De-imFAR phase II project: a study protocol for a cluster randomised implementation trial to evaluate the effectiveness of de-implementation strategies to reduce low-value statin prescribing in the primary prevention of cardiovascular disease.

INTRODUCTION: This study aims to reduce potentially inappropriate prescribing (PIP) of statins and foster healthy lifestyle promotion in cardiovascular disease (CVD) primary prevention in low-risk patients. To this end, we will compare the effectiveness and feasibility of several de-implementation strategies developed following the structured design process of the Behaviour Change Wheel targeting key determinants of the clinical decision-making process in CVD prevention. METHODS AND ANALYSIS: A cluster randomised implementation trial, with an additional control group, will be launched, involving family physicians (FPs) from 13 Integrated Healthcare Organisations (IHOs) of Osakidetza-Basque Health Service with non-zero incidence rates of PIP of statins in 2021. All FPs will be exposed to a non-reflective decision assistance strategy based on reminders and decision support tools. Additionally, FPs from two of the IHOs will be randomly assigned to one of two increasingly intensive de-implementation strategies: adding a decision information strategy based on knowledge dissemination and a reflective decision structure strategy through audit/feedback. The target population comprises women aged 45-74 years and men aged 40-74 years with moderately elevated cholesterol levels but no diagnosed CVD and low cardiovascular risk (REGICOR<7.5%), who attend at least one appointment with any of the participating FPs (May 2022-May 2023), and will be followed until May 2024. We use the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate outcomes. The main outcome will be the change in the incidence rate of PIP of statins and healthy lifestyle counselling in the study population 12 and 24 months after FPs' exposure to the strategies. Moreover, FPs' perception of their feasibility and acceptability, and patient experience regarding the quality of care received will be evaluated. ETHICS AND DISSEMINATION: The study was approved by the Basque Country Clinical Research Ethics Committee and was registered in ClinicalTrials.gov (NCT04022850). Results will be disseminated in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04022850.

Global intellectual ability and adaptive functioning in children with FASD with and without sentinel facial features.

Background: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder characterized by cognitive and adaptive impairment. FASF can be presented or not with sentinel facial features (SFF). The presence of such SFF have been positively correlated with cognitive impairment in children with FASD.Objectives: The current study explores difference in global intellectual functioning and how cognition affects adaptive behavior in children with and without SFF.Methods: A total of 88 children and adolescents (55 males, 33 females) with confirmed FASD diagnosis were included in the study, of which 16 had sentinel facial features. Childrens' neuropsychological functioning was assessed using the Wechsler Intelligence Scale for Children (WISC-V) and The Behavioral Assessment of the Dysexecutive Syndromes for Children (BADS-C). Adaptive behavior was explored through the Adaptive Behavior Assessment System (ABAS-3).Results: Children with SFF performed more poorly in tasks assessing processing speed (t = 2.495, t = .020) and executive functioning (t = 4.147, t = .001). Those children also had lower IQ scores than children without SFF (t = 2.658, t = .016). BADS-C overall scaled score was related to three of the four domains of the ABAS scale (conceptual, social, and practical) but only in the group of FASD children without SFF (B = 0.547, t = .020; B = 0.544,t = .049; B = 0.431,t = .040, respectively).Conclusions: The present study founds poorer cognitive outcomes in children who have FASD with sentinel facial features. In children without SFF, stronger executive functioning is also related to significantly stronger reported conceptual, social, and practical adaptive behaviors. Better understanding of cognitive and adaptive functioning in children with FASD may help in the design of tailored evidenced-based interventions.

Outcomes associated with different vaccines in individuals with bipolar disorder and impact on the current COVID-19 pandemic- a systematic review.

Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.

Inflammation biomarkers in suicide attempts and their relation to abuse, global functioning and cognition.

OBJECTIVES: To explore the link between cytokines and suicide attempts and their relationship with the psychological aspects of this complex multifactorial phenomenon. METHODS: 96 participants, including 20 patients with a recent suicide attempt and diagnosis of Major Depression Disorder (MDD), 33 MDD patients with a lifetime history of suicide attempt, 23 non-attempter MDD patients, and 20 healthy controls underwent an assessment on depressive symptoms, global functioning, aggressive behaviour, presence of abuse and attention performance. Additionally, all participants had a blood extraction for IL-2, IL2-R, IL-4, IL-6, and TNF-α plasma levels analysis. RESULTS: IL-6 levels were significantly different across groups (F(3,89)=3.690; p = 0.015), with higher concentrations in both recent (p = 0.04) and distant (p = 0.015) attempt in comparison to MDD non-attempters. IL-6 was associated with adult physical abuse (B = 2.591; p = 0.021), lower global functioning score (B = -0.512; p = 0.011), and poorer performance on attention (B = -0.897; p = 0.011). CONCLUSIONS: Recent and distant suicidal behaviour is associated with elevated IL-6 levels, which may be influenced by stressful and traumatic experiences. Elevated concentrations of IL-6 could have a negative impact on attention, increasing suicide risk. More research is needed to clarify the role of cytokines in suicide-related features to explore novel treatments and more effective preventive interventions.

