Bipolar II Disorder: Frequent,Valid,and Reliable

The inclusion of bipolar II disorder as a subtype of bipolar illness in the DSM-IV is probably, from a clinical perspective, the most important change in the classification of mental disorders over the past 25 years. The recognition of this condition as a specific mental disorder has enhanced health care access, medical awareness, and research on a medical entity that had been neglected for ages in the official taxonomies. Clinicians were totally aware of this challenging group of patients who had some sort of apparently milder form of manic-depressive illness but who were burdened with frequent recurrences, ¹ lack of evidence-based treatments, ² and high rates of disability. ³ Unfortunately, only in 1994 was this group of patients given a diagnostic status, with official blessing from the DSM. ⁴

Some of the difficulties that academic centers, taxonomists, and researchers have had with this condition are exemplified in the article by Malhi et al. ⁵ While it is true that, originally, the description of what we know today as bipolar II disorder was focused on hospitalized depressed patients with a history of hypomania, we know now that most bipolar II patients are never hospitalized but have very frequent depressive and hypomanic episodes that carry enormous morbidity and mortality. ⁶ The difference between mania and hypomania is based on not only duration of symptoms but also severity and disability. Malhi et al. ⁵ insist on the little relevance of the distinction between bipolar I and bipolar II disorder (which might be true for a subset of severe bipolar II patients), but they forget to mention that the actual relevance of defining bipolar II disorder lies in the distinction between this condition and major depressive disorder. Hence, while hypomania can be sometimes (but only sometimes) enjoyable and not particularly disturbing, it is possibly the best predictor of a shortly emerging depressive relapse (indicating the need of maintenance therapy with mood stabilizers) and also a strong indicator of poor response to antidepressants. ⁷ Hence, for many patients with bipolar II disorder for whom depression is the main source of burden, the identification of hypomanias during the course of illness is critical to develop a treatment plan that includes, as options, mood stabilizers such as lithium or lamotrigine over antidepressants. In reality, most hypomanias carry an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic, as defined in the DSM-5. ⁸

The DSM-5 field trials showed that both bipolar I disorder and bipolar II have good reliability. ⁹ Interestingly, this was not the case for several other conditions that have been much less the focus of controversy, such as major depression and generalized anxiety disorder. As regards to personality disorders, the symptoms of bipolar II disorder are different from those of borderline personality (e.g., hypomania is not part of the definition of borderline personality disorder), and what really needs urgent improvement is the diagnosis and classification of personality disorders in the DSM. ¹⁰ A diagnosis of a personality disorder should not be made during an untreated mood episode unless the lifetime history supports the presence of a personality disorder, which can be comorbid with an affective disorder.

The arguments as regards to industry promoting the diagnosis of bipolar II disorder make little sense; in fact, for pharmaceutical companies, it would be much better from a business perspective to merge all bipolar disorders into one, making no distinctions between subtypes and saving money from costly clinical trials. The arguments against a point of rarity in the distinction between bipolar I and bipolar II disorders are well taken, but they actually apply to all the artificial distinctions that we make when categorizing psychiatric conditions. All the issues about lack of specificity of biomarkers, genetics, and neuroimaging apply not only to the boundaries between bipolar I and II but also to the ones between bipolar disorder and schizophrenia, as well as bipolar disorder and major depressive disorder. Should we put all those disorders under the same umbrella? Psychiatry is dimensional, but in clinical practice, categories are necessary, especially for the purpose of establishing a prognosis and effective treatment. ¹¹ In my practice, the management of bipolar and bipolar II disorder is often quite different. Some antipsychotics with a high polarity index ¹² can actually worsen the course of bipolar II disorder, and in my experience, group psychoeducation needs to be implemented quite differently in these patients because the prevention and management of mania and hypomania, for some of the reasons that Malhi et al. ⁵ mention in their article, need different approaches. ¹³

I like the plan of exploring new ideas. Lumping bipolar I and II into a single condition might not be a good idea: for example, what do we do with cyclothymia? Do we lump it too? That would indeed expand the scope of bipolarity quite significantly; some would argue that this is to please pharmaceutical companies. I see more future in exploring the course of bipolar illness and defining a specifier in the next edition of the DSM ¹⁰ and ICD-11. ¹⁴ For example, the fact that some patients have a stronger tendency to relapse into depression than mania, or the other way around, has important therapeutic implications. Hence, the concept of “predominant polarity” ^15,16 is timely and relevant and needs to be acknowledged in the stratification of bipolar disorder, which is the closest we can get now to personalized psychiatry. ¹⁷ Clearly, some drugs work better in preventing mania than depression, and therefore they work better in patients with greater proneness to mania and hypomania. ¹⁸ This needs to be further explored.

At the end of the day, identifying subjects with recurrent depressions who eventually develop mild and transient manic symptoms in the form of hypomania is extremely relevant for clinical management, and this is why bipolar II disorder is such an important category. There is an unmet need in identifying such patients in primary care, where many of them are still treated with antidepressant monotherapy, which is not good practice. ¹⁹ Only recently have international treatment guidelines devoted specific sections to bipolar II disorder, ²⁰ and there are complete books on this particular topic. ²¹ Emphasis on early intervention in bipolar II disorder is also paramount, especially because most early intervention strategies are focused on first-episode psychosis, which rarely applies to that condition. ^{22 –24} The good news is that a task force of international experts is currently dealing with all these diagnostic nuances that make the diagnosis of bipolar disorder and its subtypes such a challenging purpose, ²⁵ and the largest genome-wide association study to date has recently shown that bipolar II disorder is more strongly correlated with major depressive disorder than bipolar I disorder. ²⁶