Prospects for early intervention in bipolar disorders
2007-05-01

The prospects for early intervention in bipolar disorders (BD) hinge on our ability to identify individuals at risk of developing BD at the earliest possible moment in time and the capacity to provide targeted treatments that specifically prevent the onset or recurrence of BD episodes. This is no small task – research in BD is not only about two decades behind similar work in schizophrenia, but also there are uncertainties about the identification of BD prodromes, the diagnosis of BD in children and adolescents, and the timing of introduction of and the content of care and treatment packages. This editorial highlights some of what we know, what we need to understand more, and ends by offering some thoughts on what treatment interventions may logically improve the clinical prognosis and quality of life of individuals in the early stages of their BD career. To discuss early intervention it is important to distinguish between primary, secondary and tertiary prevention and the goals of each. The most rational target population for primary prevention would be those at high risk for BD who do not yet meet formal diagnostic criteria. Although several studies have shown that first-degree relatives of patients with BD are at higher risk for BD than the general population, this genotype is neither a necessary nor a sufficient condition. The endophenotyope may also be predicted by temperament or personality styles, particularly mood lability, affective dysregulation, and early life events such as maternal loss or cumulative stress during childhood and adolescence.1–6 Of the risk factors identified, few have been studied prospectively and no study has yet reported adequate sensitivity and specificity rates to make intervention realistic. If primary prevention is defined as preventing the switch from a hypothesized risk status into diagnosable BD, then primary prevention is currently non-existent – the first step will be to define and evaluate a set of reliable risk indicators that lead to the development of a more coherent theoretical framework. This would allow specific treatment goals to be developed rather than reliance on non-specific, generic targets such as stress reduction, enhancing self-esteem or improving problem-solving skills.7 Secondary prevention is often used to refer to the treatment of acute symptoms meeting syndromal level. What are the chances for early intervention with new cases of BD? This question is complex – by definition secondary prevention targets early treatment of individuals with a disorder – but in reality many individuals who go on to develop BD have had symptoms or problems that precede the diagnosis by about 7–10 years.8 We do not know if the consequences of this delay in BD will be similar to schizophrenia, where duration of untreated psychosis may predict future prognosis.9 In BD this period of time does not necessarily indicate that the individual is untreated (as individuals often received interventions targeted at e.g. social anxiety problems, substance misuse or conduct disorder). The issue is more likely one of misdiagnosis or ‘missed diagnosis’ with consequent inappropriate treatment as the initial interventions would have been different or at least modified if the risk of or presence of BD was known. Disentangling this is by no means straightforward. First, the low specificity of symptoms (such as anxiety or depression) makes the prodrome of BD difficult to recognize.10 Second, symptoms viewed as specific by some researchers and clinicians are interpreted differently by others – this is clearly demonstrated by the differences between Europe and the USA regarding the diagnosis of children with concurrent symptoms of hyperactivity, attention deficit and mood lability: Europeans are more likely to favour a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) over BD in younger children, while American psychiatrists are more likely to favour the latter.11,12 There are also differences in opinion regarding the core phenomenology of mania in children and adolescents with Europeans suggesting euphoria is pathognomonic for the diagnosis, while the American classification system allows irritability to be a core mood state in this age group.13 In such an environment, clinicians have been accused of missing cases of BD on the one hand, and on the other of overdiagnosing and ‘medicalizing’ adolescent emotional turmoil. Similar problems arise when adolescents present with substance-related problems, conduct problems, or borderline or narcissistic traits. Clinicians may be offering ‘secondary prevention’ for these problems while unwittingly, and therefore less proficiently, providing ‘primary prevention’ for BD. Prospects for early intervention here relate to the clinicians’ capacity to remain mindful of the many ways in which BD may initially present and to constantly review and revise their provisional diagnosis and the treatment response of adolescents presenting in these many different ways. BD may evolve from these states and more typical symptoms may be revealed over time. Awareness of its early age of onset (median about 15–21 years) and ensuring its inclusion as a differential diagnosis to be considered may at least allow some cases to be identified earlier. A better option for secondary prevention of BD is identifying it as the underlying disorder when an individual presents with a major depressive episode (MDE), especially if this has an early onset. Of adolescents who present with a MDE 20–30% will develop BD, so if clinicians are more sensitive to the presence of features indicative of a greater likelihood of BD, they can adapt their proposed interventions accordingly. For example, a personal history of labile mood and fluctuating symptoms, a long history of sleep inefficiency, MDE of sudden onset and an atypical symptom profile (e.g. hypersomnia, motor retardation) may alert the clinician to a high risk of development of BD or a bipolar spectrum disorder.1,14 Family history is also important, with some suggestion that the level of loading (>3 first-degree relatives with BD or >3 generations having one or more affected relative) may be a stronger indicator than simply evidence of familiality on its own.15 What is not yet known, but early intervention service may help to discover, is whether these indicators act as individual or cumulative risk factors and whether the course of the disorder would be changed radically if treatment were targeted at BD at this presentation rather than the treatment of an acute MDE. In the interim, early intervention may be enhanced if clinicians ensure individuals with such a history do not disengage early from services, as ongoing monitoring of symptoms and coping skills at least keeps the door open to intervene if problems evolve into BD. Superficially, the prospects for early treatment interventions are easier to discuss than the prospects for early identification of cases. However, few treatment trials in BD have specifically targeted young adults or those with first-episode BD (an exception is the study by Feeny et al.).16 Although there is consensus that the earlier targeted treatment begins the better, what the most appropriate treatments are requires further clarification. It is interesting to note that clinicians involved in the day-to-day treatment of BD often view therapy as a luxury and medication as the absolute must. However, pharmacotherapy trials rarely target bipolar II or bipolar spectrum disorders, and it is a brave clinician who would try to convince an adolescent that they had a lifetime need for a mood stabilizer on the basis of one episode of MDE and the suspicion of a high risk of BD. Indeed, we would argue that there is a case for BD II being treated by a psychological therapy rather than medication is a young adult. Perhaps less controversial is the extrapolation to clinical practice of the findings of a large-scale multicentre randomized trial undertaken in the UK.17 This demonstrated a significant ‘dose–response’ effect, where the addition of cognitive therapy to usual psychiatric care and treatment was highly significantly more effective than usual treatment alone in improving many aspects of outcome including risk of relapse. The trial demonstrated that once BD was an established part of the individual’s life, with frequent relapses and typical complications such as persistent subsyndromal depressive symptoms, substance misuse, etc., it was no longer a realistic proposition to engage an individual in the process and achieve their key goals for change in a time-limited therapy. The case for therapy with or without medication as part of the intervention in early BD is hard to ignore – medication alone cannot help adjustment to the disorder, does not produce coping skills that never existed, cannot repair fragile self-esteem and will not teach individuals what they can or cannot control and does not help the family adapt. Indeed therapy may be needed simply to enable an individual who may benefit from medication to adhere with it over time. The important issue in early intervention in BD is to strike a balance between the desire to reduce acute distress and prevent or delay relapse versus the need to engender hope and to decatastrophize the fact that the existence of BD will have an impact on the individuals’ future. The general task of therapy is to help minimize how devastating or restrictive the diagnosis of BD is for the individual. But for therapy and medications to be better targeted at the spectrum of BD and its many presentations we need to be more sensitive to the possibility of the diagnosis clinically and more specific in our theoretical models of defining those at high risk of developing BD.