BEHAVIORAL HEALTH CONSULT

Emily Aquadro, BS; Nagy A. Youssef, MD Medical College of Combine these screening tools Georgia at Augusta University, Augusta to detect bipolar [email protected]

The authors reported no Used together, brief assessment tools, such as the PHQ9 potential conflict of interest relevant to this article. and MDQ, have greater sensitivity and accuracy than clinician assessment alone.

THE CASE A 35-year-old police officer visited his family physician (FP) with complaints of low energy, trouble sleeping, a lack of enjoyment in life, and feelings of hopelessness that have persisted for several months. He was worried about the impact they were having on his marriage and work. He had not experienced suicidal thoughts. His Patient Health Questionnaire (PHQ9) score was 18 (moderately severe depression). He had been seen intermittently for similar complaints and had tried several medications (fluoxetine, bu- propion, and citalopram) without much effect. He was taking no medications now other than an over-the-counter multivitamin. He had one brother with anxiety and depression. He said his marriage counselor expressed concerns that he might have or borderline .

● HOW WOULD YOU PROCEED WITH THIS PATIENT?

he prevalence of a spectrum of bi- Accurately recognizing BPD is essential polarity in the community has been in selecting effective treatment. It’s estimated shown to be 6.4%.1 Depressive epi- that approximately one-third of patients given T 2 sodes predominate in bipolar disorder (BPD), antidepressants for major depression show no with patients spending less time in manic or treatment response,7 possibly due in part to hypomanic states.3 Not surprisingly, then, undiagnosed BPD being more prevalent than depressive episodes are the most common previously thought.4,8 Failure to distinguish be- presentation of BPD. tween depressive episodes of BPD and MDD The depressive symptoms of BPD and uni- before prescribing medication introduces the polar depression, or major depressive disorder risk of ineffective or suboptimal treatment. (MDD), are similar, making it difficult to distin- Inappropriate treatment can worsen or de- guish between the disorders.3 As a result, BPD stabilize the course of bipolar illness by, for is often misdiagnosed as MDD.4,5 Zimmerman instance, inducing rapid cycling or, less com- et al point out that “bipolar disorder is prone to monly, manic symptoms. being overlooked because its diagnosis is more often based on retrospective report rather than Screen for BPD when depressive presenting symptoms of or symptoms are present assessment.”6 Identifying BPD in a patient with current or

