Antipsychotics-induced hyperprolactinemia and screening for macroprolactin.

INTRODUCTION: High prolactin (PRL) concentrations are found in laboratory test results of patients on majority of antipsychotic drugs. Prevalence rates and degrees of severity of hyperprolactinemia (HPRL) based on PRL concentration may depend on the presence of macroprolactin in the serum. The aim of the study was to investigate the difference between PRL concentrations before and after precipitation of macroprolactin and to examine if there were any changes in the categorization of HPRL between samples prior and after precipitation. MATERIALS AND METHODS: Total of 98 female patients (median age 33; range 19-47 years) diagnosed with a psychotic disorder, proscribed antipsychotic drugs, and with HPRL were included. Total PRL concentration and PRL concentration after macroprolactin precipitation with polyethylene glycol (postPEG-PRL) were determined by the chemiluminometric method on the Beckman Coulter Access2 analyser. RESULTS: Total PRL concentrations (median 1471; IQC: 1064-2016 mlU/L) and postPEG-PRL concentrations (median 1453; IQC: 979-1955 mlU/L) were significantly correlated using intraclass correlation coefficient for single measurements (mean estimation 0.96; 95%CI 0.93-0.97) and average measurement (mean estimation 0.98; 95%CI 0.96-0.99), and all investigated female patient had HPRL according to PRL and postPEG-PRL concentration. The median PRL recovery following PEG precipitation was 95; IQC: 90-100%. There was substantial agreement (kappa test = 0.859, 95% CI: 0.764-0.953) between the categories of HPRL severity based on total PRL concentrations and postPEG-PRL concentrations. CONCLUSION: The study demonstrated that HPRL was present in all subjects using the reference interval for total PRL concentration and postPEG-PRL concentration with no significant impact of macroprolactin presence in the serum on the categorization of patients according to severity of HPRL.

Time from the Admission as the Predictor of Aggressive Behavior of Inpatients with Schizophrenia Spectrum Disorder.

The aim was to assess the incidence of aggressive events (AE) committed by patients diagnosed with schizophrenia spectrum disorethder (SSD) after the first 7 days of hospitalization in psychiatric institution, in comparison to other psychiatric patients. This retrospective cohort study was performed at Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia, using hospital safety records of all patients admitted between 2015 and 2017. Primary outcome was the proportion of patients who committed AE more than a week after the admission to the hospital. Secondary outcome was the time in days from admission to the first incident of AE. The primary analysis was performed using a multivariable binary logistic regression. SSD patients committed AE more often than other patients (incidence rate ratio 3.97 (95% CI 2.35-6.69; p < 0.001; FDR q = 0.002), but these occurred earlier in the course of hospitalization: median (IQR) 2 (1-10) days from admission compared to 11 (2-32) days in other patients. SSD patients had significantly and clinically relevantly lower odds for AE after the first week of hospitalization adjusted for the large number of pre-planned possible confounders (OR = 0.10; 95% CI 0.02-0.45; p = 0.003; FDR q = 0.002). SSD patients seem to express more aggression earlier in the course of hospitalization. Findings of this study indicate that hospitalization-inherent AE risk factors may play an important role in the etiology of AE and inpatients aggressive behavior. Their possible moderating effect should be included in risk-assessment instruments.

Patterns of chronic physical multimorbidity in psychiatric and general population.

