Is “early intervention” in bipolar disorder what it claims to be?

Malhi, Gin S; Morris, Grace; Hamilton, Amber; Outhred, Tim; Mannie, Zola

doi:10.1111/bdi.12576

Cited by 22 publications

(22 citation statements)

References 98 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until a decade ago, the focus was on effective acute treatment in adult patients with established illness. The timely review by Malhi provides an insightful appraisal of the relevant literature pertaining to early intervention in bipolar disorder. The article cautions that further advances should be based on rigorous evidence rather than on good intentions and what appear on the surface to be reasonable extrapolations from other psychiatric and medical illnesses.…”

mentioning

confidence: 99%

“…Once the clinical trajectory of developing bipolar disorder is charted for valid subtypes, intensive study of candidate biomarkers and genetically sensitive psychosocial risk processes can be mapped. As pointed out by Malhi, until this necessary groundwork is complete and replicated, the appropriateness and development of a staging framework, akin to that in oncology, seems premature—and should be based on evidence of emergent bipolar disorder rather than generalized from studies of early‐onset psychosis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Early intervention in bipolar disorders: Where we are now and need to go next

Duffy

2018

Bipolar Disorders

View full text Add to dashboard Cite

The notion of intervening early in a disease process to prevent onset, halt progression, decrease illness burden, and improve quality of life is a quintessential tenet of medical treatment. However, in contrast to other specialties such as oncology, early intervention is a relatively new focus in psychiatry. Until a decade ago, the focus was on effective acute treatment in adult patients with established illness. The timely review by Malhi 1 provides an insightful appraisal of the relevant literature pertaining to early intervention in bipolar disorder.The article cautions that further advances should be based on rigorous evidence rather than on good intentions and what appear on the surface to be reasonable extrapolations from other psychiatric and medical illnesses. As discussed, major obstacles to advancing early intervention include heterogeneity, different emergent illness trajectories across subtypes, and lack of diagnostic precision-especially early in the course.However, despite the challenges, there have been strides forward.In addressing heterogeneity, for example, an excellent response to long-term lithium prophylaxis has been key to identifying a more homogenous illness subtype characterized by an episodic course, good quality of remission, specific genetic and neurobiological findings, and a characteristic spectrum of illness segregating in family members representing the phenotype (ie episodic major depression, and bipolar I and II). Moreover, studies of the children of lithium-responsive and non-responsive bipolar parents demonstrate significant differences in the emergent illness course, further validating that they belong to distinctly different bipolar subtypes. 2The characterization of reliable illness trajectories in homogeneous high-risk subgroups is a fundamental and necessary step towards identifying specific prevention and early intervention targets.Once the clinical trajectory of developing bipolar disorder is charted for valid subtypes, intensive study of candidate biomarkers and genetically sensitive psychosocial risk processes can be mapped. As pointed out by Malhi 1 , until this necessary groundwork is complete and replicated, the appropriateness and development of a staging framework, akin to that in oncology, seems premature-and should be based on evidence of emergent bipolar disorder rather than generalized from studies of early-onset psychosis.The lack of precision in the bipolar diagnosis presents an obstacle for effective early intervention. For instance, evidence supports substantial instability of the diagnosis in first episode manic patients followed up a decade later, a lack of predictive significance of manic-like symptoms in adolescents, and nonspecific antecedent psychopathology characterizing the emergent course. Reliance solely on symptoms is a major contributor to the lack of diagnostic precision. Symptoms considered alone, without context or additional information about development, family history, and clinical course, are simply an insufficient evidential base on whi...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Early intervention in bipolar disorders: Where we are now and need to go next

Duffy

2018

Bipolar Disorders

View full text Add to dashboard Cite

show abstract

“…The authors raise the spectre of premature medication use to support their case . One can agree that more research is needed to guide such treatment, especially medication timing and sequence.…”

mentioning

confidence: 93%

“…One of the drivers of Malhi et al's pessimistic perspective on early intervention for those meeting criteria for bipolar disorder (BD) is the Hippocratic principle of ‘first do no harm’. Paradoxically, if their overly cautious prescription were followed, then more harm would likely occur through continuing neglect of young people with a substantial, immediate need for care .…”

mentioning

confidence: 99%

“…This uncertainty is used as a straw man by the authors, but it is by no means a fatal flaw as Duffy acknowledges. The authors channel staging when they state that ‘research involving pharmacotherapies should be refined to focus on perhaps more novel agents that target the potentially unfolding pathophysiology, rather than encouraging the earlier commencement and administration of potent medications designed to treat more chronic and severe phases of illness’ (p. 632).…”

mentioning

confidence: 99%

See 1 more Smart Citation

‘Is “early intervention” in bipolar disorder what it claims to be?’ Malhi et al

et al. 2018

View full text Add to dashboard Cite

One of the drivers of Malhi et al's 1 pessimistic perspective on early intervention for those meeting criteria for bipolar disorder (BD) is the Hippocratic principle of 'first do no harm'. Paradoxically, if their overly cautious prescription were followed, then more harm would likely occur through continuing neglect of young people with a substantial, immediate need for care. 2 Their conclusions derive from two familiar misunderstandings of the clinical staging model. Firstly, they have restricted their gaze within the silo of BD in considering how early intervention could be offered. Clinical staging in psychiatry uses a transdiagnostic framework, acknowledging the heterogeneity and overlap of early clinical phenotypes. Secondly, they misrepresent staging as requiring inevitable progression, rather than each stage connoting only a risk for progression with remission possible at any stage.The authors observe that the early-and late-stage bipolar phenotype has become blurred, and that there is a dimensional or porous aspect to the silo, a truth with a wider significance. Mental disorders are not static, sharply defined illnesses with separate aetiologies and courses, but rather overlapping syndromes that develop in stages, with common risk factors and mechanisms. The latter explains why most psychological interventions are transdiagnostic, and why clinicians often use medications 'off-label', challenging fictional discrete diseases reinforced by the Diagnostic and Statistical Manual of Mental Disorders (DSM), Food and Drug Administration (FDA) and pharmaceutical industry. Development of new diagnostic concepts, an important target of early intervention, will define new ways to inform treatment selection. Daily human experience involves periodic and sometimes intense, mercurial changes in mood, perception, salience and behaviour. Where prominent and sustained, they can be discerned as subclinical 'microphenotypes', which wax and wane, interact sequentially or become confluent, and may mature or stabilize towards pure or hybrid 'macrophenotypes.' The manic syndrome is just one of these macrophenotypes. Unlike current psychiatric diagnoses, staging recognizes that single or multiple persistent microphenotypes can justify a need for care on their immediate merits as well as the risk for progression to more familiar macrophenotypes. Such models ensure that interventions are proportional to both current need and the risk of future extension of the clinical phenotype and its consequences, while balancing risks of treatment according to the principle 'first do no harm'.The heterogeneity of BD is advanced by the authors as an argument that staging is unlikely to apply, but, seen in a transdiagnostic context, the opposite is the case. Staging acknowledges such phenotypic heterogeneity. The authors search for an elusive specificity too early. From a transdiagnostic perspective, early intervention addressing factors such as substance abuse, lifestyle and stress management is already feasible as Duffy 3 acknowledges, despite p...

show abstract

Effects of Family-Focused Therapy vs Enhanced Usual Care for Symptomatic Youths at High Risk for Bipolar Disorder

et al. 2020

View full text Add to dashboard Cite

IMPORTANCE Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths.OBJECTIVE To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms. DESIGN, SETTINGS, AND PARTICIPANTSThis multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first-or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019. INTERVENTIONS High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition. MAIN OUTCOMES AND MEASURESThe coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories.RESULTS All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (χ 2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ 2 = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank χ 2 = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories.CONCLUSIONS AND RELEVANCE Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01483391.

show abstract

Is “early intervention” in bipolar disorder what it claims to be?

Cited by 22 publications

References 98 publications

Early intervention in bipolar disorders: Where we are now and need to go next

Early intervention in bipolar disorders: Where we are now and need to go next

‘Is “early intervention” in bipolar disorder what it claims to be?’ Malhi et al

Effects of Family-Focused Therapy vs Enhanced Usual Care for Symptomatic Youths at High Risk for Bipolar Disorder

Contact Info

Product

Resources

About