A systematic review of interventions in the early course of bipolar disorder I or II: a report of the International Society for Bipolar Disorders Taskforce on early intervention.

BACKGROUND: Given the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness course. We conducted a systematic review of the effectiveness of interventions in the early course of BD I or II. METHODS: We completed a systematic search on MEDLINE, PsycINFO, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL and Google Scholar from 1/1/1979 till 14/9/2022. We included controlled trials examining intervention effects on symptomatic, course, functional and tolerability outcomes of patients in the 'early course' of BD I or II. We classified patients to be in early course if they (a) were seeking help for the first time for a manic episode, (b) had a lifetime history of up to 3 manic episodes, or (c) had up to 6 lifetime mood episodes. Evidence quality was assessed using the GRADE approach. RESULTS: From 4135 unique publications we included 25 reports representing 2212 participants in 16 randomized studies, and 17,714 participants from nine non-randomized studies. Available evidence suggested that in early illness course, lithium use was associated with lower recurrence risk compared with other mood stabilizers. Mood stabilizers were also associated with better global functioning, compared with the use of antipsychotics in the medium term. While summative findings regarding psychological therapies were limited by heterogeneity, family-focused and cognitive-behavioral interventions were associated with reduced recurrence risk or improved symptomatic outcomes. There was some evidence that the same pharmacological interventions were more efficacious in preventing recurrences when utilized in earlier rather than later illness course. CONCLUSIONS AND RECOMMENDATIONS: While there are promising initial findings, there is a need for more adequately powered trials to examine the efficacy and tolerability of interventions in youth and adults in early illness course. Specifically, there is a compelling need to compare the relative benefits of lithium with other pharmacological agents in preventing recurrences. In addition to symptomatic outcomes, there should be a greater focus on functional impact and tolerability. Effective pharmacological and psychological interventions should be offered to those in early course of BD, balancing potential risks using shared decision-making approaches.

Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

BACKGROUND: The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy. METHOD: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments. RESULTS: Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10-20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes. CONCLUSIONS: Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

Rumination, gender, and depressive symptoms associated with caregiving strain in bipolar disorder.

OBJECTIVE: To evaluate the associations between indices of caregiving strain, ruminative style, depressive symptoms, and gender among family members of patients with bipolar disorder. METHOD: One hundred and fifty primary caregivers of patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) participated in a cross-sectional study to evaluate the role of ruminative style in maintaining depressive symptoms associated with caregiving strain. Patient lifetime diagnosis and current episode status were evaluated by the Affective Disorder Evaluation and the Clinical Monitoring Form. Caregivers were evaluated within 30 days of the patient on measures of family strain, depressive symptoms, and ruminative style. RESULTS: Men and women did not differ on depression, caregiver strain, or ruminative style scores. Scores suggest an overall mild level of depression and moderate caregiver strain for the sample. Greater caregiver strain was significantly associated (P<0.05) with rumination and level of depressive symptoms, controlling for patient clinical status and demographic variables. Rumination reduced the apparent association between strain and depression by nearly half. Gender was not significantly associated with depression or rumination. CONCLUSION: Rumination helps explain depressive symptoms experienced by both male and female caregivers of patients with bipolar disorder. Interventions for caregivers targeted at decreasing rumination should be considered.

Personality and bipolar disorder: dissecting state and trait associations between mood and personality.

BACKGROUND: Some personality characteristics have previously been associated with an increased risk for psychiatric disorder. Longitudinal studies are required in order to tease apart temporary (state) and enduring (trait) differences in personality among individuals with bipolar disorder (BD). This study aimed to determine whether there is a characteristic personality profile in BD, and whether associations between BD and personality are best explained by state or trait effects. METHOD: A total of 2247 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder study completed the NEO Five-Factor Inventory administered at study entry, and at 1 and 2 years. RESULTS: Personality in BD was characterized by high neuroticism (N) and openness (O), and low agreeableness (A), conscientiousness (C) and extraversion (E). This profile was replicated in two independent samples, and openness was found to distinguish BD from major depressive disorder. Latent growth modeling demonstrated that manic symptoms were associated with increased E and decreased A, and depressed symptoms with higher N and lower E, A, C and O. During euthymic phases, high N and low E scores predicted a future depression-prone course. CONCLUSIONS: While there are clear state effects of mood on self-reported personality, personality variables during euthymia predict future course of illness. Personality disturbances in extraversion, neuroticism and openness may be enduring characteristics of patients with BD.

