Effects of transcranial direct current stimulation (tDCS) in "Kiss nightclub fire" patients with post-traumatic stress disorder (PTSD): A phase II clinical trial.

Objective: Considered the second biggest tragedy with fatal victims caused by fire, the Kiss nightclub fire tragedy that occurred in the interior of southern Brazil brought several problems to survivors. It is reported that 30-40% of victims of disasters can develop post-traumatic stress disorder. Application of repetitive transcranial magnetic stimulation has shown promising results in the treatment of post-traumatic stress disorder. Transcranial direct current stimulation similar to repetitive transcranial magnetic stimulation, a neuromodulation technique, has shown promise in treatment of neuropsychiatric disorders. Method: A clinical trial was conducted from March 2015 to July 2016 in "KISS nightclub fire" disaster patients diagnosed with post-traumatic stress disorder without complete remission of symptoms, over 18 years, and who maintained pharmacological treatment. Treatment was given using electrodes as cathode (right dorsolateral prefrontal cortex) and anode (contralateral deltoid muscle); a current of 2 mA was used for 25 cm² area (0.08 mA/cm² current density); 30 min once a day for 10 days continuously. Patients assessed pre- and post-intervention, 30 days' and 90 days' post-intervention. Post-Traumatic Stress Disorder Checklist, Civilian version, Montreal Cognitive Assessment, and Hamilton Depression and Anxiety Rating Scale were used. Results: One hundred forty-five subjects were screened and eight analyzed; 87.5% were female; 30.88 ± 7.74 years were of mean age. Post-intervention results: no cognitive impairment (Montreal Cognitive Assessment), 60% reduction in Hamilton Depression Rating Scale (moderate depression turns normal) (p < 0.001), 54.39% Hamilton Anxiety Rating Scale reduction (moderate-to-severe symptoms turn into mild symptoms) (p < 0.001), and 20% Post-Traumatic Stress Disorder Checklist, Civilian version scale decrease (high severity post-traumatic stress disorder symptoms turn moderate to moderately high severity) (p < 0.001). Post-traumatic stress disorder symptoms improvement was maintained 30-days post-intervention (Post-Traumatic Stress Disorder Checklist, Civilian version, p = 0.025) and improvement in symptoms of depression (Hamilton Depression Rating Scale, p = 0.006) and anxiety (Hamilton Anxiety Rating Scale, p = 0.028) in 90 days post-intervention. Conclusion: Despite decrease over time, improvement in post-traumatic stress disorder, depression and anxiety symptoms was maintained throughout the first month after treatment. Transcranial direct current stimulation adjuvant can be an alternative treatment to refractory post-traumatic stress disorder, either as monotherapy or as treatment enhancement strategy. They can also be an option for patients who do not want or do not tolerate pharmacological management.

Epidemiological Profile of Patients with Infective Endocarditis at three Tertiary Centers in Brazil from 2003 to 2017

Abstract Background Infective endocarditis (IE) is a disease with high morbimortality and an increasing incidence. With improved diagnosis and treatment, a number of epidemiological changes have been reported over time. Objectives We sought to describe the epidemiological profile, mortality predictors, and analysis of a possible microbiological transition in patients admitted to three tertiary centers in Brazil. Methods In this cross-sectional retrospective study, data from 211 patients with definite or probable IE were analyzed according to the modified Duke criteria between 2003 and 2017. The association between categorical variables was assessed using the chi-square or Fisher's exact test, and binary logistic models were built to investigate mortality. We considered p <0.05 statistically significant. Results The median age of the sample was 48 (33-59) years old, 70.6% were men, and the most prevalent pathogen was Staphylococcus spp. (19%). Mortality was 22.3%, with increasing age being the leading risk factor for death (p = 0.028). Regarding the location of the disease, native valves were the most affected site, with the aortic valve being more affected in men than women (p = 0.017). The mean number of cases of Staphylococcus spp. (τ = 0.293, p = 0.148) and Streptococcus spp. (τ = -0.078, p = 0.727) has remained stable over the years. Conclusion No trend towards reduced or increased mortality was evident between 2003 and 2017. Although Staphylococcus spp. were the most prevalent pathogen, the expected epidemiological transition could not be observed.

The role of personality in posttraumatic stress disorder, trait resilience, and quality of life in people exposed to the Kiss nightclub fire.

OBJECTIVE: To evaluate the relationship among personality (according to Cloninger's psychobiological model), posttraumatic stress disorder (PTSD) symptoms, trait resilience and quality of life (QoL) in people who were exposed to the Kiss nightclub fire. METHODS: 188 participants were assessed with the Posttraumatic Checklist-civilian version (PCL-C), the Resilience Scale (RS), the Temperament and Character Inventory (TCI), the World Health Organization Quality of Life-Bref (WHOQOL-Bref), and the WHOQOL-100 Spirituality, religiousness, and personal beliefs (WHOQOL-100-SRPB). Data were analyzed in a dimensional approach, with correlation analysis, multiple linear regression and Structural Equation Modeling (SEM), with PCL-C, RS, and WHOQOL-Bref dimensions as dependent variables. RESULTS: Multiple linear regression showed that PTSD symptoms were predicted by harm avoidance (ß = .34, p < .001), self-directedness (ß = -.28, p < .01), and self-transcendence (ß = .24, p < .01). Trait resilience was predicted by harm avoidance (ß = -.38, p < .01), self-directedness (ß = .20, p < .05), and self-transcendence (ß = .18, p < .05). Also, PTSD symptoms had considerable negative effect on all dimensions of QoL. Self-transcendence was a positive predictor of subjective and spiritual QoL. SEM showed that QoL was predicted by PTSD symptoms (ß = -.52, p < .001), trait resilience (ß = .30, p < .001), cooperativeness (ß = .135, p = 0.40), and self-directedness (ß = .27, p < .01). The effect of self-directedness on QoL was mediated by PTSD symptoms and trait resilience. PTSD symptoms also mediated the relationship between trait resilience and QoL, and RS mediated the relationship of personality and PTSD symptoms. CONCLUSION: The study gives insights on prediction of PTSD severity, trait resilience and QoL from temperament and character traits, in a sample of people exposed to the Kiss nightclub fire. Harm avoidance was the most influent trait on PTSD symptoms and trait resilience. Self-directedness was the most import trait related to QoL, still that it was more related to PTSD severity than personality traits. Self-transcendence had positive effects on both PTSD symptoms and trait resilience, indicating a coping style that may coexist with psychopathology.

The positive impact of physical activity on the reduction of anxiety scores: a pilot study.

OBJECTIVES: To compare anxiety scores between physical activity practitioners and sedentary, men and women and to relate them to physical activity frequency and age. METHODS: In this cross-sectional study, a sample of 256 regular aerobic physical activity practitioners was compared to a sample of 256 sedentary individuals (control group). Anxiety scores were quantified by Anxiety Inventory Spielberger State-Trait (STAI). The scores of the groups were compared using the Student t-test and chi-square test for parametric and non-parametric data, respectively. The correlation between scores of different variables was performed using the Pearson test. RESULTS: There was a significant difference between the average anxiety scores (p <0.001) and the chi-square test proved there is a higher prevalence of severe anxiety (p <0.001) in the sedentary group. Age did not correlate with worse anxiety scores (p <0.05). Comparing by gender, women had a higher prevalence of intense anxiety. CONCLUSIONS: Individuals who engage in regular physical activity have lower levels of anxiety, and both sexes are benefited with the anxiolytic potential of physical activity. Therefore, this study proved that the Roman poet Juvenal was right, and his expression "Mens sana in corpore sano," could also be interpreted in the opposite direction, i.e., a healthy body correlates with a healthy mind.

