Early Intervention Works in Schizophrenia: Also Needed in Bipolar Disorder
For twenty years, evidence has shown that early intervention can ameliorate many of the adverse consequences of schizophrenia. In a 2018 article in the journal Annual Review of Clinical Psychiatry titled “Transforming the treatment of schizophrenia in the United States: The RAISE Initiative,” Lisa B. Dixon and colleagues described the importance of early intervention in schizophrenia. RAISE stands for Recovery After an Initial Schizophrenia Episode. Dixon and colleagues emphasize that shortening the time that a patient’s psychosis goes untreated, which averages 74 months, is critical to achieving good outcomes. In parallel to these consistent findings, researchers of bipolar disorder (including this editor Robert M. Post and colleagues) have found that an increased length of the interval before treatment is initiated in childhood-onset bipolar disorder is associated with a poor outcome in adulthood.
The RAISE program consists of four interventions: personalized psychopharmacology using a computerized decision support system, individual resilience therapy, family psychoeducation and therapy, and supportive employment and education. Compared with patients receiving standard treatments, patients who participated in the RAISE program showed greater improvements on almost all measures, including the Heinrichs-Carpenter Quality of Life Scale (main outcome), the Calgary Depression Scale for Schizophrenia, the Positive and Negative Syndrome Scale, treatment duration, and engagement in work and school. Moreover, the improvements were more substantial among patients with a shorter duration of untreated psychosis.
Editor’s Note: These findings are of great importance in their own right, but they also have great implications for treatment and research efforts in bipolar disorder. A 2013 randomized study by Lars Kessing and colleagues published in the British Journal of Psychiatry found that in bipolar patients hospitalized for a first or second episode of mania, two years of comprehensive treatment with psychotherapy, pharmacotherapy, and illness education that included mood monitoring and early symptom recognition was vastly superior to typical treatment, and this held true even six years later. In a 2014 article in the Journal of Clinical Psychiatry and a 2016 article in the journal Bipolar Disorders, researcher Jan Marie Kozicky and colleagues reported that in patients hospitalized with a first episode of mania, cognitive functioning and brain imaging abnormalities, respectively, returned to normal over the next year only if the patients experienced no further mood episodes. The message is clear: we must treat the first episode of mania comprehensively to avoid long-term deterioration, which occurs as a function of the number of episodes of mania or depression a patient experiences. However, this early multimodal approach is rarely taken in the US.
In schizophrenia, Dixon and colleagues noted that: “After the RAISE study reports were made available, Congress allocated additional funding to the community mental health …program, leading to growth in the number of…programs across the United States; they were expected to reach 48 states in 2018.”
The contrast between these efforts in schizophrenia and their virtual absence in bipolar disorder is incomprehensible and tragic. Studies in early schizophrenia have been funded for 25 years, while almost none have been funded in bipolar disorder, even in recent years. Community mental health programs for early schizophrenia will soon exist in 48 states; for patients with bipolar disorder there are no programs available in any state that I am aware of. The incidence of bipolar is about three times that of schizophrenia, and the long-term outcomes are often as devastating in bipolar disorder as in schizophrenia. There is a high incidence of drug abuse; social, educational and occupational deficits; and suicide in bipolar disorder. Early intervention with the many safe supplements, nutraceuticals, and well-tolerated drugs that are currently available to adult patients should be studied in young people with bipolar disorder, but such studies neither being funded nor conducted.
The reality is that childhood-onset bipolar disorder is poorly recognized and treated in the US, largely because of a paucity of treatment-related studies and knowledge about the best options for these young patients. If a reader of the BNN knows how to influence advocacy groups, leaders in the Substance Abuse Mental Health Services Administration (SAMHSA) and the National Institutes of Mental Health (NIMH), or influential politicians, it would be useful to take the initiative in bringing some of these deficits and disparities to their attention. Something must be done; ideas about how to do it are welcome. My own efforts to get funding for a childhood-onset bipolar research network in collaboration with such luminaries in the field as David Miklowitz (UCLA), Kiki D. Chang (Stanford University), Boris Birmaher (University of Pittsburg), Benjamin Goldstein (Stonybrook Research Institute), Eric Youngstrom (UNC, Chapel Hill), Soledad Romero (Hospital Clinic of Barcelona), and Josefina Castro Fornieles (University of Barcelona) have not been successful. We will keep trying, but the field needs to reach beyond the many investigators who are advocating for more treatment research to other people with more influence.
