The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis.

INTRODUCTION: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. METHODS: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). DISCUSSION: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP). METHOD: MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. RESULTS: The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES -0.213, 95% confidence interval (CI) (-0.344 to -0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES -0.031, 95% CI (-0.048 to -0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. CONCLUSION: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.

Mental disorders of known aetiology and precision medicine in psychiatry: a promising but neglected alliance.

Personalized or precision medicine is predicated on the assumption that the average response to treatment is not necessarily representative of the response of each individual. A commitment to personalized medicine demands an effort to bring evidence-based medicine and personalized medicine closer together. The use of relatively homogeneous groups, defined using a priori criteria, may constitute a promising initial step for developing more accurate risk-prediction models with which to advance the development of personalized evidence-based medicine approaches to heterogeneous syndromes such as schizophrenia. However, this can lead to a paradoxical situation in the field of psychiatry. Since there has been a tendency to loosely define psychiatric disorders as ones without a known aetiology, the discovery of an aetiology for psychiatric syndromes (e.g. 22q11.2 deletion syndrome in some cases of schizophrenia), while offering a path toward more precise treatments, may also lead to their reclassification away from psychiatry. We contend that psychiatric disorders with a known aetiology should not be removed from the field of psychiatry. This knowledge should be used instead to guide treatment, inasmuch as psychotherapies, pharmacotherapies and other treatments can all be valid approaches to mental disorders. The translation of the personalized clinical approach inherent to psychiatry into evidence-based precision medicine can lead to the development of novel treatment options for mental disorders and improve outcomes.

Insight correlates in child- and adolescent-onset first episodes of psychosis: results from the CAFEPS study.

BACKGROUND: The correlates of insight in early-onset psychosis have received little previous attention. METHOD: We studied clinical correlates of insight in a sample of 110 adolescent recent-onset psychosis patients (mean age 15.53 years; psychotic symptoms present for <6 months). Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) at baseline, 6 months and 12 months follow-up. RESULTS: Insight improved over the early phases of the illness, in parallel with psychopathological improvement. Poor insight at baseline and 6 months correlated with poor functioning at 6 and 12 months respectively. Schizophrenia patients had poorer insight than patients with bipolar disorder at 6 and 12 months but not at baseline. Logistic and linear regressions were used to predict 12-month diagnoses and functioning based on insight measurements. Baseline awareness of illness was a significant predictor for diagnosis [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.05-1.97]. Treatment compliance at 6 months did not correlate with baseline SUMD subscores, but correlated with insight into having a disorder (Spearman's rho=0.21, p=0.039), its consequences (Spearman's rho=0.28, p=0.006) and the need for treatment (Spearman's rho=0.26, p=0.012) at 6 months. The 'attribution of symptoms' dimension of insight is poorly correlated with other insight dimensions and with other clinical variables. CONCLUSIONS: Poor insight correlates with symptom severity and global functioning but also has some trait value for schizophrenia, which is apparent once acute psychotic symptomatology is not prominent. A multi-dimensional approach to the assessment of insight is necessary, as different dimensions are influenced by different factors.

Posttraumatic stress disorder in victims of the March 11 attacks in Madrid admitted to a hospital emergency room: 6-month follow-up.

PURPOSE: To determine the change in prevalence of posttraumatic stress disorder (PTSD) symptoms in victims of the March 11 attacks and their relatives, 1 and 6 months after the attacks. SUBJECTS AND METHODS: Evaluation of PTSD symptoms using the Davidson Trauma Scale (DTS) and General Health Questionnaire (GHQ) in a sample of 56 patients admitted to an emergency room of a general hospital, and assessment of PTSD symptoms in relatives of the patients. RESULTS: At Month 1, 41.1% of patients (31.3% of males and 54.2% of females) presented with PTSD. At Month 6, this figure was 40.9% (30.4% of males and 52.4% of females). There was a significant improvement in perception of health among females between Month 1 and Month 6. Relatives presented similar DTS scores at baseline and at 6 months. DISCUSSION: We verified that rates of PTSD did not vary substantively between the two evaluations. PTSD symptoms positively correlated with psychological health involvement. This correlation points out that both PTSD symptoms and subjective general health involvement are part of the psychological response to trauma. CONCLUSION: The prevalence of PTSD symptoms was high and remained stable between Month 1 and Month 6, while subjective perception of health improved significantly.