Broadening the concept of bipolar disorder: what should be done in the face of uncertainty?

Early in the course of treatment I am sometimes not sure if a currently depressed patient has bipolar disorder. This uncertainty occurs despite an extensive evaluation that includes the administration of a semi-structured interview, a review of prior records, and an interview with an informant. When diagnosis is based on the occurrence of symptom episodes in the past, as is the case with bipolar disorder in currently depressed patients, diagnostic clarity is sometimes elusive. Similarly, I am not sure how the bipolar spectrum should be defined. This is despite conducting research in the area and keeping up with the literature. What should be done in the face of uncertainty? With my patients I adopt a wait and see approach. That is, I closely monitor my patients’ symptoms over time, looking for the emergence of hypomanic or, less frequently, manic episodes. Treatment for bipolar disorder follows when the diagnostic declaration is made. In a like manner, changes to the nosology should follow a sober, conservative approach and only be made when replicated, empirical evidence has demonstrated that the new method is superior to the old. As summarized by Strakowski et al, such empirical evidence is lacking with regards to an expansion of the boundaries of bipolar disorder. They therefore urged caution. Wherever the boundaries of bipolar disorder are drawn, there will be some false positive as well as false negative diagnoses. The question is not whether there is diagnostic error, but rather which type of error predominates and how much will shifting the diagnostic threshold impact the number of each of these diagnostic errors. Also important to consider are the clinical consequences of each type of error, and which error is more difficult to undo after it has been made. In support of the expansion of the diagnostic boundary for bipolar disorder, some studies have suggested that the duration of a hypomanic episode should be lowered to 1 or 2 days 1,2. However, I am not aware of any studies of the potential impact this change would have on diagnosis and outcome in clinical practice. With the existing diagnostic criteria, overdiagnosis (i.e., false positives) is already a problem 3. If the duration threshold is lowered, how many more patients will be overdiagnosed with bipolar disorder because episodes of affective instability characteristic of cluster B personality pathology are incorrectly considered indicative of hypomania 4? Of course, the question should also be asked: how frequently does a clinician currently underdiagnose “true” bipolar disorder because the observed, or recently occurring, hypomanic syndrome has not lasted long enough to qualify as a DSM-IV hypomanic episode? However, clinicians are not rigid in the application of the DSM-IV diagnostic thresholds 5; thus, patients with recurrent hypomanic episodes of presumably insufficient duration would nonetheless likely be diagnosed with bipolar disorder and treated accordingly. Both false positive and false negative diagnoses are associated with adverse consequences. Unrecognized bipolar disorder is associated with underprescription of mood stabilizing medications, an increased risk of rapid cycling, and increased costs of care 6,7,8. Overdiagnosed bipolar disorder is associated with overtreatment with unneeded medications and consequent exposure to potential side effects and medical risk and the potential failure to offer more appropriate treatments. In trying to decide where to set the threshold for diagnosing bipolar disorder and minimize diagnostic errors of all types, it should be acknowledged that the consequence of a false positive diagnosis is likely to be more long-lasting than a false negative diagnosis. While diagnosis may be a dynamic, fluid process, that is reconsidered as additional clinical material becomes available, it is probably easier to add a diagnosis than to take one away. Thus, it is easier to change a patient’s diagnosis from nonbipolar depression to bipolar disorder than from bipolar to nonbipolar depression. I suspect that a patient with a false positive diagnosis of bipolar disorder who is doing well on an antidepressant and a mood stabilizer is unlikely to have the mood stabilizer discontinued. Let us consider the recently published 10-year prospective study of community residents which found that individuals with a subthreshold number of manic/hypomanic symptoms had an elevated rate of bipolar disorder in their families, elevated comorbidity rates, and an increased rate of converting to DSM-IV bipolar I or bipolar II disorder during the follow-up interval 9. The authors interpreted the findings as support for broadening the concept of bipolar disorder. However, less than 15% of the subjects actually converted to bipolar I or bipolar II disorder. As noted by Strakowski et al, there are no studies establishing the efficacy of mood stabilizers in the treatment of subthreshold bipolar disorder. Thus, if the diagnostic boundary was expanded, many individuals who would never develop DSM-IV-defined bipolar disorder would be prescribed such medications in the absence of controlled research establishing their efficacy. First and Frances 10 have cautioned the developers of DSM-5 against making changes in diagnostic criteria without sufficient consideration of the unforeseen consequences of such changes. DSM-IV symptom-based diagnoses represent a probabilistic estimate of a disease whose underlying pathophysiology we hope to one day understand. Shifting the diagnostic boundary downward will reduce the rate of underdiagnosis of true bipolar disorder at the cost of increasing the rate of overdiagnosing pseudobipolar disorder. We are therefore left with several nodes of uncertainty. In the absence of valid biological diagnostic markers, the relative frequency of each type of phenomenology-based diagnostic error is uncertain. The efficacy of mood stabilizers in treating subthreshold bipolar disorder is uncertain. The impact of lowering the threshold to diagnose bipolar disorder on overdiagnosing bipolar in clinical practice is uncertain. From a public health perspective, the benefit of expanding the diagnostic boundary is uncertain. In the face of such uncertainty, a wait and see attitude is the most prudent before redrawing bipolar disorder’s diagnostic boundaries.