The network structure of core depressive symptom-domains in major depressive disorder following antidepressant treatment: a randomized clinical trial.

BACKGROUND: Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment. METHODS: In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy. RESULTS: At baseline, the most connected MDD symptom-domains were fatigue-cognitive disturbance, whereas at week 8 they were depressed mood-suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar. CONCLUSION: Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Post-traumatic Stress Disorder: A Systematic Review and Network Meta-analysis: La Stimulation Magnétique Transcrânienne Répétitive Pour le Traitement du Trouble de Stress Post-Traumatique : Une Revue Systématique et une Méta-Analyse en Réseau.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment modality for Post-traumatic stress disorder (PTSD). Several targets and stimulation parameters have been investigated, and while previous meta-analyses have suggested that rTMS is efficacious, these have pooled different stimulation parameters and targets, and the relative efficacy of each is unknown. METHODS: We therefore performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) by searching MEDLINE, EMBASE, CENTRAL, and PsycINFO and retaining RCTs with at least 5 individuals per arm and clinician-rated PTSD symptoms (PROSPERO CRD42019134984). We adhered to PRISMA guidelines, and 2 independent reviewers screened studies for eligibility and extracted the primary outcome of clinician-rated PTSD symptoms. Dropouts were extracted as a proxy for acceptability. Random effects pairwise meta-analyses and a network meta-analysis were performed. RESULTS: We synthesize data from 10 RCTs with a total of 421 participants. Two rTMS interventions targeting the right dorsolateral prefrontal cortex (DLPFC) improved PTSD symptoms relative to sham: low-frequency stimulation (SMD = 0.70; 95% CI, 0.22 to 1.18) and high-frequency stimulation (SMD = 0.71; 95% CI, 0.11 to 1.31). Medial PFC dTMS, right DLPFC intermittent theta-burst stimulation, and left DLPFC high-frequency stimulation did not separate from sham. Dropouts as a proxy for acceptability revealed no differences between any of the active conditions or sham nor did any of the active conditions differ from each other. CONCLUSION: The current literature does not support efficacy differences between interventions; however, protocols stimulating the right DLPFC appear superior to sham. It is unclear whether this reflects heterogeneity in pathology requiring a personalized medicine approach or nonspecific mechanisms of rTMS.

Adjunctive ketamine in electroconvulsive therapy: updated systematic review and meta-analysis.

BackgroundKetamine has emerged as a novel therapeutic agent for major depressive episodes, spurring interest in its potential to augment electroconvulsive therapy (ECT).AimsWe sought to update our preliminary systematic review and meta-analysis, focusing on randomised controlled trials (RCTs) involving an index course of ECT, and testing the hypothesis that lack of efficacy is due to barbiturate anaesthetic co-administration.MethodWe searched EMBASE, CENTRAL and Medline to identify RCTs examining the efficacy of ketamine during a course of ECT. Data were synthesised from ten trials (ketamine group n = 333, comparator group n = 269) using pooled random effects models.ResultsElectroconvulsive therapy with ketamine was not associated with greater improvements in depressive symptoms or higher rates of clinical response or remission, nor did it result in pro-cognitive effects. This held true when limiting analysis to trials without barbiturate anaesthetic co-administration. Increased rates of confusion were reported.ConclusionsOverall, our analyses do not support using ketamine over other induction agents in ECT.

Neural correlates of clinical improvement after deep transcranial magnetic stimulation (DTMS) for treatment-resistant depression: a case report using functional magnetic resonance imaging.

We report the effects of a 4-week trial of deep transcranial magnetic stimulation (DTMS) on depressive and anxious symptoms and brain activity in a patient (Mrs A) with treatment-resistant depression (TRD). The protocol involved a pre- and a post-functional magnetic resonance imaging (fMRI) scan during which Mrs A had to perform a working memory task (i.e., n-back). Her baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D21) was 24, indicating severe depressive symptoms. Immediately after 4 weeks of daily DTMS treatment applied over the left dorsolateral prefrontal cortex (DLPFC), her HAM-D21 score decreased to 13 (a 46% reduction), and 1 month later, it was 12 (a 50% reduction). Moreover, Mrs A's accuracy scores on the n-back task (i.e., 2-back condition) improved from 79% (baseline) to 96% (after DTMS treatment). At the neural level, Mrs A showed significantly increased brain activity in the working memory network (e.g., DLPFC, parietal cortex) during the execution of the 2-back condition after DTMS treatment compared to baseline.

