Lithium-discontinuation-induced treatment refractoriness revisited.

BACKGROUND: Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). RESULTS: We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. CONCLUSIONS: There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy.

Predicting which intervention works better for whom: Moderators of treatment effect of Mindfulness-Based Cognitive Therapy and Positive Psychology Intervention in patients with bipolar disorder.

BACKGROUND: This study aimed to identify moderators of treatment effect (i.e. depressive symptoms and well-being) of Mindfulness-Based Cognitive Therapy (MBCT) and Positive Psychology Intervention (PPI) in patients with bipolar disorder. METHODS: Data were drawn from two multicenter randomized controlled trials investigating effectiveness of MBCT vs treatment as usual (TAU; n = 144) and PPI vs TAU (n = 97) in bipolar disorder. Outcomes were assessed at baseline, posttreatment, and 12 months after baseline. Data were analyzed using separate linear regression models, comparing the pooled MBCT or PPI outcomes to TAU, and comparing MBCT to PPI. RESULTS: The exploratory analyses not corrected for multiple comparisons showed a number of variables that were associated with stronger response to the interventions, including higher baseline anxiety, lower well-being, and lower levels of self-focused positive rumination, well-being, and self-compassion, and variables associated with a stronger response to either MBCT (higher levels of depression and anxiety and being married) or PPI (being male). After correcting for multiple testing, depressive symptoms appeared to be the most robust variable associated with better response to MBCT than PPI. LIMITATIONS: The RCTs handled slightly different enrollment criteria and outcome measures. CONCLUSIONS: The most robust finding is that patients with more severe symptomatology seem to benefit more from MBCT than PPI. CLINICAL IMPLICATIONS: This is a first step to improve personalized assignment of third-wave CBT interventions for patients with bipolar disorder. However, before definite treatment assignment criteria can be formulated and implemented in clinical practice, these findings should be replicated.

Bipolarity in Older individuals Living without Drugs (BOLD): Protocol and preliminary findings.

INTRODUCTION: Although clinical guidelines regard prophylactic medication as the cornerstone of treatment, it is estimated almost half of patients with bipolar disorder (BD) live without medication. This group is underrepresented in research but can provide indispensable knowledge on natural course, resilience and self-management strategies. We aim to describe the clinical phenotype of patients diagnosed with BD who have discontinued maintenance treatment. METHODS: The mixed-methods BOLD study included 58 individuals aged 50 years and over with BD that did not use maintenance medication in the past 5 years. A preliminary, quantitative comparison of clinical characteristics between BOLD and our pre-existing cohort of >220 older BD outpatients with medication (Dutch Older Bipolars, DOBi) was performed. RESULTS: BD-I, psychiatric comorbidities, number of mood episodes and lifetime psychotic features were more prevalent in BOLD compared to DOBi. BOLD participants had a younger age at onset and reported more childhood trauma. BOLD participants reported fewer current mood symptoms and higher cognitive, social, and global functioning. LIMITATIONS: Our findings may not be generalizable to all individuals diagnosed with BD living without maintenance medication due to selection-bias. CONCLUSION: A group of individuals exists that meets diagnostic criteria of BD and is living without maintenance medication. They appear to be relatively successful in terms of psychosocial functioning, although they do not have a milder clinical course than those on maintenance medication. The high prevalence of childhood trauma warrants further investigation. Future analyses will examine differences between BOLD and DOBi per domain (e.g. cognition, physical health, psychosocial functioning, coping).