Mood Stabilizer Monotherapy Research Articles

Korean Medication Algorithm for Bipolar Disorder: changes in preferred medications for mania over 20 years

Introduction Majority of international guidelines for bipolar disorders are based on evidences from clinical trials. In contrast, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea.ObjectivesIn this study, preferred medication strategies for acute mania over six consecutively published KMAP-BP (2002, 2006, 2010, 2014, 2018, and 2022) were investigated.MethodsA written survey using a nine-point scale was asked to Korean experts about the appropriateness of various treatment strategies and treatment agents. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line.ResultsThe most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) in every edition. Preference for combined treatment for euphoric mania increased, peaked in KMAP-BP 2010, and declined slightly. Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. Among MSs, lithium and valproate are almost equally preferred except in the mixed subtype where valproate is the most recommended MS. The preference of valproate showed reverse U-shaped curve. This preference change of valproate may indicate the concern about teratotoxicity in women. Quetiapine, aripiprazole, and olanzapine were the preferred AAP for acute mania since 2014. This change might depend on the recent evidences and safety profile. In cases of unsatisfactory response to initial medications, switching or adding another first-line agent was recommended. The most notable changes over time included the increasing preference for AAPs.ConclusionsThe Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute mania. There have been evident preference changes: increased for AAP and decreased for carbamazepine.Disclosure of InterestNone Declared

Multi-trial, aggregated, individual participant data mega-analysis of short-term antidepressant versus mood stabilizer monotherapy of bipolar type II major depressive episode.

Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega-analyses of prospective trials of individual participant-level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy. Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (n = 393) were aggregated into an IPD dataset (i.e., mega-analysis). Hierarchical log-linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI/S) and change (CGI/C) scores, and change over time in Young Mania Rating (YMR) scores. Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (b = -2.33, t = -6.68, p < 0.0001), significantly greater symptom reduction on the CGI/S across time (b = -0.414, t = -6.32, p < 0.001), and a significant improvement in CGI/C across time (b = -0.47, t = -7.43, p < 0.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (b = 0.06, t = 0.49, p = 0.62). Findings from this IPD mega-analysis of bipolar II depression trials suggest a divergence from current evidence-based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega-analysis suggests that antidepressant monotherapy may provide superior short-term effectiveness without clinically meaningful increase in treatment-emergent hypomanic symptoms compared to lithium monotherapy.

Courses of treatment and risk factors for treatment-resistant depression in Finnish primary and special healthcare: A nationwide cohort study

ObjectiveInvestigate incidence, risk factors and courses of treatment for treatment-resistant depression (TRD) in primary and special healthcare. MethodsAll patients identified from nationwide registers, aged 16–65 years, diagnosed with depression in Finland during 2004–2016 were included. New antidepressant users were identified with six-month washout period and followed-up for two years to observe for presence of TRD, which was defined as initiation of a third trial after having failed two pharmacological treatment trials with adequate duration. ResultsDuring follow-up, 177,144 persons had their first registered antidepressant treated depression (mean age: 39.5, 62.5% women). Of them, 10.9% (N = 19,322) met TRD criteria. Among the TRD patients, most common first and second antidepressants trials were: SSRIs (44.6%), mirtazapine (19.0%) and SNRIs (16.5%). As the third treatment line, antidepressant monotherapy (44.2% of TRD patients) was most common, followed by a combination of ≥2 antidepressants (32.1%), antipsychotic or mood stabilizer augmentation and an antidepressant (15.8%), both combination of antidepressants and an augmentation with a mood stabilizer or antipsychotic (4.9%), antipsychotic or mood stabilizer monotherapy (2.7%) and ECT (0.3%). Of TRD patients, 16.5% (N = 3188) progressed to the fifth treatment line, in which the most common treatments were antidepressant monotherapy (33.4%), antidepressant combinations (27.5%) and augmentation (24.2%). Factors associated with higher risk of TRD included male gender, younger age, higher initial disease severity and hospitalization at initial onset of depression. ConclusionsAntidepressant monotherapies were still the most common fifth line of depression treatment. Severe depression, hospitalization due to depression, young age and male gender may predispose to TRD.

Prescription Patterns for Bipolar Disorder in Asian Countries: Findings from Research on Asian Prescription Pattern-Bipolar Disorder.

ObjectivePharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed.MethodsThe data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method.ResultsAmong 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries.ConclusionOver 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.

Comparative evaluation of psychopharmacotherapy of atypical depression in bipolar and recurrent affective disorder, psychogenic depression

Objective: to evaluate the treatment effectiveness for atypical depression (AtD) depending on its nosology: in bipolar affective disorder (BAD), recurrent depressive disorder (RDD) and psychogenic depression (PD).Patients and methods. A total of 250 patients with depression were screened, of which 77 patients with symptoms of AtD were enrolled in the study, 35 of them with BAD, 18 with RDD, and 24 with PD. Patients in all three groups received an antidepressant (AD) or a mood stabilizer (MS) monotherapy, or a combination of AD and antipsychotic (A), AD and A, MS and A, as well as a combination of AD, A and MS. The patients' condition was assessed clinically using a specially designed questionnaire and MADRS and CGI scales at the baseline and the 2nd, 3rd, 4th, 6th, 12th weeks of treatment. Quality of life satisfaction was assessed with the Q-LES-Q-SF (Scoring the Quality-of-Life Enjoyment and Satisfaction Questionnaire) scale at the treatment onset and after the 12th week of treatment.Results and discussion. Treatment regimens that included AD were the most eff in all groups of patients with AtD. The proportion of responders among those who received AD for bipolar disorder (75% or more) was significantly higher than among those who did not receive it (˂50%). In the RDD and PD groups, patients responded significantly better to AD monotherapy (RDD – 93.2%; PD – 91.5%) compared to other regimens. Agomelatine was the most frequently used (31.8%) and effective AD in all groups. Also, escitalopram, vortioxetine, and venlafaxine (p˂0.05) showed high efficacy, good tolerance, and absence of side effects that aggravate the main symptoms that characterize AtD. Among the antipsychotics in combination with AD, sulpiride was significantly more effective in patients with PD (p˂0.05). The highest rates of quality of life satisfaction were achieved in the BAD group, the lowest – in patients with PD (p˂0.05), which indirectly indicates the quality of remission, which is determined not only by the degree of reduction of depressive symptoms but also by the patients' subjective perception of their mental state.Conclusion. The inclusion of AD in the AtD treatment regimen significantly increases its effectiveness in patients of all groups, including BAD. AtD treatment should be administered not only taking into account its clinical signs and severity, but also depending on the nosology of the disease, the characteristics of its course. During drug administration, it is necessary to consider the spectrum of side effects, especially those that increase the symptoms of AtD itself.

Use of pharmacotherapies for treatment resistant depression in finland: A nationwide cohort study

IntroductionThere is a lack of knowledge on utilized pharmacotherapies for treatment resistant depression (TRD).ObjectivesTo investigate the courses of treatment of TRD.MethodsAll patients aged 16-65 years and diagnosed with depression in Finland during 2004-2016 were included (identified from nationwide registers for inpatient and specialized outpatient care, sick leaves and disability pensions). New antidepressant users were identified with six-month washout period and followed up for two years to observe the possible emergence of TRD, which was defined as initiation of a third treatment after having two failed pharmacological treatments with adequate duration. Pharmacological treatments were analyzed using PRE2DUP-method.ResultsDuring follow-up, 177,144 persons had their first registered depression (mean age:39.5, 62.5% women). Of them, 10.9% (N=19,322) met TRD criteria. Among the TRD patients, most common first and second lines antidepressants were as follows: SSRIs (44.6%), mirtazapine (19.0%) and SNRIs (16.5%). As the third line of treatment, 44.2% of TRD patients had antidepressant monotherapy, 32.1% a combination of ≥2 antidepressants, 15.8% antipsychotic or mood stabilizer augmentation and an antidepressant, 4.9% both combination of antidepressants and an augmentation with a mood stabilizer or antipsychotic, 2.7% antipsychotic or mood stabilizer monotherapy and 0.3% ECT monotherapy. Of TRD patients, 36.2% (N=6985) progressed to the fourth line of treatment and most common treatments were antidepressant monotherapy (37.5%), antidepressant combinations (30.8%) and augmentation (20.3%).ConclusionsAlthough antidepressant combination and augmentation strategies became more frequent, antidepressant monotherapies were still the most common third and fourth lines of depression treatment.DisclosureThe study was funded by Janssen and SR is an employee of Janssen.

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP): Changes in preferred treatment strategies and medications over 16 years and five editions.

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in treatment strategies advocated by the KMAP-BP over time. The five editions of the KMAP-BP were reviewed, and the recommendations of the KMAP-BP were compared with those of other bipolar disorder (BP) treatment guidelines. The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first-line option for severe and psychotic depression. In general, the recommended strategies of the KMAP-BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP-BP is that it is a consensus-based rather than an evidence-based tool. Nevertheless, it may confer advantages in actual clinical practice.

Anticonvulsant Mood Stabilizer and Lithium Use and Risk of Adverse Pregnancy Outcomes.

To determine the comparative safety of mood stabilizers with respect to risk of preeclampsia, placental abruption, growth restriction, and preterm birth. A cohort study was carried out using Medicaid Analytic eXtract data for pregnant women linked to live born infants enrolled from 2000 to 2010. Exposure to lamotrigine, valproate, topiramate, carbamazepine, oxcarbazepine, and lithium during the first 20 weeks of pregnancy was assessed. The reference group did not fill a prescription for an anticonvulsant or lithium during the 3 months prior to conception or the first half of pregnancy. Women who continued mood stabilizer monotherapy after 20 weeks were also compared to those who discontinued. Risk ratios (RRs) and 95% CIs were estimated with propensity score stratification to control for confounding. Among 1,472,672 pregnancies, 10,575 (0.7%) were exposed to anticonvulsant mood stabilizer or lithium monotherapy and 917 (0.06%) were exposed to polytherapy. In unadjusted analyses, exposure to each specific mood stabilizer and polytherapy was associated with increased risks of all adverse outcomes considered compared to no exposure (RR ranged from 1.15 to 1.56). However, these RR estimates were not meaningfully elevated with adjustment for confounding (0.89 to 1.16). Continuation of mood stabilizers was not associated with an increased risk for any outcomes compared to discontinuation and was associated with a reduced risk of placental abruption and growth restriction. Anticonvulsant mood stabilizers and lithium are not associated with an increased risk of placenta-mediated complications or preterm birth after accounting for confounding by indication.

Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018): Fourth Revision.

ObjectiveThe Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP.MethodsA 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts.ResultsThe preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression.ConclusionThe recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.

Effects of venlafaxine versus lithium monotherapy on quality of life in bipolar II major depressive disorder: Findings from a double-blind randomized controlled trial

Bipolar disorder is associated with decreased quality of life, especially during depressive episodes. There are few studies that have examined whether quality of life improves following pharmacological treatments of bipolar depression. In this exploratory study, we examined the effects of antidepressant versus mood stabilizer monotherapy on quality of life ratings in bipolar II subjects during acute (12 week) treatment. Data were derived from a randomized double-blind comparison of venlafaxine (n = 65) versus lithium (n = 64) monotherapy. The Quality of Life Index (QLI) was administered at baseline (n = 126; 98%) and again at the end of treatment. We explored treatment differences in continuous changes on the QLI using last-observation carried forward. Additionally, we explored the likelihood of experiencing clinically-significant improvements as well as baseline correlates of QLI and changes in QLIe. Venlafaxine was superior to lithium in reducing symptoms of depression during acute treatment. However, there were no significant differences between treatments in QLI ratings. Changes in symptoms of depression were correlated to, but not redundant, with improvements in QLI ratings. These findings suggest that quality of life may be an important secondary outcome to target and measure as a part of comparative clinical trials of pharmacotherapy for bipolar II depression.

Predictors of a Shorter Time to Hospitalization in Patients with Bipolar Disorder: Medication during the Acute and Maintenance Phases and Other Clinical Factors.