Personality Trait Predictive Utility and Stability in Transcranial Magnetic Stimulation (rTMS) for Major Depression: Dissociation of Neuroticism and Self-Criticism.

BACKGROUND: Cost-efficient and non-invasive predictors of antidepressant response to repetitive transcranial magnetic stimulation (rTMS) are required. The personality vulnerabilities­neuroticism and self-criticism­are associated with antidepressant outcomes in other modalities; however, self-criticism has not been examined in response to rTMS, and the literature on neuroticism and rTMS is inconsistent. METHODS: This naturalistic, 4-week study involved daily dorsolateral prefrontal cortex (DLFPC) rTMS for major depression (15 unipolar, 2 bipolar). Participants completed the Big Five Inventory (neuroticism) and the Depressive Experiences Questionnaire (self-criticism) at baseline and at the end of treatment. Changes in depressive symptoms, as rated by the clinician, were quantified using the 21-item Hamilton Depression Rating Scale. Given the inconsistencies in data regarding the stability of neuroticism in patients receiving rTMS, we performed a systematic review and quantitative meta-analysis of trials examining rTMS and neuroticism. RESULTS: rTMS significantly improved depressive symptoms, and this was predicted by higher levels of self-criticism but not neuroticism. Self-criticism was stable over the 4 weeks of rTMS; however, neuroticism decreased, and this was not related to decreases in depressive symptoms. Our quantitative meta-analysis of 4 rTMS trials in major depression (n = 52 patients) revealed decreases in neuroticism, with a moderate effect size. LIMITATIONS: Our results are limited by a small sample size, and the absence of a sham-rTMS group. Our meta-analysis included only 4 trials. CONCLUSION: Highly self-critical patients appear to benefit more from rTMS than less self-critical patients. Neuroticism, a conceptually similar but distinct personality domain, does not appear to predict antidepressant response, yet this vulnerability factor for depression decreases after rTMS.

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.

The impact of antidepressant treatment on the network structure of neurocognition and core emotional depressive symptoms among depressed individuals with a history of suicide attempt: An 8-week clinical study.

BACKGROUND: A more in-depth understanding of the relationship between depressive symptoms, neurocognition and suicidal behavior could provide insights into the prognosis and treatment of major depressive disorder (MDD) and suicide. We conducted a network analysis among depressed patients examining associations between history of suicide attempt (HSA), core emotional major depression disorder, and key neurocognitive domains. METHOD: Depressed patients (n = 120) aged 18-65 years were recruited from a larger randomized clinical trial conducted at the Douglas Institute in Montreal, Canada. They were randomly assigned to receive one of two antidepressant treatments (i.e., escitalopram or desvenlafaxine) for 8 weeks. Core emotional MDD and key neurocognitive domains were assessed pre-post treatment. RESULTS: At baseline, an association between history of suicide attempt (HSA) and phonemic verbal fluency (PVF) suggested that HSA patients reported lower levels of the latter. After 8 weeks of antidepressant treatment, HSA became conditionally independent from PVF. Similar results were found for both the HAM-D and the QIDS-SR core emotional MDD/neurocognitive networks. CONCLUSION: Network analysis revealed a pre-treatment relationship between a HSA and decreased phonemic VF among depressed patients, which was no longer present after 8 weeks of antidepressant treatment.

Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression (MD). However, the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials. Thus, we conducted a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials (RCTs) on high frequency (HF-), low frequency (LF-) and bilateral rTMS for MD. We searched the literature from January 1995 to July 2012 using Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and Scopus. The main outcome measure was participants' ability to correctly guess their treatment allocation at study end. We used a random-effects model and risk difference (RD). Overall, data were obtained from seven and two RCTs on HF- and bilateral rTMS, respectively. No RCT on LF-rTMS reporting on blinding success was found. HF- and bilateral rTMS trials enrolled 396 and 93 depressed subjects and offered an average of approximately 13 sessions. At study end, 52 and 59% of subjects receiving HF-rTMS and sham rTMS were able to correctly guess their treatment allocation, a non-significant difference (RD = -0.04; z = -0.51; p = 0.61). Furthermore, 63.3 and 57.5% of subjects receiving bilateral and sham rTMS were able to correctly guess their treatment allocation, also a non-significant difference (RD = 0.05; z = 0.49; p = 0.62). In addition, the use of angulation and sham coil in HF-rTMS trials produced similar results. In summary, existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation.

Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials.

Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta-analysis to examine this issue. We searched the literature for randomized trials on head-to-head comparisons between HF-rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre-post changes in depression ratings, as well as overall dropout rates at study end. We used a random-effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges' g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF-rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges' g = -0.93; p = 0.007). No differences on dropout rates for HF-rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF-rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow-ups and more intense stimulation protocols are warranted.

Dysregulation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis and executive function in individuals at risk for suicide.

BACKGROUND: Suicidal behaviour aggregates in families, and the hypothalamic-pituitary-adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function. METHODS: In this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST. RESULTS: Despite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of inhibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independent of major depression. LIMITATIONS: The sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide. CONCLUSIONS: Blunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.

Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression.

BACKGROUND: Brain imaging studies of major depressive disorder have shown alterations in the brain regions typically involved in episodic memory, including the prefrontal cortex and medial temporal areas. Some studies of major depressive disorder have linked episodic memory performance to treatment response. In this study, we sought to identify brain regions whose activity, measured during the encoding of pictures, predicted symptomatic improvement after 8 weeks of citalopram treatment. METHODS: We included 20 unmedicated depressed patients. These patients performed an episodic recognition memory task during functional magnetic resonance imaging. During the encoding phase, 150 pictures depicting emotionally positive, negative or neutral content were presented, and the participants were required to classify each picture according to its emotional valence. The same 150 pictures were presented, along with 150 new ones, for a recognition task. We asked participants to distinguish the old pictures from the new ones. We assessed symptom severity by use of the 21-item Hamilton Rating Scale for Depression (HAM-D) at baseline and after 8 weeks of citalopram treatment. We performed subsequent memory effect analyses using SPM2 software. We explored the relation between brain activation during successful encoding of pictures and symptomatic improvement. RESULTS: Patients showed a mean symptomatic improvement of 54.5% on the HAM-D after 8 weeks. Symptomatic improvement was significantly and positively correlated with picture recognition memory accuracy. We also found that the activity of the ventromedial prefrontal cortex and anterior cingulate cortex during successful encoding was significantly correlated with symptomatic improvement. Finally, we found greater activation in the ventromedial prefrontal cortex during the successful encoding of positive pictures in comparison with neutral pictures. LIMITATIONS: During the recognition memory task, 5 participants (among the best responders to treatment) were not included in the valence-specific analyses because they had very few errors. A more challenging task would have allowed the inclusion of most patients. CONCLUSION: Different types of functional imaging paradigms have been used to explore whether the activity of specific brain regions measured at baseline is predictive of a better response to treatment in major depressive disorder. Among these regions, the medial prefrontal cortex and anterior cingulate cortex usually show the strongest predictive value. According to our results, the medial prefrontal cortex and anterior cingulate cortex could have an effect on treatment response in major depressive disorder by contributing to the successful encoding of positively valenced information.

Sexual orientation and gender identity in youth suicide victims: an exploratory study.

