The longitudinal effect of antipsychotic burden on psychosocial functioning in first-episode psychosis patients: the role of verbal memory.

BACKGROUND: Previous literature supports antipsychotics' (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning. METHODS: A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables. RESULTS: Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011-0.0091) and (b = 0.0026, 95% CI 0.0001-0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033-0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden. CONCLUSION: CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.

Neuropsychological, clinical and environmental predictors of severe mental disorders in offspring of patients with schizophrenia.

Offspring of individuals with schizophrenia (SZCOff) are at an increased risk for this disorder. Neuropsychological decline is a core feature of the disorder and researchers have reported increasing impairments in cognition during the prodromal phase in high-risk adolescents. Additionally, factors like the presence of prodromal symptoms or specific behavioral patterns could predict, together with neurocognitive functioning, the risk of conversion to severe mental disorders in SCZOff. This study aims to compare the neuropsychological functioning of a sample of 41 SCZOff children and adolescents and 105 community control offspring (CCOff) and to develop a prediction model to examine whether neuropsychological functioning, clinical and behavioral factors predict subsequent risk of severe mental disorders. We collected demographic, clinical and neuropsychological data. We found significant differences between groups in working memory, speed of processing, verbal memory and learning, visual memory and intelligence quotient (IQ). The socioeconomic status, verbal memory, working memory and positive prodromal symptoms predicted a significant proportion of the dependent variable variance. In conclusion, SCZOff showed neurocognitive impairments in several neuropsychological domains compared to CCOff. Neuropsychological functioning, environmental factors and positive prodromal symptoms could predict the risk of onset of severe mental disorders in SCZOff.

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis.

The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP.

Polypharmacy with antidepressants in children and adolescents.

The aim of this study was to review current epidemiological data on the use of antidepressants in co-prescription with other psychotropic drugs in children and adolescents, as well as available efficacy and safety information. A Medline search from inception until February 2012 was performed to identify epidemiological and clinical studies, reviews and reports containing potentially relevant information on polypharmacy with antidepressants in young people. There has been an increase in polypharmacy in children and adolescents involving antidepressants in recent years. Antidepressants have become one of the drug classes most frequently prescribed in combination and are commonly co-prescribed with stimulants and antipsychotics. Most information regarding efficacy and safety of polypharmacy patterns was provided by case series and open-label studies. Efficacy studies gave some support for the use of a combination of antidepressants and antipsychotics in the management of refractory obsessive-compulsive disorder and some residual symptoms in major depressive disorder. Even less empirical support was found for a combination of stimulants and antidepressants in co-morbid attention deficit hyperactivity disorder and mood or anxiety disorders. Adverse events were similar to those found with individual medication groups, with severe adverse events mostly reported by individual case reports. The use of polypharmacy with antidepressants has become a regular practice in clinical settings. Although there is still little efficacy and safety information, preliminary evidence points to the potential clinical usefulness of some polypharmacy patterns. Further research on patients with co-morbidities or more severe conditions is needed, in order to improve knowledge of this issue.

Practitioner review: Long-term pharmacological treatment of pediatric bipolar disorder.

BACKGROUND: Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder (BD), most clinical recommendations are based on results from short-term studies or adult data. In order to guide clinical practice, we review the efficacy and safety profile of mood stabilizers, antipsychotics, and other pharmacological strategies for the long-term treatment of BD in pediatric patients. METHODS: A MEDLINE, EMBASE, Cochrane and PsycInfo search (inception through November 2013) was performed to identify prospective studies longer than 12 weeks assessing the use of pharmacological strategies for the long-term treatment of BD in pediatric patients (0-18 years of age). RESULTS: Four randomized controlled trials (RCT) [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head-to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies (six open-label studies assessing lithium or anticonvulsants, five assessing second-generation antipsychotics (SGAs) and four assessing combination strategies) were included in the review. Aripiprazole has shown efficacy for relapse prevention in children with pediatric bipolar disorder (PBD) 4-9 years of age in one placebo-controlled RCT. Positive results have been reported in noncontrolled studies with quetiapine and lithium for relapse prevention, as well as with lithium, quetiapine, ziprasidone, and the combination of risperidone and divalproex or lithium for long-term symptom reduction in PBD. The most frequently reported adverse events in children and adolescents treated with lithium and anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is mainly related to weight gain and sedation. CONCLUSION: According to the limited empirical evidence, aripiprazole can be useful for relapse prevention in children with PBD. Given the lack of consistent efficacy data, clinical decision making should be based on individual clinical aspects and safety concerns.

Impact of traumatic life events on clinical variables of individuals with first-episode psychosis and healthy controls.

BACKGROUND: Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). AIMS: To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. METHODS: Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. RESULTS: We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. CONCLUSIONS: The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.

Development of an early intervention programme for adolescents with emotion dysregulation and their families: Actions for the treatment of adolescent personality (ATraPA).

AIM: Borderline personality disorder and severe emotion dysregulation in adolescence is a major public health concern. Dialectical Behaviour Therapy is a promising treatment for suicidality in adolescents. The aim of this work is to present an adaptation of this intervention to the Spanish national health system, Actions for the Treatment of Adolescent Personality (ATraPA). METHOD: Data consists of a description of the different ATraPA subprogrammes, including interventions for adolescents aged 13 to 17 and their families. Participants were referred to ATraPA from different hospitals within the region of Madrid, Spain. RESULTS: ATraPA has been developed as an intensive outpatient treatment and it comprises different subprogrammes. ATraPA-TAI is an intensive outpatient treatment, including a skills-based group, individual therapy and email therapy. ATraPA-FAL is a psychoeducational intervention for families, including emotion regulation strategies for parents themselves. Finally, the Alternatives Group is offered to adolescents during the hospital admission, with the aim of promoting alternative coping skills. The group of therapists provides a support network to the professionals involved in ATraPA. CONCLUSIONS: ATraPA has been successfully implemented in a Child and Adolescent Psychiatry Service within the Spanish national health system. Future studies should address the efficacy of ATraPA using a controlled design.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study.

AIMS: This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS: In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS: There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS: We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

Placebo effect in child and adolescent psychiatric trials.

Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings.