Disorganization in first episode affective psychosis: Treatment response and clinical considerations from a 2-year follow-up study in a "real world" setting.

INTRODUCTION: Disorganization is a crucial domain in affective psychoses. However, it has received poor research attention, especially at the illness onset. The aims of this study were: (a) to monitor the longitudinal course of disorganization in young people with first episode affective psychosis (FEAP) across 2 years of follow-up, and (b) to investigate any relevant correlation of disorganized symptoms with psychopathology, functioning and the specific treatment elements of an "Early Intervention in Psychosis" (EIP) protocol along the follow-up period. MATERIALS AND METHODS: Seventy-five FEAP participants (aged 12-35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's rank correlation coefficients were calculated. RESULTS: During the follow-up, disorganized symptoms showed significant enduring positive correlations with PANSS items representing delusional thought content and uncooperativeness, as well as a persistent negative association with the GAF score. Across the 2-year follow-up period, FEAP individuals also had a relevant reduction in disorganization levels. This symptom decrease was specifically related with the combination of antipsychotic medication with the specific psychosocial components of our EIP intervention offered to FEAP patients during the first 12 months of treatment. CONCLUSIONS: Disorganization is relevant in FEAP subjects already at their enrollment in specialized EIP protocols. However, it decreases over time, together with the delivery of specific, combined (person-tailored) EIP interventions.

Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses.

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.

Methamphetamine Use and Antipsychotic-related Extrapyramidal Side-effects in Patients with Psychotic Disorders.

Objective: Extrapyramidal side-effects (EPSE) are frequent in patients treated with antipsychotics and comorbid substance use disorders (SUDs). Methamphetamine has been shown to act as a dopaminergic neurotoxin. We aimed to determine whether EPSE occur more often in patients with psychotic disorders and co-occurring methamphetamine (MA) use disorders, and we examined the relationship between MA use, antipsychotic type, dose and EPSE. Methods: This study was a secondary analysis of data from three separate primary studies. Across all studies, psychiatric and SUD diagnoses were determined using the SCID-I for DSM-IV. EPSE were determined using the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating scale (BARS), and the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia. Participants were classified as having any EPSE if they scored above the cutoff on any of the EPSE scales (SAS, BARS, AIMS). We analyzed data using multivariable logistic regression analysis. Results: The sample included 102 patients with non-affective or affective psychotic disorders. Of the total sample, 65.7% were male, 54.9% had schizophrenia spectrum disorders, 20.5% bipolar type I disorder with psychotic features, 11.7% schizoaffective disorder and 12.7% had substance-induced psychosis. A diagnosis of a methamphetamine use disorder (abuse or dependence) was present in 25.5% of participants. EPSE occurred in 38.2% of patients and were significantly associated with MA use in the unadjusted and adjusted analysis, ORadj = 4.01, 95% CI [1.07, 14.98], p = .039. Patients with MA dependence and MA use >3 years were significantly more likely to have EPSE. We found a significant interaction effect between MA use disorders and standardized antipsychotic dose on the occurrence of EPSE, ORadj = 1.01, 95% CI [1.00, 1.01], p = .042, with MA users having a disproportionally higher likelihood of having EPSE compared to MA non-users as antipsychotic dosage increased. There were no significant associations of EPSE with comorbid alcohol, cannabis, or methaqualone use disorders. Conclusions: Patients with a MA use disorder were significantly more likely to have EPSE with evidence for a dose-response effect. Clinicians should carefully titrate antipsychotic dosage from lower to higher doses to avoid EPSE in patients with MA use disorders.

Olanzapina para el tratamiento de la psicosis en la enfermedad de Huntington: informe de un caso / Olanzapine in the management of psychosis in Huntington's disease: a case report

No disponible

Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial.

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.

Impact of Ramadan fasting on medical and psychiatric health.