OBJECTIVE: Our study was designed to explore additional outcome variables of a suicide case-control study to determine the association between sexual orientation and gender identity in suicide completion in children and adolescents. METHOD: Fifty-five child and adolescent suicide victims and 55 community control subjects were assessed using semi-structured, proxy-based interviews and questionnaires regarding sexual orientation and gender issues, psychopathological diagnoses, and service use. RESULTS: In our sample, no significant differences between suicide victims and control subjects were found regarding same-sex sexual orientation nor intimidation related to same-sex sexual orientation. Suicide victims with same-sex sexual orientation were more likely than suicide victims without same-sex sexual orientation, to meet criteria for anxiety disorders. Within the month preceding their deaths, these youth were more likely to have consulted a health professional, a psychiatrist, as well as having been hospitalized, and were more likely to have consulted a psychiatrist in the last year. CONCLUSIONS: In our sample, same-sex sexual orientation and gender identity issues do not appear to be more prevalent among youth who die by suicide, compared with youth recruited from the general population, nor for same-sex sexual-related intimidation. While exhibiting comparable levels of general psychopathological diagnoses associated with suicide, suicide victims with same-sex sexual orientation were more likely to meet criteria for anxiety disorders and to have consulted mental health professionals before their deaths.

Balance Problems, Paralysis, and Angina as Clinical Markers for Severity in Major Depression.

Major depressive disorder (MDD) is a heterogeneous disorder. Our hypothesis is that neurological symptoms correlate with the severity of MDD symptoms. One hundred eighty-four outpatients with MDD completed a self-report questionnaire on past and present medical history. Patients were divided into three roughly equal depression severity levels based on scores from the APA Severity Measure for Depression-Adult (n = 66, 58, 60, for low, medium, high severity, respectively). We saw a significant and gradual increase in the frequency of "muscular paralysis" (1.5-5.2-16.7%) and "balance problems" (21.2-36.2-46.6%) from low to medium to high severity groups. We repeated the analysis using only the two most extreme severity categories: low severity (66 samples) vs. high severity (60 samples). High severity patients were also found to experience more "angina" symptoms than low severity patients (27.3 vs. 50%). The three significant clinical variables identified were introduced into a binary logistic regression model as the independent variables with high or low severity as the dependent variable. Both "muscular paralysis" and "balance problems" were significantly associated with increased severity of depression (odds ratio of 13.5 and 2.9, respectively), while "angina" was associated with an increase in severity with an odds ratio of 2.0, albeit not significantly. We show that neurological exam or clinical history could be useful biomarkers for depression severity. Our findings, if replicated, could lead to a simple clinical scale administered regularly for monitoring patients with MDD.

[Transcranial direct current stimulation: a promising alternative for the treatment of major depression?]. / Estimulação transcraniana por corrente direta: uma alternativa promissora para o tratamento da depressão maior?

OBJECTIVE: In recent years, a number of new somatic (non-pharmacological treatments) have been developed for the treatment of major depression and other neuropsychiatric disorders. Among these, one of the most promising is transcranial direct current stimulation. METHOD: For the present literature review we searched the PubMed between January 1985 and February 2009. To be included, articles should have been published in English and should address general principles of transcranial direct current stimulation and its use in major depression. DISCUSSION: Current protocols for the treatment of major depression with transcranial direct current stimulation usually involve the application of two sponge-electrodes in the scalp. In general, the positive electrode is applied in the region above the left dorsolateral prefrontal cortex (i.e., F3 region of the 10/20 International System for EEG) and the negative electrode is applied in the region above the right supra-orbital area. A direct electrical current of 1-2 mA is then applied between the electrodes for about 20 minutes, with sessions being daily performed for one to two weeks. Initial studies (including a randomized, double-blind, placebo-controlled clinical trial) showed that transcranial direct current stimulation is effective for the treatment of non-complicated major depression and that this technique, when used in depressed patients, is associated with improvement in cognitive performance (including working memory). Finally, transcranial direct current stimulation is safe and well tolerated. CONCLUSION: Recent studies show that transcranial direct current stimulation is an important neuromodulatory method that may be useful for the treatment of depressed patients. However, further studies are needed to better clarify its precise role in the management of depressive disorders.

[Review of the guidelines of the Brazilian Medical Association for the treatment of depression (Complete version)]. / Revisão das diretrizes da Associação Médica Brasileira para o tratamento da depressão (Versão integral).

OBJECTIVE: Depression is a frequent, recurrent and chronic condition with high levels of functional disability. The Brazilian Medical Association Guidelines project proposed guidelines for diagnosis and treatment of the most common medical disorders. The objective of this paper is to present a review of the Guidelines Published in 2003 incorporating new evidence and recommendations. METHOD: This review was based on guidelines developed in other countries and systematic reviews, randomized clinical trials and when absent, observational studies and recommendations from experts. The Brazilian Medical Association proposed this methodology for the whole project. The review was developed from new international guidelines published since 2003. RESULTS: The following aspects are presented: prevalence, demographics, disability, diagnostics and sub-diagnosis, efficacy of pharmacological and psychotherapeutic treatment, costs and side-effects of different classes of available drugs in Brazil. Strategies for different phases of treatment are also discussed. CONCLUSION: The Guidelines are an important tool for clinical decisions and a reference for orientation based on the available evidence in the literature.

A systematic meta-review of predictors of antidepressant treatment outcome in major depressive disorder.

INTRODUCTION: The heterogeneity of symptoms and complex etiology of depression pose a significant challenge to the personalization of treatment. Meanwhile, the current application of generic treatment approaches to patients with vastly differing biological and clinical profiles is far from optimal. Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. These machine learning models will allow us to learn associations between patient features and treatment response which have predictive value at the individual patient level; this learning can be optimized by selecting high-quality input features for the model. While current research is difficult to directly apply to the clinic, machine learning models built using knowledge gleaned from current research may become useful clinical tools. METHODS: The EMBASE and MEDLINE/PubMed online databases were searched from January 1996 to August 2017, using a combination of MeSH terms and keywords to identify relevant literature reviews. We identified a total of 1909 articles, wherein 199 articles met our inclusion criteria. RESULTS: An array of genetic, immune, endocrine, neuroimaging, sociodemographic, and symptom-based predictors of treatment response were extracted, varying widely in clinical utility. LIMITATIONS: Due to heterogeneous sample sizes, effect sizes, publication biases, and methodological disparities across reviews, we could not accurately assess the strength and directionality of every predictor. CONCLUSION: Notwithstanding our cautious interpretation of the results, we have identified a multitude of predictors that can be used to formulate a priori hypotheses regarding the input features for a computational model. We highlight the importance of large-scale research initiatives and clinically accessible biomarkers, as well as the need for replication studies of current findings. In addition, we provide recommendations for future improvement and standardization of research efforts in this field.

Current psychiatric morbidity, aggression/impulsivity, and personality dimensions in child and adolescent suicide: a case-control study.

OBJECTIVE: The present study was designed to evaluate psychiatric risk factors for child and adolescent suicide, and to determine the association between impulsive-aggressive and other personality traits, and suicide completion in this population. METHOD: Psychiatric diagnoses, impulsive-aggressive and other personality traits were assessed in 55 child and adolescent suicide victims and 55 community controls using semi-structured proxy-based interviews and questionnaires. RESULTS: The most significant psychiatric risk factors associated with child and adolescent suicide were depressive disorders (OR=48.414, 95% CI 6.247-375.185), substance/alcohol abuse disorder (OR=5.365, 95% CI 1.434-20.076), and disruptive disorders (OR=13.643, 95% CI 2.292-23.16). Additionally, suicide victims showed higher scores on lifetime aggression/impulsivity, and harm avoidance. However, after logistic regression, the only independent significant predictors of suicide in this age group were the presence of depressive disorders (Adjusted OR (AOR)=39.652, 95% CI 4.501-349.345), substance/alcohol abuse disorders (AOR=7.325, 95% CI 1.127-47.62), and disruptive disorders (AOR=6.464, 95% CI 1.422-29.38). LIMITATIONS: Relatively small sample size, and cross-sectional design. CONCLUSIONS: Our findings confirm the existence of a particular clinical profile of children and adolescents at high risk for suicide. Additionally, our results reinforce the need for improved understanding of the interrelationships between stressors, depression, substance/alcohol abuse disorders, disruptive disorders and personality traits/dimensions in youth suicidal behavior.

