Combination Of Mood Stabilizers Research Articles

Machine Learning-Driven Evaluation of Antidepressant and Mood Stabilizer Combination Therapy in Bipolar Disorder

Background Bipolar disorder (BD) is characterized by recurrent episodes of mania and depression, requiring long-term mood stabilization. While mood stabilizers such as lithium and valproate are the cornerstone of BD treatment, the use of antidepressants in combination with mood stabilizers has been explored to enhance therapeutic outcomes, particularly in managing depressive episodes. Objective This case series aims to demonstrate the superior effectiveness of antidepressants combined with mood stabilizers over mood stabilizers alone in stabilizing mood in patients with bipolar disorder. Methods Two patients with bipolar disorder who initially received mood stabilizers monotherapy and exhibited suboptimal responses were subsequently treated with a combination of mood stabilizers and antidepressants. Clinical assessments were conducted using the Mood Disorder Questionnaire (MDQ), Clinical Global Impression-Severity (CGI-S), Hamilton Depression Rating Scale (HDRS), and Global Assessment of Functioning (GAF) before and after combination therapy. Results Combination therapy with antidepressants and mood stabilizers significantly improved mood stability in both patients compared to mood stabilizers alone. MDQ scores decreased, CGI-S scores improved, HDRS scores reduced, and GAF scores increased, with improvements sustained over a follow-up period of 12 months. Conclusion The combination of antidepressants and mood stabilizers provides superior mood stabilization in patients with bipolar disorder compared to mood stabilizers alone. These findings suggest that combination therapy should be considered in patients who do not achieve adequate symptom control with mood stabilizers monotherapy

Challenges in the Treatment of Psychotic Bipolar Depression.

Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD. We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD. PBD is a complex disorder, with 50%-75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary. PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.

Phantom vision or psychotic malady? A case report of Charles Bonnet syndrome plus

Charles Bonnet syndrome (CBS) is commonly experienced by elderly individuals after acute or gradual loss of vision. It is characterized by complex and vivid visual release hallucinations with insight into the unreality of visual experiences, which cannot be explained by any other psychiatric or neurodegenerative disorder. Most often these hallucinations are visual only without hallucinations in other sensory modalities. Here, we report an atypical case of CBS in an 80-year-old male who presented with complex visual scenic, auditory, and olfactory hallucinations after visual loss secondary to glaucoma with no insight and no cognitive decline. He further showed improvement in the low-dose antipsychotic and mood stabilizer combination.

Real-world use of pharmacological treatments for incident bipolar disorder: A Finnish nationwide cohort study

BackgroundPharmacotherapy remains crucial for treating bipolar disorder (BD), but knowledge on the treatments actually used by newly diagnosed patients in real-world settings is sparse. MethodsIndividuals newly diagnosed with BD during 1996–2018, aged 15–65 years, were identified from national Finnish registers. The patients' use of different drug classes (mood stabilizers, antipsychotics and antidepressants) or combinations of these drug classes were followed from initial pharmacotherapy (first line) after BD diagnosis until the fifth line of treatment or until the two-year follow-up time ended. Clinical and sociodemographic factors associated with antidepressants-only as the first treatment line were assessed with logistic regression. Results82.6 % of all patients used BD medication during the follow-up. 33.9 % had antidepressants-only as the first, 22.9 % as the second and 19.7 % as the third treatment line. Use of combinations of mood stabilizers, antipsychotics and antidepressants increased by successive treatment lines. Factors associated with antidepressants-only as the first treatment line included older age (>45 years aOR 2.20, 95% CI: 2.01–2.40, 25–45 years: 1.55, 1.42–1.68, compared with those aged <25), diabetes (1.35, 1.17–1.55) and female sex (1.29, 1.21–1.37). BD diagnosis registered in 2016–2018 (0.48, 0.42–0.55) and substance abuse (0.77, 0.71–0.83) were associated with decreased odds. LimitationsDue to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. ConclusionsA large proportion of patients with bipolar disorder are not treated according to treatment guidelines, as use of antidepressants alone is common. Reasons for not following evidence-based recommendations need to be further researched.

Treatment-resistant Bipolar Disorder and Thyroid Cancer

IntroductionBipolar disorder (BD) is a chronic and recurrent illness frequently associated with functional deterioration and treatment challenges. High rates of thyroid dysfunction have been found in patients with BD, compared to the general population.ObjectivesTo illustrate through a case-report the therapeutic challenges of treatment-resistant bipolar disorder and its relationship with thyroid dysfunction.MethodsCase report of a 41-year-old male patient with BD and comorbid anxiety disorders who has been diagnosed with thyroid cancer and underwent total thyroidectomy.ResultsMr B is a 41 year old patient diagnosed with BD and comorbid anxiety disorders (panic disorder, social anxiety disorder and generalized anxiety disorder) at age 18. He has presented in total 17 relapses and was hospitalized 7 times between the ages of 18 and 24. He experienced predominantly major depressive episodes with mixed features and debilitating anxiety symptoms. He was put on several treatments including a combination of mood stabilizers, antidepressants and benzodiazepines. Due to unsatisfactory treatment response, he was put on clozapine 150mg to 175mg/d combined with valproic acid, clonazepam. In 2009, the patient developed a nodular goiter caused by papillary thyroid carcinoma and underwent total thyroidectomy and radioactive iodine therapy. Following the surgical operation and stabilization of thyroid functioning, a decrease in the number of relapses and the severity of mood and anxiety symptoms have been noted.ConclusionsThis case reports highlights the importance of thyroid function assessment in patients with bipolar disorder and the possible correlation to treatment resistance and symptom severity.DisclosureNo significant relationships.

Post-stroke mania

IntroductionApproximately one-third of stroke survivors develop poststroke depression. Post-stroke mania is relatively rare, with a prevalence of less than 2%. One review of case reports of late-onset mania in 2015 demonstrated that 51% of the patients had established vascular risk factors. In 28% of cases, the treatment of underlying organic cause contributed to successful remission of the manic episode.ObjectivesFor this review, we aimed to compile published case reports from the past 20 years to review late-onset mania as one of the neuropsychiatric outcomes of stroke and its management.Methodsliterature search on Pubmed, PsychInfo, and Embase utilizing keywords combinations: Bipolar, Manic, Mania, Secondary, Stroke, Poststroke, Post-stroke, Elderly, Old, Late onset, Late-onset, Lateonset, Hemisphere, Brain, Vascular, Infarction.ResultsAmong the 17 case reports, the age of onset of manic episode ranged from 47 to 86 with a mean of 67 years. Of the 17 cases, the right hemisphere was the most frequently affected (14/17, 82%), with cerebrovascular lesion involving the left hemisphere in 3 cases (17.6%).ConclusionsClinicians should consider mania secondary to an organic cause in patients presenting with focal or soft neurological signs or symptoms, manic episode with atypical symptoms such as visual or olfactory hallucinations, altered mental status, disorientation, impairment in memory or cognition, unusual age of onset for bipolar disorder, or unusual illness course such as single episode of mania or poor response to psychopharmacologic treatment. Some reviews suggest combination of mood stabilizers and second-generation antipsychotics. Benzodiazepines recommended as an adjunctive drug for acute management such as agitation, aggressive behavior or disinhibition.DisclosureNo significant relationships.