500 THE JOURNAL OF FAMILY PRACTICE | AUGUST 2018 | VOL 67, NO 8 past depressive symptoms requires screening 0.12- 0.25]) and without loss of specificity (0.9 for manic, hypomanic, and mixed episodes [95% CI, 0.86-0.96] vs 0.9 [95% CI, 0.88-0.97]).15 (TABLE 19). Two brief, complementary screen- In this same study, using a structured clini- ing tools — the Questionnaire cal interview for DSM-III-R Axis I Disorders (MDQ) and the 9-item PHQ9—are help- (SCID-I) as the gold standard, researchers also ful in this assessment. Both questionnaires found the screening tools to be more accurate (TABLE 28,10-14) can be conveniently completed (Cohen’s Kappa 0.7 [SE=0.05; 95% CI, 0.5- by the patient in the waiting room or with staff 0.7]) than the general practitioner assessment assistance before the physician encounter. (Cohen’s Kappa 0.2 [SE=0.07 (95% CI, 0.12- The MDQ screen is for past/lifetime 0.27]).15 or current manic/hypomanic symptoms (https://www.integration.samhsa.gov/ Delve deeper with a patient interview images/res/MDQ.pdf). A positive screen re- Use targeted questions and laboratory tests quires answering “Yes” to at least 7 of the to rule out other possible causes of depressed 13 items on question 1, answering “yes” mood, such as or medical on question 2, and answering “moder- conditions (eg, hypothyroidism). Keep in mind ate problems” or “serious problems” on that even when MDD or BPD is present, other question 3. One study done in the primary medical disorders or substance abuse could be care setting found that the MDQ most ac- coexistent. Also ask about a personal or family curately identified BPD when using a cut- psychiatric history and assess for suicidality. If Depressive off of 5 “Yes” answers to question 1.14 family members are available, they may be able episodes (During the clinical interview, discussed in a to help in identifying the patient’s age when predominate in bit, confirming the positive MDQ items with symptoms first appeared or in adding infor- bipolar disorder DSM-5 criteria requires only current presen- mation about the affective episode or behavior and symptoms tation or history of 3 symptoms of euphoric that the patient may not recollect. can be manic episode and 4 symptoms of irritable Beyond a history of manic, hypomanic, indistinguishable mania for bipolar I and II [may be less for bipo- or mixed episodes, other symptoms and fea- from those lar spectrum].) Although the MDQ was origi- tures may assist in distinguishing between of unipolar nally developed to be clinician administered, bipolar and unipolar depression or in help- depression. later evidence and clinical experience found ing the clinician identify depressed patients that it can also be self-administered.6,15 who may be at higher risk for, or have, BPD. The PHQ9 screens for current depressive One meta-analysis of 3 multicenter clinical symptoms/episodes (https://www.uspreven trials assessed sociodemographic factors and tiveservicestaskforce.org/Home/GetFileBy clinical features of BPD compared with uni- ID/218). polar depression. The average age of onset of ❚ The value of combining the MDQ and mood symptoms in individuals with BPD was PHQ9. The PHQ9 screens for and assesses the significantly younger (21.2 years) than that severity of depressive episodes along with cli- of patients with MDD (29.7 years).16 Another nician assessment, but it cannot distinguish study found that patients with either bipolar I between depressive episodes of MDD or BPD. or bipolar II similarly experienced their first A brief instrument, such as MDQ, screens for mood disorder episode 10 years earlier than current or past manic or hypomanic symp- those with MDD.17 toms, which, when combined with the clinical BPD is often associated with more fre- interview and patient history, enables detec- quent depressive episodes and a higher num- tion of BPD if present and avoids erroneously ber of depressive symptoms per episode than assigning depressive symptoms to MDD. is MDD, as well as more frequent family psy- ❚ One cross-sectional study found that chiatric histories (especially of mood disor- the combined MDQ and PHQ9 question- ders), anxiety disorders, alcohol and drug use naires have a higher sensitivity in detecting disorders, and personality disorders.17 Other mood disorder than does routine assessment factors more closely associated with BPD by general practitioners (0.8 [95% confi- than MDD include atypical features such as dence interval (CI), 0.71-0.81] vs 0.2 [95% CI, and psychomotor retardation,

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TABLE 1 Features of bipolar disorders9 Bipolar I Bipolar II Other specified bipolar Other unspecified disorder bipolar disorder US prevalence (using 0.6% 0.3% ­— — DSM-5 criteria) Mean age at onset 18 Mid-20s — — Mood episodes Mania (≥1 week) Hypomania (≥4 days) Hypomania (<4 days) with Symptoms characteristic constituting the with or without with major depression major depression (>2 weeks); of bipolar disorder that disorders (all major depression (≥2 weeks) (no mania) hypomania with insufficient cause distress or impair- disorders must cause (≥2 weeks) symptoms and major depres- ment without meeting functional sion; hypomania without full criteria for any other impairment) prior depression; short dura- bipolar disorder tion (<24 months)

Comorbidities Anxiety (75%), 60% with ≥3 comorbid — — impulse-control, mental disorders; anxi- conduct and sub- ety (75%), substance stance use disorders use disorders (37%), (>50%) and eating disorders (14%) DSM 5, Diagnostic and Statistical Manual of Mental Disorders, 5th ed.

