On the Elicitation of Bipolar Symptoms in Primary Care

M3 Information is committed to improving the accurate diagnosis of Bipolar Disorder (BD) and Bipolar Spectrum Disorders and to minimizing their misdiagnosis, as the current trend in non- and mistreatment entails tremendous though avoidable morbidity and mortality, wasteful healthcare costs, and lost productivity.1–4 Yet, in our ongoing efforts we have occasionally confronted the concern that eliciting bipolar-related symptoms in primary care (PC) is fraught: 1) that without appropriate guidelines and expertise in place, the risks of identification may outweigh any potential benefits; and 2) the relatively low specificity of standard BD screening instruments render them unhelpful.

This source of resistance is also highly relevant for those unipolar depressed individuals for whom subsyndromal manic symptoms exist (the so-called, mixed state qualifier for Major Depression). These mixed state depressed patients, with higher suicide rates and greater morbidity generally, are at significant risk of being mishandled clinically when diagnosis derives from depression-only approaches to mood disorders screening.

Evidence-based guidance on this matter is available and speaks in favor of screening for bipolar symptoms (see below). Yet, to date there have been no prospective large-scale studies comparing diagnosis as usual over against diagnosis based on a validated screen for BD. Concerns that PC doctors will be overwhelmed by the treatment demands, will mistreat such cases, etc., are put forth purely on hypothetical grounds or based on intuition or anecdotal evidence, and typically without bearing in mind the alternative; i.e., allowing non- and mistreatment to persist. What needs to be asked is: how do these patients fare when left improperly diagnosed and, furthermore, how does this neglect affect their prognosis and utilization of healthcare services generally? Rather than imagining a hypothetical bipolar patient, we should compare such patients as they move through the system along two divergent paths: one where they are properly identified and one when they are not. A proper analysis needs to consider the following (with supporting evidence for this analysis to follow below):

1 — Regarding misdiagnosis: At present, we must consider which scenario carries the greater risk of mistreatment and the associated costs: a) the cohort of bipolar patients misdiagnosed as unipolar depression/anxiety, or b) that same group properly identified and managed (perhaps through referral) by their PCP? The available evidence makes clear that misdiagnosis leads to mistreatment and hence to marked increases in morbidity, mortality and disability. Meanwhile, no empirical evidence exists supporting the notion that identifying this condition in primary care results in higher rates of such negative outcomes. False positives carry manageably small risks, typically and in contrast to false negatives, leading to more careful treatment oversight. (More on this below.) Furthermore, longitudinal measurement of any identified bipolar symptoms will improve diagnostic specificity over time whenever initial findings are equivocal.

2 — Regarding non-diagnosis: How many entirely new cases of mental illness would be uncovered with an effective bipolar screen; i.e., BD patients who without such screening receive no psychiatric diagnosis whatsoever? Capturing an accurate answer to this question is not so straightforward. To reflect accurately the natural history of this condition and to properly distinguish true non-diagnosis from misdiagnosis, a 12-month incidence rate should be utilized. For example, a patient hypomanic in January may not be identified until he or she is misdiagnosed with unipolar depression in September. Although a study of this sort has not yet been carried out, our contention is that misdiagnosis of BD is far more prevalent than non-diagnosis. Yet, those patients undiagnosed at an initial point of service will go on to consume an unnecessary surplus of health care services and express high rates of medical, psychiatric and substance abuse complications.

3 — Regarding overall healthcare utilization: How do the misdiagnosed and the undiagnosed BD patients compare to the properly identified BD cohort in terms of overall healthcare consumption, employment status, marital status, legal history, and substance abuse history? We interpret the studies quoted below to support the view that recognizing BD at the earliest possible time saves lives, reduces suffering and sustains home and work life functioning.

Prevalence rates of mixed symptoms — i.e., opposite polarity symptoms found in unipolar depressed, bipolar depressed, and bipolar [hypo]manic patients are presented in the figure below (taken from Vásquez, Lolich, Cabrera, et al. 2018)5.