ObjectiveThe present study was conducted to compare the effects of pharmacological treatments during the acute and maintenance phases of mood episodes, sociodemographic, and clinical characteristics between a shorter time to hospitalization group (<12 months) and a longer time to hospitalization group (≥12 months).MethodsThe discharge medication for the first hospitalization was considered the acute treatment and the medication used during the week prior to the second hospitalization at the outpatient clinic was considered the maintenance treatment. Additionally, the charts were reviewed to examine a variety of demographic and clinical characteristics.ResultsPatients in the shorter time to hospitalization group were more likely to be unmarried and/or unemployed, have had a previous hospital admission for a mood episode, and have used antidepressant during the acute phase than those in the longer time to hospitalization group. Patients in the shorter time to hospitalization group were also less likely to use olanzapine, serotonin-norepinephrine reuptake inhibitors, or mood stabilizer monotherapy as a maintenance treatment than were patients in the longer time to hospitalization group.ConclusionPredictors for shorter time to hospitalization were associated with number of previous hospital admissions for a mood episode, being unmarried and/or unemployed, and antidepressant use during the acute phase.

Effect of Psychopharmacotherapy on Body Mass Index Among Children and Adolescents with Bipolar Disorders.

To assess the long-term effect of all treatment options for pediatric bipolar disorders on body mass index (BMI) and to explore individual characteristics associated with less BMI increase during psychotropic medication exposures. A retrospective cohort study was conducted by using the 1995 to 2010 General Electric Electronic Medical Record database. Individuals aged 18 years or younger who had a new bipolar disorder episode were identified. Treatment exposure was defined based on the medication regimens patients received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer (MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD polytherapy, MS+AD polytherapy, and no treatment. Both treatment exposure and BMI were coded as time varying, which could change from month to month. According to the duration of treatment and the availability of BMI measures, individuals were followed for up to 3, 6, 9, and 12 months since the treatment initiation. Repeated-measures mixed models were applied to compare the impact of different medication regimens and the length of drug exposure on BMI after adjusting for the baseline BMI, sociodemographic factors, comorbidities, and psychotherapy. A total of 2299 treated and 4544 untreated children and adolescents who met the inclusion criteria were identified. Analysis using repeated-measures mixed models showed that those on AT monotherapy (the reference group) had a gradually diminished, but statistically significant, monthly increase in BMI during all durations of drug exposure (3 months: 0.36 kg/m2, 6 months: 0.20 kg/m2, 9 months: 0.17 kg/m2, and 12 months: 0.16 kg/m2). As compared with AT monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy, and no treatment was significantly less at all time points, indicating less steep slopes of BMI change over time compared with AT monotherapy, especially during the short-term exposure. The combinations of AT with other psychotropic medications (ATMS, ATAD) were associated with a similar BMI increase as AT monotherapy. Individual characteristics found to be associated with a less increase in BMI during psychotropic medication exposure were being younger and having a higher baseline BMI. The long-term use of atypical antipsychotics, both as monotherapy or in combination with other psychotropic medications in children and adolescents with bipolar disorder, was associated with a steady and cumulative increase in BMI.

Descriptive study of patients with bipolar disorder and dyslipidemia

Introduction It is known the relationship between mental disorders such as bipolar disorder and metabolic disorders such as dyslipidemia, and therefore, increasing comorbid pathologies such as heart disease. Objectives Determine in patients diagnosed with bipolar disorder and dyslipidemia, which are the epidemiological characteristics, the diagnostic subtype and drug treatment prevalent. Aims Determine the profile of patients with bipolar disorder and dyslipidemia. Methods Creation of a database and conduction of a descriptive study with statistical analysis of the data extracted from the medical records of 100 patients from a public hospital. Results Higher prevalence of diagnosis of bipolar disorder type I on II (74% and 26%), male (54%) over female (46%), the age range of 40–50years, treated with antipsychotics more mood stabilizers (62%) compared to mood stabilizer monotherapy (38%) (Fig. 1). Conclusions Interventions should be conducted screening character and in patients with a diagnosis of bipolar disorder type I, male, age between 30–50years, treated with mood stabilizers plus antipsychotics (with a preference for lithium association with olanzapine).

Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk.

To examine the safety and effectiveness of antidepressant versus mood stabilizer monotherapy in rapid versus non-rapid cycling bipolar II disorder. Subjects ≥18 years old with bipolar II depression (n = 129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n = 59) received continuation monotherapy for six additional months. Rapid cycling did not affect frequency of response or change over time in depressive symptoms. Rapid cycling status did not affect frequency of depressive relapse or sustained treatment response. Rapid cyclers were more likely to experience hypomanic symptoms (P = 0.005) during continuation monotherapy; however, rates were similar in venlafaxine (17.6%) and lithium (42.9%) (P = 0.31). Rapid cycling status may not be associated with an increased risk of diminished response or greater depressive relapse during venlafaxine, relative to lithium monotherapy, in bipolar II subjects. Additional randomized studies are needed to confirm these findings.

Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study

ObjectiveCompare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing depressive relapse in bipolar II disorder. MethodsSubjects ≥18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium monotherapy for 12 weeks. Responders with a ≥50% reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy. Primary outcome was depressive relapse during continuation monotherapy. Secondary outcomes included sustained response rate from initiation of treatment to study end-point, relapse hazard, time to relapse, change in mania ratings, and frequency of treatment-emergent sub-syndromal hypomania and/or depressive episodes. ResultsVenlafaxine produced greater sustained response rate versus lithium (p<0.0001); however, there was no difference in relapse rate for venlafaxine (7.5%) versus lithium (26.7%) (p=0.079); relapse hazard (p=0.073), or time to relapse (p=0.090) between treatment conditions during continuation monotherapy. There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes. There were more sub-syndromal depressive episodes during lithium monotherapy (p=0.03). LimitationsSample size was limited by the lower sustained response rate for lithium versus venlafaxine; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups. ConclusionResults suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium, with no difference in treatment-emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring. Larger, prospective trials are needed to confirm these observations.

DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder.

This study aimed to assess the effect of second-generation antipsychotic (SGA) use and insulin resistance on a global measure of DNA methylation in patients diagnosed with bipolar disorder. Subjects stable on medication (either mood stabilizer monotherapy or adjuvant SGAs) were assessed for insulin resistance. Global methylation levels were assessed in leukocyte DNA from whole blood using the Luminometric Methylation Assay. Multivariable linear regression was used to investigate the effect of insulin resistance and SGA use on DNA methylation. A total of 115 bipolar I subjects were included in this study. The average age was 43.1 ±12.2 years and 73% were on SGAs. Average% global methylation was 77.0 ± 3.26 and was significantly influenced by insulin resistance, SGA use and smoking. This is the first study to show a relationship between SGA use, insulin resistance and global DNA methylation. Further work will be needed to identify tissue- and gene-specific methylation changes.

Korean Medication Algorithm for Bipolar Disorder 2014

Introduction There have been many changes in the treatment of bipolar disorder. Objective It is necessary to develop guidelines that can more aptly respond to cultural issues and specifics in different countries. Aims The Korean Medication Algorithm for Bipolar Disorder (KMAP-BP) was firstly published in 2002, with updates in 2006 and 2010. This third update reviewed the experts' consensus of opinion on the pharmacological treatments of bipolar disorder. Methods The newly revised questionnaire composed of 55 key questions about clinical situations including 223 sub-items was sent to the experts. Results Combination of mood stabilizer (MS) and atypical antipsychotic (AAP) was the first-line treatment option in acute mania. For the management of severe psychotic bipolar depression, combination of MS and AAP, combination of AAP and LTG, combination of MS, AAP and AD or LTG, combination of AAP and AD, and combination of AAP, AD and LTG was the first-line treatments. Combination of MS and AAP was the treatment of choice for management of mixed features. Combination of MS and AAP, MS or AAP monotherapy was the first-line options for management of maintenance phase after manic episode. For maintenance treatment after bipolar I depression, combination of MS and AAP, combination of MS and LTG, combination of AAP and LTG, MS or LTG monotherapy, and combination of MS, AAP and LTG were the first-line options. Conclusion Despite the limitations of expert consensus guideline, KMAP-BP 2014 may reflect the current patterns of clinical practice and recent researches.

Korean Medication Algorithm Project for Bipolar Disorder: third revision.

ObjectiveTo constitute the third revision of the guidelines for the treatment of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2014).MethodsA 56-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for the various phases of bipolar disorder and for special populations. The review committee included 110 Korean psychiatrists and 38 experts for child and adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23 child and adolescent psychiatrists responded to the survey.ResultsThe treatment of choice (TOC) for euphoric, mixed, and psychotic mania was the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP); the TOC for acute mild depression was monotherapy with MS or AAP; and the TOC for moderate or severe depression was MS plus AAP/antidepressant. The first-line maintenance treatment following mania or depression was MS monotherapy or MS plus AAP; the first-line treatment after mania was AAP monotherapy; and the first-line treatment after depression was lamotrigine (LTG) monotherapy, LTG plus MS/AAP, or MS plus AAP plus LTG. The first-line treatment strategy for mania in children and adolescents was MS plus AAP or AAP monotherapy. For geriatric bipolar patients, the TOC for mania was AAP/MS monotherapy, and the TOC for depression was AAP plus MS or AAP monotherapy.ConclusionThe expert consensus in the KMAP-BP 2014 differed from that in previous publications; most notably, the preference for AAP was increased in the treatment of acute mania, depression, and maintenance treatment. There was increased expert preference for the use of AAP and LTG. The major limitation of the present study is that it was based on the consensus of Korean experts rather than on experimental evidence.

A comparative study of different types of pharmacotherapy in treatment of depressive phase of bipolar II disorder

A comparative evaluation of the efficacy and safety of different types of pharmacotherapy: antidepressant monotherapy (agomelatine or sertraline), mood stabilizer monotherapy (valproate) and combination therapy (valproate + sertraline) in bipolar II disorder patients with major depressive episode. A 6-week open randomized study included 89 inpatients and outpatients. Basic criteria of efficacy were ≥50% reduction of HAMD total score and remission (≤7 points) to the end of the study. At the end of the study (day 42), the highest number of patients with 50% reduction of HAMD total score was noted in the sertraline (65%) and combination therapy (60%) groups, in the valproate group it was 57.1%, and the lowest - in agomelatine group (42.9%), but the differences were not statistically significant. Remission was observed in 45% patients in combination therapy group compared with 33.3% in valproate group, 32.1% in agomelatine group and only 20% in group of sertraline, but the differences between the groups also were not significant. Antidepressants (agomelatine and sertraline) have demonstrated fast but insufficient influence on the reduction of depression in the patients. Treatment with sertraline rarely led to remission and was frequently associated with high rate of switch into hypomania. Valproate therapy was moderately effective and well-tolerated without risk of switching. Combination of valproic acid with sertraline had the highest efficacy and was fairly well tolerated.

Risk of manic switch associated with antidepressant therapy in pediatric bipolar depression.

The purpose of this study was to assess the risk of manic switch associated with antidepressants in Medicaid-enrolled pediatric patients with bipolar depression. This retrospective cohort study involved 2003-2007 Medicaid Analytic eXtract (MAX) data from four geographically diverse states. The study sample included children and adolescents (ages 6-18 years) who had received a diagnosis of bipolar disorder on two or more separate occasions or during a hospital discharge, followed by a diagnosis of depression. According to the pharmacotherapy received by these patients in the 30 days around the index bipolar depression diagnosis, patients were categorized into five mutually exclusive groups. Manic switch was defined as having received a diagnosis of mania within 6 weeks after the initiation of bipolar depression treatment. Relative risks of manic switch between antidepressant monotherapy/polytherapy and their alternatives were assessed using Cox proportional hazards model. The robustness of the conventional Cox proportional hazards model toward possible bias caused by unobserved confounders was tested using instrumental variable analysis, and the uncertainty regarding manic switch definition was tested by altering the duration of follow-up. After applying all the selection criteria, 179 antidepressant monotherapy, 1047 second-generation antipsychotic (SGA) monotherapy, 570 mood stabilizer monotherapy, 445 antidepressant polytherapy, and 1906 SGA-mood stabilizer polytherapy users were identified. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49]; antidepressant monotherapy vs. mood stabilizer monotherapy, HR=1.41 [95% CI: 0.52-3.80); antidepressant polytherapy vs. SGA-mood stabilizer polytherapy, HR=1.61 [95% CI: 0.90-2.89]). However, only the comparison between antidepressant monotherapy and SGA monotherapy was statistically significant. The instrumental variable analysis did not detect endogeneity of the treatment variables. Extending the follow-up period from 6 weeks to 8 and 12 weeks generated findings consistent with the main analysis. Study findings indicated a higher risk of manic switch associated with antidepressant monotherapy than with SGA monotherapy in pediatric patients with bipolar depression. The finding supported the clinical practice of cautious prescribing of antidepressants for brief periods.