psychotic symptoms during the depressive THE CASE episode, and more frequent recurrences of The patient’s FP referred him to a psychiatrist depressive episodes.18-22 Also, depressive epi- colleague, whose inquiry also revealed low sodes during the postpartum period indicate a mood, anhedonia, hopelessness, difficulty higher risk of BPD than do episodes in women sleeping, low energy, poor appetite, guilt, outside the postpartum period, with a hazard poor concentration, and psychomotor retar- ratio (HR) of 1.66 (95% CI, 1.12-2.48).23 The risk dation. The patient had experienced multiple is much greater when postpartum depressive depressive episodes over the past 20 years. episodes are associated with anxiety symp- Significant interpersonal conflicts frequently toms (HR=10.15; 95% CI, 7.13-14.46).23 triggered his depressive episodes, which were accompanied by mood irritability, rac- Final thoughts ing thoughts, distractibility, increased libido, Increased awareness and screening for BPD excessive spending, increased energy, and en- in primary care—where most individuals with gagement in risky behaviors. depressive symptoms are first encountered— The patient’s score on the MDQ admin- should lead to more accurate diagnoses and istered by the psychiatrist was positive, with decrease the years-long gaps between symp- 7 points on question 1. He also had posttrau- tom onset and detection of BPD,4,5 thereby matic symptoms related to his police work, improving treatment and patient outcomes. which were not the main reason for the visit. He Still, some cases of BPD may be difficult to had been divorced 3 times. In prior manic epi- recognize—particularly patients who present sodes, he had not displayed euphoria, grandios- predominantly with depression with past irri- ity, psychotic symptoms, or anxiety, but rather tability and other hypomanic symptoms (but irritability with other manic symptoms. not euphoria). Based on his MDQ results, the clinical A positive MDQ screen should also interview, and current episode with mixed prompt, if possible, a more detailed clinical in- features, the patient was given a diagnosis of terview by a mental health care professional, bipolar II disorder. The psychiatrist prescribed particularly if there is uncertainty about the divalproex 500 mg at bedtime and scheduled diagnosis. Complex cases of BPD may require a return visit with a plan for further labora- the expertise of a psychiatrist. tory monitoring and up-titration if needed.

502 THE JOURNAL OF FAMILY PRACTICE | AUGUST 2018 | VOL 67, NO 8 TABLE 2 Screening tools for depressive and bipolar symptoms PHQ9 MDQ*

Screening utility Current depressive Current or prior mania, hypomania10 episode Number of questions 9 3 questions, with 13 items in the first question Patient/clinician Patient Patient or clinician administered Time to administer 3 min 3-5 min Sensitivity 0.8011 -0.8812 0.69 for bipolar I;13 0.3 for bipolar II/NOS;13 0.58 in patients receiving treatment for depression8 Specificity 0.9211 0.67 for bipolar I and II;13 0.93 in patients receiving treatment for depression8 MDQ, Mood Disorder Questionnaire (https://www.integration.samhsa.gov/images/res/MDQ.pdf); NOS, not otherwise specified; PHQ9, Patient Health Questionnaire (https://www.uspreventiveservicestaskforce.org/Home/GetFileByID/218). *Standard cutoff for a positive screen for bipolar disorder is 7 out of 13 items posed in question 1. However, in one primary care study, patients with depression were most accurately identified as having bipolar disorder when a cutoff of 5 was used.14