Correlates of subjective and objective burden among caregivers of patients with bipolar disorder.

OBJECTIVE: We examined the relationship between mood symptoms and episodes in patients with bipolar disorder and burden reported by their primary caregivers. METHOD: Data on subjective and objective burden reported by 500 primary caregivers for 500 patients with bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were collected using semistructured interviews. Patient data were collected prospectively over 1 year. The relationship between patient course and subsequent caregiver burden was examined. RESULTS: Episodes of patient depression, but not mood elevation, were associated with greater objective and subjective caregiver burden. Burden was associated with fewer patient days well over the previous year. Patient depression was associated with caregiver burden even after controlling for days well. CONCLUSION: Patient depression, after accounting for chronicity of symptoms, independently predicts caregiver burden. This study underscores the important impact of bipolar depression on those most closely involved with those whom it affects.

Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders.

BACKGROUND: The impact of anxiety disorders has not been well delineated in prospective studies of bipolar disorder. AIMS: To examine the association between anxiety and course of bipolar disorder, as defined by mood episodes, quality of life and role functioning. METHOD: A thousand thousand out-patients with bipolar disorder were followed prospectively for 1 year. RESULTS: A current comorbid anxiety disorder (present in 31.9% of participants) was associated with fewer days well, a lower likelihood of timely recovery from depression, risk of earlier relapse, lower quality of life and diminished role function over I year of prospective study. The negative impact was greater with multiple anxiety disorders. CONCLUSIONS: Anxiety disorders, including those present during relative euthymia, predicted a poorer bipolar course. The detrimental effects of anxiety were not simply a feature of mood state. Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course.

Family transactions and relapse in bipolar disorder.

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.

Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy.

BACKGROUND: Few studies have examined the combined effects of psychosocial treatment and pharmacotherapy for bipolar disorder. This study used a randomized, controlled design to examine a 9-month, manual-based program of family-focused psychoeducational treatment (FFT). METHODS: Bipolar patients (N = 101) were recruited shortly after an illness episode and randomly assigned to 21 sessions of FFT (n = 31) or to a comparison treatment involving two family education sessions and follow-up crisis management (CM; n = 70). Both treatments were delivered over 9 months; patients were simultaneously maintained on mood stabilizing medications. Patients were evaluated every 3 months for 1 year as to relapse status, symptom severity, and medication compliance. RESULTS: Patients assigned to FFT had fewer relapses and longer delays before relapses during the study year than did patients in CM. Patients in FFT also showed greater improvements in depressive (but not manic) symptoms. The most dramatic improvements were among FFT patients whose families were high in expressed emotion. The efficacy of FFT could not be explained by differences among patients in medication regimes or compliance. CONCLUSIONS: Family-focused psychoeducational treatment appears to be an efficacious adjunct to pharmacotherapy for bipolar disorder. Future studies should evaluate family treatment against other forms of psychotherapy matched in amount of therapist-patient contact.

Difficulty in implementing a family intervention for bipolar disorder: the predictive role of patient and family attributes.

Family affect was examined as a predictor of difficulty implementing a 9-month, manual-based, psychoeducational family therapy for recently manic bipolar patients. Prior to therapy, family members were administered measures to assess both their expressed emotion and affective behavior during a family interaction task. Following family treatment, both therapists and independent observers rated the overall difficulty of treating the family, and therapists also rated each participant's problem behaviors during treatment, in the areas of affect, communication, and resistance. Therapists regarded affective problems among relatives and resistance among patients as central in determining the overall difficulty of treating the family. Relatives' critical behavior toward patients during the pretreatment interaction task predicted both independent observers' ratings of overall treatment difficulty and therapists' perceptions of relatives' affective problems during treatment. Moreover, patients' residual symptoms predicted independent observers' ratings of overall difficulty and therapists' perceptions of patients' resistance to the family intervention. Results suggest that difficulties in conducting a manual-based family intervention can be predicted from systematic, pretreatment family and clinical assessment.

Psychosocial interventions for bipolar disorder.

