Cariprazine for treating psychosis: an updated meta-analysis.

PURPOSE: Early treatment of psychotic illness improves outcomes, reduces relapse rates and should not be delayed. Cariprazine is a promising antipsychotic drug and may be a valuable resource when clinicians are in doubt if psychotic symptoms are due to schizophrenia or bipolar disorder. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis that included seven studies (n = 2896) analyzing the effect of cariprazine in psychotic symptoms assessed by the positive and negative symptoms scale (PANSS). RESULTS: We found cariprazine to be significantly superior to placebo (Hedges' g = 0.40; 95% CI 0.32-0.49) for acute psychosis independently of primary psychiatric diagnosis and also to be superior to placebo for both schizophrenia (Hedges' g = 0.39; 95% CI 0.29-0.50) and bipolar patients (Hedges' g = 0.43; 95% CI 0.27-0.58). CONCLUSIONS: We propose that cariprazine may be useful in treating psychosis independently of nosological differentiation at the beginning of the treatment Key pointsEarly treatment of psychotic illness with antipsychotic medications improves outcomes and reduces relapse rates.Cariprazine was found to be significantly superior to placebo for acute psychosis independently of primary psychiatric diagnosis.Cariprazine may be useful in treating psychosis independently of nosological differentiation between schizophrenia and bipolar disorder at the beginning of the treatment.

A study in first-episode psychosis patients: does angiotensin I-converting enzyme (ACE) activity associated with genotype predict symptoms severity reductions after treatment with the atypical antipsychotic risperidone?

BACKGROUND: Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia (SCZ) patients compared to healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting SCZ was suggested. METHODS: ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (N = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (N = 45), assessed at baseline (FEB-B) and also after 2-months (FEP-2M) of treatment with the atypical antipsychotic risperidone. RESULTS: ACE activity measurements showed significant differences among HC, FEP-B and FEP-2M groups (F = 5.356, df = 2, p = 0.005), as well as between HC and FEP-2M (post-hoc Tukey's multiple comparisons test, p = 0.004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total PANSS (r = -0.131, p = 0.434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, p = 0.392), but ACE activity levels differences observed between these groups were influenced by age. CONCLUSIONS: The importance of measuring the ACE activity in blood plasma, associated to ACE I/D genotyping to support the follow-up of FEP patients did not show correlation with general symptoms amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.

Family members affected by multiple substance misuse relatives. / Familiares afectados por el abuso de sustancias de otros parientes: características de una muestra brasileña.

PURPOSE: The heterogenic characteristics of affected family members (AFMs) of substance misusing relative (SMR) remain understudied. This study examined the occurrence and correlates of AFMs having more than one relative with substance use problems. MATERIAL AND METHODS: A secondary analysis of a cross-sectional study on the characteristics of affected family members in Brazil was performed (N= 3157). Levels of AFM stress, strain, coping and hopefulness were assessed. Factors associated with AFMs having other substance misusing relatives (other-SMRs) were explored using univariate logistic regressions. RESULTS: The occurrence of having other-SMR was reported by 61.6% of the sample (1945/3157). Of this, 47% (904/1945) reported that the other-SMR was a member of the SMR's immediate family (spouse/partner/children/siblings). The likelihood of having other-SMRs was related to the AFM being female, from a low socioeconomic background, between the age of 35-44 years older, being SMR's mother or wife/girlfriend/fiancée, scoring higher on family member impact, psychological and physical symptoms, withdrawal coping and to have an older SMR. CONCLUSION: Information about the characteristics of AFMs is key to understanding how the experience of harm associated with the relative's problem might manifest. Our findings offer information that could be used when developing interventions aimed at reducing the harm experienced by AFMs.

Objetivo: Las características heterogéneas de familiares afectados (FA) de familiares con abuso de sustancias (FAS) han sido objeto de pocos estudios. Este estudio revisó la ocurrencia y los correlatos de FA con uno o más familiares con problemas de abuso de sustancias. Materiales y Métodos: Análisis secundario de un estudio transversal sobre las características de FA en Brasil (N = 3157). Valoramos los niveles de los FA de estrés, presión, afrontamiento y esperanza. Exploramos los factores asociados con los FA que tenían otros familiares con abuso de sustancias (otros-FAS) mediante regresiones logísticas ordinales. Resultados: El 61,6% de la muestra (1945/3157) informó de la ocurrencia de otros-FAS. De estos, el 47% (904/1945) informó que los otros-FAS eran familiares directos del FAS (cónyuge/pareja/hijos/hermanos). La probabilidad de ocurrencia de otros-FAS estaba relacionada con que el FAS fuese mujer, de bajo nivel socioeconómico (NSE), con una edad entre los 35-44 años, fuese la madre o esposa/novia/prometida del FAS, obtuviese una puntuación más alta en impacto familiar, síntomas psicológicos y físicos, evitamiento como mecanismo de afrontamiento, y que tuviese un FAS mayor. Conclusión: Información sobre las características de los FA es clave para entender cómo puede manifestarse la experiencia de daños asociados con el problema del familiar. Nuestros hallazgos aportan datos que pueden ser útiles para desarrollar intervenciones con el objetivo de reducir los daños sufridos por los FA.

Forensic Implications of the New Classification of ICD-11 Paraphilic Disorders in Brazil.

INTRODUCTION: The World Health Organization (WHO) Department of Mental Health and Substance Abuse appointed a Working Group on Sexual Disorders and Sexual Health in order to revise and propose changes to ICD-10 categories. AIM: Analyze ethical and legal implications in Brazil of the proposed ICD-11 diagnostic criteria for paraphilic disorders. METHODS: A forensic working group of Brazilian experts in collaboration with representatives of WHO reviewed the proposed modifications to the classification of Disorders of Sexual Preference in ICD-10 (F65), which is recommended to be replaced by Paraphilic Disorders in ICD-11. Proposals were reviewed through a medicolegal lens, using a legal and policy analysis guide put forth by WHO. The premise of this review was to understand that, although the ICD classification is intended to provide a basis for clinical and statistical health interventions, medical diagnostics may also be entangled in the complex legal, normative, and political environment of various countries. MAIN OUTCOME MEASURE: The most important proposed change to this section is to limit the concept of paraphilic disorders primarily to patterns of sexual arousal involving a focus on others who are unwilling or unable to consent, but this change has not affected the ethical and legal aspects of psychiatric functioning in the Brazil. RESULTS: Because Brazilian criminal law is directed toward criminal behavior and not to specific psychiatric diagnoses, the changes proposed for ICD-11 are not expected to create obstacles to health services or to modify criminal sentencing. CLINICAL IMPLICATIONS: Although ICD-11 has a number of changes in its content, there are no significant clinical implications in the Brazilian context, but a better clarity of conceptual definitions and diagnostic criteria. STRENGTHS & LIMITATIONS: The study is conducted with people from different Brazilian states, which is important for a comprehensive view. On the other hand, considering that it is a very heterogeneous country, there is the limitation that an even wider scope of the study is not possible. CONCLUSION: In the Brazilian context, the new guidelines for paraphilic disorders contribute to clinical utility and are not expected to create difficulties related to the legal, social, and economic consequences of sexual offenses in the country. Abdalla-Filho E, de Jesus Mari J, Diehl A, et al. Forensic Implications of the New Classification of ICD-11 Paraphilic Disorders in Brazil. J Sex Med 2019; 16:1814-1819.

Effect of a 10-day transcutaneous trigeminal nerve stimulation (TNS) protocol for depression amelioration: A randomized, double blind, and sham-controlled phase II clinical trial.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. OBJECTIVE: We examined the effects of TNS in MDD after a 10-day experimental protocol. METHODS: This was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. RESULTS: Patients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms. CONCLUSION: The present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.

Predictors of Disagreement Between Diagnoses From Consult Requesters and Consultation-Liaison Psychiatry.

We evaluated disagreement between reported symptoms and a final diagnosis of depression, anxiety, withdrawal, psychosis, or delirium through regression models assessing individual and combined diagnoses. Highest disagreement rates were reported for services classified as others (88.2%), general surgery (78.5%), and bone marrow transplant (77.7%). Disagreement rates varied widely across different diagnoses, with anxiety having the highest disagreement rate (63.3%), whereas psychosis had the lowest disagreement rate (10.6%). When evaluating kappa coefficients, the highest agreement occurred with diagnoses of withdrawal and psychosis (0.66% and 0.51%, respectively), whereas anxiety and depression presented the lowest values (0.31% and 0.11%, respectively). The best-performing predictive model for most outcomes was random forest, with the most important predictors being specialties other than the ones focused on single systems, older age, lack of social support, and the requester being a resident. Monitoring disagreement rates and their predictors provides information that could lead to quality improvement and safety programs.

