Luís Fernando Tófoli

The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

Brazilian multicentre study of common mental disorders in primary care: rates and related social and demographic factors

Problemas de saude mental sao comuns na atencao primaria e sao geralmente relacionados a ansiedade e a depressao. Este estudo tem o objetivo de avaliar a taxa de transtornos mentais comuns e suas associacoes com caracteristicas sociodemograficas em unidades de saude da familia. E um estudo multicentrico, transversal, com os usuarios da atencao primaria do Rio de Janeiro, Sao Paulo, Fortaleza (Ceara) e Porto Alegre (Rio Grande do Sul), Brasil. Utilizou-se o General Health Questionnaire (GHQ-12) e o Hospital Anxiety and Depression Scale (HAD). A taxa de transtornos mentais nos usuarios do Rio de Janeiro, Sao Paulo, Fortaleza e Porto Alegre foram, respectivamente, 51,9%, 53,3%, 64,3% e 57,7%, com diferencas significativas entre Porto Alegre e Fortaleza comparando-se ao Rio de Janeiro. Problemas de saude mental foram especialmente altos em mulheres, desempregados, em pessoas com baixa escolaridade e com baixa renda. Dadas as iniciativas do governo brasileiro para o desenvolvimento os cuidados primarios e para reorganizacao da politica publica de saude mental, e importante considerar os transtornos mentais comuns como uma prioridade tal como outras morbidades cronicas.Mental health problems are common in primary health care, particularly anxiety and depression. This study aims to estimate the prevalence of common mental disorders and their associations with socio-demographic characteristics in primary care in Brazil (Family Health Strategy). It involved a multicenter cross-sectional study with patients from Rio de Janeiro, São Paulo, Fortaleza (Ceará State) and Porto Alegre (Rio Grande do Sul State), assessed using the General Health Questionnaire (GHQ-12) and the Hospital Anxiety and Depression Scale (HAD). The rate of mental disorders in patients from Rio de Janeiro, São Paulo, Fortaleza and Porto Alegre were found to be, respectively, 51.9%, 53.3%, 64.3% and 57.7% with significant differences between Porto Alegre and Fortaleza compared to Rio de Janeiro after adjusting for confounders. Prevalence proportions of mental problems were especially common for females, the unemployed, those with less education and those with lower incomes. In the context of the Brazilian governments moves towards developing primary health care and reorganizing mental health policies it is relevant to consider common mental disorders as a priority alongside other chronic health conditions.

Evaluation of a mental health training intervention for multidisciplinary teams in primary care in Brazil: a pre- and posttest study

OBJECTIVES The aim of this research was to investigate whether a training intervention to enhance collaboration between mental health and primary care professionals improved the detection and management of mental health problems in primary health care in four large cities in Brazil. The training intervention was a multifaceted program over 96 h focused on development of a shared care model. METHOD A quasiexperimental study design was undertaken with assessment of performance by nurse and general practitioners (GPs) pre- and postintervention. Rates of recognition of mental health disorders (compared with the General Health Questionnaire) were the primary outcome, while self-reports of patient-centered care, psychosocial interventions and referral were the secondary outcomes. RESULTS Six to 8 months postintervention, no changes were observed in terms of rate of recognition across the entire sample. Nurses significantly increased their recognition rates (from 23% to 39%, P=.05), while GPs demonstrated a significant decrease (from 42% to 30%, P=.04). There were significant increases in reports of patient-centered care, but no changes in other secondary outcomes. CONCLUSIONS Training professionals in a shared care model was not associated with consistent improvements in the recognition or management of mental health problems. Although instabilities in the local context may have contributed to the lack of effects, wider changes in the system of care may be required to augment training and encourage reliable changes in behavior, and more specific educating models are necessary.

Psychiatry: life events and social support in late life depression.

OBJECTIVES: To examine the association of life events and social support in the broadly defined category of depression in late life. INTRODUCTION: Negative life events and lack of social support are associated with depression in the elderly. Currently, there are limited studies examining the association between life events, social support and late-life depression in Brazil. METHODS: We estimated the frequency of late-life depression within a household community sample of 367 subjects aged 60 years or greater with associated factors. “Old age symptomatic depression” was defined using the Composite International Diagnostic Interview 1.1 tool. This diagnostic category included only late-life symptoms and consisted of the diagnoses of depression and dysthymia as well as a subsyndromal definition of depression, termed “late subthreshold depression”. Social support and life events were assessed using the Comprehensive Assessment and Referral Evaluation (SHORT-CARE) inventory. RESULTS: “Old age symptomatic depression” occurred in 18.8% of the patients in the tested sample. In univariate analyses, this condition was associated with female gender, lifetime anxiety disorder and living alone. In multivariate models, “old age symptomatic depression” was associated with a perceived lack of social support in men and life events in women. DISCUSSION: Social support and life events were determined to be associated with late-life depression, but it is important to keep in mind the differences between genders. Also, further exploration of the role of lifetime anxiety disorder in late-life depression may be of future importance. CONCLUSIONS: We believe that this study helps to provide insight into the role of psychosocial factors in late-life depression.

