Screening for Bipolar Depression in the Primary Care Setting

Jay M. Pomerantz, MD


Primary care physicians (PCPs) are the main prescribers of antidepressant medications in the United States. In a typical HMO setting, psychiatrists write 15% of initial antidepressant prescriptions, with the bulk of the rest written by PCPs.[1] The prescribing of antidepressants, even for clearly depressed patients, is not without risk. One danger is when antidepressants are prescribed for the depressed phase of bipolar disorder. The use of antidepressants to treat bipolar patients in the depressed phase if they are not concurrently taking mood stabilizers (eg, lithium, valproate) can induce mania or cycle acceleration and possibly worsen long-term outcomes.[2] In a well-documented retrospective study of patients with bipolar disorder in whom unipolar depression had been misdiagnosed, 55% of patients treated with antidepressants who received an incorrect diagnosis experienced a manic or hypomanic episode, and 23% developed new or accelerated rapid cycling.[3]

Bipolar disorder is not a rare event in patients presenting for treatment in primary care settings. A naturalistic study found 26% of 108 patients who presented with symptoms of anxiety and/or depression in a family practice setting actually had underlying bipolar disorder.[4] This high figure is not completely unexpected given that community surveys reported a 3% to 6.5% prevalence of bipolar disorder in the US population.[5] This prevalence includes up to 1.6% for bipolar I (typical manic-depressive mood swings),[6] with the rest having bipolar II (mostly depressive swings with occasional hypomanic episodes) or less well-defined bipolar spectrum disorders. European studies also show bipolar disorder to be relatively common. The Zurich cohort study identified a prevalence of 5.5% for hypomania/mania, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, with an additional 2.8% if one includes brief hypomania (recurrent but lasting only 1 to 3 days).[7]

Frequently, patients with bipolar disorder will experience several episodes of depression before a manic episode occurs.[8] Consequently, bipolar disorder should always be considered in the differential diagnosis of depression. That history is not necessarily one that emerges spontaneously because patients often do not report prior episodes of mania and hypomania when seeking therapy for depression.[9] The PCP needs to ask explicitly about prior manic or hypomanic episodes and a family history of mood disorders, including mania and hypomania. Consultation with family members and others with close ties to the patient may be extremely useful in identifying prior affective episodes and completing the family history.

The clinical complaints of bipolar patients are more likely than those of unipolar patients to be feelings of worthlessness, restlessness, hypersomnia, hyperphagia, and leaden paralysis, and bipolar patients may also be more likely to report a history of a psychotic depression. Yet none of these signs is exclusive to bipolar disorder.[10] Only mania or hypomania applies exclusively to bipolar patients. Even then, other causes of such behavior (eg, use or abuse of amphetamine or other psychostimulants) have to be excluded. An article currently in press suggests that a 2-question screen for mood lability may help distinguish patients with bipolar II disorder from patients with unipolar major depression.[11] The 2 questions are: "Are you a person who frequently experiences ups and downs in mood over life?" and "Do these mood swings occur without cause?" A positive response to at least 1 question indicates mood lability and an increased likelihood of bipolar disorder.

The practical importance of differentiating bipolar disorder from other psychiatric conditions is that bipolar disorder is a completely different syndrome from unipolar depression, which PCPs have more experience in treating. In particular, there is the suicide risk: bipolar disorder is associated with the highest suicide rate of all major psychiatric illnesses. In a review of 31 studies that included nearly 10,000 patients with recurrent affective disorder (primarily bipolar), the proportion of deaths attributable to suicide was nearly 19%.[12] Suicide is most likely to occur during a depressive or mixed episode.[13]

Persons whose screening results are positive for bipolar spectrum disorders are more than twice as likely to have work-related problems and 5 times as likely to be jailed, arrested, or convicted of a crime than others in a community sample.[14] This same study also found 4 times the incidence of anxiety and panic attacks and twice the incidence of migraine headaches in the bipolar spectrum population. Such physical and mental comorbidity make for complicated medication algorithms, with the average patient's maintenance therapy comprising 3 or 4 mood-active agents.[15] All these characteristics make bipolar patients a formidable treatment challenge with a large potential malpractice liability risk when the disorder is not correctly diagnosed and treated.

The peak age at onset of the first symptoms of bipolar disorder is between 15 and 19 years, followed closely by ages 20 to 24 years. Bipolar disorder at first may be difficult to diagnose in teenagers and young adults because it is often confused with, or comorbid with, attention-deficit hyperactivity disorder. Bipolar disorder combined with a comorbid substance use disorder is also a common presentation. Large epidemiologic studies have found rates of alcohol abuse and/or drug abuse in more than 40% of patients with bipolar disorder.[16,17]

In a study derived from a questionnaire distributed to patients with bipolar disorder who are members of the Depression and Bipolar Support Alliance (DBSA), Hirschfeld and colleagues[18] reported that 69% of respondents alleged that they initially received a misdiagnosis. Thirty-five percent of respondents waited 10 years or more for a correct diagnosis, and many had consulted 5 or more physicians before receiving the correct diagnosis. The likelihood of underdiagnosis or a missed diagnosis will be greatly lessened by the routine use of a screening instrument, such as the Mood Disorder Questionnaire (MDQ).[19] The MDQ is a validated, self- or clinician-administered questionnaire that takes about 5 minutes to complete and consists of 17 questions. The first 13 questions require yes or no answers about possible symptoms, with the others assessing family history, past diagnoses, and severity. The MDQ can identify 7 of 10 patients with bipolar disorder while eliminating 9 or 10 without it. The MDQ is available on the DBSA Web site at

In the event of a positive result on the MDQ, the PCP should refer the patient for evaluation and treatment of bipolar disorder by a mental health specialist. Only when such a referral is not possible should the PCP consider taking on what is likely to be complex and high-risk treatment. Even then, unless especially skilled in the mental health arena, the PCP would be wise to review his or her treatment plan with a consultant. Some might argue that the management of bipolar depression with newer medications, such as lamotrigine or fluoxetine/olanzapine, is not that complicated and is well within the competence of many PCPs, but I believe that argument minimizes the treatment difficulties that most bipolar patients present over the long haul. Also, in this litigious society, either not diagnosing bipolar disorder or attempting to treat bipolar patients in the usual PCP environment may expose the prescriber to a malpractice suit should there be a suicide or other harm to the patient or others.


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