Can sociodemographic and clinical variables predict the quality of life of outpatients with major depression?

Quality of life (QOL) in depression could be of great value as an outcome measure, especially in determining the effectiveness of treatment strategies. However, for this aim to be accomplished, it is important to clarify the relationship between QOL and a number of potentially mediating factors, such as sociodemographic and clinical variables. For this purpose, we assessed 140 depressed outpatients with the Mini International Neuropsychiatric Interview, the WHOQOL BREF, and the Beck Depression Inventory (BDI). After standard and stepwise multiple regression analyses, the following variables were found to be independent predictors of QOL: BDI score for the physical (adjusted R(2)=0.125) and psychological (adjusted R(2)=0.23) domains, and for the overall QOL estimate (adjusted R(2)=0.226); age, suicidality according to the MINI and BDI score for the social relations domain (adjusted R(2)=0.244); and ethnicity, psychiatric comorbidity, psychotic symptoms and BDI score for the environmental domain (adjusted R(2)=0.328). Limitations of the study include its cross-sectional design, relatively small sample size, and lack of objective measures of depressive symptomatology. Sociodemographic and clinical variables appear to explain less than 32.8% of the variance of QOL in subjects with depressive disorders. Clearly, further studies are needed to clarify which additional factors play a role in determining QOL in major depression.

Clinical Usefulness of Therapeutic Neuromodulation for Major Depression: A Systematic Meta-Review of Recent Meta-Analyses.

The authors conducted a meta-review of meta-analyses published in the past decade on therapeutic neuromodulation (ie, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation and deep brain stimulation) for major depression. Active repetitive transcranial magnetic stimulation and transcranial direct current stimulation have been generally associated with small to moderate effect sizes vis-à-vis their efficacy and with similar acceptability compared with sham. Vagus nerve stimulation and deep brain stimulation (although more challenging to investigate) have demonstrated preliminary effectiveness, particularly during longer-term follow-up.

What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials.

OBJECTIVE: To summarize and discuss the conceptual and operational definitions of treatment resistant/refractory depression (TRD) by systematically reviewing randomized controlled trials (RCTs) on its somatic treatment. DATA SOURCES: We searched the MEDLINE, Cochrane Library, PsycINFO, and EMBASE for potentially relevant RCTs on the somatic treatment of TRD published from January 1996 to June 2006. STUDY SELECTION: Studies were included if they: (a) enrolled patients at least 18 years old with a primary diagnosis of unipolar major depression considered resistant/refractory to treatment at baseline, (b) had a randomized design, (c) were published in peer-reviewed journals, and (d) were written in English. Trials that enrolled patients with secondary depression were excluded from our review. Finally, the bibliographies of relevant articles were hand-searched for additional references. In total, 233 full electronic references were retrieved, from which 47 meet the inclusion criteria. DATA EXTRACTION: Through a standardized form, we collected data describing the diagnostic procedure, the terminology and definition of TRD employed, the methodology for assessing the adequacy of previous treatments (in terms of type of ascertainment, dose, and duration), and the minimum required depressive symptoms at baseline. DATA SYNTHESIS: Overall, RCTs diverged regarding the majority of the conceptual and methodological issues involved in the ascertainment of TRD. For example, eleven terms were used to describe resistance/refractoriness in depression, and six different criteria were employed to define the categorical presence of TRD (ranging form non-response to one antidepressant to non-response to two or more antidepressants from different pharmacological classes). Regarding the evaluation of previous treatments, the majority of RCTs did not use systematic methods to gather data, and diverge substantially on the minimum acceptable medication doses and trial durations. CONCLUSIONS: There is a clear need for an internationally shared framework of concepts and methods for the investigation of TRD that could reduce current idiosyncrasies and provide a reference system. Such a foundation is essential for the interpretation of research findings and for their translation to clinical practice.