Research paperThe effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysis
Introduction
The global prevalence of bipolar disorder (BD) in primary care is 1.8% (Stubbs et al., 2016), and it is one of the leading causes of disability worldwide (Garland et al., 2016). BD is characterized primarily by recurring affective episodes of depression, (hypo)mania and mixed states. In addition, patients with BD often have impaired psychosocial functions, even when in remission (Garland et al., 2016). Even after drug treatment, up to 48.5% of patients with BD have been reported to experience relapses and/or recurrence of major affective episodes within a 2-year follow-up period (Perlis et al., 2006). Furthermore, even if these patients improve after acute episodes, pervasive depressive symptoms remain (Judd et al., 2003) in addition to the cognitive symptom of emotional regulation disability (Gruber, 2011). Several psychosocial interventions including interpersonal therapy, family therapy, and cognitive-behavioral therapy have been developed as adjunctive therapy to treat BD (Grande et al., 2016). Among these psychosocial interventions, psychoeducation, interpersonal therapy, family therapy, non-mindfulness based cognitive-behavioral therapy, and systematic care have been proven to be effective in preventing relapses, stabilizing episodes, and reducing episode length (Miklowitz, 2008, Miziou et al., 2015, Oud et al., 2016). For example, a recent meta-analysis by Oud et al. reported that individual psychological interventions could reduce the severity of depressive but not manic symptoms (standardized mean difference [SMD] = −0.23, 95% confidence interval [CI] = −0.41 to 0.05; SMD = −0.05, 95% CI = −0.35 to 0.25, respectively). Another study also suggested that these non-medical therapies could help in ameliorating core inter-episode symptoms (Opialla et al., 2015).
Recently, interest has grown in the potential of mindfulness-based interventions (MBIs) to improve outcomes of patients with psychiatric illnesses. MBIs are based on the premise of paying total attention on purpose in the present moment and non-judgmental attention to inner and outer experiences moment by moment (Kabat-Zinn, 1994). MBIs were first developed by Kabat-Zinn as mindfulness-based stress reduction (MBSR) in the 1970s to enhance the stress coping skills of patients with chronic pain (Kabat-Zinn, 1990). Later, MBIs were used as the core of mindfulness-based cognitive therapy (MBCT) by combining elements of MBSR and cognitive therapy in order to prevent relapses/recurrence of unipolar depressive episodes (Teasdale et al., 1995, Teasdale et al., 2000). For example, a recent meta-analysis which synthesized available evidence from 1329 participants found that MBCT reduced depressive relapse rates within a 60-week follow-up period compared to participants who did not receive MBCT (Kuyken et al., 2016). Another meta-analysis suggested that MBIs could also be effective as an adjunctive treatment for negative symptoms among patients with psychosis (Khoury et al., 2013).
However, relatively few studies have investigated the effect of MBIs on treatment outcomes in patients with BD. Uncontrolled (Biseul et al., 2016, Bos et al., 2014, Crane et al., 2008, Deckersbach et al., 2012, Howells et al., 2014, Miklowitz et al., 2009, Miklowitz et al., 2015, Murray et al., 2015, Perich et al., 2013a, Stange et al., 2011, Weber et al., 2010) and controlled trials (Ives-Deliperi et al., 2013, Perich et al., 2013b, Van Dijk et al., 2013, Williams et al., 2008) have shown that the combination of MBIs with pharmacotherapy and treatment as usual (TAU) can have beneficial effects for patients with BD. Furthermore, a previous functional magnetic resonance imaging study showed the potential involvement and beneficial effects of MBIs in specific neural circuits underlying emotional regulation (Opialla et al., 2015), which is one of the main core inter-episode symptoms in BD (Gruber, 2011). Conversely, other studies have found no significant effect of MBIs on depressive (Howells et al., 2014, Ives-Deliperi et al., 2013, Perich et al., 2013b, Weber et al., 2010), manic (Deckersbach et al., 2012, Perich et al., 2013b), or anxiety (Howells et al., 2014) symptoms.