DSM-5 and ICD-11 criteria for bipolar disorder: Implications for the prevalence of bipolar disorder and validity of the diagnosis - A narrative review from the ECNP bipolar disorders network.

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research.

Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action.

Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively.

Alterations of the HPA Axis Observed in Patients with Major Depressive Disorder and Their Relation to Early Life Stress: A Systematic Review.

BACKGROUND: Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are common in patients diagnosed with major depressive disorder (MDD). Nevertheless, these alterations are not found in every patient. There is evidence to indicate a possible mediating role of early life stress (ELS) in the relation between dysfunction of the HPA axis and MDD. We conducted a systematic review to understand if the alterations of the HPA axis commonly found in patients with MDD are due to early life stress or are caused by the disorder itself. METHODS: The review was conducted by following the PRISMA guidelines. Original articles were found in PubMed and via a manual search. Only studies whose design allowed comparison of the HPA functioning in the 4 groups no-MDD/no-ELS, MDD/no-ELS, no-MDD/ELS, and MDD/ELS were included. RESULTS: Hyperactivity or hypoactivity of the HPA axis was found in 8 articles. A greater number of abnormalities and a higher rate of posttraumatic stress disorder comorbidity were found in the MDD/ELS group. Dysfunction of the HPA axis was also found in the no-MDD/ELS groups. CONCLUSION: HPA dysfunction found in MDD seems to be more related to the presence of ELS rather than to the MDD itself. Future studies are needed to clarify the exact mechanisms involved.

Influencia del sexo en el tratamiento con olanzapina: una revisión sistemática / Gender differences in olanzapine treatment: A systematic review

La olanzapina es un antipsicótico comúnmente utilizado como tratamiento de enfermedades como la esquizofrenia y el trastorno bipolar. En ocasiones la manifestación de la enfermedad difiere entre sexos, pero poco se ha investigado sobre la influencia de esta diferencia biológica en la respuesta al tratamiento o en los efectos secundarios. En esta revisión sistemática analizamos estas diferencias de sexo en la efectividad y en los efectos adversos de la olanzapina. Aunque algunos estudios mostraron mayor efectividad en mujeres, este resultado es ambiguo al no encontrar diferencias en otros trabajos. Por otro lado, encontramos mayor tendencia de los hombres a la ganancia de peso y al parkinsonismo, mientras que más mujeres experimentaron mareos, mayor aumento del colesterol y del intervalo QT. Dado el amplio uso a nivel mundial de la olanzapina, es importante realizar futuros estudios analizando las diferencias observadas, ya que podrían ser cruciales para mejorar la calidad de vida de los pacientes

Olanzapine is an antipsychotic drug commonly used in the treatment of illnesses such as schizophrenia and bipolar disorder. Occasionally the manifestation of the illness differs between genders, but little has been investigated on the influence of this biological difference in the response to the treatment or the secondary effects. In this systematic review, an analysis is made of these gender differences on the effectiveness and adverse effects of olanzapine treatment. Although some studies showed a higher effectiveness in women, this was ambiguous due to not finding any differences in other works. On the other hand, there was a greater tendency for men to gain weight and suffer from Parkinson symptoms, while the women were more likely to suffer from dizzy spells, a greater increase in cholesterol, and in QT interval. Given the worldwide use of olanzapine, it is important that further studies should be performed to analyse these differences observed, since they could be crucial for improving the quality of life of the patients

Association Between Medication Adherence and Oxidative Stress in Patients With First-Episode Mania.

