How many periods of time (of at least 2 weeks have you felt deeply depressed?

2. Did you have problems with depression before the age of 18?

How old were you when you first had problems with depression? (even if you were not yet diagnosed with depression or bipolar disorder)

3. Have you tried at least 3 different antidepressants to treat your depression?

How many different antidepressants have you tried to treat your depression?

4. Have you ever had to stop or change your antidepressant because it made you highly irritable or hyper?

…

5. Have you ever been diagnosed with or treated for any of the following: an anxiety-related condition; ADD/ADHD; or problems with drugs or alcohol?

Have you ever been diagnosed with or treated for any of these conditions? Anxiety or panic attacks ADD/ADHD Problems with drugs or alcohol

6. Has anyone in your family ever been diagnosed with or treated for any of the following: bipolar disorder; problems with drugs or alcohol; or “nervous breakdown”?

Has anyone in your family ever been diagnosed with or treated for any of these conditions? Bipolar disorder Problems with drugs or alcohol Nervous breakdown Anxiety or panic attacks Depression

7. Have you ever had a period of at least 1 week during which you were more talkative than normal with thoughts racing in your head?

…

8. Have you ever had a period of at least 1 week during which you felt any of the following: unusually happy; unusually outgoing; or unusually energetic?

Have you ever had a period of at least 1 week during which you were…? Unusually happy Unusually outgoing Unusually energetic Unusually irritable

9. Have you ever had a period of at least 1 week during which you needed much less sleep than usual? …

10. Have you ever been admitted to the hospital for reasons related to your mood, emotions, or behavior? …

… indicates that no thresholds were tested for this item.

• The final RMS item set consisted of 6 items selected from the 10 draft items and additional question variations; items were chosen based on clinical validity, item parsimony, pragmatism, and better test characteristics compared with the MDQ (Table 3)

Table 3. The Rapid Mood Screener: Final 6-Item Set Item Response

1. Have there been at least 6 different periods of time (at least 2 weeks) when you felt deeply depressed? Yes No2. Did you have problems with depression before the age of 18? Yes No3. Have you ever had to stop or change your antidepressant because it made you highly irritable or hyper? Yes No4. Have you ever had a period of at least 1 week during which you were more

talkative than normal with thoughts racing in your head? Yes No

5. Have you ever had a period of at least 1 week during which you felt any of the following: unusually happy; unusually outgoing; or unusually energetic? Yes No

6. Have you ever had a period of at least 1 week during which you needed much less sleep than usual? Yes No

• Endorsement of 4 or more final RMS items (ie, answers of “Yes”) yielded the best overall performance (Table 4)

– The concordance index value of 0.87 indicated that the RMS had strong ability to discriminate between patients with MDD and patients with bipolar I disorder experiencing depressive symptoms

Table 4. The Rapid Mood Screener Test Performance Rapid Mood Screener Endorsement Thresholds

Cumulative Percentage Sensitivity Specificity PPV NPV

Percentage Positively Corrected

Predicted Events0 6.56 1.00 0 0.48 0 47.541 18.03 1.00 0.13 0.51 1.00 54.102 32.79 0.98 0.33 0.57 0.95 63.933 47.54 0.97 0.59 0.68 0.95 77.054 64.75 0.88 0.80 0.80 0.88 83.615 79.51 0.60 0.88 0.81 0.71 74.596 100.00 0.34 0.92 0.80 0.61 64.75

Cumulative percentage includes all patients.NPV, negative predictive value; PPV, positive predictive value.

• The 6-item RMS had higher sensitivity and specificity values than the 15-item MDQ, which was also administered in the study population (Table 5)

Table 5. Rapid Mood Screener and MDQ: Comparison of Test Characteristic in the Same Analysis Population

ToolConcordance

Indexa Sensitivity Specificity PPV NPVPercentage Positively

Corrected Predicted EventsRMSb 0.87 0.88 0.80 0.80 0.88 83.61MDQc 0.82 0.86 0.78 0.78 0.86 81.97

aRanges between 0.5 (equivalent to chance) to 1.00 (zero false positives and zero false negatives); a concordance index > 0.7 is considered better than chance. bTo screen positive for possible bipolar disorder on the RMS, “Yes” is endorsed for 4 or more items.cTo screen positive for possible bipolar disorder on the MDQ, 3 criteria must be met: “Yes” to 7 or more of the 13 items in Question 1 AND “Yes” to Question 2 AND “Moderate Problem” or “Serious Problem” to Question 3.MDQ, Mood Disorder Questionnaire; NPV, negative predictive value; PPV, positive predictive value; RMS, Rapid Mood Screener.

Background • Approximately 70% of patients with bipolar disorder are initially misdiagnosed, with a

mean delay of 5 to 10 years between illness onset and diagnosis1,2 • Because most patients with bipolar disorder seek treatment during a depressive

episode, major depressive disorder (MDD) is the most common misdiagnosis (60%)1; 1 in 4 patients treated for MDD may actually have bipolar disorder3,4

• Lack of time and difficulty identifying prior manic symptoms are key barriers to adequately diagnosing bipolar disorder in primary care settings

• Misdiagnosis and diagnostic delay adversely affect health outcomes and may lead to inappropriate use of monotherapy antidepressants, which lack efficacy and may increase the risk of manic episodes in patients with bipolar disorder3

• There are several self-rated screening instruments for bipolar disorder,5 but their length and reliance on uncovering manic symptoms may be barriers to implementation

– For example, the previously validated and widely recognized Mood Disorder Questionnaire (MDQ) is lengthy (15 items) and solely based on manic symptoms4

– MDQ scoring is based on a multilayered scoring algorithm• We developed the Rapid Mood Screener (RMS), a brief, pragmatic bipolar I disorder

screening tool that not only screens for manic symptoms utilizing perspicuous terminology, but also includes bipolar I disorder risk factors (eg, age of depression onset, number of depressive episodes) to help clinicians identify patients that may have bipolar I disorder

Objective• To present the development and validation of the RMS, a screening tool that was

designed to differentiate bipolar I disorder from MDD in patients with depressive symptoms

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N Development of the Rapid Mood Screener: A 3-Step Process

Concept and Item

Development

• Targeted literature search: identified predictive and differentiating concepts for bipolar I disorder and MDD• Multidisciplinary group of mood disorder and screener development experts participated in 2 Delphi consensus panels; 54 preliminary concepts chosen for discussion• Preliminary concepts collapsed/reduced to the 6 most discriminative concepts (number of prior depressive episodes, comorbidities, age of onset, family history, treatment response, manic symptoms)• 10 draft screener items developed for qualitative and quantitative testing

Qualitative Interviews

With Patients

• Cognitive debriefing interviews were conducted in individuals with self-reported MDD or bipolar I disorder (n=12)• Draft screener items evaluated for basic ease of understanding, clarity, and correct interpretability • Wording refined based on interview feedback to improve the 10 draft screener items for quantitative evaluation

Quantitative Evaluation

• A multisite, observational study was conducted in consented participants with a previous self-reported diagnosis of MDD or bipolar I disorder, current or past depressive symptoms, and currently taking an antidepressant, dopamine antagonist/partial-agonist, or mood stabilizing medication; diagnoses confirmed by the MINI (n=139)• Draft 10-item BPD-I screening tool, CES-D, and MDQ administered to participants• Further clinical information elicited via a self-reported form of additional questions to provide variations for some draft items• Combinations of item sets utilizing various item permutations (eg, number of episodes, age of onset, comorbidity) were simultaneously evaluated by the development team to optimize scoring and test characteristics in as few items as necessary

CES-D, Center for Epidemiologic Studies Depression Scale; MDD, major depressive disorder; MDQ, Mood Disorder Questionnaire; MINI, Mini International Neuropsychiatric Interview.

MET

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DS Item Set Evaluation

• The draft items were evaluated using the following test characteristics:

– Sensitivity: the proportion of patients with bipolar I disorder who screen positive

– Specificity: the proportion of patients without bipolar I disorder who screen negative

– Positive predictive value (PPV): the proportion of patients with a positive screening tool score who have bipolar I disorder

– Negative predictive values (NPV): the proportion of patients with a negative screening tool score who do not have bipolar I disorder

• The concordance index (C-index, equivalent to the area under the receiver operating characteristic curve) was calculated to assess RMS overall performance

• Ultimately, the final combination of items and thresholds was selected based on multiple considerations including clinical validity, optimization of sensitivity and specificity, and pragmatism

This study was sponsored by Allergan plc (prior to its acquisition by AbbVie). Writing and editorial assistance were provided to the authors by Prescott Medical Communications Group (Chicago, IL), a contractor of AbbVie. Project development assistance was provided by Sheri Fehnel, PhD, of RTI-HS. Statistical assistance was provided by Nicole Williams of RTI-HS. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship.

P.S. Masand has received research grant support from Allergan (now AbbVie). He has received speaker/consultant fees from Acadia, Allergan (now AbbVie), Intra-Cellular Therapies, Lundbeck, Sunovion, Takeda. He is also a shareholder of Centers of Psychiatric Excellence (COPE), and Global Medical Education.R.S. McIntyre has received research grant support from Lundbeck, Shire, Otsuka, National Institute of Mental Health, Stanley Medical Research Institute, Canadian Institutes for Health Research, and The Brain and Behavior Research Foundation, and the Chinese National Natural Research Foundation. He has also received speaker/consultant fees from Lundbeck, Pfizer, AstraZeneca, Eli Lilly, Janssen Sunovion, Bausch Health, Takeda, Otsuka, Shire, Allergan (now AbbVie), Purdue, Minerva, and Neurocrine. M. Patel, A. Harrington, and P. Gillard are employees of AbbVie Inc., and may hold AbbVie stock. S.L. McElroy has been a consultant to or member of the scientific advisory board of Allergan (now AbbVie), Avanir, Bracket, F. Hoffmann-La Roche Ltd., Idorsia, Mitsubishi Tanabe Pharma Corporation, Myriad, Naurex, Novo Nordisk, Otsuka, Shire, Sunovion, and Takeda Pharmaceutical Company Limited (Shire). She has also been a principal or co-investigator on studies sponsored and/or funded by Alkermes, Allergan (now AbbVie), Avanir, Azevan Pharmaceuticals, Forest, Marriott Foundation, Medibio, Myriad, National Institute of Mental Health, Naurex, Neurocrine, Novo Nordisk, Otsuka, Shire, Sunovion, and Takeda Pharmaceutical Company Limited (Shire). She is also an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent’s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent.K. Sullivan has received consultant and speaker honoraria from Allergan (now AbbVie).C.B. Montano has received research funding from Arbor, Avanir, Axsome, Sanofi, Sunovion, and Tonix. He has received speaker/consultant fees from Allergan (now AbbVie), Arbor, Neos, Rhodes, Shire, and Takeda.T.M. Brown and L. Nelson are employees of RTI-HSR. Jain has served as a consultant to Addrenex, Allergan (now AbbVie), Avanir, Janssen, Lilly, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Supernus, Takeda, and Teva; paid speaker for Addrenex, Alkermes, Allergan (now AbbVie), Lilly, Lundbeck, Merck, Neos Therapuetics, Otsuka, Pamlab, Pfizer, Rhodes, Shionogi, Shire, Sunovion, Takeda, and Tris Pharmaceuticals; received research support from Allergan (now AbbVie), AstraZeneca, Lilly, Lundbeck, Otsuka, Pfizer, Shire, and Takeda; and served on advisory board for Addrenex, Alkermes, Avanir, Forum, Janssen, Lilly, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Supernus, Takeda, and Teva.

References1. Hirschfeld, RM, Lewis L, Vornik LA. Perceptions and impact of bipolar

disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003; 64(2):161-174.

2. Berk M, Dodd S, Callaly P, et al. History of illness prior to a diagnosis of bipolar disorder or schizoaffective disorder. J Affect Disord. 2007;103(1-3):181-186.

3. Hirschfeld RM. Differential diagnosis of bipolar disorder and major depressive disorder. J Affect Disord. 2014;169 S1:S12-S16.

4. Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Pract. 2005;18(4):233-239.

5. Miller CJ, Johnson SL, Eisner L. Assessment tools for adult bipolar disorder. Clin Psychol (New York). 2009 June 1; 16(2): 188-201.

Contact the presenter with questions and/or comments at pmasand2001@yahoo.com

Presented at the Virtual Psych Congress • September 10-13, 2020

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