These inconsistencies may be due to the small sample size in most studies (Crane et al., 2008, Deckersbach et al., 2012, Miklowitz et al., 2009, Murray et al., 2015, Perich et al., 2013a, Stange et al., 2011, Van Dijk et al., 2013, Williams et al., 2008), lack of standardized outcome measurement, different intervention characteristics (e.g. study duration varying from 3 to 12 weeks of MBCT training), different characteristics of the participants (Bos et al., 2014, Weber et al., 2010, Williams et al., 2008), high attrition rates early in the study (Bos et al., 2014, Murray et al., 2015), and disparate study designs (Bos et al., 2014, Howells et al., 2014, Murray et al., 2015, Van Dijk et al., 2013). In addition, the absence of a comparison treatment control group in many studies makes the findings less robust when considered in isolation (Bos et al., 2014, Crane et al., 2008, Deckersbach et al., 2012, Miklowitz et al., 2009, Murray et al., 2015, Stange et al., 2011, Weber et al., 2010).
Two meta-analyses investigating MBIs in patients with mental disorders have previously been conducted with mixed groups of patients with mood or anxiety disorders (Chiesa and Serretti, 2011, Hofmann et al., 2010). Whilst helpful, the generic focus, the fact that only two trials involving participants with BD were included, and failure to consider core symptoms of BD such as mania (Chiesa and Serretti, 2011), limits the conclusions regarding the efficacy of MBIs in patients with BD. More recently, several uncontrolled clinical trials examined the effectiveness of MBIs in patients with BD (Biseul et al., 2016, Bos et al., 2014, Miklowitz et al., 2015, Murray et al., 2015), however no dedicated systematic review and meta-analysis has investigated the use of MBIs as treatment for BD.
Given these limitations and gaps in the literature, we conducted this comprehensive systematic review and meta-analysis to investigate the role of MBIs as an adjunctive therapy for patients with BD.
Section snippets
Method and materials
The current systematic review and meta-analysis was conducted in line with the PRISMA guidelines (Liberati et al., 2009) (Supplement Table 1 and Supplement Fig. 1).
Studies included in the meta-analysis
After excluding five studies with mixed populations of patients (e.g. both patients with BD and major depression joined together) (Crane et al., 2008, Garland et al., 2016, Hamilton et al., 2012, Kenny and Williams, 2007, Ramel et al., 2004)(full details in Fig. 1 and Supplementary Table 2), 12 articles met the inclusion criteria (Biseul et al., 2016, Bos et al., 2014, Deckersbach et al., 2012, Howells et al., 2014, Ives-Deliperi et al., 2013, Miklowitz et al., 2009, Miklowitz et al., 2015,
Discussion
The results of this current meta-analysis indicate that patients with BD may experience significant improvements in depressive and anxiety symptoms but not manic symptoms after receiving MBIs, according to endpoint versus baseline severity scores. However, these apparently beneficial effects were derived from uncontrolled trials (pre- to post-test studies), whilst in the few (k=3) included controlled trials, MBIs failed to significantly improve the severity of depressive, anxiety, or manic
Limitations
There are several limitations to this study. First, the included trials had a small sample size and often provided no details on randomization procedures. In addition, we only enrolled three controlled studies, of which two used a low-quality control design (such as a waiting list) (Ives-Deliperi et al., 2013, Williams et al., 2008) and the other used a relatively better control design of TAU (applied psychoeducation) (Perich et al., 2013b) as the control group. Usually, MBI sessions can
Conclusion
The current meta-analysis does not support that MBIs can alleviate depressive and anxiety symptoms in patients with BD compared to controls. However, there was some tentative evidence of favorable outcomes in the pre- and post-test studies, although a non-specific effect cannot be ruled out. Hence, the few (k=3) controlled studies did not support the efficacy of MBIs for the treatment of BD. Even though MBIs appeared to be a feasible therapeutic option for patients with BD, the accessibility of
Competing interest
The authors state that there are no any competing interests or funding sources in the current literature.
Role of the funding source
The authors stated that there is no any funding source to current study.
Contributors
Che-Sheng Chu, the first author, takes the responsibility of writing this manuscript.
Tien-Yu Chen, Chia-Hung Tang, Dian-Jeng Li, Wei-Cheng Yang, and Ching-Kuan Wu contribute hugely in the study design.
Brendon Stubbs and André F. Carvalho, the specialties of meta-analysis, help in the meta-analysis construction.
Eduard Vieta and David J. Miklowitz, the specialties of mindfulness based intervention, take the responsibilities of formation of concept of mindfulness based intervention.
Ping-Tao Tseng
Acknowledgement
The authors declare that there are no conflicts of interest or funding in relation to the subject of this study. We thank the following authors for providing additional data for our meta-analysis contacted authors Garland E.L., Mathew K.L., Miklowitz D.J., Mothersill K.J., Ramel W., van Dijk S., and Williams J.M.
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