This essay begins an ongoing series on bipolar disorder focused on clinical utility.
This essay begins an ongoing series on bipolar disorder focused on clinical utility. From the point of view of psychiatrists seeing patients every day, I’ll examine treatment options, such as N-acetyl-l-cysteine and supraphysiologic doses of thyroid hormone, that appeal to patients but are inadequately researched.
I'll look at common problems in differential diagnosis as well as at specific challenges, such as pregnancy, and big-picture issues, such as the effect of socioeconomic factors on outcomes. In each case, the goal is to bring insights from research-and sometimes from history, philosophy, and social sciences-to the daily practice of psychiatry.
Let us start with the dilemma posed by Vieta and Suppes.1 As elsewhere, controversies in psychiatry commonly revolve around dichotomizing a complex issue, eg, do antidepressants cause suicidality, or reduce the risk? Are antipsychotics just too risky for young children, or does delaying treatment worsen the long-term picture? Is your patient’s depression unipolar or bipolar in origin?
Turning complex issues into simple questions makes them easier to consider and sometimes easier for patients to understand (in less time). Moreover, treating patients often requires making judgments in the face of overwhelming complexity: Is this depression due to circumstance? Does the timing really suggest causality? Or is this an endogenous mood shift that suggests “cycling”? How can this be teased out in the face of his financial problems, his job loss, his relationship struggles, and the difficulties his children are experiencing?
Sometimes one must simplify in the name of action. Take, for example, a 30-year-old man who does not have access to cognitive-behavioral therapy, whose diagnosis could be generalized anxiety disorder (GAD) with a history of multiple episodes of MDD, but who may also be regarded as having bipolar II (BP-II)-depending on how you interpret his agitation, insomnia, distractibility, irritability, and impulsivity. Are you going to prescribe an antidepressant or a mood stabilizer? Temporizing and gathering more data, to gain more insight into this patient’s problem, is appealing; but he is suffering and wants help as soon as possible, preferably today.
However, in psychiatry, making things simple, as in the statement “you have generalized anxiety disorder,” is frequently an oversimplification. Comorbidity is the norm, not the exception. DSM diagnoses overlap to a tremendous degree, with the bipolar/GAD overlap one of the most striking, as shown in the Table. (The DSM-intercommittee conversation that didn’t happen: “You have all those on your list too?”)
DSM-IV criteria: overlap of symptoms in bipolar disorder and generalized anxiety disorder
Narrowing one’s focus to arrive at a formal diagnosis risks premature closure: what looks like “cycling,” suggesting bipolar disorder, could be the chaos of the patient’s life. Treatment with a mood stabilizer might have no benefit, but it may subject the patient to risks such as Stevens-Johnson syndrome (divalproex and carbamazepine as well as lamotrigine) or hypothyroidism (not just lithium; quetiapine also carries this risk to some degree2,3). On the other hand, patients frequently do not recognize subtle hypomanic symptoms and focus instead on the dysphoric aspects of insomnia, disorganized thought, and agitation (often referred to as anxiety). Starting treatment with an antidepressant could precipitate a mixed state, which may be a greater concern than precipitating a frank manic episode, because mixed states are associated with suicide.4
Or, the patient might improve and continue to take the antidepressant for years, then experience adverse effects after long-term exposure.5,6 Whether antidepressants can sometimes induce mood instability or dysphoria is far from established. To date, this concern is based only on association studies and informed speculation. However, if it were to prove true, some bipolar treatments might not appear so risky by comparison. Contrary to frequent characterization (eg, Frances and Jones7), lamotrigine, lithium, valproate, and carbamazepine-not atypical antipsychotics-are the relevant mood stabilizers for risk-benefit analyses of overdiagnosis.7 BP-II and many cases of BP-I do not require ongoing antipsychotics for management. Including atypicals in this discussion polarizes the issue unnecessarily and falsely skews the risk com-parison of bipolar treatment.
But the patient awaits treatment. To cope with the twin risks of inaccuracy by oversimplification and immobilization by complexity, consider Hegel’s dialectic concept once again (with thanks to Linehan8 for making this way of thinking commonplace in our discipline). Hegel used the term “aufheben” (literally, to “lift up,” but rich in complexity itself) to describe the dialectic spiral: two apparently contradictory ideas or ways of seeing things interact to produce a synthesis, a new idea, or approach that contains and rises above the contradiction.
Through “aufheben” lenses (left eye simplicity, right eye complexity, if you will), a patient with a differential of GAD+MDD versus BP-II has multiple options. Although the data are slim and unreplicated so far, divalproex as a treatment for GAD is not without precedent.9,10 One might also consider lorazepam or a few days of low-dose olanzapine while gathering more data to understand “how bipolar is he?” (in the manner of the STEP-BD’s “Bipolarity Index”11). You may yet come around to an antidepressant approach after gathering collateral data; eg, if the patient’s partner or close friend endorses few items from a hypomania screening tool such as the HCL-32.12 If psychotherapy remains inaccessible or impractical for him, antidepressants can address both his current anxiety and his mood history. Or you might decide that continued divalproex is the best approach for now.
How is the patient to understand all this? Answer: one step at a time-starting with your counsel that although he could be regarded as having GAD, there are alternative considerations and more investigation is warranted even while his symptoms are being addressed. As you know, many patients follow up their doctor visit with an Internet visit, so helping the patient understand that the diagnosis is not simple and not straightforward may actually save you time later.
In subsequent columns, I’ll use “aufheben” lenses to examine other controversies and challenges. For example: will the new DSM-5 criteria obviate the need for a “Bipolarity Index” approach?
1. Vieta E, Suppes T. Bipolar II disorder: arguments for and against a distinct diagnostic entity. Bipolar Disord. 2008;10(1, pt 2):163-178.
2. Poutanen O, Iso-Koivisto E, TyÃ¶lÃ¤jÃ¤rvi M, Leinonen E. Quetiapine-associated hypothyroidism in young female patients: a report of three cases. Pharmacopsychiatry. 2010;43:237-239.
3. Park YM, Kang SG, Lee BH, Lee HJ. Decreased thyroid function in Korean women with bipolar disorder receiving valproic acid [published correction appears in Gen Hosp Psychiatry. 2011;33:300]. Gen Hosp Psychiatry. 2011;33:200.e13-e15.
4. ValentÃ M, Pacchiarotti I, Rosa AR, et al. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients. Bipolar Disord. 2011;13:145-154.
5. Ghaemi SN. Treatment of rapid-cycling bipolar disorder: are antidepressants mood destabilizers? Am J Psychiatry. 2008;165:300-302.
6. El-Mallakh RS, Gao Y, Briscoe BT, Roberts RJ. Antidepressant-induced tardive dysphoria. Psychother Psychosom. 2011;80:57-59.
7. Frances A, Jones KD. Bipolar disorder type II revisited. Bipolar Disord. 2012;14:474-477.
8. Linehan MM. Dialectical behavior therapy for borderline personality disorder. Theory and method. Bull Menninger Clin. 1987;51:261-276.
9. Aliyev NA, Aliyev ZN. Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: randomized, double-blind placebo-controlled study. Eur Psychiatry. 2008;23:109-114.
10. Roy-Byrne PP, Ward NG, Donnelly PJ. Valproate in anxiety and withdrawal syndromes. J Clin Psychiatry. 1989;50(suppl):44-48.
11. Bipolarity Index. http://www.psycheducation.org/depression/STEPBipolarityIndex.htm. Accessed October 8, 2012.
12. Hypomania/mania symptom checklist (HCL-32). http://www.psycheducation.org/depression/HCL-32ListOnly.pdf. Accessed October 8, 2012.