N-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was to assess the evidence of efficacy of NAC for craving in substance use disorders in randomized clinical trials (RCTs). METHODS: Systematic review of the RCTs literature (PROSPERO number 56698) until February, 2017, using MEDLINE, Cochrane Library and clinicaltrials.gov. We included seven RCTs (n = 245); most with small-to-moderate sample sizes. The main outcome was the Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was evaluated using the Begg's funnel plot and the Egger's test. Meta-regression was performed using the random-effects model. RESULTS: Comparing NAC versus placebo, NAC was significantly superior for craving symptoms (Hedges' g = 0.94; 95%CI 0.55-1.33). The funnel plot showed the risk of publication bias was low and between-study heterogeneity was not significant (I2 = 44.4%, p = 0.07 for the χ2 test). A subgroup analysis performed using meta-regression showed no particular influence. DISCUSSION AND CONCLUSIONS: NAC was superior to placebo for craving reduction in SUDs. The relatively small number of trials and their heterogeneous methodology were possible limitations; however, these positive thrilling results stimulate further studies for clarifying the potential impact of NAC for craving symptoms in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and favorable tolerability, in addition to being an over-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and its favorable tolerability, in addition to being anover-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. (Am J Addict 2017;26:660-666).

Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder.

AIM: This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55) and healthy controls (n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and ß-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in individuals with BD, relative to healthy controls (P < 0.001). There were significant interactions between BD and plasma copeptin on ß-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between ß-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population.

Misidentification of mental health symptoms in presence of organic diseases and delirium during psychiatric liaison consulting.

OBJECTIVE: To identify predictors of misidentification of organic mental disorders and delirium in patients undergoing psychiatric liaison consultation. METHODS: Data were collected at Santa Casa de São Paulo between July of 2009 and March of 2013. We included in our analysis all inpatients for whom the requesting service judged that a psychiatric consultation was required for a possible mental health condition. Outcomes of interest were the instances of misidentification where a condition was initially deemed to be of a psychiatric nature, whereas the final diagnosis by the liaison psychiatric team was of an organic disease or delirium. Our predictors were the clinical specialty of the requesting service, requester and patient characteristics. A series of generalised linear models were used to evaluate misidentification risks. RESULTS: A total of 947 subjects met our inclusion criteria, 14.6% having a final liaison diagnosis of organic mental disorder and 8.1% of delirium. Older patients were significantly associated with increased risk of misidentification for both organic conditions (OR 3.01 - 95% CI 2.01, 4.5) and delirium (OR 3.92 - 2.4, 6.39). CONCLUSIONS: Educational interventions in general hospitals focused on preventing psychiatric misdiagnosis should target in-hospital services where patients tend to be older.

Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.

OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.

Inter-relation between brain-derived neurotrophic factor and antioxidant enzymes in bipolar disorder.

OBJECTIVES: Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. RESULTS: There were negative correlations between BDNF, GPx (r=-.449, P≤.001) and GPx/SOD ratio (r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. CONCLUSIONS: There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD.

Establishing an effective TMS protocol for craving in substance addiction: Is it possible?

BACKGROUND AND OBJECTIVES: Repetitive transcranial magnetic stimulation (TMS) is a non-invasive tool with known therapeutic efficacy in various neuropsychiatric disorders, such as depression, schizophrenia, mania, and anxiety disorders. We hereby, briefly present a brief review and meta-analysis on the use of TMS for craving in substance addiction. METHODS: We present our brief review and meta-analysis following the recommendations of the Cochrane group. A total of eight randomized controlled trials fulfilled eligibility criteria and were selected. A total of 199 patients were studied. RESULTS: We found active stimulation to be superior than sham protocols only for trials focused on right DLPFC (with Hedge's g = 1.48; ES (95%CI: 0.126-2.834), p = 0.032. DISCUSSION AND SCIENTIFIC SIGNIFICANCE: Main meta-analysis limitations include small number of studies, high heterogeneity among studies, and high publication bias. However challenging, our exploratory analysis underscored the amelioration of craving in substance addiction for trials using high frequency TMS protocols over the right DLPFC. We hereby, propose the use of this particular TMS protocol as a promising tool in clinical research.

Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a promising noninvasive brain stimulation intervention. Transcranial magnetic stimulation has been proposed for obsessive-compulsive disorder (OCD) with auspicious results. OBJECTIVE: To assess the efficacy of TMS for OCD in randomized clinical trials (RCTs). METHODS: Systematic review using MEDLINE and EMBASE from the first RCT available until March 11, 2016. The main outcome was the Hedges g for continuous scores for Yale-Brown Obsessive Compulsive Scale in a random-effects model. Heterogeneity was evaluated with the I and the χ test. Publication bias was evaluated using the Begg funnel plot. Metaregression was performed using the random-effects model modified by Knapp and Hartung. RESULTS: We included 15 RCTs (n = 483), most had small-to-modest sample sizes. Comparing active versus sham TMS, active stimulation was significantly superior for OCD symptoms (Hedges g = 0.45; 95% confidence interval, 0.2-0.71). The funnel plot showed that the risk of publication bias was low and between-study heterogeneity was low (I = 43%, P = 0.039 for the χ test). Metaregression showed no particular influence of any variable on the results. CONCLUSIONS: Transcranial magnetic stimulation active was superior to sham stimulation for the amelioration of OCD symptoms. Trials had moderate heterogeneity results, despite different protocols of stimulation used. Further RCTs with larger sample sizes are fundamentally needed to clarify the precise impact of TMS in OCD symptoms.

Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites.

The vagus nerve (VN) is the longest cranial nerve, extending from the brain to the abdominal cavity. The VN consists of both afferent and efferent fibers (respectively 80% and 20%). Vagus nerve stimulation (VNS) is a neuromodulation strategy first developed in the 1980s for epilepsy. More recently, growing efforts in clinical research have been underscoring possible clinical benefits of VNS for different medical conditions such as epilepsy, major depression, anxiety disorders, and Tourette syndrome. Following the rational of VN anatomy and cranial innervation presented above, we hereby hypothesize that transcutaneously placing electrodes over the mastoid process could be a useful study protocol for future tVNS trials.

Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II, sham-controlled, randomized clinical trial.

BACKGROUND: Considering both the burden determined by major depressive disorder (MDD) itself and the high refractoriness and recurrence index, alternative strategies, such as trigeminal nerve stimulation (TNS), are the cutting edge instruments to optimize clinical response and to avoid treatment discontinuation and relapse of symptoms. Trigeminal nerve stimulation is an incipient simple, low-cost interventional strategy based on the application of an electric current over a branch of the trigeminal nerve with further propagation of the stimuli towards brain areas related to mood symptoms. METHOD: The study was a phase II, randomized, sham-controlled trial with 40 patients with MDD. Patients with moderate or severe depressive symptoms as assessed by adequate clinical scales underwent a 10-day intervention protocol. Regarding main clinical outcome, analysis of variance (ANOVA) was performed to evaluate mean change scores in depressive symptoms as assessed by the HDRS-17 between baseline (t1), after intervention protocol (t2), and during one-month follow-up (t3). RESULTS: There was a significant interaction between the mean percentage changes in depressive symptoms according to the HDRS in the two groups across the three assessments (F=6.38, df=2, p=0.0033). Post hoc analyses (Bonferroni method) demonstrated a statistically significant difference between depressive symptoms at baseline and t1 (p=0.01) and between depressive symptoms at baseline and t2 (p=0.009). No severe adverse effects were reported. DISCUSSION: Our results in the present controlled trial highlight the possibility of more practical treatment protocols for clinical research, which are similar to those for different neuromodulation strategies such as transcranial direct current stimulation (tDCS). The in-office administration of TNS in our protocol is similar to the schedule for repetitive transcranial magnetic stimulation (rTMS), though over fewer treatment sessions. CONCLUSION: Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD.

Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance: A Case Study.

We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.

Reducing transcranial direct current stimulation-induced erythema with skin pretreatment: considerations for sham-controlled clinical trials.

OBJECTIVES: Transcranial direct current stimulation (tDCS)-induced erythema (skin reddening) has been described as an adverse effect that can harm blinding integrity in sham-controlled designs. To tackle this issue, we investigated whether the use of topical pretreatments could decrease erythema and other adverse effects associated with tDCS. MATERIALS AND METHODS: Thirty healthy volunteers were recruited, and four interventions were applied 30 min prior to tDCS in a Latin square design: placebo, ketoprofen 2%, hydroxyzine 1%, and lidocaine 5%. TDCS was applied for 30 min (2 mA, anode and cathode over F3 and F4, respectively) in two active sessions with a minimum 1-week interval. The Draize erythema scoring system scale was used to assess erythema intensity; a tDCS questionnaire was used to assess other adverse effects (e.g., tingling, itching, burning sensation, and pain). RESULTS: We found that ketoprofen (but not hydroxyzine or lidocaine) significantly attenuated tDCS-induced erythema regarding intensity and duration, with a medium effect compared with placebo. Erythema was overall mild, short-lived (lasting 18-24 min after tDCS ending), and more intense under the anode. Subjects with darker skin color also tended to present less intense tDCS-induced erythema. The prevalence of other adverse effects was low and did not differ between dermatological groups. CONCLUSIONS: Ketoprofen 2% topical pretreatment might be an interesting strategy to reduce tDCS-induced erythema and might be useful for blinding improvement in further sham-controlled tDCS trials.

A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients.

BACKGROUND: The use of repetitive transcranial magnetic stimulation (rTMS) remains a promising therapeutic tool in the treatment of schizophrenia. Symptoms such as auditory hallucinations (AH) find contradictory results in many studies. Here we present an up-to-date systematic review and meta-analysis of rTMS in the treatment of AH in schizophrenia. METHODS: We searched Pubmed-MEDLINE from 1999 to 2013 for double-blinded randomized sham-controlled trials that applied slow rTMS on the left temporoparietal cortex and assessed the outcome results using Hallucination Change Scale or Auditory Hallucination Rating Scale or Scale for Auditory Hallucinations (SAH). We identified 10 studies suitable for the meta-analysis. RESULTS: We found a positive sized effect in favor of rTMS [random-effects model Hedges' g = 0.011, I-squared = 58.1%]. There was some variability between study effect sizes, but the sensitivity analysis concluded that none of them had sufficient weight to singularly alter the results of our meta-analysis. DISCUSSION: rTMS appears to be an effective treatment for AH. The left temporoparietal cortex seems to be the area in which rTMS is effective. Although meta-analysis is a powerful analytical tool, more studies must be conducted in order to obtain a more expressive sample size to perform a more accurate analytical approach.

Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis.

Transcranial direct cranial stimulation (tDCS) is a promising non-pharmacological intervention for treating major depressive disorder (MDD). However, results from randomized controlled trials (RCTs) and meta-analyses are mixed. Our aim was to assess the efficacy of tDCS as a treatment for MDD. We performed a systematic review in Medline and other databases from the first RCT available until January 2014. The main outcome was the Hedges' g for continuous scores; secondary outcomes were the odds ratio (ORs) to achieve response and remission. We used a random-effects model. Seven RCTs (n = 259) were included, most with small sample sizes that assessed tDCS as either a monotherapy or as an add-on therapy. Active vs. sham tDCS was significantly superior for all outcomes (g = 0.37; 95% CI 0.04-0.7; ORs for response and remission were, respectively, 1.63; 95% CI = 1.26-2.12 and 2.50; 95% CI = 1.26-2.49). Risk of publication bias was low. No predictors of response were identified, possibly owing to low statistical power. In summary, active tDCS was statistically superior to sham tDCS for the acute depression treatment, although its role as a clinical intervention is still unclear owing to the mixed findings and heterogeneity of the reviewed studies. Further RCTs with larger sample sizes and assessing tDCS efficacy beyond the acute depressive episode are warranted.

Effects of risperidone on cytokine profile in drug-naïve first-episode psychosis.

BACKGROUND: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder. METHODS: The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls. RESULTS: We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms. CONCLUSIONS: In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.