Relationship among Medical Student Resilience, Educational Environment and Quality of Life

Context Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students. Methods We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young’s resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire – short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Results Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score ≥ 14 and STAI state or anxiety scores ≥ 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (β=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (β=-0.85; 95%CI=-1.25 to -0.45) QoL scores, environment (β=-6.48; 95%CI=-10.01 to -2.95), psychological (β=-22.89; 95%CI=-25.70 to -20.07), social relationships (β=-14.28; 95%CI=-19.07 to -9.49), and physical health (β=-10.74; 95%CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (β=-31.42; 95%CI=-37.86 to -24.98), learning (β=-7.32; 95%CI=-9.23 to -5.41), teachers (β=-5.37; 95%CI=-7.16 to -3.58), academic self-perception (β=-7.33; 95%CI=-8.53 to -6.12), atmosphere (β=-8.29; 95%CI=-10.13 to -6.44) and social self-perception (β=-3.12; 95%CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements. Conclusions Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training.

Apoio matricial em saúde mental na atenção primária à saúde: uma análise da produção científica e documental

O desafio da efetivacao da integralidade da atencao no Sistema Unico de Saude (SUS) favorece a discussao sobre o apoio matricial (AM) para a Estrategia Saude da Familia (ESF) e evidencia a necessidade de mais estudos sobre o tema. Neste artigo analisa-se criticamente o apoio matricial por meio de publicacoes em periodicos e documentos do Ministerio da Saude, especialmente aqueles focados no apoio matricial em saude mental (SM) na atencao primaria. O material estudado enfatiza a importância da articulacao entre a SM e a atencao primaria, embora tambem indique que o AM em SM faz parte de um modelo de atencao a saude em construcao e novos aportes teorico-praticos e estudos avaliativos sao indispensaveis para seu aperfeicoamento.

DETERMINANTS OF COMMON MENTAL DISORDERS DETECTION BY GENERAL PRACTITIONERS IN THE PRIMARY HEALTH CARE IN BRAZIL

Objective: Common Mental Disorders (CMD) are highly prevalent among patients attending primary care. Many of these disorders remain unrecognized by general practitioners (GPs), with the detection rates varying from 30 to 60%. This study aims to evaluate the CMD detection rates by Primary Heath Care (PHC) practitioners in Brazil—and factors that affect CMD detection. Methods: A cross sectional study was conducted with users of five PHC units in the city of Petrópolis. The CMD prevalence of psychiatric morbidity was estimated by the General Health Questionnaire-12, and the physicians CMD detection was evaluated by a questionnaire completed by GPs after each consultation. Results: Seven hundred and fourteen subjects participated of the study, and 400 (56%) were screened positive using GHQ-12 cut-off point of 2/3. GPs diagnosed 379 people with CMD (53.1%), and 256(36%) subjects were detected by both GHQ and the GPs with an OR of 3.04 (95%CI 2.23–4.13). CMD detection accuracy by GPs was 65%. There was a strong association between the detection of CMD and the report of medically unexplained physical symptoms by GPs. Being female, married, and a frequent service user was also related to higher detection rates. Conclusion: CMD detection rate was similar to those reported worldwide, but contrary to other studies, the presence of MUS increased detection rates. The high frequency of CMD in Primary Health Care highlights the need for improving GP and health workers training in order to enable them to accurately recognize and treat psychological distress with evidence-based interventions.

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Background Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. Methods To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. Results We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohens d = 0.84; D2: Cohens d = 0.84; D7: Cohens d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). Conclusions To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression

Major Depressive Disorder affects about 350 million people worldwide, and about one-third of the patients are considered treatment-resistant. Furthermore, available antidepressants take usually two weeks for the onset of their antidepressant effect. Recent open label trials show that psychedelics, such as ayahuasca and psilocybin, hold promise as fast-onset antidepressants. Although promising, these studies were not controlled for the placebo effect. To address this issue, and to further test the antidepressant effects of ayahuasca, we conducted a parallel arm, double-blind randomised placebo-controlled trial, in patients with treatment-resistant major depression. Thirty-five patients with treatment-resistant major depression received a single dose of ayahuasca or placebo. We measured as primary outcome the change in the Hamilton Depression Rating scale (HAM-D) seven days after the dosing session, and as secondary outcomes the changes in Montgomery–Åsberg Depression Rating Scale (MADRS), and response rates at one day (D1), two days (D2) and seven days (D7) after dosing, and remission rates at D7. This study is registered with http://clinicaltrials.gov (NCT02914769). We observed robust evidence of rapid antidepressant effects of a single dosing session with ayahuasca when compared to placebo. HAM-D scores at D7 were significantly lower in patients treated with ayahuasca than in those treated with placebo (p=0·019; Cohen’s d=0·98). MADRS scores were significantly reduced in the ayahuasca group compared to the placebo group at all endpoints (at D1 and D2, p=0·04; at D7, p<0·0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d=0·84; D2: Cohen’s d=0·84; D7: Cohen’s d=1·49). Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group only at D7 (64% vs. 27%; OR = 4·95; p = 0·04; NNT = 2·66). Remission rate was not significantly different between groups. Our study provides new evidence of rapid antidepressant effects of ayahuasca for treatment-resistant major depression.Recent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2: p=0.04; and at D7: p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohens d=0.84; D2: Cohens d=0.84; D7: Cohens d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. Clinical trial registration ID #NCT02914769

Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.