Effectiveness of antidepressants in bipolar depression

IntroductionPrescribing antidepressants in the treatment of bipolar depression remains highly controversial due to the inconsistency between routine clinical practice and the results of controlled trials.ObjectivesTo assess the validity of antidepressants use in bipolar depression from the point of view of evidence-based medicine.MethodsDatabase search (Scopus and MEDLINE) followed by analysis of studies concerning the efficacy and safety of antidepressants in the bipolar depression treatment.ResultsThe search found 23 studies. There was a high degree of inconsistency in the results, apparently related to the methodology. Only two studies compared the effectiveness of antidepressants in monotherapy with placebo. No differences were found in the study with 740 participants but in the study with 70 participants with type 2 bipolar disorder antidepressants were found to be more effective than placebo. Nevertheless, both studies had significant methodological issues. In 6 studies comparing the effectiveness of the combination of antidepressants with mood stabilizers against the combination of mood stabilizers with placebo, only the effectiveness of fluoxetine in combination with olanzapine was confirmed, other antidepressants were ineffective. At the same time, studies where antidepressants were compared with each other in combination with mood stabilizers revealed a significant clinical response to therapy. Risk of the treatment emergency adverse events were relatively low for SSRI.ConclusionsDespite the contradictory literature data, the use of antidepressants in bipolar depression is justified from the point of view of evidence-based medicine for certain groups of patients with taking into account risk factors.

Analisis Efektivitas Biaya Terapi Kombinasi Mood Stabilizer dan Antipsikotik pada Pasien Gangguan Afektif Bipolar di Rawat Inap RSJ Grhasia Yogyakarta

Bipolar affective disorder is an episodic mental disorder characterized by manic, hypomanic, depressive, and mixed episodes, usually recurring and can last a lifetime. Patients with bipolar disorder have annual medical costs that were four times those of patients without bipolar disorder. The aim of this study is to analyze the cost-effectiveness of combination therapy between mood stabilizers and antipsychotics in patients with the bipolar affective disorder at Grhasia Mental Hospital Yogyakarta. This study is a retrospective with cohort study design using medical records and direct medical cost data during Januari-December 2018 period. Subjects are patients who were diagnosed with bipolar affective disorder manic episode (F31.2) and received a combination of mood stabilizer and antipsychotic therapy. The results were obtained in 46 patients with the affective disorder who met the inclusion criteria. The average direct medical cost of the sodium divalproate group was IDR 6.319.933 per day and in the lithium group was IDR 5.705.953 per day. The average length of stay in the sodium divalproate group was 25,79 days and in the lithium group was 25,75 days (P = 0,991). The Average Cost Effectivity Ratio (ACER) sodium divalproat group is lower than the lithium group (IDR 221.246 per day and IDR 245.434 per day, respectively). The conclusion of this study is that the combination of sodium divalproate-antipsychotic therapy is more cost-effective than lithium-antipsychotic therapy in a patient with bipolar affective disorder manic episode

Defining phenotypes of long-term lithium and valproate response, including combination therapy: a modified application of the Alda scale in patients with bipolar disorders

BackgroundWhen evaluating the long-term treatment response to mood stabilizers using the Alda scale, mood stabilizer combination therapy is typically considered a confounding factor, and patients receiving combination therapy are excluded from the analysis. However, this may result in bias if those under combination therapy are worse treatment responders. This study aims to explore whether the Alda scale is applicable to patients taking lithium and valproate combination therapy. We compared long-term treatment response in patients receiving monotherapy and combination therapy of the two drugs, and investigated clinical correlates of the responses to each drug.MethodsThe study subjects consisted of 102 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder who had been undergoing maintenance treatment with lithium and/or valproate for more than 2 years at a single specialized bipolar disorder clinic. Long-term treatment response was measured using the Alda scale and compared among the lithium monotherapy group, the valproate monotherapy group, and the mood stabilizer combination group. Clinical correlates of long-term treatment response were evaluated in lithium users and valproate users separately.ResultsThere were no significant differences in terms of baseline illness characteristics among groups. The combination group showed the worst treatment response for all the response measurements applied. This group also had the higher rate of ‘poor responder’ with a statistically significant difference compared to valproate group. Older age at onset and (hypo)manic episode at onset showed significant positive associations with total Alda score in lithium users, while comorbid anxiety disorders, obsessive–compulsive disorder and mixed episode showed significant negative associations in valproate users.ConclusionsThe combination group had poorer long-term treatment response but did not show distinct clinical characteristics compared to the monotherapy groups. When exploring the long-term effects of mood stabilizers, excluding patients undergoing combination treatment could result in bias because they may represent a poor response group. The long-term treatment responses of lithium and valproate had different clinical correlates.