Patients with bipolar disorder are prone to recurrences even when they are maintained on lithium or anticonvulsant regimens. The authors argue that the outpatient treatment of bipolar disorder should involve both somatic and psychosocial components. Psychosocial interventions can enhance patients' adherence to medications, ability to cope with environmental stress triggers, and social-occupational functioning. Family and marital psychoeducational interventions and individual interpersonal and social rhythm therapy have received the most empirical support in experimental trials. These interventions, when combined with medications, appear effective in improving symptomatic functioning during maintenance treatment. A beginning literature also supports the utility of individual cognitive-behavioral and psychoeducational approaches, particularly in enhancing medication adherence. Identifying the optimal format for psychosocial treatments and elucidating their mechanisms of action are topics for further study.

Expressed emotion and attributions in the relatives of bipolar patients: an analysis of problem-solving interactions.

Among the relatives of schizophrenic and depressed patients, high expressed emotion (EE) attitudes are associated with "controllability attributions" about the causes of patients' symptoms and problem behaviors. However, previous studies have judged EE attitudes and causal attributions from the same assessment measure, the Camberwell Family Interview (CFI; C. E. Vaughn & J. P. Leff, 1976). The authors examined causal attributions among relatives of 47 bipolar patients, as spontaneously expressed to patients in family problem-solving interactions during a postillness period. Relatives rated high EE during the patients' acute episode (based on the CFI) were more likely than relatives rated low EE to spontaneously attribute patients' symptoms and negative behaviors to personal and controllable factors during the postillness interactional assessment. Thus, the EE-attribution linkage extends to the relatives of bipolar patients evaluated during a family interaction task.

Psychosocial factors in the course and treatment of bipolar disorder: introduction to the special section.

Bipolar disorder is associated with high rates of relapse and high social and economic costs, even when patients are maintained on proper pharmacotherapy. The background and rationale are offered here for a series of articles that address the role of psychosocial agents in the course of bipolar disorder and psychosocial treatments as adjuncts to pharmacotherapy in the disorder's outpatient maintenance. It is argued that stressful life events and disturbances in social-familial support systems affect the cycling of the disorder against the backdrop of genetic, biological and cognitive vulnerabilities. Current models of psychosocial treatment focus on modifying the effects of social or familial risk factors as an avenue for improving the course of the disorder.

Bipolar disorder and family communication: effects of a psychoeducational treatment program.

Family psychoeducational programs are efficacious adjuncts to pharmacotherapy for patients with schizophrenic and bipolar disorders, but little is known about what these programs change about families. The authors assessed changes in face-to-face interactional behavior over 1 year among families of bipolar patients who received a 9-month family-focused psychoeducational therapy (FFT; n = 22) or crisis management with naturalistic follow-up (CMNF; n = 22), both administered with maintenance pharmacotherapy. Members of families who received FFT showed more positive nonverbal interactional behavior during a 1-year posttreatment problem-solving assessment than families who received CMNF, although no corresponding decreases were seen in negative interactional behaviors. The positive effect of family treatment on patients' symptom trajectories over 1 year was partially mediated by increases in patients' positive nonverbal interactional behaviors during this same interval.

Developing family psychoeducational treatments for patients with bipolar and other severe psychiatric disorders. A pathway from basic research to clinical trials.

Developing family treatments for patients with severe and persistent psychiatric disorder begins at the basic research level, through identifying psychosocial variables that have prognostic significance. Treatment protocols informed by this basic research can then be designed, manualized, and piloted. Next, the efficacy of a new treatment is examined, first in a randomized trial and then, if successful, in a community effectiveness study. We describe this treatment development pathway in a population for whom family attributes have prognostic importance: patients with bipolar affective disorder. The methodological complexities of psychosocial treatment studies are many. Moreover, the results of these studies often reflect interactions between treatment, process, and outcome variables.

Expressed emotion and interactional patterns in the families of bipolar patients.

The predictive validity of expressed emotion (EE) may derive in part from its relationship to important interactional processes in families of patients with major psychiatric disorders. The authors examined the relationship between relatives' EE attitudes, assessed during patients' bipolar, manic, or mixed episodes, and the interactional behavior of bipolar patients (n = 48) and their relatives as revealed in problem-solving discussions during the postepisode period. High-EE relatives were more verbally negative than low-EE relatives in these discussions. Patients from high-EE families were more nonverbally negative than those from low-EE families, whereas patients from low-EE families were more nonverbally positive than those from high-EE families. Sequential analyses revealed that high-EE families engage in negative interchanges of up to 3 volleys. Thus, levels of EE are associated with stressful patterns of interaction between bipolar patients and their relatives during the postepisode period.

Evaluating therapist competency and adherence to behavioral family management with bipolar patients.