The MDQ and He was also encouraged to follow up with 10. Poon Y, Chung KF, Tso KC, et al. The use of Mood Disorder Ques- PHQ9 tionnaire, Hypomania Checklist-32 and clinical predictors for his FP. JFP screening previously unrecognised bipolar disorder in a general questionnaires, psychiatric setting. Psychiatry Res. 2012;195:111-117. CORRESPONDENCE used together, Nagy A. Youssef, MD, Medical College of Georgia at Augusta 11. Gilbody S, Richards D, Brealey S, et al. Screening for depres- University, 997 St. Sebastian Way, Augusta, GA 30912; sion in medical settings with the Patient Health Questionnaire are more (PHQ): a diagnostic meta-analysis. J Gen Intern Med. 2007;22: [email protected]. 1596-1602. sensitive in SUPPORT AND ACKNOWLEDGMENT 12. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a detecting mood Dr. Youssef’s work on this paper was supported by the Office brief depression severity measure. J Gen Intern Med. 2001;16: of Academic Affairs, Medical College of Georgia at Augusta 606-613. disorder than University. We thank Mark Yassa, BS, for his assistance in 13. Miller CJ, Klugman J, Berv DA, et al. Sensitivity and specificity of is routine editing. the Mood Disorder Questionnaire for detecting bipolar disorder. J Affect Disord. 2004;81:167-171. assessment by 14. Sasdelli A, Lia L, Luciano CC, et al. Screening for bipolar disorder general symptoms in depressed primary care attenders: comparison be- References tween Mood Disorder Questionnaire and Hypomania Checklist practitioners 1. Judd LL, Akiskal HS. The prevalence and disability of bipolar (HCL-32). Psychiatry J. 2013;2013:548349. alone. spectrum disorders in the US population: re-analysis of the ECA 15. Vohringer PA, Jimenez MI, Igor MA, et al. Detecting mood dis- database taking into account subthreshold cases. J Affect Disord. order in resource-limited primary care settings: comparison of a 2003;73:123-131. self-administered screening tool to general practitioner assess- 2. Yatham LN, Lecrubier Y, Fieve RR, et al. Quality of life in patients ment. J Med Screen. 2013;20:118-124. with bipolar I depression: data from 920 patients. Bipolar Disord. 16. Perlis RH, Brown E, Baker RW, et al. Clinical features of bipolar 2004;6:379-385. depression versus major depressive disorder in large multicenter 3. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural his- trials. Am J Psychiatry. 2006;163:225-231. tory of the weekly symptomatic status of . Arch 17. Moreno C, Hasin DS, Arango C, et al. Depression in bipolar dis- Gen Psychiatry. 2002;59:530-537. order versus major depressive disorder: results from the National 4. Ghaemi SN, Sachs GS, Chiou AM, et al. Is bipolar disorder still un- Epidemiologic Survey on Alcohol and Related Conditions. Bipo- derdiagnosed? Are antidepressants overutilized? J Affect Disord. lar Disord. 2012;14:271-282. 1999;52:135-144. 18. Mitchell PB, Malhi GS. Bipolar depression: phenomenologi- 5. Cha B, Kim JH, Ha TH, et al. Polarity of the first episode and time cal overview and clinical characteristics. Bipolar Disord. 2004;6: to diagnosis of bipolar I disorder. Psychiatry Investig. 2009;6:96- 530-539. 101. Available at: http://psychiatryinvestigation.org/journal/ 19. Solomon DA, Leon AC, Maser JD, et al. Distinguishing bipo- view.php?doi=10.4306/pi.2009.6.2.96. Accessed June 25, 2018. lar major depression from unipolar major depression with the 6. Zimmerman M, Galione JN, Chelminski I, et al. Psychiatric di- screening assessment of depression-polarity (SAD-P). J Clin Psy- agnoses in patients who screen positive on the Mood Disorder chiatry. 2006;67:434-442. Questionnaire: implications for using the scale as a case-finding 20. Bowden CL. A different depression: clinical distinctions between instrument for bipolar disorder. Psychiatry Res. 2011;185:444-449. bipolar and unipolar depression. J Affect Disord. 2005;84:117-125. 7. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, 21. Goes FS, Sadler B, Toolan J, et al. Psychotic features in bipolar and challenges, and future directions. Patient Prefer Adherence. unipolar depression. Bipolar Disord. 2007;9:901-906. 2012;6:369-388. 22. Buzuk G, Lojko D, Owecki M, et al. Depression with atypical 8. Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar features in various kinds of affective disorders. Psychiatr Pol. disorder in patients treated for depression in a family medicine 2016;50:827-838. clinic. J Am Board Fam Pract. 2005;18:233-239. 23. Liu X, Agerbo E, Li J, et al. Depression and anxiety in the post- 9. American Psychiatric Association. Diagnostic and Statistical partum period and risk of bipolar disorder: a Danish Nation- Manual of Mental Disorders, 5th ed. Washington, D.C.: American wide Register-Based Cohort Study. J Clin Psychiatry. 2017;78: Psychiatric Publishing. 2013. e469-e476.

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