This study found that nearly one quarter of unipolar depressed patients exhibit three or more [hypo]manic symptoms during their depressive episodes. Mixed state prevalence rates rise to 35% among bipolar depressed individuals, a group — as related above — often misdiagnosed as unipolar.

The following excerpts come from Keck, Kessler & Ross (2008)1, still the most current large-scale survey of the epidemiology on this topic.

• For every behavioral health care dollar spent on outpatient care for bipolar disorder, $1.80 was spent on inpatient care, suggesting that strategies to prevent acute episodes could decrease the financial burden of the illness. When the diagnosis of bipolar disorder is missed or the presentation is misdiagnosed and inappropriately treated as unipolar depression, as frequently occurs . . . this can lead to even higher healthcare cost.6,7
• Birnbaum et al.8 compared treatment patterns and costs for patients with recognized and unrecognized bipolar disorder with those of depressed patients without bipolar disorder, using claims data from seven large national employers for 585,584 individuals younger than 65 years of age. . . The patients with unrecognized bipolar disorder incurred significantly greater mean monthly medical ($1179) and indirect ($570) costs in the 12 months after initiation of antidepressant treatment compared with those with recognized bipolar disorder ($801 and $514). These investigators concluded that accurate recognition of bipolar disease was associated with lower medical costs as well as lower indirect costs due to work loss.
• Shi et al.9 compared hospital use, suicide risk, and healthcare costs of patients with recognized and unrecognized bipolar disorder with those of patients with nonbipolar mood disorders, using data from 25,460 adults in the California Medicaid program with a new episode of antidepressant therapy. They found that patients with unrecognized bipolar disorder were more likely to attempt suicide and be hospitalized than those with recognized bipolar disorder and nonbipolar mood disorders. Patients with bipolar disorder also had significantly higher total costs (almost $1,000 per person per year more in direct healthcare costs) than those with nonbipolar illness in the first year post-treatment; likewise, healthcare costs for patients with recognized bipolar disorder were also nearly $700 less per person per year than for those with unrecognized bipolar disorder, primarily due to lower costs for ambulatory care and hospital services.
• McCombs et al.2 examined California Medicaid data from patients who had started new courses of antidepressant therapy for whom at least 6 years of post-treatment data were available. They found that growth in costs for patients with unrecognized bipolar disorder over 6 years was 171%, greatly exceeding the increase in costs associated with recognized bipolar disorder (82%) and depression (95%). They also found that costs increased by $91/month for each month the diagnosis of bipolar disorder was delayed . . . These researchers concluded that early diagnosis of bipolar disorder may significantly reduce healthcare costs.
• Studies have also found that bipolar disorder can have severe and often enduring negative effects on occupational functioning,10resulting in significant indirect costs through lost productivity. Wyatt and Henter11 estimated that the economic costs of bipolar disorder from a societal perspective were $45 billion a year in the United States, with the economiclosses due to work impairment accounting for the largest proportion (nearly $18 billion annually) of this total. This estimate translates into annual workplace costs of over $125,000 for a company with 1,000 employees.
• A primary care study found that employed patients with bipolar disorder missed seven times as much work as other patients.12
• A recent study by Guo et al.13 found that treatment of comorbid conditions (including substance use disorders, cerebrovascular disease, ischemic heart disease, and hypertension) accounted for 70% of treatment costs for patients with bipolar disorder. Because of the risks associated with treating bipolar disorder with antidepressant monotherapy, it is important that primary care physicians be educated about how to screen for and treat bipolar disorder.14
• The current American Psychiatric Association guideline for the treatment of patients with bipolar disorder states that “one way to improve the efficiency and increase the sensitivity in detecting bipolar disorder is to screen for it, particularly in patients with depression, irritability or impulsivity”.14

The nation-wide suicide and opiate misuse epidemic should draw attention especially to Shi et al’s finding about suicide risk. A 2018 investigation of mixed symptoms among suicide attempters15 found a consistent increased risk when mixed mood symptoms were found among unipolar and bipolar patients. And these more severely ill patients are the ones who are most likely to abuse drugs and alcohol, both closely associated with impulsive suicidality and accidental overdose.