The positive impact of physical activity on the reduction of anxiety scores: a pilot study

SUMMARY OBJECTIVES: To compare anxiety scores between physical activity practitioners and sedentary, men and women and to relate them to physical activity frequency and age. METHODS: In this cross-sectional study, a sample of 256 regular aerobic physical activity practitioners was compared to a sample of 256 sedentary individuals (control group). Anxiety scores were quantified by Anxiety Inventory Spielberger State-Trait (STAI). The scores of the groups were compared using the Student t-test and chi-square test for parametric and non-parametric data, respectively. The correlation between scores of different variables was performed using the Pearson test. RESULTS: There was a significant difference between the average anxiety scores (p <0.001) and the chi-square test proved there is a higher prevalence of severe anxiety (p <0.001) in the sedentary group. Age did not correlate with worse anxiety scores (p <0.05). Comparing by gender, women had a higher prevalence of intense anxiety. CONCLUSIONS: Individuals who engage in regular physical activity have lower levels of anxiety, and both sexes are benefited with the anxiolytic potential of physical activity. Therefore, this study proved that the Roman poet Juvenal was right, and his expression "Mens sana in corpore sano," could also be interpreted in the opposite direction, i.e., a healthy body correlates with a healthy mind.

RESUMO OBJETIVOS: Comparar escores de ansiedade entre praticantes de atividade física e sedentários, entre homens e mulheres e relacioná-los com frequência de atividade física e idade. MÉTODOS: Amostra de 256 praticantes de atividade física aeróbica regular foi comparada à amostra de 256 sedentários (grupo controle). Escores de ansiedade foram quantificados por meio do Inventário de Ansiedade Estado-Traço de Spielberger (Idate). Os escores dos grupos foram comparados por meio dos testes t de Student e qui-quadrado para dados paramétricos e não paramétricos, respectivamente. A correlação entre escores de diferentes variáveis foi realizada pelo teste de Pearson. RESULTADOS: Houve diferença significativa entre os escores médios de ansiedade (p < 0,001) e o teste qui-quadrado comprovou haver maior prevalência de escores de ansiedade intensa (p < 0,001) no grupo de sedentários. Idade não se correlacionou com piores escores de ansiedade (p < 0,05). Em relação ao sexo, mulheres apresentaram maior prevalência de escores de ansiedade intensa. CONCLUSÕES: Praticantes de atividade física possuem menores escores de ansiedade e ambos os sexos se beneficiam com o potencial ansiolítico da prática de atividade física. Portanto, foi comprovado que a máxima de Juvenal, Mens sana in corpore sano, também pode ser interpretada em sentido inverso, em que um corpo são se correlaciona com uma mente sã.

Effectiveness of a Mindfulness-Based Intervention in the Management of Musculoskeletal Pain in Nursing Workers.

BACKGROUND: Chronic pain is a prevalent disorder in nursing workers worldwide. Several studies have proposed measures to mitigate this critical scenario. Mindfulness-based interventions (MBI) have been found to have promising results in the treatment of this disorder. AIMS: To quantify the effectiveness of an adapted mindfulness program (AMP) in the management of musculoskeletal pain (MSP) in nursing technicians of a Brazilian university hospital. DESIGN: This study was a clinical, prospective, open, repeated measures trial, with data collection between January and July 2015. SETTINGS: Brazilian university hospital. PARTICIPANTS/SUBJECTS: Sixty-four female nursing technicians with a mean age of 47.01 years (standard deviation = 9.50) with chronic pain symptoms. METHODS: Sixty-four female nursing technicians with a mean age of 47.01 years (standard deviation = 9.50) and MSP participated in this prospective study. Before the intervention (T0), scores of anxiety, depression, mindfulness, musculoskeletal complaints, pain catastrophizing, self-compassion, and perception of quality of life were quantified. These scores were reevaluated after 8 weeks (T1) and 12 weeks (T2) of weekly AMP sessions (60 minutes each). The variables were evaluated by analysis of variance for repeated measures, followed by the Bonferroni test. RESULTS: AMP reduced the scores of musculoskeletal symptoms, anxiety, depression, and pain catastrophizing (p < .001). A significant increase was identified in self-compassion scores and perception of quality of life in the physical, psychological, and overall assessment (p ≤ .04). Positive effects of AMP occurred at T1 and remained unchanged at T2. CONCLUSION: AMP contributed to a reduction in painful symptoms and improved the quality of life of nursing workers, with a lasting effect until the 20th week of follow-up, indicating utility as an effective strategy for the management of MSP in the group studied.

