Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.

Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients.

Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its use as a clinical biomarker of addiction. In addition, they might have a role as mediators of the pharmacological effects of psychotropic drugs. Thus, in mild depression, the response to selective serotonin reuptake inhibitor-type antidepressants (SSRI) is associated with a marked increase in circulating NAEs. To further investigate if antidepressants are able to modify the plasma concentration of NAEs in SUD patients, we analyzed the circulating levels of NAEs in 333 abstinent and 175 healthy controls on the basis of the treatment with SSRI antidepressants. As described previously, SUD patients display higher concentrations of NAEs than those measured in a control population. This increase was not further modified by antidepressant therapy. Only marginal increases in palmitoylethanolamide (PEA), oleoylethanolamide (OEA), or docosatetraenoyl-ethanolamide (DEA) were found, and the net effect was very small. Thus, our study shows that treatment with SSRI-type antidepressants does not modify the clinical utility of monitoring enhanced NAE production as biomarkers of SUD. In addition, the possibility that a blunted NAE response to antidepressant therapy might be related to the loss of efficacy of SSRIs in dual depression emerges as an attractive hypothesis that needs to be addressed in future studies.

Plasma Concentrations of Neurofilament Light Chain Protein and Brain-Derived Neurotrophic Factor as Consistent Biomarkers of Cognitive Impairment in Alcohol Use Disorder.

For a long time, Substance Use Disorders (SUDs) were not considered a component in the etiology of dementia. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced substance-induced neurocognitive disorders, incorporating this notion to clinical practice. However, detection and monitoring of neurodegenerative processes in SUD patients remain a major clinical challenge, especially when early diagnosis is required. In the present study, we aimed to investigate new potential biomarkers of neurodegeneration that could predict cognitive impairment in SUD patients: the circulating concentrations of Neurofilament Light chain protein (NfL) and Brain-Derived Neurotrophic Factor (BDNF). Sixty SUD patients were compared with twenty-seven dementia patients and forty healthy controls. SUD patients were recruited and assessed using the Psychiatric Research Interview for Substance and Mental (PRISM) and a battery of neuropsychological tests, including the Montreal Cognitive Assessment test for evaluation of cognitive impairment. When compared to healthy control subjects, SUD patients showed increases in plasma NfL concentrations and NfL/BDNF ratio, as well as reduced plasma BDNF levels. These changes were remarkable in SUD patients with moderate-severe cognitive impairment, being comparable to those observed in dementia patients. NfL concentrations correlated with executive function and memory cognition in SUD patients. The parameters "age", "NfL/BDNF ratio", "first time alcohol use", "age of onset of alcohol use disorder", and "length of alcohol use disorder diagnosis" were able to stratify our SUD sample into patients with cognitive impairment from those without cognitive dysfunction with great specificity and sensibility. In conclusion, we propose the combined use of NfL and BDNF (NfL/BDNF ratio) to monitor substance-induced neurocognitive disorder.

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Iconic Therapy for the reduction of borderline personality disorder symptoms among suicidal youth: a preliminary study.

BACKGROUND: Iconic therapy (IT) is a new therapy that uses images to teach skills with the aim of improving the symptoms of borderline personality disorder. Preliminary results are promising, and there is indication that IT may be effective. The purpose of this preliminary study was to test the effectiveness of IT compared to a psychological supportive intervention (SI). METHODS: The study was carried out at the University Regional Hospital of Malaga. Young patients (N = 40; 15-30 years) with suicidal or parasuicidal behavior and borderline personality traits were randomized into IT (N = 20) or SI (N = 20). The main outcome variable was a change in the symptoms of borderline personality disorder (BSL-23) at the end of treatment. The secondary outcome variables were suicidal ideation and behavior, self-harm, the need for medication, the number of visits to mental health professionals, maladaptive behavior, satisfaction with therapy and perceived improvement, both at the end of the intensive treatment and at the 12-month follow-up. RESULTS: As expected, the two therapies produced a reduction in BPD symptoms at 10 weeks post-treatment and at the 12-month follow-up. Contrary to expectation, there were no statistically significant differences in the effectiveness of the two therapies (p > 0.05). However, at the 12-month follow-up, the effect sizes for the difference between the effectiveness of the two therapy groups on BSL-23 scores (d = 0.33) and on maladjustment to daily life (d = 0.39) was found to exceed the commonly used convention for a small effect (d = 0.20). Besides, participants in the IT group showed greater satisfaction with therapy than those who received SI. The mean difference between groups was statistically significant after the 10-week treatment period (p < .01), with a large effect size (d = 1.11). Nevertheless, this difference was not maintained at the 12-month follow-up (p > .05), although the effect size for this analysis (d = 0.34) was found to exceed a small effect. CONCLUSIONS: This preliminary study did not find a statistically significant difference in the effectiveness of the two therapies, probably due to the small sample of participants, but there are some indicators (effect sizes) suggesting that perhaps IT may be superior for reducing BPD symptoms and maladjustment in daily life. Future studies with larger samples and comparisons with established treatments for borderline personality disorder are necessary to confirm that IT effects are significant and persistent in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03011190 . First posted 05/01/2017. Last update posted 15/05/2018.

Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Efficacy of a blended low-intensity internet-delivered psychological programme in patients with multimorbidity in primary care: study protocol for a randomized controlled trial.

BACKGROUND: The World Health Organization (WHO) has included comorbidity between depression and a chronic disease among the 10 leading global health priorities. Although there is a high prevalence of multimorbidity, health care systems are mainly designed for the management of individual diseases. Given the difficulty in delivering face-to-face psychological treatments, alternative models of treatment delivery have been proposed, emphasizing the role of technologies such as the Internet. The aim of this study is to assess the efficacy in Primary Care (PC) of a blended low-intensity psychological intervention applied using information and communication technologies (ICTs) for the treatment of multimorbidity in PC (depression and type 2 diabetes/low back pain) by means of a randomized controlled trial (RCT). Our main hypothesis is that improved usual care combined with psychological therapy applied using ICTs will be more efficacious for improvement in the symptomatology of multimorbidity, compared to a group with only improved treatment as usual six months after the end of treatment. METHODS: A protocol has been designed combining a face-to-face intervention with a supporting online programme that will be tested by an RCT conducted in three different regions (Andalusia, Aragon and the Balearic Islands). The RCT will evaluate three hundred participants diagnosed with depression and type 2 diabetes/low back pain. Four highly experienced research groups specializing in clinical psychology are involved in this trial, and there will be ample possibilities for translation and transfer to usual clinical practice. DISCUSSION: This clinical trial will lead to improvement in financial sustainability, maximizing the use of resources and responding to principles of efficiency and effectiveness. Furthermore, based on the evaluation of the feasibility of implementing this intervention in primary care facilities, we expect to be able to suggest the intervention for incorporation into public policy. In conclusion, positive results of this study could have a significant impact on one of the most important health-related problems, multimorbidity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03426709 . Registered retrospectively on 08 February 2018.

TV-based assistive integrated service to support European adults living with mild dementia or mild cognitive impairment (TV-AssistDem): study protocol for a multicentre randomized controlled trial.

BACKGROUND: Mild cognitive impairment and mild dementia progressively compromise the ability of people to live independently and can have a negative impact on their quality of life. Within the current European Active and Assisted Living programme (AAL), project TV-AssistDem has been developed to deliver a TV-based platform service to support patients with mild cognitive impairment or mild dementia and provide relief to their caregivers. The application is intended to be used daily at home, mainly by the participants themselves, with the help of their informal caregivers. The aim of this study is to evaluate the effectiveness of TV-AssistDem to improve quality of life in people with mild cognitive impairment or mild dementia. METHODS: This is a 12-month European multicentre randomized controlled trial which will be performed in two countries: Spain and Romania. Two hundred and forty older adults will be recruited using identical inclusion/exclusion criteria. The primary outcome will be the change from baseline of TV-AssistDem on patient quality of life at 12 months. The secondary outcomes will be the changes from baseline of: 1) informal caregiver quality of life, 2) informal caregiver burden, 3) patient treatment adherence, 4) patient treatment compliance, 5) patient functional status, and 6) healthcare cost-effectiveness at 12 months. Patients in the intervention group will have access to an interactive platform which offers remote assistive services through a device connected to the television. The core services of the platform are: 1) Calendar and reminders, 2) Health monitoring and data transmission to a health server and 3) Videoconference; service-oriented applications are: 4) Cognitive stimulation; 5) Reminiscences; and 6) Patient and caregiver healthcare education. The analysis will be made following an intention-to-treat procedure. Linear and Generalized Mixed Model analysis will be performed. DISCUSSION: We hypothesize that the regular use of TV-AssistDem will result in an improvement in patient quality of life. The uniqueness of this home TV-based intervention lies on its widespread accessibility and its integrative approach to quality of life in people with mild cognitive impairment or mild dementia and their informal caregivers. However, several anticipated challenges will need to be faced: poor engagement and connectivity problems. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03653234 , Date of registration: 31 August 2018.

Interventions of computerized psychotherapies for depression in Primary Care in Spain.

Currently, depression is a global health problem recognized by the WHO. The prevalence of this pathology in Primary Care is estimated at 19.5% worldwide, and 20.2% in Spain. In addition, the current intervention policies and protocols involve significant costs, both personal and economic, for people suffering from this disorder, as well as for society in general. On the other hand, the relapse rates after pharmacological interventions that are currently applied and the lack of effective specialized attention in mental health services reflect the need to develop new therapeutic strategies that are more accessible and profitable. Therefore, one of the proposals that are being investigated in different parts of the world is the design and evaluation of therapeutic protocols applied through Information and Communication Technologies, especially through the Internet and computer programs. The objective of this work was to present the current situation in Spain regarding the use of these interventions for the treatment of depression in Primary Care. The main conclusion is that although there is scientific evidence on the effectiveness of these programs, there are still important barriers that hinder their application in the public system, and also the need to develop implementation studies that facilitate the transition from research to clinical practice.

Effectiveness of iconic therapy for the reduction of borderline personality disorder symptoms among suicidal youth: study protocol for a randomised controlled trial.

BACKGROUND: Borderline personality disorder (BPD) is associated with an intensive use of mental health services, even in the absence of a full diagnosis. Early symptom detection and intervention may help alleviate adverse long-term outcomes. Iconic Therapy is an innovative manual-driven psychotherapy that treats BPD symptoms in a specific and intensive manner. Preliminary results are promising and the indication is that Iconic Therapy may be effective in reducing BPD symptoms. The aim of this study is to assess how effective Iconic Therapy is compared to Structured Support Therapy in a real clinical setting. METHODS/DESIGN: Our study will be a controlled 12-month pragmatic, two-armed RCT. A total of 72 young people (15 to 25 years old) with suicidal ideation/self-injuring behaviour and BPD traits and symptoms will participate in the study. The subjects will be randomised into two groups: Iconic Therapy or Structured Support Therapy. The participants will be assigned to either group on a 1:1 basis. Both the Iconic Therapy and the Structured Support Therapy programmes consist of 11 weekly sessions delivered by two trained psychologists in a group format of between 8 to 12 outpatients. The primary outcome will be measured by the change in symptom severity. Secondary outcomes include changes in suicidal ideation/ behaviour, non-suicidal self-injury, maladjustment to daily life and cost-effective analysis. The primary outcome will be a decrease in the severity of BPD symptoms as assessed by the Borderline Symptom List (BSL-23). For the clinical evaluation, three study assessments will take place: at baseline, after treatment and at 12-month follow-up. We hypothesise that patients attending the Iconic Therapy group will show a significantly higher reduction in symptoms than those in the Structured Support Therapy group. Data will be analysed using generalised estimating equation (GEE) models. DISCUSSION: By responding to the need for briefer and more comprehensive therapies for BPD, we foresee that Iconic Therapy may provide an alternative treatment whose specific therapeutic principles, visually represented on icons, will overcome classical Structured Support Therapy at reducing BPD symptoms. TRIAL REGISTRATION: NCT03011190.

Adherence predictors in an Internet-based Intervention program for depression.

Internet-delivered psychotherapy has been demonstrated to be effective in the treatment of depression. Nevertheless, the study of the adherence in this type of the treatment reported divergent results. The main objective of this study is to analyze predictors of adherence in a primary care Internet-based intervention for depression in Spain. A multi-center, three arm, parallel, randomized controlled trial was conducted with 194 depressive patients, who were allocated in self-guided or supported-guided intervention. Sociodemographic and clinical characteristics were gathered using a case report form. The Mini international neuropsychiatric interview diagnoses major depression. Beck Depression Inventory was used to assess depression severity. The visual analogic scale assesses the respondent's self-rated health and Short Form Health Survey was used to measure the health-related quality of life. Age results a predictor variable for both intervention groups (with and without therapist support). Perceived health is a negative predictor of adherence for the self-guided intervention when change in depression severity was included in the model. Change in depression severity results a predictor of adherence in the support-guided intervention. Our findings demonstrate that in our sample, there are differences in sociodemographic and clinical variables between active and dropout participants and we provide adherence predictors in each intervention condition of this Internet-based program for depression (self-guided and support-guided). It is important to point that further research in this area is essential to improve tailored interventions and to know specific patients groups can benefit from these interventions.

Factor Structure of the Spanish Version of the Edinburgh Postnatal Depression Scale.

INTRODUCTION: The Edinburgh Postnatal Depression Scale (EPDS) is considered the gold standard in screening for postpartum depression. Although the Spanish version has been widely used, its factorial structure has not yet been studied . METHODS: A total of 1,204 women completed the EPDS 32 weeks after delivery. To avoid multiple testing, we split the sample into two halves, randomly drawing two subsamples of 602 participants each. We conducted exploratory factor analysis (EFA), followed by an oblimin rotation with the first sub-sample. Confirmatory factor analysis (CFA) was conducted using a Weighted Least Squares Means and Variance (WLSMV) estimation of the data. We explored different solutions between two and four factors. We compared the factors between two groups with depression and non-depression (evaluated with the Diagnostic Interview for Genetic Studies (DIGS) for the DSM-IV). RESULTS: The EFA indicated a three-factor model consisting of anxiety, depression and anhedonia. The results of the CFA confirmed the three-factor model (χ2=99.203, p<0.001; RMSEA=0.06, 90% CI=0.04/0.07, CFI=0.87 and TLI=0.82). Women with depression in the first 32 weeks obtained higher scores for anxiety, depression and anhedonia dimensions (p<0.001). CONCLUSIONS: This is the first study of confirmatory analysis with the Spanish version of EPDS in a large sample of women without psychiatric care during pregnancy. A three-factor model consisting of anxiety, depression and anhedonia was used. Women with depression had a higher score in the three dimensions of the EPDS.

Gender matters in schizophrenia-spectrum disorders: Results from a healthcare users epidemiological study in Malaga, Spain.

PURPOSE: Women suffering from schizophrenia-spectrum disorders may differ from men in clinical course and outcome. Still, those differences can only be portrayed accurately by means of studies that derive information from multiple sources. One such study was performed in a well-defined area supported by a Mental Health Clinical Management Unit in Malaga, Spain. METHODS: Data from 1640 patients (1048 men and 592 women) that were in contact with services during 2008 were examined for the purpose of the present analysis. Gender differences in sociodemographic and clinical characteristics and the role of gender for explaining clinical characteristics (diagnosis, disease severity and service use) beyond potential sociodemographic confounders were explored. RESULTS: The chi-squared analysis results revealed that in comparison to men, women were older, married or widowed/divorced and living as housewives with their families in cities. Genders also differed across diagnoses, with men being at higher risk for suffering from paranoid schizophrenia, while women being at higher risk for persistent delusional, acute/transitory and schizoaffective disorders. Furthermore, men had greater disease severity and higher chances to visit the mental health rehabilitation unit (MHRU). Further regression analyses revealed that after controlling for confounders, gender differences remained significant across diagnoses and severity. However, they lost their significance under the influence of marital, living and occupational status when predicting the use of MHRU. CONCLUSION: Results confirm the existence of gender differences and highlight the importance of other factors for designing effective psychosocial services that are tailor-made to the patients' needs.

Coping strategies for postpartum depression: a multi-centric study of 1626 women.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

An Internet-Based Intervention for Depression in Primary Care in Spain: A Randomized Controlled Trial.

BACKGROUND: Depression is the most prevalent cause of illness-induced disability worldwide. Face-to-face psychotherapeutic interventions for depression can be challenging, so there is a need for other alternatives that allow these interventions to be offered. One feasible alternative is Internet-based psychological interventions. This is the first randomized controlled trial (RCT) on the effectiveness of an Internet-based intervention on depression in primary health care in Spain. OBJECTIVE: Our aim was to compare the effectiveness of a low-intensity therapist-guided (LITG) Internet-based program and a completely self-guided (CSG) Internet-based program with improved treatment as usual (iTAU) care for depression. METHODS: Multicenter, three-arm, parallel, RCT design, carried out between November 2012 and January 2014, with a follow-up of 15 months. In total, 296 adults from primary care settings in four Spanish regions, with mild or moderate major depression, were randomized to LITG (n=96), CSG (n=98), or iTAU (n=102). Research completers at follow-up were 63.5%. The intervention was Smiling is Fun, an Internet program based on cognitive behavioral therapy. All patients received iTAU by their general practitioners. Moreover, LITG received Smiling is Fun and the possibility of psychotherapeutic support on request by email, whereas CSG received only Smiling is Fun. The main outcome was the Beck Depression Inventory-II at 3 months from baseline. Mixed-effects multilevel analysis for repeated measures were undertaken. RESULTS: There was no benefit for either CSG [(B coefficient=-1.15; P=.444)] or LITG [(B=-0.71; P=.634)] compared to iTAU, at 3 months. There were differences at 6 months [iTAU vs CSG (B=-4.22; P=.007); iTAU vs LITG (B=-4.34; P=.005)] and 15 months [iTAU vs CSG (B=-5.10; P=.001); iTAU vs LITG (B=-4.62; P=.002)]. There were no differences between CSG and LITG at any time. Adjusted and intention-to-treat models confirmed these findings. CONCLUSIONS: An Internet-based intervention for depression combined with iTAU conferred a benefit over iTAU alone in the Spanish primary health care system. TRIAL REGISTRATION: Clinicaltrials.gov NCT01611818; https://register.clinicaltrials.gov/prs/app/action/SelectProtocol? selectaction=Edit&uid=U0001NPQ&ts=2&cx=gctdh2&sid=S0003KJ6 (Archived by WebCite at http://www.webcitation.org/6jbsUvUDz).

Qualitative study of the agitation states and their characterization, and the interventions used to attend them.

INTRODUCTION: Agitation is a common problem in psychiatric care with serious clinical and economic consequences. METHODOLOGY: The aim of the study was to define and characterize the agitation states present in usual medical practice in the acute and emergency units of a psychiatric hospital. Two nominal groups, one with 7 nurses and the other with 10 psychiatrists from the Parc Sanitari Sant Joan de Déu, were established. RESULTS: The nurses described two main states forming the endpoints of a spectrum: from mild (pre-agitation) to severe (agitation). A third state was outlined in which agitation was characterized by disorganized behavior problems. Various care packages were described for each agitation state. The care packages were divided into first, second and third line approaches. The first line approaches (i.e., verbal containment) were used on every (pre)agitated patient. If the first line approach was not effective, the second and third line approaches were implemented, culminating with physical restraint. The psychiatrists described 3 states: a mild initial state (anxiety and irritability), moderate (pre-agitation without aggressiveness) and a severe state of agitation with aggressiveness and/or violence. CONCLUSIONS: In order to avoid progression to a severely agitated state, both groups agreed on the importance of appropriate verbal containment for all states. This would be followed by environmental measures, medication and mechanical restrain depending on the severity of the state.

Efficacy of low-intensity psychological intervention applied by ICTs for the treatment of depression in primary care: a controlled trial.

BACKGROUND: Depression is one of the most common disorders in Psychiatric and Primary Care settings and is associated with significant disability and economic costs. Low-intensity psychological interventions applied by Information and Communication Technologies (ICTs) could be an efficacious and cost-effective therapeutic option for the treatment of depression. The aim of this study is to assess 3 low-intensity psychological interventions applied by ICTs (healthy lifestyle, positive affect and mindfulness) in Primary Care; significant efficacy for depression treatment has previously showed in specialized clinical settings by those interventions, but ICTs were not used. METHOD: Multicenter controlled randomized clinical trial in 4 parallel groups. Interventions have been designed and on-line device adaptation has been carried out. Subsequently, the randomized controlled clinical trial will be conducted. A sample of N = 240 mild and moderate depressed patients will be recruited and assessed in Primary Care settings. Patients will be randomly assigned to a) healthy lifestyle psychoeducational program + improved primary care usual treatment (ITAU), b) focused program on positive affect promotion + ITAU c) mindfulness + ITAU or d) ITAU. The intervention format will be one face to face session and four ICTs on-line modules. Patients will be diagnosed with MINI psychiatric interview. Main outcome will be PHQ-9 score. They will be also assessed by SF-12 Health Survey, Client Service Receipt Inventory, EuroQoL-5D questionnaire, Positive and Negative Affect Scale, Five Facet Mindfulness Questionnaire and the Pemberton Happiness Index. Patients will be assessed at baseline, post, 6 and 12 post-treatment months. An intention to treat and per protocol analysis will be performed. DISCUSSION: Low-intensity psychological interventions applied by Information and Communication Technologies have been not used before in Spain and could be an efficacious and cost-effective therapeutic option for depression treatment. The strength of the study is that it is the first multicenter controlled randomized clinical trial of three low intensity and self-guided interventions applied by ICTs (healthy lifestyle psychoeducational program; focused program on positive affect promotion and brief intervention based on mindfulness) in Primary Care settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82388279 . Registered 16 April 2014.