Psychoeducation Is a Must for Bipolar Disorder
In 2018, researcher S.A. Soo and colleagues published a systematic review in the Journal of Clinical Psychiatry that analyzed findings from 40 randomized studies of psychoeducation for the management of bipolar disorder and compared the results for different types of psychoeducation: group, family, individual, and internet-based. Most of the randomized controlled trials (28 of 40 studies, 70.0%) assessed group or family psychoeducation, which had many benefits, while studies of individual or internet-based psychoeducation tended to be inconsistent.
The findings: “Group psychoeducation was associated with reduced illness recurrences, decreased number and duration of hospitalizations, increased time to illness relapse, better treatment adherence, higher therapeutic lithium levels, and reduced stigma. Family psychoeducation was associated with reductions in illness recurrence, hospitalization rates, and better illness trajectory as well as increased caregiver knowledge, skills, support, and sense of well-being and reduced caregiver burden.”
Editor’s Note: Given these results, it appears that group or family psychoeducation is a critical component to good care. Soo and colleagues suggest that future studies should directly compare different types of psychoeducation to each other to evaluate whether specific benefits are useful at various stages of illness.
Therapy Reduces Relapses, Promotes Medication Adherence
A 2017 meta-analysis published in the British Journal of Psychiatry indicates that psychosocial interventions were linked to reduced relapse rates, better adherence to medication, and other benefits in people with bipolar disorder. The meta-analysis by researcher Mary Lou Chatterton and colleagues evaluated data from 41 studies with a total of 3,119 participants. The studies examined psychosocial interventions such as cognitive-behavioral therapy, psychoeducation, and family-focused therapy compared to treatment as usual.
Chatterton and colleagues found that interventions that targeted family members who act as caregivers reduced manic and depressive relapse rates. Combined psychoeducation and cognitive-behavioral therapy was more successful than any other intervention, and had a large effect in reducing symptoms of mania. This combination also improved general functioning. Psychoeducation alone and in combination with cognitive behavioral therapy reduced medication non-adherence. Unfortunately, no intervention reduced depressive symptoms.
Psychotherapy Improves Outcomes for People with Bipolar Disorder
Studies have shown that therapy can be helpful for people with bipolar disorder. In a 2016 article in the British Journal of Psychiatry, researchers led by M. Oud described the findings of their systematic review of studies evaluating different types of therapy for bipolar disorder. The research team reviewed the findings of 55 randomized controlled trials of psychotherapeutic interventions that included a total of 6,010 adult participants with bipolar disorder. The team found moderate-quality evidence that psychological interventions reduced relapses following treatment, and that collaborative care reduced hospital admissions for adults with bipolar disorder. Oud and colleagues found lower-quality evidence that group interventions reduced depression relapses following treatment, and that family psychoeducation reduced symptoms of depression and mania.
The reseachers concluded that there is evidence that therapy can be helpful for people with bipolar disorder. Since some of the evidence was of low quality, more research is needed to identify the most effective therapies for different phases of bipolar disorder.
Editor’s Note: The data are clear that therapy is helpful. In particular, one approach worth emulating is that described in an article by Lars V. Kessing and colleagues in the British Journal of Psychiatry in 2013. They found that comprehensive care in an outpatient mood disorder clinic, which included psychotherapy, psychoeducation, mood monitoring, and drug treatment, reduced relapses significantly compared to treatment as usual.
Collaborative Care and Education Reduces Bipolar Depression
There is increasing evidence that patients with bipolar disorder benefit from special programs or clinics designed to teach them skills to cope with their illness. A 2015 article by Trijntje Y.G. van der Voort and colleagues in the British Journal of Psychiatry evaluated the effectiveness of a Dutch program that provided collaborative care to people with bipolar disorder.
One hundred thirty-eight patients in an outpatient clinic were randomized to receive either treatment as usual or a program of nurse-provided collaborative care that included psychoeducation, problem-solving treatment, systematic relapse prevention contracts, and monitoring of outcomes. These services were managed by mental health nurses. Those patients who received collaborative care had significantly less time with depressive symptoms at the 6-month and 12-month marks, and less severe depressive symptoms at 12 months (all findings with p values less than .01).