The present study assessed fidelity to the behavioral family management (BFM) model for treating bipolar disorder patients and their families. The BFM Therapist Competency/Adherence Scale (BFM-TCAS) was developed to evaluate clinicians' competency and adherence to BFM, as outlined by Miklowitz' (1989) BFM Manual for use with bipolar patients. Therapist competency and treatment adherence was also evaluated with regard to two family characteristics: overall level of family difficulty and family expressed emotion (EE) status. The BFM-TCAS was used to code 78 videotaped sessions of 26 families with a bipolar member, selected from a larger treatment study of bipolar disorder patients. The findings suggest that, overall, clinicians adhered closely to the BFM manual. Specific areas in which there was high competency and treatment adherence were (a) skill in conveying factual information about bipolar illness, (b) establishment of a therapeutic environment, and (c) ability to take command of therapy sessions. The one area in which there was less competency and relatively weak adherence to the manual was the use of between-session homework assignments to assist families in mastering the BFM exercises. Results of this study also suggest that, for the most part, therapist competency and adherence ratings were not related to overall level of difficulty or to family EE status.

Global assessment of relational functioning scale (GARF): II. Reliability and validity in a sample of families of bipolar patients.

The companion article by the Group for the Advancement of Psychiatry (GAP) Committee on the Family (see p. 155, this issue) describes the development of the Global Assessment of Relational Functioning (GARF) scale. The present study evaluated the reliability and concurrent validity of a manualized version of the GARF in recently episodic bipolar patients (N = 73) participating with family members in laboratory interaction tasks. The GARF was applied with high reliability by raters with little clinical experience. GARF ratings discriminated between families rated high and low in expressed emotion, with families rated as high in emotional overinvolvement showing the lowest relational functioning scores. GARF scores also correlated with affective negativity scores derived from the interactional task-based affective style and coping style coding systems. However, relational ratings were independent of levels of concurrent symptoms or illness chronicity among individual patients. GARF ratings may inform the treatment plans for patients with psychiatric disorders, but the optimal methods of data collection and rater training must be determined.

Psychotherapy in combination with drug treatment for bipolar disorder.

There is a new movement toward delivering manualized, empirically validated psychotherapies in combination with pharmacologic maintenance in the outpatient treatment of bipolar disorder. This article describes the specific goals of psychotherapy with bipolar patients: modifying social risk factors, enhancing medication adherence, increasing the patient's and family's willingness to accept the reality of the disorder, and reducing suicidal risk. It also reviews the nature and underlying assumptions for two new psychotherapies: a family psychoeducational treatment and an individual treatment. Problems in delivering new treatments in the era of managed care, and some solutions to these problems, are also discussed.

Nonverbal interactional behavior in the families of persons with schizophrenic and bipolar disorders.

Whereas verbal interactional behaviors have been repeatedly found to distinguish the families of persons with and without major psychiatric disorders, there has been comparatively little examination of the discriminative value of nonverbal interactional behaviors. We developed the Nonverbal Interactional Coding System to measure "affiliative" and "distancing" nonverbal behaviors in 18 schizophrenic and 18 bipolar patients and their parents during 10-minute interactions conducted during a posthospital period. Bipolar patients and their parents displayed affiliative nonverbal behaviors ("illustrator gestures" or "prosocial behaviors") for longer durations than schizophrenic patients and their parents. In contrast, parents of schizophrenic patients displayed distancing nonverbal behaviors (looking away) for longer durations than those of bipolar patients. The nonverbal interactional data added to the statistical strength of patients' and parents' verbal interactional data in distinguishing between these diagnostic groups. Nonverbal interactional behaviors are important variables to consider in interventions aimed at improving the communication skills of families coping with psychiatric disorders.

New psychosocial treatments for the outpatient management of bipolar disorder.

The psychosocial treatment of bipolar disorder has the potential to augment the efficacy of outpatient pharmacotherapy if it succeeds in enhancing the protective effects of the social and familial environment and the patient's adherence to drug regimes. We describe two manual-based psychotherapies under evaluation in controlled clinical trials: a family-focused psychoeducational treatment and an individual, interpersonally-oriented psychotherapy. Both target recently ill patients and are delivered in combination with standard pharmacotherapies on an outpatient basis. Results from the ongoing clinical trials suggest high patient retention rates for both models over the first year of treatment. Future research should focus on the appropriate sequencing of pharmacologic and psychosocial treatments, and the conditions under which psychosocial treatment will be most effective.