Expectations, experiences and attitudes of patients and primary care health professionals regarding online psychotherapeutic interventions for depression: protocol for a qualitative study.

BACKGROUND: In the year 2020, depression will cause the second highest amount of disability worldwide. One quarter of the population will suffer from depression symptoms at some point in their lives. Mental health services in Western countries are overburdened. Therefore, cost-effective interventions that do not involve mental health services, such as online psychotherapy programs, have been proposed. These programs demonstrate satisfactory outcomes, but the completion rate for patients is low. Health professionals' attitudes towards this type of psychotherapy are more negative than the attitudes of depressed patients themselves. The aim of this study is to describe the profile of depressed patients who would benefit most from online psychotherapy and to identify expectations, experiences, and attitudes about online psychotherapy among both patients and health professionals that can facilitate or hinder its effects. METHODS: A parallel qualitative design will be used in a randomised controlled trial on the efficiency of online psychotherapeutic treatment for depression. Through interviews and focus groups, the experiences of treated patients, their reasons for abandoning the program, the expectations of untreated patients, and the attitudes of health professionals will be examined. Questions will be asked about training in new technologies, opinions of online psychotherapy, adjustment to therapy within the daily routine, the virtual and anonymous relationship with the therapist, the process of online communication, information necessary to make progress in therapy, process of working with the program, motivations and attitudes about treatment, expected consequences, normalisation of this type of therapy in primary care, changes in the physician-patient relationship, and resources and risks. A thematic content analysis from the grounded theory for interviews and an analysis of the discursive positions of participants based on the sociological model for focus groups will be performed. DISCUSSION: Knowledge of the expectations, experiences, and attitudes of both patients and medical personnel regarding online interventions for depression can facilitate the implementation of this new psychotherapeutic tool. This qualitative investigation will provide thorough knowledge of the perceptions, beliefs, and values of patients and clinicians, which will be very useful for understanding how to implement this intervention method for depression.

Low intensity vs. self-guided internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study.

BACKGROUND: Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. METHODS: The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. DISCUSSION: The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. TRIAL REGISTRATION: Clinical Trials NCT01611818.

Working alliance in low-intensity internet-based cognitive behavioral therapy for depression in primary care in Spain: A qualitative study.

Introduction: Psychotherapies delivered via the Internet have been promoted as an alternative for improving access to psychological treatments. A conceptual working alliance model of blended (i.e., traditional face-to-face consultation combined with Internet-delivered psychotherapy) cognitive-behavioral therapy (b-CBT) for depression has been developed in the UK. However, little is known about how this important therapeutic process, namely the working alliance (WA), is developed and maintained in Internet-delivered cognitive-behavioral therapy without face-to-face consultation (i-CBT). The aim of this study was to evaluate the validity of the WA model of b-CBT in Spanish patients with depression receiving i-CBT. Methods: Forty-one patients suffering from mild-moderate depression were interviewed to assess their experiences of an i-CBT program. Interviews were conducted with participants who received a self-guided application (n = 9), and low-intensity support (n = 10). Three group interviews were also conducted with patients who either did not start the program (n = 8) or did not complete it (n = 6), and with patients who did complete it (n = 8). Results: Qualitative thematic content analysis was performed using the constant comparative method, which revealed four main themes: "bond," "goals," "task," and "usability heuristics," all consistent with the existing literature. However, a new subcategory emerged, called "anonymity," which may highlight the social stigma that mental illness still has in the Spanish context. Conclusion: Results suggest that the development and maintenance of the WA through i-CBT could offer a better experience of the therapeutic process and improve the clinical impact. Clinical Trial Registration: Clinicaltrials.gov, identifier: NCT01611818.