Poor adherence is a major problem in patients with manic episodes that impairs functionality and has unknown effects on oxidative stress. The objective of this study was to analyze the relationship between adherence to medication, severity of symptoms and oxidative stress in a sample of patients with a first episode of mania. A longitudinal, 6-month study was performed in 60 patients, who were classified as adherent and non-adherent to medication (mainly antipsychotics). Blood levels of oxidative stress parameters and expression of the antioxidant nuclear transcription factor NRF2 in mononuclear cells of peripheral blood were assessed at baseline and at the end of follow-up. In addition, clinical symptoms and functioning were evaluated. Linear multivariate regression was used to determine the relationship between adherence, oxidative stress, and clinical symptoms. Finally, 44 patients completed follow-up. The results of this study showed that at 6-month follow-up, adherence was significantly associated with better functioning and reduced clinical symptoms. Additionally, more severe symptoms were associated with increased levels of oxidative stress and antioxidant parameters. At study completion, non-adherents exhibited greater levels of antioxidants than adherent patients. In conclusion, poor adherence to medication is associated with a poorer prognosis in the medium term and causes increased antioxidant response.

Can lithium salts prevent depressive episodes in the real world?

To critically examine the effectiveness of lithium in preventing depressive symptoms (mixed and depressive episodes) in real life settings, taking into account adherence to drug treatment and its implications for the clinical costs of the disease. Overall, 72 patients with bipolar disorder initially treated with lithium carbonate were included and followed-up for 10 years. Patients were assessed every 8 weeks for morbidity and alcohol/drug consumption. Patients with good adherence to lithium had fewer episodes with depressive features than poor adherers (B = 2.405, p = 0.046) and also fewer manic and hypomanic episodes (B = 2.572; p < 0.001), after controlling for confounders. Time to relapse into a depressive or mixed episode and into a manic or hypomanic episode was shorter in patients with poor adherence. The costs of the 1.95 ±â€¯2.38 (mean ±â€¯standard deviation) admissions of adherent patients through the 10 years of follow-up were €10,349, while the costs of the 6.25 ±â€¯4.92 admissions of non-adherent patients were €44,547. In clinical practice settings, long-term lithium salts seem to have a preventive effect on depressive symptoms.

Correlates of neurocognitive functions in individuals at ultra-high risk for psychosis - A 6-month follow-up study.

Cognitive deficits are evident at the prodromal phase of psychosis. It has been noted that brain-derived neurotrophic factor (BDNF) is correlated with cognition in both preclinical and clinical studies. However, to our knowledge, no study has evaluated blood BDNF levels and their association with cognitive impairment in individuals at ultra-high risk for psychosis (UHR). We included 13 individuals at UHR and 30 healthy controls (HC) matched by sex, age, and educational level. Plasma BDNF levels were measured at baseline and 6 months. Neurocognitive functions (executive functions, speed of processing, verbal learning and memory, working memory) were examined at 6 months. Regression analyses were conducted to examine the relationship between BDNF levels and cognitive performance. BDNF levels were lower in UHR group than in HC group both at baseline and at 6 months (P = 0.001, and P = 0.007, respectively). There were no associations between plasma BDNF levels and all of the cognitive domains in both groups. Our findings showed that peripheral BDNF levels were not related to cognitive deficits in UHR and HC groups while the lower BDNF level in the former persisted up to 6 months. Further research is needed in a large sample.

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

INTRODUCTION: Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. METHODS: We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. RESULTS: A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDDolderadults). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. CONCLUSIONS: Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system.

The complex association between the antioxidant defense system and clinical status in early psychosis.

Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years. Clinical symptoms and functioning were also assessed at the same time points using various scales. Linear regression analysis was performed to investigate the relationship between TAS and clinical status at each assessment, adjusting for potential confounding factors. The distribution of clinical variables was grouped in different percentiles to assess the dose-response in the relation between clinical variables and TAS. At baseline, patient's score on Children's Global Assessment Scale (CGAS) was directly and significantly associated with TAS with a monotonic increase in percentiles, and surprising this association was reversed after one and two years of follow-up with a monotonic decrease. In summary at the onset of the illness, TAS is positively related to clinical status, whereas as the illness progresses this correlation is reversed and becomes negative. This may be the result of an adaptive response.

Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos / Benzodiazepine prescriptions and falls in older men and women

Objetivo. A pesar de las advertencias de numerosas asociaciones profesionales, las benzodiacepinas (BZD) y los hipnóticos Z (Z) son ampliamente prescritos a los ancianos ya que son especialmente susceptibles de padecer insomnio y ansiedad, pero a su vez resultan especialmente sensibles a la aparición de efectos secundarios a dichos medicamentos. En este estudio evaluamos la prescripción de BZD/Z en una muestra de ancianos (≥65) que se presentan en el servicio de urgencias de un hospital por haber sufrido una caída. Métodos. Recogimos información del tipo, número y dosis de los fármacos BZD/Z prescritos y exploramos la presencia de diferencias de género en dicha prescripción. Resultados. Las BZD/Z habían sido prescritas a un 43,6% de la muestra (n=654), más frecuentemente a las mujeres. El 78,4% de las prescripciones fueron de BZD/Z de vida media corta. La mayoría de los pacientes (83,5%) tomaban solamente un fármaco BZD/Z, pero un 16,5% consumían más de una BZD/Z, sin diferencias de género. Un 58% de los pacientes consumían dosis de BZD/Z más elevadas que las recomendadas para ancianos, siendo la proporción significativamente más elevada para los hombres (70% vs. 53,1%). Conclusiones. Alrededor de un 40% de los ancianos que acuden a un servicio de urgencias por haber sufrido una caída se encontraban tomando BZD/Z. Hemos hallado algunas diferencias de género en la prescripción de BZD/Z, especialmente en la prescripción por encima de la dosis recomendada para ancianos y de fármacos de vida media larga (AU)

Objective. Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. Methods. We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. Results. BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). Conclusions. Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life (AU)

Benzodiazepine prescriptions and falls in older men and women. / Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos.

OBJECTIVE: Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. METHODS: We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. RESULTS: BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). CONCLUSIONS: Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life.

Nutritional supplements in depressive disorders.

There is increasing evidence about the role of nutrients in mental health. An adequate intake of nutrients contributes to better overall health and mental health in particular. Major depression is a severe mental illness with a high prevalence for which effective treatments exist but not in all cases the patient’s remission is achieved. Therefore, it is increasingly aimed at optimizing the supply of nutrients necessary for adequate brain functioning as adjunctive therapy to antidepressant treatment in depressive disorders. In this article we review those nutrients that have been related to depression: Omega-3 fatty acids, B vitamins, s-adenosylmethionine, tryptophan, magnesium, zinc and probiotics.

Eficacia y seguridad de la ketamina en depresión bipolar: una revisión sistemática / Efficacy and safety of ketamine in bipolar depression: a systematic review

El componente depresivo es el más prevalente del trastorno bipolar. La ketamina ha mostrado eficacia y rapidez como tratamiento de episodios depresivos. El objetivo del presente trabajo es realizar una revisión sistemática sobre la eficacia y seguridad de la ketamina como tratamiento de la depresión bipolar, y sus tipos de administración. Se obtuvieron 10 artículos relevantes que cumplían con los criterios del estudio: un ensayo clínico, 5 estudios de cohorte y 4 series de casos. La forma de administración utilizada en el 60% de los trabajos fue la infusión intravenosa. La ketamina parece ser un tratamiento seguro y eficaz para la depresión bipolar, aunque la duración de la acción es breve. Los efectos adversos que se observaron se produjeron generalmente en el momento de la infusión y tendieron a desaparecer completamente al cabo de 1-2h. Por tanto, es necesario realizar más estudios para explorar nuevas vías de administración, así como su seguridad y efectos adversos (AU)

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects (AU)

Relationship between the use of benzodiazepines and falls in older adults: A systematic review.

Falls in the elderly represent a major health problem. The etiology of falls is usually multifactorial. Special attention should be paid on benzodiazepines (BZDs) since they are widely used by older adults. A literature search of the PUBMED and EMBASE databases from January 2007 to February 2017 was conducted using the MeSH terms "benzodiazepines", "elderly" and "falls" or "accidental falls". The systematic review was performed according to PRISMA criteria. Of the 27 references selected for full reading from 235 found, 15 were eliminated and 12 papers were selected for systematic review. Exposure to BZDs was associated with a higher risk of falls in older adults, which is consistent with the results reported in the literature and previous reviews and meta-analyses. BZDs increase the risk of falling when used either as monotherapy or in combined therapies. It is preferable to use short-acting BZDs, to avoid cumulative effects over time predisposing to falls. A high proportion of falls in older adults are related to the use of BZDs. They should be prescribed to older patients in accordance with current clinical guidelines and reviewed over time. BZDs should be prescribed as a short-term therapy and progressively withdrawn. Short-acting BZDs should be the treatment of choice.

Efficacy and safety of ketamine in bipolar depression: A systematic review. / Eficacia y seguridad de la ketamina en depresión bipolar: una revisión sistemática.

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects.