Jorge M. Tamayo

Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis

In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes.

Outcomes for Latin American versus White patients suffering from acute mania in a randomized, double-blind trial comparing olanzapine and haloperidol.

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score ≤12 and Hamilton Depression Rating Scale score of ≤8). Patients were analyzed on an intent-to-treat basis. The mean modal doses (milligrams per day) were similar in Latin American (OL) (14.2; n = 51) and white (OC) (15.1; n = 120) patients treated with olanzapine, and in Latin American (HL) (7.1; n = 48) and white (HC) (8.5; n = 113) patients treated with haloperidol. At week 6, remission rates were similar among the OL and HL patients (64.7% vs. 68.8%) but were higher in the OC than in HC (49.2% vs. 32.7%; P = 0.012). Significantly more HL than OL patients experienced extrapyramidal symptoms such as akathisia and tremor. Tremor was significantly higher in HL than in HC patients, whereas a significant increase in the Barnes Akathisia Scale and Abnormal Involuntary Movement Scale scores was observed in HC versus HL. Somnolence and weight gain were significantly higher in OL than in OC patients, and more OL and OC patients experienced weight gain in comparison with the HL and HC groups, respectively. The incidence of nonfasting glucose levels above normal levels did not statistically differ between groups. In conclusion, in contrast to our findings among white patients, the Latin American patients who have acute mania did not differ in overall response to olanzapine or haloperidol. The pattern of adverse events differed between treatment groups. Prospective clinical trials in Latin American bipolar populations are justified.

La importancia de la detección y el tratamiento de los síntomas somáticos en pacientes latinoamericanos con depresión mayor

OBJECTIVE: Major depression is a disease characterized by the presence of mental and somatic symptoms, the latter affecting considerably the diagnostic and therapeutic procedures and the prognosis. METHOD: We searched for published articles until June 2006 crossing several terms which allow us to include those articles referring to the comorbidity of major depression and somatic symptoms, the prevalence of that comorbidity in Latino Americans, and/or the impact and patterns of use of the antidepressant treatments in patients with major depression and associated somatic symptoms. RESULTS: Somatic symptoms in Latino Americans with major depression are common, probably more than in other populations around the world. They compromise the response to treatment, are associated with refractoriness and chronicity, and are usually denied in the psychiatry practice in some Latin American countries, where the practice in prescribing low doses of antidepressants is common and could affect the control of residual somatic symptoms with higher rates of recurrences. CONCLUSION: Clinicians working in Latin American countries must be prepared to detect somatic symptoms in their patients with major depression, looking for the prescription of appropriate therapeutic doses of the antidepressants.

Multisite international collaborative clinical trials in mania

Multi-regional collaborative clinical trials include those conducted across heterogeneous areas of the world under common protocols. Such trials appear to be driven primarily to provide data required for regulatory approval or licensing of new drug products in a relatively rapid and presumably efficient and cost-effective manner. Commonly, they include underserved populations and areas where costs of trials are lower than in most developed countries. In addition, such studies can potentially make innovative treatments widely and rapidly available in vast, international markets. Other potential benefits to collaborating sites may include diffusion of knowledge and improvement of research skills, as well as improvement of treatment and a broader salutary impact on health services and perhaps on employment opportunities and economic growth (Demol +6; Weihrauch, 1997; Glickman et al. 2009; Gopal et al. 2005; Greco +6; Diniz, 2008; ICH Guideline, 2002; Smulevich et al. 2005; U.S. FDA, 1998). Successful conduct of international trials requires compliance with varying local and international laws, regulations and ethical requirements, and confronting a range of systems of review of ethical aspects of subject recruitment, compensation, consenting procedures, research protocols, and provision of aftercare – all which can add complexity. In addition, there is variance among regions, countries and cultures in levels of education, and in the nature of information, financial inducements, clinical care and aftercare provided to research subjects. Complexities arise also from culture-dependent conceptualizations of mental disorders, criteria for diagnosis, and efforts at validating, interpreting and scoring of symptom ratings designed to characterize changes during treatment, and methods for detecting adverse events. In the continuing quest to define core or universal features of psychiatric disorders, it is crucial to consider the anthropological and cultural context in which they develop and are modified (Karno +6; Jenkins, 1993; Lopez-Ibor, 2003; …

Relationship between African―American or Caucasian origin and outcomes in the olanzapine treatment of acute mania: a pooled analysis of three adult studies conducted in the United States of America