Is the Prescription of Antidepressants for Bipolar Depression Justified from the Point of View of Evidence-Based Medicine?

Background: prescribing antidepressants in the treatment of bipolar depression remains highly controversial due to the inconsistence between routine clinical practice and the results of controlled trials. Purpose: to assess the validity of antidepressants use in bipolar depression from the point of view of evidence-based medicine. Material: database search (Scopus and MEDLINE) followed by analysis of studies concerning the efficacy and safety of antidepressants in bipolar depression treatment. Сonclusion: the search found 23 studies. There was a high degree of inconsistency in the results, apparently related to the methodology. Only two studies compared the effectiveness of antidepressants in monotherapy with placebo, with no differences found in the study with 740 participants and in the study with 70 participants with type 2 bipolar disorder antidepressants were found to be more effective than placebo. Nevertheless, both studies had significant methodological issues. In 6 studies comparing the effectiveness of the combination of antidepressants with mood stabilizers against the combination of mood stabilizers with placebo, only the effectiveness of fluoxetine in combination with olanzapine was revealed, other antidepressants were ineffective. At the same time, studies where antidepressants were compared with each other in combination with mood stabilizers revealed a significant clinical response to therapy. Analysis of routine clinical practice studies has shown that antidepressants are prescribed very often, for about 50% of patients with bipolar depression. International guidelines for therapy differ quite widely on the use of antidepressants in bipolar depression, but in principle allow their use. Thus, despite the contradictory literature data, the use of antidepressants in bipolar depression is justified from the point of view of evidence-based medicine for certain groups of patients with taking into account risk factors.

Decelerated epigenetic aging associated with mood stabilizers in the blood of patients with bipolar disorder

There is high mortality among patients with bipolar disorder (BD). Studies have reported accelerated biological aging in patients with BD. Recently, Horvath and Hannum et al. independently developed DNA methylation (DNAm) profiles as “epigenetic clocks,” which are the most accurate biological age estimate. This led to the development of two accomplished measures of epigenetic age acceleration (EAA) using blood samples, namely, intrinsic and extrinsic EAA (IEAA and EEAA, respectively). IEAA, which is based on Horvath’s clock, is independent of blood cell counts and indicates cell-intrinsic aging. On the other hand, EEAA, which is based on Hannum’s clock, is associated with age-dependent changes in blood cell counts and indicates immune system aging. Further, Lu et al. developed the “GrimAge” clock, which can strongly predict the mortality risk, and DNAm-based telomere length (DNAmTL). We used a DNAm dataset from whole blood samples obtained from 30 patients with BD and 30 healthy controls. We investigated Horvath EAA, IEAA, Hannum EAA, EEAA, Grim EAA, DNAmTL, and DNAm-based blood cell composition. Compared with controls, there was a decrease in Horvath EAA and IEAA in patients with BD. Further, there was a significant decrease in Horvath EAA and IEAA in patients with BD taking medication combinations of mood stabilizers (including lithium carbonate, sodium valproate, and carbamazepine) than in those taking no medication/monotherapy. This study provides novel evidence indicating decelerated epigenetic aging associated with mood stabilizers in patients with BD.

Complex Combination Pharmacotherapy for Bipolar Disorder: Knowing When Less Is More or More Is Better.

Combination pharmacotherapy for bipolar disorder is commonplace and often reflects the severity and complexity of the illness and the comorbid conditions frequently associated with it. Across treatment settings, about one-fifth of patients with bipolar disorder appear to receive four or more psychotropic medications. Practice patterns often outpace the evidence-based literature, insofar as few systematic studies have examined the efficacy and safety of two or more medications for any given phase of illness. Most randomized trials of combination pharmacotherapy focus on the utility of pairing a mood stabilizer with a second-generation antipsychotic for prevention of either acute mania or relapse. In real-world practice, patients with bipolar disorder often take more elaborate combinations of mood stabilizers, antipsychotics, antidepressants, anxiolytics, stimulants, and other psychotropics for indefinite periods that do not necessarily arise purposefully and logically. In this article, I identify clinical factors associated with complex combination pharmacotherapy for patients with bipolar disorder; describe approaches to ensuring that each component of a treatment regimen has a defined role; discuss the elimination of unnecessary, ineffective, or redundant drugs in a regimen; and address complementary, safe, rationale-based drug combinations that target specific domains of psychopathology for which monotherapies often provide inadequate benefit.

