Editorial: "Clinical Guidelines in Bipolar Disorder: Applications and Evaluation"

Heinz Grunze^1,2*

• ¹Psychiatrie Schwäbisch Hall, Schwäbisch Hall, Germany
• ²Paracelsus Medizinische Privatuniversitat - Nurnberg, Nuremberg, Germany

It appears to be common sense throughout guidelines to try and avoid polypharmacy and to use medication proven effective and recommended in bipolar disorder. Analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig), Kirner and colleagues (2) found that clinical reality does not reflect guideline recommendations, at least in bipolar depression. More than one-third of patients were not prescribed any drug explicitly recommended for treatment of BPD, and only 6% of the patients received monotherapy with a recommended medication, whereas more than one-third of patients were administered ≥4 psychotropic drugs simultaneously. They also observed a trend towards prescribing more lithium instead of valproate and an increasing preference towards atypical antipsychotics, and, in summary, a remarkable heterogeneity in treatment regimens.Not only pharmaceutical treatment, but also the application of psychoeducation shows remarkable heterogeneity, possibly reflecting the complexity of the disorder. The review by Levrat and colleagues (3) summarizes the literature on current practices and forms of psychoeducation in the management of patients with bipolar disorder including only randomized controlled trials. The literature search yielded 381 studies of which seventy articles were finally included. Different forms of psychoeducation were compared on its own or combined with other psychosocial interventions. In summary, psychoeducation appears important in the treatment of BD, as it leads to a decrease in relapses, mood episodes, hospitalizations, and improved functioning or quality of life. In addition, some forms of psychoeducation were able to increase patient's level of knowledge of pharmacological treatment and the disorder or compliance with medication, as well as reduced selfstigma.Compared to psychoeducation, Mindfulness Based Cognitive Therapy (MBCT) has been studies less extensively in Bipolar disorder so far. Carracedo-Sanchidrián and colleagues (4) report on their randomized controlled trial testing the effect of adjunctive mindfulness-based cognitive therapy versus psychoeducational intervention on plasma brain-derived neurotrophic factor (BDNF) and cognitive function in bipolar patients. Of special interest, this trial combined and related psychometric outcomes with a biological measure. The hypothesis was that MBCT would improve cognitive functioning and BDNF more than psychoeducation and treatment as usual (TAU). Eightyfour bipolar outpatients were recruited and assessed at baseline, 8 weeks and 6 months. The result was negative, with MBCT not achieving better results than Psychoeducation or TAU. The authors suggest that the negative outcome might be a result of the fact that TAU is already quite effective in mildly and moderately ill outpatients, so that effectiveness can hardly been topped by additional psychotherapies.Two articles of this collection focussed on biological markers of bipolar disorder. For the editors of this collection, it was quite surprising that the old-fashioned EEG can still serve as a valuable tool supporting a bipolar depression diagnosis. The study by Yang et al (5) systematically evaluate the efficacy of the three classic EEG paradigms-eyes open, eyes closed, and free viewing-in diagnosing bipolar disorder. They compared EEGs from 28 individuals diagnosed with BD and 42 healthy controls. The eyes closed paradigm turned out to be a superior, straightforward EEG experimental approach for the diagnosis of bipolar depression.However, when it comes to diagnostic tools, nowadays research is focusing more on genes that may regulate neurodegenerative processes such as oxidative stress. Wu and colleagues (6) identified three hub genes and crucial pathways linked to oxidative stress in bipolar depression using bioinformatics analysis. These three potential biomarkers for bipolar disorder were involved in neuronal signal transduction, oxidative phosphorylation, and metabolic obstacle pathways, and may become a future target for diagnosing and treating bipolar disorder.Finally, Kong and co-workers (7) examined the relationship between depression and hepatobiliary diseases using genome-wide association studies. They looked into a potential bidirectional causal relationship between depression and various hepatobiliary diseases, and found that depression is a susceptibility factor for non-alcoholic fatty liver disease, with the causal effect of genetic susceptibility to depression on non-alcoholic fatty liver disease being mediated by waist-hip ratio, hypertension, and daytime nap. Although this study did not look specifically into bipolar depression, the mediating factors are also abundant in bipolar depressed patients, and may explain the increased incidence of hepatic disease also in bipolar disorder (8).In summary, this compilation depicts different aspects of diagnosing and treating bipolar disorder, but also the difficulties to extract a guideline fitting a majority of patients. Bipolar disorder remains a complex disorder demanding a high degree of personalized medicine.