Ramadan is a religious month dedicated to prayer, fasting and feasting. Recently, there has been an increased interest among healthcare providers regarding possible health-related complications as a consequence of religious fasting such as that seen during Ramadan. In , a 34-year-old female patient with a diagnosis of schizoaffective disorder, depressive type, was admitted for inpatient hospitalization to an inpatient psychiatric hospital in Buffalo, New York. The earliest date of initial diagnosis is unclear; however, the patient reports an increase in symptoms during her early twenties. Upon admission, the patient was continued on haloperidol, lithium and fluphenazine decanoate which had been initiated prior to this admission. Medication administration and meal times were adjusted to accommodate her observance of Ramadan. Despite efforts to mitigate the potential impact, the patient complained of dizziness and weakness following initiation and titration of clozapine. Due to psychiatric exacerbation, inpatient hospitalization and continuous monitoring, clozapine titration occurred quickly. Upon admission, the patient's blood pressure was 137/85 mmHg, which decreased to a low of 87/58 mmHg as her clozapine dose was increased, leaving the patient requesting bedrest due to significant dizziness and weakness. On the 21st day of Ramadan, the patient broke her fast due to substantial adverse effects. Five days after breaking her fast, the patient's blood pressure increased and returned to baseline. Individuals participating in Ramadan tend to have disrupted sleep cycles, including nocturnal sleep reduction and broken sleep patterns, which can impact overall health. Additional health-related complications that have been reported include dehydration and changes in blood glucose, blood pressure, lipid panel, body weight and exacerbation of psychiatric symptoms. These adverse effects can result in serious complications in fasting individuals with acute medical and psychiatric illness. Clozapine was initiated and rapidly titrated during the patient's observance of Ramadan. She exhibited signs and symptoms of hypotension, which were also subjectively reported by the patient. The significant drop in blood pressure while fasting, and rapid increase once the fast was broken, confirm that medication changes implemented during religious fasting, such as that seen during Ramadan, can increase a patient's risk of serious adverse effects.

The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.

Heterogeneity of Treatment Effects of Long-Acting Injectable Antipsychotic Medications.

OBJECTIVE: To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. METHODS: A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. RESULTS: An interaction between age and treatment (P = .009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P = .047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P = .033). CONCLUSIONS: Among younger persons, HD was associated with lower rates of efficacy failure than PP. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01136772.

Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses - Systematic reviews and birth cohort study.

The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.

Risk Factors Associated With Antidepressant Exposure and History of Antidepressant-Induced Mania in Bipolar Disorder.

OBJECTIVE: Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. METHODS: Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. RESULTS: Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). CONCLUSIONS: These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome.

El litio y otros fármacos para el trastorno maníaco-depresivo y bipolar / Lithium and other drugs for manic-depressive and bipolar disorder

El trastorno maníaco depresivo tal como se entendió en el pasado es una condición muy infrecuente. Sin embargo, la evolución del concepto ha dado lugar al constructo bipolar, que incluye diversas condiciones, de límites difusos, que se pueden encontrar frecuentemente, por lo que los trastornos del llamado "espectro bipolar" tienen actualmente una alta incidencia en la clínica de adultos. Los fármacos a los que se atribuyen propiedades para disminuir las alteraciones afectivas del trastorno bipolar se han denominado "estabilizadores" o "reguladores del estado de ánimo", aunque no hay pruebas de estas supuestas propiedades "estabilizadoras" de las fluctuaciones afectivas. El objeto central de este artículo es revisar las bases científicas de los tratamientos farmacológicos de las condiciones bipolares. Solo el trastorno bipolar tipo I cuenta con un cuerpo de estudios sobre la intervención farmacológica, tanto en situaciones agudas como en las de mantenimiento, para reducir el riesgo de recaídas. No hay pruebas robustas respecto a la superioridad del litio sobre el resto de fármacos sedantes. Tampoco respecto a su especificidad para tratar las manifestaciones del trastorno bipolar tipo I. En las demás condiciones del espectro bipolar, los estudios son más escasos. En este artículo se consideran también las evidencias en las que se basa la creencia actual de que el litio podría tener propiedades antisuicidas, que resultan ser muy endebles. Ante un diagnóstico de trastorno bipolar, se anima al clínico a informar sobre las pruebas reales de la ayuda que pueden prestar los fármacos y de los riesgos que supone su uso, para que la persona diagnosticada pueda tomar decisiones sobre la estrategia a usar ante la posibilidad de nuevas crisis, manteniendo o no un tratamiento farmacológico a largo plazo o implementando otras estrategias

Manic-depressive disorder, as it was understood in the past, is a rare condition. However, the evolution of the concept has generated the bipolar construct. This concept includes several conditions, of diffuse limits, which can be frequently found. Disorders of the so-called "bipolar spectrum" have nowadays a high prevalence in adults. Drugs known as "mood stabilizers" are supposed to decrease the affective alterations of bipolar disorder. However, there is no evidence of this supposed stabilizer action on mood swings. The main object of this paper is to look through the scientific bases of pharmacological treatments for bipolar disorder. Only type I bipolar disorder counts on a body of research on pharmacological interventions in acute situations, as well as on maintenance treatments that claim to prevent relapses and recurrences. There is no strong evidence for the superiority of lithium over the rest of sedative drugs, or for its specific action on treating type I bipolar manifestations. In the rest of conditions of the bipolar spectrum, research studies are limited. In addition, in this paper, evidence underlying the current belief about anti-suicidal properties of lithium is considered, resulting to be very weak. Clinicians are encouraged to inform the individuals diagnosed with bipolar disorder about the scientific evidence regarding benefits and risks of medication, so that they can make decisions about the strategy to follow in case of a new crisis, maintaining, or not, a pharmacological long-term treatment or implementing other strategies

