Genetic variation of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The negative symptom is a severe form of the illness related to prefrontal hypodopaminergia. In the present study, we attempted to perform a quantitative trait test for genetic association between the COMT gene and the negative symptoms in a Chinese population.

A total of 160 unrelated schizophrenic individuals were recruited for genetic analysis and their symptoms were assessed and scored by Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program to see the correlation between scored negative symptoms and some single nucleotide polymorphisms (SNPs) present in the COMT gene.

rs362204 (Del/Ins SNP) showed allelic association with four negative symptoms, including blunted affect (p=0.00008), poor rapport (p=0.00006), passive/apathetic social withdrawal (p=0.0003) and lack of spontaneity and flow of conversation (p=0.001). The rs165656(C)-rs6267(G)-rs4680 (G)-rs362204 (Del) haplotype was strongly associated with both blunted affect (p=0.0245) and poor rapport (p=0.0186).

The present study suggests that COMT may etiologically contribute to the severity of negative symptoms of schizophrenia but its precise mechanism needs further investigating.

to look peculiarities of mental disorders in the elderly in different regions of Lithuania.

We analyzed three regions of Lithuania: Panevėžys region, Palanga region and Varėna region. They are in the different parts of Lithuania. We have chosen data about mental disorders according International Statistical Illness and Health Problems Classification. We collected data with code F20- F25. We have analyzed case-records, which were filled in January 2006.

In Panevėžys region the elderly was 28, 89% (n= 39) of all collected data about mental disorders. Respectively in Varėna region- 42, 86 proc. (n= 6); in Palanga region- 21,05 proc. (n= 4). Average age of elderly was 66, 65 years. Respectively in Panevėžys region- 66,31 years; in Varėna region- 67,17 years; in Palanga region- 69,25 years. 65, 31% of all elderly with mental disorders were women. 75, 51% of all elderly diagnosis was schizophrenia (F20) in all regions. Mental disorders identified before 2006 were 95, 92% and mental disorders identified in January 2006 were 4, 08%. The difference in the disease rate in studied regions correlate with P, Li, Zn, Mn concentrations in the soil and possibly had an effect via the food chain. Also, the drinking water can to be of some importance. Comparing these three regions, there was seen clear natural environment differences. Magnetic field has different activity in these regions. All through Panevėžys region pass the largest tectonic zone in Lithuania.

Risperidone the first atypical antipsychotic available in a long-acting injection formulation. In the United Kingdom is licensed to use in psychosis in patients tolerant of oral Risperidone and the Summary of Product Characteristics clearly defines the methods of initiation and titration.

We performed a naturalistic observation of 25 patients belonging to 3 different community mental health teams and one in-patient facility that have been prescribed Risperidone long-acting injection (RLAI) and collected data about immediate prior use of antipsychotic medication, patient preference, compliance with treatment, documentation of effectiveness and tolerance of Risperidone oral, supplementation with Risperidone oral during the first three weeks, initial dose, intervals between dose changes, monitoring of benefits and side-effects, and reasons for discontinuation.

Only 7/25 patients have been prescribed oral Risperidone prior to the injectable formulation and none had received clozapine. 13/25 received oral supplementation during initiation, 3/25 dose was changed in less than 4 weeks intervals. 14/25 non-compliance was suspected and only 2/25 patients stated a preference for an injectable formulation. 17/25 continued to receive RLAI and those discontinued in 3/25 due to patient refusal, 1/25 not tolerated, 1/25 patient did not attend treatment, 1/25 not effective, 1/25 patient deceased, 1/25 no reason was specified.

prescribing of RLAI did not follow the recommendation from the manufacturers mainly during initiation. Non-compliance with previous medication was the main reason for use of an injectable formulation but use of RLAI seems to be associated with low discontinuation rates.

Clozapine remains the gold standard for the management of treatment-resistant schizophrenia. Due to the need for close medical supervision at initiation it is usually started in hospital although this is no longer mandatory. It is estimated that speed of up-titration will affect length of stay.

Retrospective study of prescription charts of 14 patients representing the most recent who have been prescribed clozapine as in-patients. Data would be compared against the titration doses recommended by the British National Formulary and by the manufacturers (Novartis).

5/14 patients were admitted solely for clozapine initiation. 1/14 did not tolerate it after 5 days. 2/14 patients were re-started clozapine following a period of discontinuation and their discharge dose was achieved faster than initial titration as recommended. 9/14 patients’ titration was slower than recommended by the guidelines with a minimum difference of 113 days if using the slower recommended titration or a maximum of 208 days if using the faster one. None of the patients’ titration appeared to be slowed down due to the presence of emerging side-effects.

Prescribing practice appears to lengthen hospital admissions due to delays in changing doses. This was less relevant for patients admitted exclusively for clozapine initiation. The development of a policy for community initiation and the development of a pre-printed up-titration chart for clozapine are potential solutions to minimise bed occupancy therefore improving both patients’ experiences and bed management.

Amongst oral antipsychotics, tolerance and adherence are thought to be higher with atypicals versus conventional agents. Fewer data exist for parenteral antipsychotics regarding the atypical–conventional comparison.

to compare adherence rates and subjective response between long-acting risperidone (LAR) and conventional depots.

Cross-sectional, naturalistic, one-site study of all outpatients with severe mental disorders treated with injectable antipsychotics over a 12–month period at one Spanish mental health unit. Different sets of broadly– and narrowly–defined criteria for adherence were calculated from mental health nurse´s registry data. Patients´ subjective response was self-assessed with the Subjective Well-being under Neuroleptic treatment (SWN) and the Drug Attitude Inventory (DAI-10).

Subjects treated with LAR (n=27) and conventional depots (n=22) were similar in clinical and demographic terms. Both groups reported mostly positive subjective responses with the SWN (LAR=71.8+18.4 vs depots=81.7+15.3) and the DAI-10 (LAR=3.0+4.8 vs depots=4.0+4.5), with non-significant differences. Regardless the criteria of adherence used, rates of non-adherent subjects were also comparable, ranging from 36% (narrowly–defined) to 82% (broadly–defined). Although mean telephone prompts were higher for the LAR group (p=0.002), this difference disappeared when interval of administration (14 vs 28 days) was taken into account (ANCOVA: F=0.76; p=0.4).

In this small study, atipicity would not influence attitudes or subjective response to parenteral antipsychotics. Furthermore, the two–fold administration frequency of long-acting risperidone compared to depots does not seem to lead to higher rates of non–compliance amongst outpatients with severe mental disorders.

Effectiveness of parenteral antipsychotics (PAP) to prevent relapses in persons with severe mental disorders (SMD) is limited by adherence. However, data about potential risk factors for non- or partial compliance with PAP are relatively scarce and inconsistent.

to determine variables associated with partial compliance in a naturalistic one-site study.

The sample comprised all outpatients with SMD treated with PAP over a 12–month period at one mental health unit in Spain. Different sets of broadly– and narrowly–defined criteria for adherence were calculated from mental health nurse´s registry data. Retrospective chart review yielded sociodemographic (age, gender, educational level, civil and vocational status) and clinical (ICD–10 diagnosis, age of onset, illness duration, number of admissions, past/current substance abuse disorders, and community treatment order) variables.

Forty-nine patients were identified; most were single (83%), received a government pension (73%) and lived with their family (67%). When the strictest criteria for adherence were used, illness duration was positively associated with a > 4 day-delay in PAP injection (r=0.36; p=0.01). Furthermore, patients under community treatment orders (χ2=7.5; p=0.006) and those with past substance abuse (χ2=8.9; p=0.003) showed higher rates of non–compliance. This latter variable was the only predictor of non–compliance (exp.β=0.15; IC 95%=0.04– 0.6; p=0.007) and correctly classified 80% of the sample (χ2=8.3; R2=0.23; p=0.004).

Confirming previous results, substance abuse may lead to a poorer compliance with parenteral antipsychotics. Conversely, demographic variables would play a less relevant role in adherence to PAP.

There is extensive evidence that clozapine and olanzapine produce the largest increase in weight or BMI among the atypical antipsychotic drugs. There is also considerable, if controversial evidence, that clozapine-induced weight gain is predictive of clinical response in patients with schizophrenia.

The aim of this study was to determine if weight gain and changes in metabolic measures with olanzapine and risperidone also predict clinical response in patients with schizophrenia, schizoaffective disorder, or bipolar disorder.

Data from a 12 month, randomized, prospective study of the effects of olanzapine and risperidone in 160 patients with schizophrenia (SCH) and schizoaffective disorder (SAD), and bipolar disorder (BPD) on weight gain, BMI increase and metabolic measures including fasting blood glucose, hemoglobin A1c, total cholesterol, triglycerides, HDL, triglycerides/HDL ratio, log triglycerides, LDL to predict improvement in PANSS total scores.

Weight gain and increase in BMI predicted the clinical response to olanzapine, but not risperidone, in patients with SCH or SAD, but not BPD, at 1, 3 and 6 months, when used in combination with other psychotropic medications or no concomitant mood stabilizers. Changes in lipid and glucose measures did not predict response to either drug.

Olanzapine-induced weight and BMI increase predicted decrease in PANSS total score at 1, 3, 6 months. No such relationship was found for risperidone- treated patients in either diagnostic group. These results suggest weight gain and clinical response to olanzapine and clozapine may be based on similar mechanism which differentiates them from risperidone.

Hyperprolactinemia can inhibit sex steroids, resulting in bone loss. We, thus, set out to evaluate the effect of risperidone-induced hyperprolactinemia on bone mineral density in youth.

Children and adolescent males treated with risperidone for a minimum of six months underwent volumetric bone mineral density (vBMD) measurement using peripheral quantitative computerized tomography of the ultra-distal nondominant radius. Their treatment history was reviewed and their prolactin and testosterone serum levels measured.

We recruited 73 males (mean age: 12.1yrs [SD=2.9], mean Tanner stage: 2.6 [SD=1.4]) treated with 0.03mg/kg (SD=0.02) of risperidone per day for an average of 3.1yrs (SD=1.9). Hyperprolactinemia (defined as a prolactin level > 18.4ng/ml) was present in 51% of the sample. After controlling for Tanner stage which was strongly associated with serum testosterone, we found a trend for a negative effect of prolactin on testosterone. As expected, ultra-distal radius cross-sectional area and cortical vBMD, but not trabecular vBMD, increased with pubertal development. After adjusting for prolactin and pubertal stage, in the subgroup of peri/pubertal (i.e. Tanner stage ≥ 2) participants with hyperprolactinemia, prolactin was negatively associated with trabecular, but not cortical, vBMD.

To our knowledge, our data are the first to describe the negative effect of risperidone-induced hyperprolactinemia on bone mineral density following long-term treatment in youth.

Placebo-controlled (PC) Phase 3 trials are critical for the registration of new atypical antipsychotic medications (AAP) for schizophrenia but use of placebo when efficacious treatments exist has been questioned.

To investigate evidence for the use of placebo in clinical trials of schizophrenia via a meta-analysis of large, PC trials of new AAPs.

Using the FDA Summary Basis of Approval reports, we examined outcome data from all Phase 3 clinical trials that evaluated investigational AAPs. Publications from peer-reviewed literature were also identified. The main outcome variables were: symptom improvement in individual treatment arms, clinical response, therapeutic failure.

Meta-regression indicated a highly significant difference between improvement in the placebo and the active arm (p<0.0001). Effect size (ES) estimate for the placebo arm revealed that patients in this arm obtained a statistically significant but clinically negligible symptom reduction (Cohen d: ~0.15; p<0.004) while active-treated patients displayed a substantial symptom reduction (Cohen d: ~0.70; p<0.0001). Active treatments showed a highly significant (p<0.001) superiority vs. placebo in clinical response and therapeutic failure, with failure rates often exceeding the rate of clinical response. ESs for change varied substantially across trials, with an ES range of d=0.8 for the placebo and the active arms, respectively.

Variable ESs across studies support the view that placebo control has major importance in trials of new AAPs. However, efforts should focus on finding design alternatives and to minimize the risks of PC trials so that they may be conducted in ethically acceptable manner.

Demostrate that clozapine decrease the number of hospitalizations, and improve the adherence to treatment.

The sample consisted of 36 schizophrenia patients who were in treatment with a typical and atypical neuroleptic and then had their medication changed to clozapine. We ascertained the number of inpatient hospitalizations before starting clozapine and compared this with the number of hospitalizations after starting clozapine. We also followed an age- and gender-matched comparison group of other schizophrenia patients who were at treatment approximately the same time. Results indicate that the mean number of rehospitalizations while on other neuroleptic was bigger than after the commencement of clozapine treatment. The decrease in hospitalization rate for the comparison group was also statistically significant. The pre-post change was much greater for the clozapine patients than comparison patients. A 2 x 2 repeated measures analysis of variance (ANOVA) contrasting the comparison group to the clozapine patients both before and after the index date indicates a significant time by group interaction, thus documenting the greater relative decrease in rehospitalization rate in the clozapine gr.

We also used a compliance scale pre and post-begining of treatment with clozapine for evaluate the adherence to treatment. Clozapine improve the compliance of treatment, in comparison to the neuroleptics that patient has taken before.

the clozapine seems to be more effective than other antipsychotics in decrease the risk of hospitalizations, and improve the adherence to treatment

Whether the modest QTc-prolonging effect of ziprasidone increases cardiovascular event risk is unknown.

The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC), an open-label, randomized, postmarketing study, enrolled patients with schizophrenia from routine clinical practice settings in 18 countries. The primary outcome was non-suicide mortality in the year after initiation of assigned treatment. A total of 18,154 subjects were randomized to ziprasidone or olanzapine, dosed according to enrolling physician's clinical judgment. A physician-administered baseline questionnaire collected information on demographics, medical and psychiatric history, and concomitant medication use. Brief follow-up questionnaires elicited hospitalization data since the last study visit, vital status, study medication continuation, and concomitant antipsychotic medication(s) use. ZODIAC study subjects reflected the general population of patients with schizophrenia.

The incidence of nonsuicide mortality within one year of initiating therapy was 0.91% for the ziprasidone group and 0.90% for the olanzapine group (both n = 9,077), relative risk (95% confidence interval [CI]) of 1.01 (0.75, 1.37). This finding was robust in numerous secondary and sensitivity analyses. Regarding secondary endpoints, the risk of all-cause mortality or cardiovascular mortality was similar among ziprasidone and olanzapine users; the incidence of all-cause hospitalizations was higher among ziprasidone users. The proportion of patients remaining on treatment at 6 months was lower for the ziprasidone group.

ZODIAC is one of the largest randomized studies conducted to date of patients with schizophrenia. With substantial statistical power, the study found no difference in risk of nonsuicide death associated with the use of ziprasidone vs. olanzapine.

Revealing of unknown adverse effects of atypical antipsychotics on pediatric population may take a long period of time. The purpose of this prospective study is to document changes in the liver function tests (LFTs) associated with Risperidone usage in a group of children and adolescents.

Study subjects consist of 120 youths with ages ranging from 3-17 years. For this study, patients' baseline and follow-up weight and liver function tests (LFT) including alanine aminotransferases(ALT) and aspartat aminotransferases (AST), gamma gluatamyl transerase (GGT), alkaline phosphatase (ALP) and serum bilirubin levels were measured before and after the treatment period of one month.