The impact of asthma on quality of life and anxiety: a pilot study.

INTRODUCTION: Asthmatic patients are at risk for psychiatric symptoms. The objective of this study is to test the hypothesis that asthmatics have worse quality of life and anxiety scores in relation to a control group. METHODS: This study is a cross-sectional study in which quality of life and anxiety scores were compared in a sample of 102 individuals, 51 asthmatics and 51 non-asthmatics. Quality of life and anxiety scores were quantified using validated questionnaires. The differences between the averages and the correlations between the total score for quality of life and anxiety were compared with t-tests and Pearson's correlation tests, respectively. The odds ratio compared the prevalence of moderate and severe anxiety between the groups. RESULTS: The asthma group had higher average anxiety (p < 0.001) and lower averages in all areas of quality of life: physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning and mental health (p < 0.05 for all variables). There was a significant and inverse correlation between the total score for quality of life and anxiety scores but only in the asthma group (r = -0.71). CONCLUSIONS: Asthmatics have worse indicators of quality of life and anxiety, even though the symptoms of asthma are under clinical control. Moreover, the inverse correlation between the quality of life and the average anxiety scores in the asthma group suggests that the pulmonary inflammatory process of asthma may be related to the pathophysiology of emotional commitment in that group.

Aggressive behavior during the first 24 hours of psychiatric admission / Comportamento agressivo durante as primeiras 24 horas de internação psiquiátrica

OBJECTIVE: To investigate the association between aggression in the first 24 hours after admission and severity of psychopathology in psychiatric inpatients. METHODS: This cross-sectional study included psychiatric patients admitted to Hospital Universitário de Santa Maria, in Santa Maria, southern Brazil, from August 2012 to January 2013. At their arrival at the hospital, patients were interviewed to fill in the Brief Psychiatric Rating Scale (BPRS) form, and any aggressive episodes in the first 24 hours after admission were recorded using the Overt Aggression Scale (OAS). The Mann-Whitney U test was used to compare patients according to aggressiveness: aggressive versus non-aggressive, hostile versus violent, and aggressive against others only versus self-aggressive. RESULTS: The sample was composed of 110 patients. Aggressive patients in general had higher BPRS total scores (p = 0.002) and individual component scores, and their results showed more activation (p < 0.001) and thinking disorders (p = 0.009), but less anxious-depression (p = 0.008). Violent patients had more severe psychomotor agitation (p = 0.027), hallucinations (p = 0.017) and unusual thought content (p = 0.020). Additionally, self-aggressive patients had more disorientation (p = 0.011) and conceptual disorganization (p = 0.007). CONCLUSIONS: Aggression in psychiatric patients in the first 24 hours after admission is associated with severity of psychopathology, and severity increases with severity of patient psychosis and agitation (AU)

