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: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 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 athttp://clinicaltrials.gov(NCT02914769).

Key words: Psychedelic agents; dimethyltryptamine; harmine; monoamine oxidase inhibitors; therapeutic use

Aim: The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID‐5‐CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test–retest, joint interview, face‐to‐face vs telephone application) of the SCID‐5‐CV in a large sample of 180 non‐prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience.Methods: The SCID‐5‐CV was administered face‐to‐face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM‐5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses.Results: The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test–retest interviews.Conclusion: The SCID‐5‐CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.

To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.

This study aimed to assess the discriminative validity of the Brazilian version of the Patient Health Questionnaire (PHQ-9) and of its reduced version (PHQ-2). The sample consisted of 177 women (60 cases of depression and 117 noncases). The SCID-IV was used as the gold standard. For the PHQ-9, a cutoff score equal to or higher than 10 proved to be the most adequate for the screening of depression, whereas the best cutoff score for the PHQ-2 was found to lie between 3 and 4. The systematic use of these instruments in nursing and in the context of primary health care could favor the early detection of depression.