The aim of this study was to explore the role of ethnic origin in the treatment of acute bipolar mania. Treatment outcomes were studied in a post-hoc analysis of African–American (AA, n=41) and Caucasian (CA, n=190) adults treated with olanzapine in three studies conducted in the United States of America. Baseline demographics were similar except that the AA cohort had fewer women compared with the CA cohort (37 vs. 58%; P=0.01). Daily mean modal olanzapine dose and study discontinuation rate for AA and CA were: 16.2 mg vs. 16.6 mg and 41.5 vs. 25.3% (P=0.03), respectively. There were four (23.5% of discontinuers) and 19 (39.6% of discontinuers, P=0.14) discontinuations because of a poor response in the AA and CA groups, respectively. Drug exposure for the AA cohort was 18.7 days and that of the CA cohort was 19.3 days. Both cohorts showed similar symptom improvements, and safety outcomes were not statistically significantly different except for the following treatment-emergent adverse event frequencies for AA and CA cohorts, respectively: agitation (24.4 vs. 10.5%, P=0.04); dysmenorrhoea (20.0 vs. 3.6%, P=0.04); and dizziness postural (7.3 vs. 1.1%, P=0.04). Although study findings [limited by a smaller (18% of total population) AA cohort] need replication, they suggest that while many outcomes were similar in both cohorts, clinicians could benefit from the awareness of factors in the AA population that possibly influence study discontinuation rates, treatment-emergent adverse event reporting, and participation by sex.

Bipolar Spectrum Disorder: Origins and State of the Art

The threshold chosen by categorical mental health classifications like DSM-IV-TR or ICD-10 for the diagnosis of bipolar disorders (BP) is too high, elevating the risk of misdiagnosing cases that closely resemble BP under several clinical variables like “major depressive disorder”. Acknowledging and providing the necessary weight to the BP subthreshold forms may improve the clinical practice and reduce the number of patients with misdiagnosis, creating opportunities for better treatment. Increasing evidence support the bipolar spectrum disorder (BPS) concept and factors such us earlier onset age of the first major depressive episode (MDE), brief duration of MDEs, rapid onset of MDEs, more than five previous MDEs, family history of BP, treatment-resistant depression, suicidal behavior, postpartum depression, atypical features, psychotic traits, irritability, overactivity, comorbidity with anxiety disorders, substance abuse, borderline personality disorder, migraine, and irritable temperament are well validated differentiators between unipolar and bipolar depressive disorders. Identifying those factors could increase the lifetime prevalence of BPS to at least 4.8%. New studies on the diagnosis and management of BP should focus on the development of diagnostics dimensional models with categorical benchmarks to recognize BP sub-threshold forms, on the selection of biomarkers for early identification of patients with BPS, especially those with BP family history, and on the promotion of joint efforts between academia, industry, government, and community to search new interventions in BPS management.

Therapy of No-Type I Bipolar Spectrum Disorders: A Systematic Review

Although No-Type I Bipolar spectrum disorders (NBP-I) are common, recurrent, and disabling, they are underdiagnosed and misdiagnosed in clinical practice. Several data show that NBP-I (especially BP type II) are a significant public health problem, and there is a dearth of studies of effective treatment modalities for the control of acute symptoms and the prevention of mood recurrences (mainly major depressive episodes). Considering the growing need to find effective therapies for patients with NBP-I, this review is based on a systematic search of evidence about the efficacy of treatments for each phase of the NBP-I. Fifty-seven studies were identified and reviewed. Most studies investigating the pharmacotherapy of NBP-I were methodologically limited, having observational or retrospective designs and small samples. Regarding short-term treatment, there is some limited support for the use of risperidone, valproate, and quetiapine in hypomania, and for valproate, quetiapine, fluoxetine, and venlafaxine in treating depression. For long-term treatment, the only preventive therapy for both depression and hypomania that is supported by several controlled studies is quetiapine. Lithium and fluoxetine have shown efficacy in delaying depressive recurrences. Although the adequate treatment for these patients remains to be determined, mood stabilizers and some forms of psychotherapy may be useful for these patients. We conclude that there is a paucity of sound evidence to guide clinicians in treating NBP-I patients. Although progress has been made, more quality research is needed to delineate effective treatment strategies.

Editorial (Hot Topic: The State of the Art in Diagnosis and Treatment of Soft Bipolar Disorders)

Aims & Scope: In the past four decades there has been great controversy about the publications that have led to rethink the dimensional perspective of the bipolar disorders, suggesting a paradigm shift in their diagnosis and treatment. Soft bipolar disorders constitute about two-thirds of all patients with bipolar disorder and refer mostly to highly frequent and recurrent switching in mood and energy (hypomania alternating with minor, major, or mixed depressive episodes). More than a half of patients with bipolar disorders have cyclothymic or hyperthymic temperaments, family history of bipolar disorders, and many of them exhibit comorbidity with anxiety disorders and personality disorders (clusters B or C). Early detection of soft bipolar disorders in young people is essential as long as it is done in a reliable way to avoid the risk of trivialization of the disorder and the utilization of interventions that may endanger the patients. The search for biomarkers, endophenotypes, and classification systems that combine categorical items with dimensional descriptors, besides the development of clinical scales with high levels of validity and sensitivity, are essential for the proper recognition and differential diagnosis of soft bipolar disorders. This thematic issue focuses on four aspects of the soft bipolar disorders: bipolar spectrum, temperaments, staging, and treatment.