There was no significant difference in manic symptoms or treatment adherence. The authors suggest that collaborative care improves treatment for people with bipolar disorder, especially depression, which is most closely linked to impaired quality of life and disability.
Editor’s Note: Given this study and about a dozen others like it, it is time to conclude that psychoeducation and other components of collaborative care noted here are critical to the long-term management of bipolar disorder. Patients and their family members should insist that this be a part of routine care.
Traditional Antidepressants Are Not Effective in Bipolar Depression
Bipolar illness affects 4.5% of the US population. According to researcher Kathleen Merikangas, 1.0% have bipolar I disorder, 1.1% have bipolar II disorder, and the remainder have subthreshold symptoms. Mark Frye, Chairman of the Department of Psychiatry at the Mayo Clinic, gave a lecture on antidepressants in bipolar illness at the 2014 meeting of the American Psychiatric Association.
The newest data from meta-analyses indicate that traditional antidepressants that are effective in unipolar depression are not effective in bipolar depression. Some patient groups, especially those with very early onset depression and mixed depression, are at increased risk of switching into mania and making a suicide attempt while taking antidepressants.
Unipolar depressed patients with a genetic variation that produces a short form of the serotonin transporter (5HT-LPRs/s) are at increased risk for depression in adulthood following a history of childhood adversity, and tend to respond less well to antidepressants. Frye found that 5HT-LPRs/s is weakly associated with switching into mania when antidepressants are given to patients with bipolar depression.
At the same symposium, researcher Mike Gitlin reviewed data on combination therapy, which is rapidly becoming the norm, indicating that in most circumstances, it is superior to monotherapy.
Researcher David Miklowitz reviewed the impressive data on the superiority of most forms of targeted psychotherapy or psychoeducation compared to treatment as usual for bipolar depression. He noted his own finding that Family Focused Therapy (FFT) not only is effective in adolescents and adults with bipolar disorder, but also in reducing illness and dysfunction in those with prodromal disorders (such as depression, cyclothymia, and bipolar not otherwise specified) in situations where there is a family history of bipolar disorder.
Eight components of FFT are:
- Recognition of prodromal symptoms and development of treatment strategies for them.
- Recognition and management of stress and triggers using cognitive restructuring.
- Development of a relapse prevention plan and rehearsal of what to do.
- Regularization of sleep.
- Encouragement of treatment adherence with an eye to a good future.
- Enhancement of emotional self-regulation skills, including cognitive restructuring.
- Improvement of family relationships and communication.
- Education about substance abuse avoidance and treatment for that and other comorbidities.
Many of these are also key components of group psychoeducation, cognitive-behavioral therapy, and interpersonal and social rhythms therapy, and all of these are effective in treating and preventing bipolar depression compared to treatment as usual. It is noteworthy that in the research of Francesc Colom, 90% of patients randomized to treatment as usual relapsed within 24 months, while psychoeducation was highly effective in preventing relapses over the next five years.
This editor (Robert M. Post), the discussant for the symposium, emphasized that the main take-away messages of the speakers were: use more lithium, use more caution and fewer antidepressants in treating bipolar depression, use more combination therapy for acute illness and for maintenance, and definitely use more psychotherapy. Read more
Psychoeducation and Medication Better for Depression than Medication Alone
There is mounting evidence that medication alone is not enough to bring about full remission in bipolar disorder. At the 2014 meeting of the International Society for Bipolar Disorders, researcher T.A. Batista et al. presented evidence that psychoeducation combined with medication may be more helpful than medication alone. In the research team’s randomized controlled study of 30 patients with bipolar I or bipolar II disorder, eight weekly home visits that included both pharmacotherapy and psychoeducation produced more favorable results than eight weekly visits with pharmacotherapy alone. Those patients who received psychoeducation had reduced depression scores and increased medication adherence compared to the others.
Editor’s Note: There are now about a dozen controlled studies indicating the efficacy of psychoeducation. It is time that systematic delivery of psychoeducation, either in a private practice setting, a clinic, or the home environment, become a mandatory part of the treatment of bipolar disorder.
Researchers Vieta and Colom of Barcelona have some of the best positive longitudinal data on psychoeducation versus treatment as usual and find benefits lasting five years or more. Key components of psychoeducation include learning about disease course and medications, developing a careful monitoring system, and recognition of early signs and symptoms of an impending manic or depressive episode, and key drug treatment maneuvers that could be instituted should such early warning signs develop.
