Bipolar disorder: diagnostic issues

The term bipolar disorder applies to a range of conditions that are likely to have different aetiologies, including genetic or family vulnerability, precipitation by stressful life events, physical illness or drugs including antidepressants. The essential features of bipolar disorders are cyclical mood disorders including distinct sustained periods of mood elevation. Mood elevation is critical in differentiation from unipolar disorders, specifically major depressive disorder, recurrent type.

Bipolar disorders are classified in a number of ways. One diagnostic system is described in the Diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR),1 which is United States based; another is described in the International statistical classification of diseases and related health problems, 10th revision (ICD-10),2 which is World Health Organization and predominantly European based. Although these diagnostic classifications have similarities, there are several differences in their detail. Here we refer to the DSM-IV-TR1 criteria, unless otherwise specified. Box 1 provides a summarised approach to classifying bipolar disorder.

Bipolar disorder is divided into a number of types and subtypes, depending on the patient’s history, the clinical presentation phase (elevated, depressed, rapid cycling or otherwise), the duration and severity of symptoms, and associated features. These factors are important as they help to indicate the likely outcome of current and future illness episodes, and inform possible treatments.

Mixed episodes occur when patients have features of mood elevation and depression simultaneously. DSM-IV-TR1 criteria for a mixed episode require that the patient has full features of both mania and depression. Using this approach, mixed episodes do not include mixed states where only some criteria are met, or states in which there are simultaneous features of both elevation and depression but not the severity of either mania or major depression. Many experts in psychiatry view the DSM-IV-TR1 criteria as being too strict and limiting. In contrast, ICD-102 criteria allow for the diagnosis of a mixed episode in the presence of either of a mixture of manic and depressive symptoms or a rapid alteration between manic and depressive symptoms.

Clinicians must be mindful that mania and depression can coexist, and that patients with bipolar disorder may present as angry, irritable and dysphoric. In these circumstances, antidepressants may worsen symptoms.

When there is no clear category for a patient’s diagnosis, yet they have had features of mood elevation and depression, with disability, the term bipolar disorder not otherwise specified can be used. Some experts have broadened the diagnosis of bipolar disorder to include a range of disorders and disabilities with a central quality of cyclical mood disorder, yet not strictly meeting criteria for bipolar I, bipolar II or a mixed state.

Some experts argue strongly that the traditional definition of bipolar disorder is too narrow and that milder indicators of mood elevation should be viewed as part of the bipolar spectrum. For instance, if a patient’s mood becomes elevated during treatment with an antidepressant, during a medical illness or while under the influence of illicit drugs, they could be classified under the category of bipolar disorder. Individuals with certain personality types — such as those who are mostly ebullient, buoyant and especially optimistic, or those who are emotionally over-reactive and may be diagnosed with borderline personality disorder — show evidence of so-called soft bipolarity. It has been proposed that such patients should be referred to as having bipolar disorder. These ideas are controversial, and the roles of traditional mood stabilisers have not been established in these states.

Although mania or hypomania are referred to as phases of mood elevation, they may involve concurrent dysphoria, particularly with distressing anxiety symptoms. Anxiety and irritability occur commonly in bipolar depression. Suicide is a greater risk during depression when there is associated anxiety. Comorbid anxiety disorders, such as panic disorder and generalised anxiety disorder, are common in bipolar disorder.

Bipolar illnesses are often complicated by use of alcohol or illicit drugs. Substance misuse is more common in bipolar I disorder (50%) than bipolar II disorder (39%); alcohol is the most commonly misused substance (42% and 34% for bipolar I and II, respectively),3 and illicit drug use is also common. Sometimes the mood disorder will be undiagnosed in the context of florid substance misuse. Diagnosis can be problematic in such patients because alcohol and many drugs can cause substantive mood alterations that remit without treatment once substance use ceases.

Differentiation of bipolar disorders from schizophrenia may be difficult, especially in young people with short medical histories. Severe bipolar depression may present as catatonia, and mania with psychosis may present as catatonic excitement. Substance misuse may contribute to mood swings that resolve on drug withdrawal. Unipolar depression, or recurrent unipolar depressions, which may be treatment resistant, can be present before mania or hypomania are apparent. Attention deficit hyperactivity disorder may be misdiagnosed as hypomania. The mood swings with borderline personality disorder may be misdiagnosed as bipolar disorder, but this is a challenging issue as borderline personality disorder and bipolar disorder may coexist.

Most patients with bipolar disorder will have two or fewer episodes of mood disorder per year. Some may have many years between episodes. In this latter case, when there is an episode of bipolar mood elevation or depression after many years of euthymia, the clinician should always check for possible organic precipitants. Patients who have four or more episodes in one year are referred to as having a rapid cycling disorder. These patients are typically difficult to treat and often unresponsive to conventional mood stabiliser regimens (see Malhi et al, The pharmacological treatment of bipolar disorder in primary care).12 Occasionally, patients may experience mood changes more than once per day, typically being depressed in the morning, with mood elevation in the evening or at night. This has been referred to as ultradian cycling, and can raise diagnostic confusion with borderline personality disorder.

Consistent with a prevailing view that bipolar disorder has a primary biological basis, structural neuroimaging studies have revealed a reduction in central nervous system volume in patients with bipolar I disorder and increased rates of deep white matter hyperintensities.13 There may be a loss of hippocampal volume, consistent with that seen in untreated depression.14,15 There are also significant cognitive deficits in bipolar disorder, even during euthymia, which can impede functioning.16 These impairments can result in patients who seem to have achieved symptomatic recovery not regaining full social and occupational rehabilitation. Thus, a goal of treatment should be a full remission of all symptoms and rehabilitation, rather than only alleviation of mood symptoms.16

Antecedent depression may predate the first episode of mood elevation by many years. Mood elevation may seem to be the element which defines bipolar disorder, but depression is the more enduring element of the illness and results in the greatest disability over time.17

There is controversy over the long-term outcome of bipolar depression. Clinically, some experts believe that depressive episodes tend to become more severe over time, while mood elevation tends to decline over time. However, some data suggest that the proportions of mania and depression remain stable into old age.18 Depression is not always full syndromic major depression. Even less severe depressive states can cause considerable disability, demoralisation, and increase the likelihood of a more complete relapse that may result in hospitalisation.

Treatment progress tends to be hindered by substance misuse, repeated relapses, gaps in pharmacotherapy and psychosocial disruptions. Prognosis appears to be better for patients in continued treatment that includes pharmacotherapy, psychological and social interventions, exercise, social rhythm therapy, and effective work and social rehabilitation.

Diagnosis of bipolar disorder requires at least one episode of mood elevation, either mania or hypomania. However, the dominant and most disabling phase of this illness is depression. Establishing the correct diagnosis is important as the prognosis is different to that for major depressive disorder, and treatments are generally different. Diagnosis may not be possible on first presentation of depression, but only made after a subsequent mood elevation. Clinicians should review diagnoses regularly, and remain open to bipolar diagnoses as it is possible to confuse these with major depressive disorder, schizophrenia and substance misuse. Corollaries of effective diagnosis are an informed patient and appropriate treatments, with the potential for better outcomes.

1 Diagnosis of bipolar disorder