The best way to manage bipolar symptoms is to find them at the earliest possible time. This means finding them in the primary care setting. Burying one’s head in the sand is not a defensible clinical strategy for any medical condition whose early identification makes such a profound difference to outcome. Relying on a depression-only, or depression-anxiety-only screen as a first tier, with positive results leading to a bipolar assessment badly misunderstands the natural course of this condition. A false result in an initial screen for bipolarity runs the risk of providing false reassurance. Rather, as bipolar symptom-atology often first develops after treatment for depression or anxiety is underway, it is vital that longitudinal testing for this condition takes place for every patient identified with a mood and anxiety disorder.

In an important 2016 review article from Carta & Angst,16 the authors emphasize that bipolar-positive screening results are clinically relevant even when a categorical BD diagnosis is not corroborated by a clinician-rated gold standard. They present evidence that bipolar spectrum disorders often first present as cases of depression, anxiety, eating disorders, substance misuse, etc. Identifying such manifestly ill patients, earlier rather than later, as existing on a bipolar spectrum is of critical importance in those patients’ management and illness course. Their analysis calls into question the validity of the so-called “false positive problem” in screening for bipolar disorder in primary care. From a practical clinical standpoint, we agree with these researchers: screening for bipolar disorder is a population health strategy whose time has come.

N O T E S

1 Keck PE, Kessler RC, Ross R. Clinical and Economic Effects of Unrecognized or Inadequately Treated Bipolar Disorder. J Psychiatr Pract 2008; 14(Suppl 2):31–38.

2 McCombs JS, Ahn J, Tencer T, et al. The impact of unrecognized bipolar disorders among patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program: A 6-year retrospective analysis. J Affect Disord 2007; 97:171–9

3 Li C-T, Bai Y-M, Chen Y-S, et al. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: a cohort study. Br J Psychiatry 2012; 200:45–51

4 Marangell LB, Dennehy EB, Wisniewski SR, et al. Case-control analyses of the impact of pharmaco-therapy on prospectively observed suicide attempts and completed suicides in bipolar disorder: findings from STEP-BD. J Clin Psychiatry 2008; 69(6):916–922

5 Vásquez GH, Lolich M, Cabrera C, et al. Mixed symptoms in major depression and bipolar disorders: A systematic review. J Affect Disord 2018; 225(1): 756–760

6 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; 4:161–74.

7 Hirschfeld RMA, Vornik LA. Bipolar disorder: Costs and comorbidity. Am J Manag Care 2005; 11:S85–S90.

8 Birnbaum HG, Shi L, Dial E, et al. Economic consequences of not recognizing bipolar disorder patients: A cross-sectional descriptive analysis. J Clin Psychiatry 2003; 64:1201–9

9 Shi L, Thiebaud P, McCombs JS. The impact of unrecognized bipolar disorders for patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) Program. J Affect Disord 2004; 82:373–83

10 Michalak EE, Yatham LN, Maxwell V, et al. The impact of bipolar disorder upon work functioning: A qualitative analysis. Bipolar Disord 2007; 9:126–43

11 Wyatt RJ, Henter I. An economic evaluation of manic-depressive illness — 1991. Soc Psychiatry Psychiatr Epidemiol 1995; 30:213–9

12 Olfson M, Fireman B, Weissman MM, et al. Mental disorders and disability among patients in a primary care group practice. Am J Psychiatry 1997; 54:1734–40

13 Guo JJ, Keck PE, Li H, et al. Treatment costs related to bipolar disorder and comorbid conditions among Medicaid patients with bipolar disorder. Psychiatr Serv 2007; 58:1073–8

14 Das AK, Olfson M, Gameroff MJ, et al. Screening for bipolar disorder in a primary care practice. JAMA 2005; 293:956–63

15 American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry2002; 159:1–50

16 Persons JE, Coryell WH, Solomon DA, et al. Mixed state and suicide: Is the effect of mixed state on suicide behavior more then the sum of its parts? Bipolar Disord 2018; 20:35–41

18 Carta MG, Angst J. Screening for bipolar disorders: a public health issue J Affect Disord 2016; 205: 139–143