OBJECTIVE: A growing body of evidence has demonstrated the high prevalence and complexity of chronic physical multimorbidity defined as ≥2 chronic physical illness in people with psychiatric disorders. The present study aimed to assess differences in the prevalence and patterns of self-reported chronic physical illness and multimorbidity in the general and psychiatric populations. METHODS: We performed a latent class analysis of 15 self-reported chronic physical illnesses on a sample of 1060 psychiatric patients and 837 participants from the general population. RESULTS: Self-reported chronic physical illness and multimorbidity were significantly more prevalent in the population of psychiatric patients than in the general population (P < .001). Psychiatric patients had 27% (CI95% 24% - 30%) higher age-standardized relative risk for chronic physical illness and a 31% (CI95% 28% - 34%) higher for multimorbidity (P < .001). The number of chronic physical illnesses combinations was 52% higher in the psychiatric than in general population (255 vs 161 combinations respectively; P < .001). We identified four distinct latent classes: "Relatively healthy", "Musculoskeletal", "Hypertension and obesity", and "Complex multimorbidity" with no significant differences in the nature of multimorbidity latent classes patterns. The class "Relatively healthy" was significantly less (ARI = -25% (CI95% -30% -21%), and the class "Hypertension and obesity" was significantly more prevalent in the population of psychiatric patients (ARI = 20% (CI95% 17% - 23%). CONCLUSIONS: These findings indicate that mental disorders are associated with an increased risk of a wide range of chronic physical illnesses and multimorbidity. There is an urgent need for the development of the guidelines regarding the physical healthcare of all individuals with mental disorders with multimorbidity in focus.

Early intervention programme for patients with psychotic disorders in "Sveti Ivan" Psychiatric hospital (RIPEPP) - sociodemographic and baseline characteristics of the participants.

BACKGROUND: Psychiatric hospital "Sveti Ivan" in Zagreb, Croatia, offers an outpatient Early intervention programme for patients with psychotic disorders (RIPEPP), consisting of psychoeducational workshops and group psychodynamic psychotherapy. The aim of this study was to describe sociodemographic and baseline characteristics of the participants, in order to provide better understanding of this population, and to assist with the development of more effective therapeutic approaches. SUBJECTS AND METHODS: Since 2008, a total of 245 patients with first episodes of psychosis and their family members participated in the programme. They filled out several questionnaires within the framework of the programme evaluation, but for the purposes of this study, only data collected on sociodemographic questionnaire and the Health of the Nation Outcome Scales (HoNOS) are presented. RESULTS: Majority of the participants were male (66%), at the average age of 28 (SD=6.6), living with their parents (73.5%). Most of them finished secondary school (45.7%) but almost a quarter of the sample (23.7%) is currently studying at university. The average duration of untreated period was 101.60 days, with a median of 30 days. According to results of HONOS questionnaire, upon entry into the programme, the patients most often listed cognitive functioning (attention, concentration, memory) and professional issues (performance of work tasks and activities tied to work) as the most problematic areas. CONCLUSION: The findings of this study provide more detailed description of the beneficiaries of the RIPEPP programme, which can contribute to forming future programmes for the prevention of psychotic disorders.

Remission and employment status in schizophrenia and other psychoses: One-year prospective study in Croatian patients treated with risperidone long acting injection.

BACKGROUND: While numerous studies have confirmed the efficacy of risperidone long-acting injectable (RLAI) on many clinical outcomes in patients with schizophrenia, there is no data regarding its influence on employment status. SUBJECT AND METHODS: This was a 12-month observational study with flexible doses of RLAI on a Croatian population of patients with schizophrenia and other psychoses. Visits were at baseline and after 1, 3, 6 and 12 months of treatment. Treatment response was evaluated using Clinical Global Impression of Illness Severity (CGI-S) and Improvement (CGI-I) scales, while remission was defined by 8 items of Positive and Negative Syndrome Scale (PANSS). Employment status was determined at baseline and at study endpoint. RESULTS: A total of 362 patients were included, with a median age of 37 (interquartile range 29-47) years, 63.5 % were males and 67.4% were hospitalised at baseline. Overall 258 (71.3%) patients completed the study. Improvements in CGI-S scores from baseline were significant (p<0.001) at all visits. Remission criteria were met in 9 (2.5%) patients at baseline, and in 199 (54.9%) at endpoint, while 144 patients (52.7%) achieved symptomatic remission. Female patients were five times more likely to achieve symptomatic remission (OR=5.2; 95%CI=2.64-10.19). At baseline, 74/362 (20.4%) patients were employed, compared to 77/257 (30.0%) at endpoint (p<0.001). Adverse events were spontaneously reported in 55 (15.2%) patients. Three patients died (judged not to be related to RLAI) and one patient committed homicide. CONCLUSIONS: Patients treated with RLAI had significant improvements in CGI-S scale scores, hospitalization status, rates of remission and employment status, indicating the benefits of continuous treatment over time. Further studies on the comparative impact of different treatment strategies on functional recovery are needed.