OBJETIVO: Avaliar a relação entre agressividade nas primeiras 24 horas após admissão e a gravidade da psicopatologia de pacientes psiquiátricos. MÉTODOS: Este estudo transversal foi realizado no Hospital Universitário de Santa Maria, na região sul do Brasil, com pacientes admitidos entre agosto de 2012 e janeiro de 2013. Ao chegar ao hospital, os pacientes foram entrevistados para completar a Escala Breve de Avaliação Psiquiátrica (BPRS), e todos os episódios de agressão nas primeiras 24 horas após a admissão foram registrados usando a Escala de Agressividade Declarada (OAS). O teste U de Mann-Whitney foi usado para as comparações entre pacientes agressivos e não-agressivos, hostis e violentos, e agressivos contra outros apenas ou autoagressivos. RESULTADOS: A amostra tinha 110 pacientes. Em geral, pacientes agressivos tiveram escores mais altos na escala BPRS (p = 0.002) e nos itens individuais, e exibiram mais ativação (p < 0.001) e distúrbios de pensamento (p = 0.009), mas menos ansiedade-depressão (p = 0.008). Os pacientes violentos tiveram escores mais altos para excitação (p = 0.027), comportamentos alucinatórios (p = 0.017) e alteração de conteúdo do pensamento (p = 0.020). Além disso, os pacientes autoagressivos mostraram maior desorientação (p = 0.011) e desorganização conceitual (p = 0.007). CONCLUSÕES: A agressão em pacientes psiquiátricos nas primeiras 24 horas da admissão é relacionada a gravidade da psicopatologia, a qual aumenta à medida que a gravidade da psicose e a excitação do paciente aumentam (AU)

Aggressive behavior during the first 24 hours of psychiatric admission.

OBJECTIVE: To investigate the association between aggression in the first 24 hours after admission and severity of psychopathology in psychiatric inpatients. METHODS: This cross-sectional study included psychiatric patients admitted to Hospital Universitário de Santa Maria, in Santa Maria, southern Brazil, from August 2012 to January 2013. At their arrival at the hospital, patients were interviewed to fill in the Brief Psychiatric Rating Scale (BPRS) form, and any aggressive episodes in the first 24 hours after admission were recorded using the Overt Aggression Scale (OAS). The Mann-Whitney U test was used to compare patients according to aggressiveness: aggressive versus non-aggressive, hostile versus violent, and aggressive against others only versus self-aggressive. RESULTS: The sample was composed of 110 patients. Aggressive patients in general had higher BPRS total scores (p = 0.002) and individual component scores, and their results showed more activation (p < 0.001) and thinking disorders (p = 0.009), but less anxious-depression (p = 0.008). Violent patients had more severe psychomotor agitation (p = 0.027), hallucinations (p = 0.017) and unusual thought content (p = 0.020). Additionally, self-aggressive patients had more disorientation (p = 0.011) and conceptual disorganization (p = 0.007). CONCLUSIONS: Aggression in psychiatric patients in the first 24 hours after admission is associated with severity of psychopathology, and severity increases with severity of patient psychosis and agitation.

Balance disturbances in asthmatic patients.

OBJECTIVE: The aim of this study was to investigate balance control in asthmatic patients. METHODS: Thirty subjects with controlled persistent asthma were compared with 30 non-asthmatic subjects who were matched by age and sex. Individuals who had received psychiatric treatment, demonstrated chronic musculoskeletal pain, had limited joint movements, or showed vestibular or other equilibrium disorders were excluded from both the groups to avoid biomechanical bias in the dynamic posturography. Balance control was evaluated with the subject standing still on a force platform under four different sensory test conditions. These conditions combined the subject's eyes being opened or closed with a fixed or mobile force platform. A mobile platform provides a somatosensory perturbation, and when associated with the eyes closed condition, only vestibular information is available to moderate balance control. Sensory manipulation provides a more sensitive condition to differentiate postural control between populations or pathologies. Data were sampled at 100 Hz in three 20-second trials and four postural conditions were assessed. The center of pressure (CoP) displacement values were used to calculate area and velocity in the medial-lateral and forward-backward directions. A two-factor analysis of variance with repeated measurements was applied to the data. RESULTS: In comparison to the control group, the asthma group demonstrated a greater area of CoP displacement in conditions using the mobile force platform (with eyes opened or closed) and a higher velocity in forward-backward direction on the mobile platform with the eyes closed. CONCLUSION: Asthmatic individuals presented a greater area for the CoP displacement under somatosensory perturbations and a higher velocity in the forward-backward direction when vestibular information only was made available. Our data suggest that balance needs to be evaluated in asthmatic patients.