59.3 Common Child Psychiatric Drug–Drug Combinations, Interaction Risks and Management

As tertiary care experts, child psychiatrists confront complex clinical presentations and medication regimens that often exceed 5 and sometimes 10 psychotropic medications for an individual child. Each additional medication increases the overall risk of side effects both directly and via drug-drug interactions. Improved electronic medical records and internet access have been of some help in monitoring and protecting against these risks. However, the psychiatrist’s clinical judgment and integrated knowledge of the literature remain the most important ingredients for safe and effective clinical care. In this presentation, participants learn about commonly used medication combinations, their side effects, and approaches to their management. Specifically, the presenter discusses combinations of stimulants and nonstimulants, combinations of mood stabilizers and second-generation antipsychotic (SGA) drugs, as well as combinations of adjunctive agents with antidepressants. The presenter also discusses those combinations that are identified as potential interactions in electronic medical record systems, even though their meaningful clinical risk may be negligible.

Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A 1H-MRS study

ObjectiveIn the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (1H-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC. Methods129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan (1H-MRS) using a PRESS ACC single voxel (8cm3) sequence. ResultsBD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy). ConclusionThe results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics.

A retrospective study of late-onset bipolar disorder: A comparison with early and intermediate onset

Aim: To evaluate the sociodemographic, clinical, and treatment characteristics profile of late-onset (LO) bipolar affective disorder (BPAD) (onset ≥50 years) and compare the patients with LO BPAD with early age of onset (10–25 years) and intermediate age of onset (26–40 years) BPAD for the demographic features, illness characteristics, and treatment characteristics. Methodology: In this retrospective study, data (demographic features, clinical characteristics, and treatment characteristics) of 115 patients with LO BPAD (onset ≥50 years) were extracted and were compared with 93 patients with intermediate-onset (IO) (26–40 years) and 130 patients with early-onset (EO) (10–25 years) BPAD groups. Results: Patients with LO BPAD differ from EO and IO BPAD in having higher rates of family history of mental disorders, higher rates of comorbid psychiatric disorders (especially substance use disorders) and physical illnesses, higher rates of suicidal ideations, lower rates of suicidal attempts, higher rates of Type-II BPAD, lower prevalence of psychotic symptoms during the episodes, shorter interepisodic duration, higher use of combination of mood stabilizers and antidepressants, lower preference of lithium, higher preference for valproate, and lower use of benzodiazepines. In addition, patients with LO BPAD differed from those with EO BPAD in having higher rates of having a depressive-manic illness pattern, longer duration of depressive episodes, and lower number of manic episodes. Patients with LO BPAD differed significantly from IO BPAD in having lower number of episodes and more often use of antipsychotic monotherapy during the acute phase. Conclusions: LO BPAD differs from IO and EO BPAD on several of the clinical characteristics. Treatment preferences by the clinicians for LO BPAD also differ from EO and IO BPAD.

Haloperidol, risperidone and quetiapine in the treatment of acute severe manic episode in bipolar disorder: The experience at the mood disorder unit in Milan

