Pharmacological Treatment Strategies for Acute Bipolar Depression / 신경정신의학

Of the different phases of bipolar disorder, bipolar depression is more prevailing and is more difficult to treat. However, there is a deficit in systemic research on the pharmacological treatment of acute bipolar depression. Therefore, consensuses on the pharmacological treatment strategies of acute bipolar depression has yet to be made. Currently, there are only three drugs approved by the Food and Drug Administration for acute bipolar depression : quetiapine, olanzapine-fluoxetine complex, and lurasidone. In clinical practice, other drugs such as mood stabilizers (lamotrigine, lithium, valproate) and/or the other atypical antipsychotics (aripiprazole, risperidone, ziprasidone) are frequently prescribed. There remains controversy on the use of antidepressants in bipolar depression. Here, we summarized the evidence of current pharmacological treatment options and reviewed treatment guidelines of acute bipolar depression from recently published studies.

The comparison of prescription pattern, adverse events, economic burden and drug-use adherence be-tween the different preferred drug in bipolar disorder / 中国神经精神疾病杂志

Objective To compare the differences of prescription pattern, adverse events, economic burden and drug-use adherence between preferred mood stabilizers and preferred antipsychotics in patients with bipolar disorder. Methods We investigated 240 cases of patients with bipolar disorder from 39 mental health institutions in 11 cities in Hebei province. The self-made questionnaire was used to investigate the demographic information, disease characteris-tics, prescription pattern and medical expense. The clinical global impression scale-severity of illness (CGI-SI) was used to assess the disease severity. The treatment emergent symptom scale (TESS) was used to assess the adverse drug reac-tions. The medication adherence rating scale (MARS) was used to assess drug therapy compliance in patients. Results One hundred fifty-two patients (63.3%) used antipsychotics as the first choice (antipsychotics group), 88 patients (36.7%) used mood stabilizers as the first choice (mood stabilizers group). The number of patients in-patient (90.1%vs. 76.1%), patients with psychotic symptom (27.0%vs. 11.4%), incidences of adverse events (46.1%vs. 31.8%), drug daily cost (me-dians 12.00 yuan vs. 8.37 yuan) and drug total cost (medians 344.61 yuan vs. 144.64 yuan) were larger in antipsychotics group than in mood stabilizers group (P0.05). Conclusion The bipolar disorder patients more frequently use antipsychotics as the first choice in Hebei province. The use of antipsychotics does not alter the combina-tion medication pattern. In addition, antipsychotics cause a higher incidence of adverse events and heavier economic bur-den compared with mood stabilizers, suggesting that mood stabilizers should be the first choice to bipolar disorder.

Pharmacotherapy of Acute Bipolar Depression in Adults: An Evidence Based Approach / 가정의학회지

In the majority of cases of bipolar disorder, manic episodes are usually brief and typically responsive to currently available psychopharmacological agents. In contrast, depressive manifestations are more prevalent and persistent, and can present as major depressive/mixed episodes or residual interepisode symptoms. The depressive phase is often associated with other neuropsychiatric conditions, such as anxiety spectrum disorders, substance use disorders, stressor-related disorders, and eating disorders. It is viewed as a systemic disease with associated ailments such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. There is an increased rate of mortality not only from suicide, but also from concomitant physical illness. This scenario is made worse by the fact that depressive symptoms, which represent the main disease burden, are often refractory to existing psychotropic drugs. As such, there is a pressing need for novel agents that are efficacious in acute depressive exacerbations, and also have applicable value in preventing recurrent episodes. The rationale of the present review is to delineate the pharmacotherapy of the depressive phase of bipolar disorder with medications for which there is evidence in the form of observational, open-label, or double-blind randomized controlled studies. In the treatment of acute bipolar depression in adults, a comprehensive appraisal of the extant literature reveals that among mood stabilizers, the most robust proof of efficacy exists for divalproex sodium; while atypical antipsychotics, which include olanzapine, quetiapine, lurasidone, and cariprazine, are also effective, as demonstrated in controlled trials.

Intervenciones terapéuticas basadas en la evidencia para niños y adolescentes con trastorno del ánimo bipolar / Evidence-based therapeutic interventions for pediatric bipolar disorder

El presente trabajo consiste en una revisión de la evidencia que existe hasta la fecha respecto a tratamientos psicosociales y farmacológicos para el trastorno de ánimo bipolar (TAB) en población pediátrica. En cuanto a tratamientos psicosociales destacan: Grupo Psicoeducativo Multifamiliar de Fristad, el Programa Rainbow de Pavuluri, Terapia Focalizada en la Familia para adolescentes, Terapia Interpersonal y de Ritmos Sociales para Adolescentes y la Terapia Dialéctica Comportamental para adolescentes (DBT). Se ha visto que los tratamientos comparten ciertas características, tales como, psicoeducación, establecimiento de hábitos y rutinas, y el trabajo con las familias en términos de desarrollo de habilidades sociales, habilidades de comunicación, afrontamiento al estrés y resolución de conflictos, que serían de relevancia para la mejoría de la sintomatología anímica, la recurrencia de los cuadros anímicos, la adherencia al tratamiento y la prevención de recaídas. Las investigaciones realizadas en intervenciones farmacoterapéuticas muestran que los antipsicóticos atípicos son eficaces en el tratamiento de episodios agudos (maníacos o mixtos), y que podrían ser superiores a los estabilizadores del ánimo en este grupo etáreo. La escasez de estudios en el tratamiento de depresión bipolar y de largo plazo limitan las conclusiones del tratamiento farmacológico en estas fases. Tanto para intervenciones psicosociales como farmacológicas se necesita mayor investigación, ya que existen pocos estudios que aborden el tratamiento del TAB pediátrico, y faltan ensayos controlados aleatorios.

This article is an updated revision of the psychosocial and pharmacological treatments for Pediatric Bipolar Disorder (PBD). Psychosocial treatments include: Fristad Multi-family Psychoeducation Groups, Pavuluri's Rainbow Program, Family Focused Therapy for adolescents, Interpersonal and Social Rhythm Therapy for adolescents and the Dialectical Behavior Therapy for adolescents. These interventions have common characteristics: psychoeducational interventions, habit and routine establishment, social and communication skills training and problem solving skills training. The evidence suggests that these characteristics would help to recover from mood symptoms, delay recurrent episodes, contribute to treatment adherence, and prevent recurrence. Research in pharmacologic interventions shows that atypical antipsychotics are efficacious in treating acute episodes (manic or mixed states), and could be superior to mood stabilizers in this age group. Lack of studies regarding treatment of bipolar depression and long-term treatment limit the conclusions for these pha- ses. Further research is warranted for both psychosocial and pharmacological interventions, specially randomized controlled trials.

Bipolar disorder: a review of current U.S. Food and Drug Administration approved pharmacotherapy.

Bipolar disorder (BD) is a chronic disorder which usually has its onset in early adulthood. At one end of the spectrum is depression and at other is mania. Like many psychiatric illnesses, it is not treatable but its symptoms are completely manageable with medications. Commonly used drugs are mood stabilizers and atypical antipsychotics along with adjunctive medications such as anxiolytics and antidepressants. In general, a combination of these drugs is used for treatment. These drugs have significant adverse effects which add to the burden of the disease. Presently, there are 11 US Food and Drug Administration - approved drugs for management of acute mania, 3 for bipolar depression and 7 for bipolar maintenance. This review article details the use of these drugs in BD.

Potential Molecular and Cellular Mechanism of Psychotropic Drugs

Psychiatric disorders are among the most debilitating of all medical illnesses. Whilst there are drugs that can be used to treat these disorders, they give sub-optimal recovery in many people and a significant number of individuals do not respond to any treatments and remain treatment resistant. Surprisingly, the mechanism by which psychotropic drugs cause their therapeutic benefits remain unknown but likely involves the underlying molecular pathways affected by the drugs. Hence, in this review, we have focused on recent findings on the molecular mechanism affected by antipsychotic, mood stabilizing and antidepressant drugs at the levels of epigenetics, intracellular signalling cascades and microRNAs. We posit that understanding these important interactions will result in a better understanding of how these drugs act which in turn may aid in considering how to develop drugs with better efficacy or increased therapeutic reach.

Effects of Combined Treatments of Lithium and Valproate on the Phosphorylation of ERK1/2 and Transcriptional Activity of ELK1 and C-FOS in PC12 Cells

OBJECTIVES: Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. METHODS: PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. RESULTS: Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. CONCLUSIONS: Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Recent advances in the pharmacotherapy of psychiatric disorders

Psychopharmacology has developed over approximately the past five decades. The remarkable proliferation of information in this area has made it difficult for clinicians to understand the characteristics of various psychotropic agents. Atypical antipsychotics including amisulpride, asenapine, aripiprazole, blonanserin, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and zotepine cause fewer extrapyramidal problems and have many clinical applications, but they can cause metabolic disturbances. Mood stabilizers and lamotrigine are widely used for bipolar disorder. Other novel anticonvulsants such as topiramate, oxcarbazepine, gabapentin, tiagabine, pregabalin, vigabatrin, levetiracetam, and riulzole have also been tested with diverging or inconclusive results. Antidepressants are commonly used in the clinical treatment of depression and anxiety disorder. However, the mechanism of action of medications used in the treatment of psychiatric disorders remains unclear. Understanding the mechanisms of action and clarifying the diagnosis may enhance the treatment outcome in psychiatry. In this review, we analyzed clinical pharmacology data for each drug within a class and discussed clinical strategies for administering currently available antipsychotics, mood stabilizer/anticonvulsants, and antidepressants widely used for various psychiatric indications.

A Meta-analysis of Mood Stabilizers for Alzheimer's Disease / 华中科技大学学报（医学）（英德文版）

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer's disease (AD). We searched 5 databases from their inception to January 2010. Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included. These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation. Methodological quality was assessed using the Jadad score. The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (Cis) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% Cis 0.15 to 7.26, P=0.04). There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total),NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo. Only one of these studies was free of methodological limitations (Jadad score=5). In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Pharmacological Treatment for Personality Disorders / 대한정신약물학회지

Up to now, it has been a prevailing concept that psychotherapy rather than pharmacotherpy is the main treatment modality for personality disorders. The use of medication to treat personality disorders has been derived from the recent confluence of anecdotal experience, a growing body of controlled studies and emerging evidence of the presence of psychobiological traits that may underlie personality disorders. Antipsychotics may be helpful for cluster A personality disorders, while antiserotonergic agents may be useful in improving mood and impulsivity for cluster B personality disorders. However data on the utility of antipsychotics and mood stabilizers are inconsistent. There have been very few studies done for cluster C personality disorders. The big problem lies in the fact that there is no consensus yet on the more fundamental areas of therapy such as classification of personality disorders, reliable measuring instruments, the relationship between axis I and axis II disorders, ruling out the effect of psychotherapy, and so on. This study reviewed the principal problems regarding the results of pharmacological treatment research of personality disorders in order to shed light on the future research directions in this area.