Obesity is associated with previous suicide attempts in bipolar disorder.

UNLABELLED: Gomes FA, Kauer-Sant'Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder. OBJECTIVE: There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder. METHODS: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese. RESULTS: Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06-3.69, p = 0.03) as likely to have a history of suicide attempt(s). CONCLUSION: Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.

Increased serum neurotrophin-4/5 levels in bipolar disorder.

Neurotrophins are central to several aspects of central nervous system function, and emerging evidence links these growth factors to mood disorders. The purpose of this study was to investigate serum neurotrophin-4/5 (NT-4/5) levels in patients with bipolar disorder, both within mood episodes and in euthymia. Patients with bipolar I disorder (n=154) and controls (n=30) had their NT-4/5 serum levels assayed using an ELISA. Levels of NT-4/5 levels were significantly higher in bipolar disorder patients than in controls; NT-4/5 levels were increased in mania, depression and euthymia, but not significantly different between BD mood states. As far as are aware, this is the first study showing NT-4/5 immunocontent alterations in bipolar disorder. A tentative explanation would be that NT-4/5 increases is compensating for ongoing oxidative damage in dopaminergic neurons.

Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes.

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes / Aumento do estresse oxidativo como um mecanismo para a diminuição dos níveis de BDNF em episódios maníacos agudos

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

OBJETIVO E MÉTODO: Existem crescentes evidências indicando que alterações no fator neurotrófico derivado do cérebro e aumento do estresse oxidativo podem estar envolvidos na fisiopatologia do transtorno bipolar. Considerando os achados recentes de que os níveis de fator neurotrófico derivado do cérebro estão diminuídos em situações de aumento de estresse oxidativo, nós testamos a correlação entre os níveis séricos de substâncias reativas do ácido tiobarbitúrico, um índice de peroxidação lipídica, e os níveis séricos de fator neurotrófico derivado do cérebro em pacientes portadores de transtorno bipolar durante mania aguda e em controles saudáveis. RESULTADOS: Os níveis séricos de substâncias reativas do ácido tiobarbitúrico e fator neurotrófico derivado do cérebro apresentaram uma correlação negativa em pacientes bipolares (r = -0,56; p = 0,001), enquanto não houve correlação significativa no grupo controle. CONCLUSÃO: Estes resultados sugerem que alterações de estresse oxidativo podem ser mecanisticamente associadas com níveis reduzidos de BDNF observados em indivíduos com transtorno bipolar.

A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania.

OBJECTIVE: The therapeutics for bipolar disorders are still far from adequate, and new options with improved effectiveness, safety, and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania. METHOD: A randomized, placebo-controlled, double-blind study was performed in adult inpatients (N = 180) with a DSM-IV-TR diagnosis of bipolar I disorder, current episode manic with or without psychotic features (rapid cyclers and mixed episodes were not included). No antipsychotic agent was used during the study. Subjects were given fixed oral doses of either allopurinol 600 mg/day (N = 60), dipyridamole 200 mg/day (N = 60), or placebo (N = 60) added to lithium for 4 weeks. Subjects were rated at baseline and days 7, 14, 21, and 28 using the Young Mania Rating Scale (YMRS) as the primary efficacy measure. The study was conducted between September 2003 and September 2006. RESULTS: Allopurinol resulted in greater mean reductions in YMRS scores from baseline to day 21 (p < .001) and day 28 (p = .003) compared with placebo using a linear model analysis (d = 0.32, 95% CI = 0.07 to 0.57). Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo (p = .008). Lithium showed a significant antimanic efficacy even in the placebo group. Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group (p < .001). CONCLUSION: Allopurinol is clinically effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania, especially for those presenting tolerability and safety issues with antipsychotics. The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder. Further placebo-controlled studies with allo-purinol compared with standard mood stabilizers in mania and maintenance are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00560079.