Somatic comorbidities are independently associated with the poor health-related quality of life in psychiatric patients.

BACKGROUND: Despite the increased risk, the quality of somatic healthcare is lower for patients with mental illnesses. Currently dominant approach separates physical and mental, primary and secondary healthcare. Objective of our study was to explore whether somatic comorbidities are associated with a poor HRQoL independently of some sociodemographic and clinical factors. Majority of studies have explored particular somatic and psychiatric illnesses. Therefore we decided to access the problem from the general perspective of the universe of somatic and mental illnesses in the large psychiatric institution. SUBJECTS AND METHODS: This nested cross-sectional study was done during May 2016 at Psychiatric hospital Sveti Ivan, Zagreb, Croatia on the sample of 506 patients diagnosed with psychiatric illnesses (ICD-10: F00-F99). Key outcome was the lowest 25% results on the SF-36 General health sub-scale, indicating the worst HRQoL. Predictors were all detected somatic illnesses. By multivariate logistic regression we controlled different sociodemographic, vital and clinical factors. RESULTS: After adjustment for different sociodemographic and clinical factors, three somatic comorbidities remained independently associated with the worst HRQoL: endocrine, nutritional and metabolic diseases (E00-E90), diseases of respiratory system (J00-J99) and diseases of musculoskeletal system and connective tissue (M00-M99) CONCLUSIONS: Somatic comorbidities in psychiatric patients are associated with the poor HRQoL independently of different sociodemographic, vital and clinical factors and they should be treated seriously and integrally with mental aspects of HRQoL. Early comorbidities detection and adequate pharmacological and psychotherapeutic treatment, as well as the prevention of risk factors, may improve the quality of life and reduce morbidity and mortality of psychiatric patients.

No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: (1)H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex.

BACKGROUND: The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. METHODS: Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17) or nonresponders (n=12) to the antidepressant therapy. RESULTS: There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr) after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. CONCLUSION: This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in regard to therapy response in the left dorsolateral prefrontal cortex or left amygdala. Further research is necessary to conclude whether NAA alterations in the first episode of depression could possibly be different from chronic or late-onset depression, and whether NAA alterations in stress-induced (reactive) depression are different from endogenous depression. The potential role of NAA as a biomarker of a treatment effect has yet to be established.

The effect of atypical antipsychotics on brain N-acetylaspartate levels in antipsychotic-naïve first-episode patients with schizophrenia: a preliminary study.

PURPOSE: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics. PATIENTS AND METHODS: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using (1)H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London - Drexel University, Letter-Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced. RESULTS: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr) level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008) and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005). On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months. CONCLUSION: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn't result in a significant rise in the NAA/Cr ratio. However, a significant rise was witnessed in the study group in which a satisfactory therapeutic response had been achieved with a single antipsychotic administration.

Early intervention program for psychotic disorders at the psychiatric hospital "Sveti Ivan".

The Early intervention program for the first episodes of psychotic disorders (RIPEPP) at the Psychiatric Hospital "Sveti Ivan" in Zagreb encompasses patients hospitalized due to various psychoses (acute psychotic disorder, schizophrenia, schizoaffective and delusional disorder, bipolar affective disorder with psychotic symptoms) in the "critical period" of illness, i.e. within five years after the occurrence of the first symptoms. The RIPEPP Program consists of an in- and out-patient part, and includes psychotherapeutic and psychoeducative components as well as the administration of antipsychotics. The Psychotherapeutic part, conducted by psychotherapists - group analysts, comprises psychodynamic group psychotherapy for patients and for family members. The Psychoeducative part, led by cognitive-behavioral therapists, is carried out through educative interactive workshops for both patients and their family members. The paper describes the theoretical framework, as well as the professional, personnel, educative and organizational basis of the Program, the principles of evaluation and some experiences after five years of implementation.