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Bipolar disorder diagnosis, management face uncertainty, unmet needs

A review published in The Lancet Psychiatry discussed major unmet needs in bipolar disorder diagnosis and management, including interventions for at-risk and early-disease stages; identifying warning signs; preventing relapses; treatment; and decreasing excess mortality.

The researchers also stressed the importance of increasing targeted funding opportunities in bipolar disorder research, reporting that funding for bipolar disorder is low compared with other diseases with similar morbidity, mortality and global burden of disability.

“Even when successfully diagnosed, the management of bipolar disorder provides major challenges including how best to optimize treatment for an individual patient, and how to balance the benefits and risks of drug therapy,” Michael Bauer, MD, PhD, from the department of psychiatry and psychotherapy, Technische Universität Dresden, Germany, and colleagues wrote. “Despite an increasing number of treatments, full recovery is infrequent and incomplete symptomatic remission with a high degree of individual variability is often the clinical norm.”

In their review, experts from the European College of Neuropsychopharmacology Bipolar Network discussed important unmet clinical areas in bipolar disorder prevention, assessment and therapeutics as well as offered guidance addressing these needs.

Early intervention

Evidence is lacking from large, multicenter randomized trials in patients with first-episode bipolar disorder that compare effects of lithium with other maintenance mood stabilizers, and from randomized controlled trials that compare psychological interventions, according to the review. The researchers recommend that future research on early intervention in bipolar disorder focus on reducing comorbid general illness risk as natural causes of death — the most common cause of life-years lost from adolescence in the disorder.

In clinical settings, it’s common for patients to experience a delay in bipolar disorder diagnosis of 8 to 10 years. Although reaching an early diagnosis based on retrospective subjective recall in the absence of manifest manic symptoms and biomarkers may always present a challenge, clinical improvements can possibly be achieved with better recognition of early symptoms and higher quality clinical practice.

Treatment, long-term management

Careful management of long-term drug therapy initiation and dealing with patients’ beliefs is important for long-term adherence, Bauer and colleagues wrote. Some evidence supports psychosocial interventions to increase treatment adherence, such as family-focused therapy. Tools that personalize treatment may enhance the effectiveness of interventions as well.

The authors wrote that current treatment guidelines support the use of quetiapine for bipolar type I and type II depression; lurasidone for bipolar type I depression; and lamotrigine in bipolar type II depression, in combination with lithium in bipolar type I depression. They advised that psychosocial interventions could also be used along with medication for acute treatment and maintenance therapy of bipolar depression.

Treatment for patients who experience rapid cycling and poor long-term response must be addressed, according to the review. Combining several drugs with complementary mechanisms of action — like lithium and a second-generation antipsychotic — may be an option. Psychoeducation might be helpful, but there are no data from controlled trials in this subgroup.

Using precision medicine approaches, like those used in genome-wide association studies, shows potential for discovering more about the underlying disease mechanisms of bipolar disorder, Bauer and colleagues explained.

“With the developments in genetics and brain imaging methods, it is not unrealistic to develop prediction and stratification tools for clinical use in bipolar disorder,” they wrote. “Particularly, there is a clear need for developing brain imaging characteristics and molecular signatures in the blood for response to lithium treatment. Development of such biomarkers could represent potential tools that can be translated from research to clinical practice.”

In addition, identifying early warning signs of mood episodes in long-term therapy is critical for bipolar disorder. The experts recommend that early detection of prodromal states should be combined with increasing illness awareness, education on the negative effects of illegal drug use, enhancing treatment adherence and urging good habits related to sleep, diet and exercise.

“All together, this strategy will enable patients and caregivers to foster their ability to prevent further episodes and improve the overall outcome of the disorder,” they wrote.

Looking toward the future

There is a glaring lack of research on how to increase life expectancy in bipolar disorder, Bauer and colleagues wrote. Future studies must focus on decreasing the risk for comorbid general illnesses. Suicide prevention for people with bipolar disorder should also be addressed, as prior evidence has found that around 25% to 50% of patients with mood disorders attempt suicide.

Although there remain major gaps in knowledge on the basic mechanisms underlying bipolar disorder and the resulting unmet needs, Bauer and colleagues are hopeful there will be advancement soon. An increase in research funding is needed.

“The large-scale collaborative studies applying new methods will provide novel insights into disease mechanisms with the potential for the development of more targeted therapeutics,” they wrote. “Innovation with digital technology has a particularly great potential to improve treatment and secondary prevention, and it is expected to see such digital tools in ordinary clinical use within a few years.” – by Savannah Demko

Disclosures: Bauer reports consulting or speaker fees from Allergan, Aristo, Boehringer-Ingelheim, Janssen, Lilly, Lundbeck, Neuraxpharm, Otsuka, Pfizer, Servier and Takeda. Please see the study for all other authors’ relevant financial disclosures.