Psicofármacos inadecuados, pero no psicofármacos adecuados, cambian las carácterísticas de la marcha / No disponible

Los factores que modifican la marcha son los que clásicamente han sido identificados como factores de riesgo de caídas y su tratamiento una de las bases de la prevención de caídas y mejora en la estabilidad de la marcha. La velocidad de la marcha ha demostrado ser un buen predictor de caídas. Siendo común en el tratamiento de inestabilidades de la marcha el ejercicio físico, la reducción de polifarmacia y la retirada de psicofármacos. Sin embargo, en la práctica clínica diaria debido a la alta prevalencia de trastornos afectivos y ansiedad en las personas mayores, no siempre es posible la retirada de los psicofármacos. Por otro lado, a la hora de hablar de fármacos en las personas mayores hay criterios bien definidos que categoriza a los fármacos según sus características farmacocinéticas en inadecuados y adecuados, pero a la hora de analizar los psicofármacos y la marcha, pocos son los artículos que hace la distinción entre psicofármacos adecuados e inadecuados. El objetivo de este estudio es analizar si los sujetos que toman psicofármacos inadecuados tienen velocidades de la marcha inferiores de los sujetos que toman psicofármacos adecuados y de los que no los toman. Métodos: Estudio observacional transversal. Se seleccionaron 120 personas con marcha independiente, libres de discapacidad. Los criterios de exclusión fueron discapacidad mental o física, enfermedades que pudieran modificar la marcha, enfermedad aguda en los últimos 6 meses o mal pronóstico a corto plazo. La velocidad de la marcha fue lanzada medida a los 6 metros. El análisis estadístico fue una regresión lineal, la variable dependiente fue la velocidad de la marcha y la independiente la edad, el sexo, los psicofármacos adecuados e inadecuados. Resultados: En el modelo multivariante ajustado por edad (B = 0,025, p<0,001) y sexo (ser hombre B = 0,226 y p = 0,047), los sujetos que tomaban psicofármacos inadecuados tenían medias de velocidad de la marcha disminuidas en 0,1 m/seg (B= 0,114, p=0,040) respecto los que no los tomaban, sin embargo los sujetos que tomaban psicofármacos adecuados no tenían cambios estadísticamente significativos en las medias de su velocidad de la marcha (B= 0,023, p=0,672).Conclusiones: Este estudio es un análisis preliminar, que abre una nueva línea de investigación. Los sujetos que tomaban psicofármacos inadecuados tenían medías de velocidad de la marcha clínica y estadísticamente inferiores que los que no los tomaban. Sin embargo, en las personas que tomaban psicofármacos adecuados no presentaban cambios estadísticamente significativos. Dada la alta prevalencia de enfermedad ansiosa depresiva en las personas mayores, sería conveniente realizar nuevos estudios para comprobar si a las personas que tomaban psicofármacos inadecuados y tienen problemas en la estabilidad de su marcha, si al cambiarles a un psicofármaco adecuado ven disminuida dicha inestabilidad

The factors that modify gait are those that have been classically identified as risk factors for falls and their treatment is one of the bases for preventing falls and improving gait stability. The speed of walking has proven to be a good predictor of falls. Physical exercise, the reduction of polypharmacy and the withdrawal of psychotropic drugs are common in the treatment of gait instabilities. However, in daily clinical practice due to the high prevalence of affective disorders and anxiety in the elderly, the withdrawal of psychotropic drugs is not always possible. On the other hand, when talking about drugs in older people there are well-defined criteria that categorize drugs according to their pharmacokinetic characteristics in inadequate and appropriate, but when analysing psychotropic drugs and walking, there are few articles that make the distinction between appropriate and inadequate psychotropic drugs. The aim of this study is to analyse whether subjects who take inappropriate psychotropic drugs have lower gait speeds of subjects who take appropriate psychotropic drugs and those who do not. Methods: Cross-sectional observational study. 120 people were selected with independent march, free of disability. Exclusion criteria were mental or physical disability, diseases that could modify the gait, acute illness in the last 6 months or poor shortterm prognosis. The speed of the march was released measured at 6 meters. The statistical analysis was a linear regression, the dependent variable was the speed of the march and the independent age, sex, the appropriate and inadequate psychotropic drugs. Results: In the multivariate model adjusted for age (B = 0.025, p <0.001) and sex (being male B = 0.226 and p = 0.047), the subjects taking inappropriate psychotropic drugs had gait speed averages decreased by 0.1 m / sec (B = 0.114, p = 0.040) with respect to those who did not take them; however, the subjects who took adequate psychotropic drugs did not have statistically significant changes in the means of their gait speed (B = 0.023, p = 0.672). Conclusions: This study is a preliminary analysis, which opens a new line of research. Subjects who took inappropriate psychotropic drugs had gait velocity medically and statistically lower than those who did not. However, in people who took adequate psychotropic drugs, they did not show statistically significant changes. Given the high prevalence of anxious depressive illness in the elderly, it would be advisable to carry out further studies to check whether people who took inappropriate psychotropic drugs and have problems in the stability of their march, if changing them to a suitable psychotropic drug, this instability is diminished

Three-Year Naturalistic Study On Early Use Of Long-Acting Injectable Antipsychotics In First Episode Psychosis.

Abstract: Poor adherence to antipsychotics, which affects outcome, is frequent in first episode psychosis (FEP). Most randomized studies demonstrate no superiority of long-acting injectable antipsychotics (LAI-AP) over oral antipsychotics (OAP). However, participants in these studies represent a minority of patients who may benefit from LAI-AP. Mirror and naturalistic studies generally demonstrate efficacy of LAI-AP on more representative samples, but studies on FEP are scarce. Aim: To describe LAI-AP's utilization and impact on FEP outcome in a naturalistic setting. Methods: A 3-year longitudinal prospective and retrospective descriptive study of all consecutive admissions from two Early Intervention Services for psychosis (EIS) in Montréal, Canada, compared the characteristics and evolution of patients who received LAI-AP for at least 12 months to those who received OAP only. Results: From 375 FEP patients included, 26,7% received LAI-AP during their follow-up. They were more likely to have poor prognostic factors (male gender, lower premorbid functioning, homelessness, substance use disorder and schizophrenia spectrum diagnoses). Despite a more severe illness and lower functioning in the LAI-AP group, at admission and study endpoint, clinical and functional improvements were observed. Conclusion: Early prescription of LAI-AP seems beneficial in FEP with poor prognostic factors.

Characterizing Treatment Effects of Valbenazine for Tardive Dyskinesia: Additional Results From the KINECT 3 Study.

BACKGROUND: In the KINECT 3 (NCT02274558; October 2014 to September 2015) study, valbenazine efficacy in tardive dyskinesia (TD) was demonstrated based on mean changes from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7). Data from this study were analyzed further to provide a more clinically meaningful interpretation of the primary AIMS results. METHODS: The study included adults who had a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or any mood disorder and also met DSM-IV criteria for neuroleptic-induced TD. Study participants received 6 weeks of double-blind treatment with valbenazine (40 or 80 mg/d) or placebo. Post hoc AIMS analyses, based on available data, included Cohen d effect sizes, response analyses with odds ratios (ORs) and numbers needed to treat (NNTs), and shift analyses. RESULTS: At week 6 (N = 202), medium-to-high effect sizes were found for mean improvements in AIMS total score (40 mg/d, d = 0.52; 80 mg/d, d = 0.89). For AIMS total score responses of ≥ 10% to ≥ 70% improvement from baseline, statistical significance was found for valbenazine 80 mg/d versus placebo (P ≤ .01), with ORs (range, 3.0-10.3) and NNTs (range, 3-9) indicating clinical relevance. For response per AIMS item (score ≤ 1 at week 6), significant differences between valbenazine (both doses or 80 mg/d) and placebo were found in the lips, jaw, tongue, and upper extremities. In participants who had an AIMS item score ≥ 1 at baseline, the percentage with a ≥ 1-point improvement at week 6 (shift) was significantly higher with valbenazine (40 and/or 80 mg/d) versus placebo in all 7 body regions. CONCLUSIONS: Consistent with primary published results for KINECT 3, these supplemental analyses indicate that participants treated with valbenazine (40 or 80 mg/d) had statistically significant and clinically relevant improvements in TD severity both overall and in specific body regions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02274558.

Augmentation of phenelzine with aripiprazole and quetiapine in a treatment-resistant patient with psychotic unipolar depression: case report and literature review.

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA-MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA-MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA-MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.

BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.