IntroductionPatients affected by severe manic episode, often with delusional symptoms, are commonly treated with a combination of mood stabilizers, antipsychotics and other sedatives. The choice of a specific drug, dose and term is still debated.ObjectivesA naturalistic study on a sample of 84 inpatients affected by acute severe mania treated with a combination therapy.AimsTo compare efficacy and tolerability of haloperidol/risperidone/quetiapine in association with lithium and/or valproate.MethodsEighty-four bipolar inpatients affected by a manic episode according to DSM-5 criteria. Drugs administered according to our best practice. Clinical course weekly monitored with Young Mania Rating Scale (YMRS) for 4weeks. Extrapiramidal side effects (EPSE) monitored with Saint Hans Rating Scale (SHRS).ResultsTwenty-five men (29.76%) and 59 women (70.24%); mean age 43.37 ± 13.58 years. Mean YMRS score T0 40.27 ± 9.04. Forty-one patients (48.81%) treated with haloperidol (3.4 mg/die); 16 (19.05%) with risperidone (4.3 mg/die); 27 (32.14%) with quetiapine (438 mg/die). The 3 groups showed no difference regarding clinical characteristics and YMRS basal scores. Chi2 analysis confirmed an higher response rate (50% of reduction of YMRS final score compared to T0) with haloperidol (χ2 = 14.88; P = 0.00). The repeated-measures model analysis showed a significant decrease (P &lt; 0.05) in YMRS scores in haloperidol vs. risperidone vs. quetiapine patients for all time points from second week. No statistical difference for EPSE was found.ConslusionsWe suggest that haloperidol could be advisable in the treatment of severe mania, with rapid efficacy, even with low doses. Occurrence of EPSE was not considerable during the acute treatment. Studies with a larger sample size, randomization, fixed doses, double blind design are needed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Mood stabilizers and/or antipsychotic drugs for the treatment of manic episodes in bipolar I disorder: study protocol for a randomized controlled trial

Background: In clinical practice, it is important to quickly and effectively treat manic episodes in patients with bipolar I disorder. Therefore, it is necessary to formulate an effective therapeutic protocol combining two or more drugs in order to rapidly alleviate symptoms within a short time frame (1 week). In this clinical trial protocol, the antipsychotics quetiapine, olanzapine and ziprasidone and the mood stabilizers valproate, oxcarbazepine and lithium will be used to treat manic episodes to investigate the efficacy and safety of these two types of drugs when used alone or in combination. Methods/Design: This trial will be performed at Guangzhou Brain Hospital, China. A total of 120 patients with bipolar I disorder, exhibiting manic or mixed episodes, will undergo two phases of medication. In the first phase, patients will be randomly assigned to receive oral valproate, oxcarbazepine, lithium, quetiapine, olanzapine or ziprasidone. In the second phase, combination drug treatment will be given, i.e., each patient will receive a combination of mood stabilizers and antipsychotics. Treatment will be given for a total of 6 weeks. Primary outcome measures will include changes in the Young Mania Rating Scale (YMRS) scores and dropout rates. Secondary outcome measures will include disease progression and the efficacy of treatment as evaluated with the Clinical Global Impression Scale, symptom severity as evaluated with the Global Assessment Scale, and anxiety and depression symptoms as evaluated with the Hamilton Anxiety Scale and the Hamilton Depression Scale, respectively. Discussion: This trial will provide preliminary evidence on the comparative efficacy and effectiveness of the commonly prescribed drugs, with attempts at optimizing pharmacological treatments of manic and mixed episodes. Trial registration: ClinicalTrials.gov identifier: NCT01893229; registered on 2 July 2013.

Comorbid bipolar disorder and obsessive-compulsive disorder in children and adolescents: Treatment implications.

Apparent comorbidity between bipolar disorder (BD) and obsessive–compulsive disorder (OCD) is a common condition in psychiatry with higher prevalence rates in youths (23.2%, 95% confidence interval [CI] = [11.5%, 41.3%]) compared to adults (13.56%, 95% CI = [10.4%, 16.25%]) (Amerio et al., 2015). The meaning of this comorbidity has not been clarified yet. The treatment of BD-OCD patients remains a great challenge since the gold standard for one disease (serotonin reuptake inhibitors [SRIs] for OCD) can worsen the other (antidepressants can cause mania and/or more mood episodes in BD; Amerio et al., 2014a). The literature on pharmacologic or psychotherapeutic approaches especially in pediatric BD-OCD patients is limited. Therefore, we updated our recent systematic review (Amerio et al., 2014b) and focused specifically on the treatment of BD-OCD comorbidity in children and adolescents. Studies were identified by searching the electronic databases MEDLINE, EMBASE and PsycINFO. We combined the search strategy of free text terms and exploded MeSH headings for the topics of BD, OCD and treatment combined as follows: ((((((‘Therapeutics’[Mesh]) OR treatment*) OR therap*) OR pharmacotherap*) OR psychotherap*)) AND (((((((((‘Bipolar Disorder’[Mesh]) OR Bipolar disorder) OR BD) OR Bipolar) OR Manic depressive disorder) OR Manic depressive) OR Manic)) AND ((((‘Obsessive-Compulsive Disorder’ [Mesh]) OR OCD) OR Obsessivecompulsive) OR Obsessive-compulsive disorder))). Studies published in English through 31 August 2015 were included. Further studies were retrieved from reference listing of relevant articles and consultation with experts in the field. Seven studies were selected (Table 1). In all selected studies, BD-OCD patients received mood stabilizers (lithium, divalproex sodium). In the largest study, 42.1% of comorbid patients required a combination of multiple mood stabilizers and 10.5% a combination of mood stabilizers with atypical antipsychotics (quetiapine, risperidone, aripiprazole). Addition of antidepressant (clomipramine) to mood stabilizers led to clinical remission of both conditions in only one study. In other cases, antidepressants (escitalopram) seemed prone to cause more manic/hypomanic episodes in BD-OCD than in non-comorbid patients. The evidence so far on BD-OCD nosology supports the view that the majority of cases of comorbid BD-OCD are in fact BD cases (Amerio et al., 2014a). Osler’s view that medicine should be treatment of diseases, not of symptoms, is consistent with the approach of mood stabilization as a first objective in apparent BD-OCD patients, as opposed to immediate treatment with SRIs.

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.

Essential Fatty Acids for Childhood Mental Health Disorders

No child psychiatric disorder has a single treatment that is completely satisfactory. Combinations are sometimes more beneficial than single treatments. This is well established for medication + behavioral treatment for depression and ADHD. There is wide variability in the evidence base for various treatments, from FDA-approved RCTs to open pilots. In the search for additional or alternative treatments, essential fatty acids seem especially to pass the SECS criterion: a treatment that is safe, easy, cheap, and sensible does not need as much evidence to justify patient trials as one that is risky, unrealistic, difficult, or expensive (RUDE). Not only do omega-3 fatty acids have some RCT evidence for a small effect in several psychiatric disorders, but they also are believed useful in preventing cardiac morbidity and excessive inflammation. Therefore, for ADHD, we recommend a combination of behavioral treatment (e.g., parent training, cognitive-behavioral therapy (CBT) for older patients), FDA-approved medication, (primarily stimulants), an RDI/RDA multivitamin/mineral to compensate for stimulant appetite suppression, and about a gram a day of EPA/DHA, possibly supplemented with 50–100 mg GLA. For mood disorders, we recommend a combination of mood stabilizer or antidepressant (depending on which mood disorder), CBT, RDA/RDI multivitamin/mineral (in view of reported vitamin D deficiencies and vitamin wasting from some anticonvulsant mood stabilizers), and a gram per day of EPA/DHA. For autism, we recommend applied behavior analysis, RDA/RDI multivitamin/mineral in view of the often idiosyncratic unbalanced diet, ADHD medication if a problem with hyperactivity, antipsychotic if a problem with irritability/aggression, and omega-3 for anti-inflammatory effect. For learning disorder and developmental coordination disorder, we recommend remedial tutoring or occupational therapy and EPA/DHA. For children at high risk for psychosis or mood disorder, we recommend counseling, monitoring for early indication of low-dose antipsychotic, and general nutritional support, including EPA/DHA. For Tourette’s and aggression, EPA/DHA and other nutritional support can be added to standard treatment. When using fish oil, it is important to make sure it was refined to eliminate contaminants such as mercury. The effect accumulates gradually over months. There is no convincing evidence of greater benefit but some risk from amounts over a gram or two per day.