Improving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife).

BACKGROUND: Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD. METHODS: Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15-35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD. DISCUSSION: Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

OBJECTIVE: Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. METHOD: In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. RESULTS: Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. CONCLUSIONS: Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.

Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.

BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.

Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: baseline results in the first 180 help-seeking individuals assessed at the Dresden high-risk project.

BACKGROUND: Considering results from the early recognition and intervention in psychosis, identification and treatment of individuals with at-risk states for the development of bipolar disorders (BD) could improve the course and severity of illness and prevent long-term consequences. Different approaches to define risk factors and groups have recently been published, data on treatment options are still missing. METHODS: Help-seeking persons at the early recognition center in Dresden, Germany, were assessed with a standardized diagnostic procedure including following risk factors for BD: familial risk, increasing mood swings, subsyndromal (hypo)manic symptoms, specific sleep and circadian rhythm disturbances, anxiety/fearfulness, affective disorder, decreased psychosocial functioning, increasing periodic substance use, and attention-deficit/hyperactivity disorder. Based on symptomatology and current and/or life-time psychiatric diagnosis, subjects with an at-risk state were offered individual treatment options. RESULTS: Out of 180 referred and screened persons, 29 (16%) met criteria for at-risk state for BD. Altogether, 27 (93%) at-risk individuals fulfilled criteria for a current and/or life-time mental illness other than BD; 14 (48%) had received pharmacological and/or psychotherapeutic treatment in the past. Treatments recommended included psychoeducation (100%), psychotherapy alone (62%), pharmacotherapy alone (17%), and psychotherapy+pharmacotherapy (14%). CONCLUSIONS: To identify at-risk states for BD, a multifactorial approach including all known risk markers should be used. As most at-risk patients meet criteria for other mental disorders, the short- and long-term impact of different treatment strategies on symptomatic, functional and diagnostic outcomes requires detailed investigation. LIMITATIONS: Small sample size of at-risk individuals, lack of sufficient prospective data and control groups.

Psychotherapeutic interventions in individuals at risk of developing bipolar disorder: a systematic review.

AIM: Accumulating data show that patients with bipolar disorder (BD) experience substantial symptomatology months or years before full manifestation. Based on the need for early preventive interventions in BD as well as data suggesting effectiveness of psychotherapeutic interventions for BD, we aimed to review the evidence for psychotherapeutic treatments in help-seeking individuals considered at risk for BD (At-Risk-BD). METHODS: Searching PubMed and PsycINFO, clinical trial registries and recently published systematic reviews, a systematic review was performed of psychoeducational and psychotherapeutic intervention studies in At-Risk-BD individuals. RESULTS: Only three completed studies were identified, two of which were randomized trials (n = 77) and one was an open pilot study (n = 13). Two ongoing studies (projected n = 150 and n = 100, respectively) were found in trial registries. The available evidence suggests potential effectiveness of multi-family psychoeducational psychotherapy and family-focussed therapy for symptom reduction and prevention of BD conversion. CONCLUSIONS: Psychotherapeutic treatments are a reasonable starting point for At-Risk-BD subjects when symptom severity, distress and impairment are sufficiently significant to initiate treatment. Ongoing studies will further clarify the effectiveness and timing of psychotherapeutic interventions for At-Risk-BD individuals and whether or not they should be given alone or in conjunction with other treatments. Large multi-site studies with standardized procedures/manuals are needed to advance the field.