Only one eight years old male patient's ALT levels increased up to three-fold and AST levels increased up to two-fold of the basal levels. First month mean levels of liver enzymes and billuribin of the patients were significantly higher than the baseline. One or more of the liver enzymes and/or billuribin levels of sixty-three patients (52,5%) showed an asymptomatic increase in the first month of this study. Weight gain was observed in 58 patients (57.4%). There was no significant association between changes in weight and liver enzymes and billuribin levels.

We found asymptomatic LFT abnormalities mostly in the form of ALP elevation in 52.5% and marked liver enzymes elevation in 0.8% of risperidone treated subjects. These findings suggest that risperidone treatment in the short term commonly leads to liver function changes however it rarely may induce a serious hepatic toxicity at therapeutic doses in children and adolescents.

The efficacy of QTP in the treatment of schizophrenia has been well established in randomised, double-blind, placebo-controlled trials, but there is a lack of data concerning its efficacy in the medium- term management of schizoaffective disorder. Aim of the study was to evaluate retrospectively the efficacy and tolerability of QTP in preventing relapses of Schizoaffective Disorder (1,2).

The study involved 18 outpatients (4 males and 14 females), at least 18 years of age, with a diagnosis of Schizoaffective Disorder, based on the DSM-IV-TR criteria.

Patients were evaluated by using BPRS, CDSS and CGI-S. Clinical evaluation was assessed retrospectively through the data obtained by the clinical records. Evaluation started when QTP was prescribed (T0), and was performed after six months (T6). Moreover, a clinical evaluation was assessed six months before the start of QTP treatment by using the same rating scale (T-6). The main outcome measure evaluated was the rate of hospitalization caused by depressive, manic or psychotic relapses.

At the end of the study (T6), a significant reduction in CGI-S, BPRS and CDSS scores was observed. CDSS mean scores showed a 60% amelioration vs T0. No patients dropped out because of side effects. The mean dosage of quetiapine in our study was 544 mg/die.

QTP, alone or in association with benzodiazepines and/or mood stabilizers, seems to be an effective tool in the treatment of Schizoaffective Disorder and in prevention of relapses and consistent with several researches it seems effective in reduction of depressive symptoms.

The auricular acupuncture (AA) detoxification was first introduced in 1974. Over the past thirty years this technique has been extensively studied, expanded and improved. Unfortunately, there is no empirical evidence to recommend the use of AA for dual diagnosis patients (DDP). The absent data on the efficacy and safety of the AA leads to inappropriate use of this therapeutic intervention in DDP.

Randomized controlled parallel groups clinical trial aimed to investigate the effectiveness and safety of AA in DDP for the management of both psychiatric and addiction issues. The study population group [10 AA tretments at least 20 minutes 4-5 times a week] comprised 10 subjects (9 males (90.0%), mean age 28.8 years (SD=5.7)). The control population group (without AA) comprised 3 subjects (3 males (100.0%), mean age 29.5 years (SD=7.8)). Antipsychotic efficacy was measured by CGI–Severity & CGI–Improvement scales, craving was measured by Drug-DALI and treatment compliance was measured by DAI-10.

There were no differences between the groups according to demographic and clinical measures at the beginning of the study. The mean DALI score change in study population was –3.7 (SD=3.9; p<.06), the mean DAI score change was 3.9 (SD=4.6; p<.06) in comparison to –6.0 (SD=4.2; NS) and 5.5 (SD=10.6; NS) in a control population, respectively. Were no differences in CGI-I (NS). There were no adverse events in both populations.

There is a trend for effect of AA to craving decrease and a trend for effect to improvement of treatment-compliance in DDP.

To assess weight gain in adolescents treated with antipsychotic drugs for early onset schizophrenia (EOS).

One-year follow-up of 13 consecutive adolescents (10 male, 3 females, age range: 11-16) treated with atypical antipsychotics for early onset schizophrenia (according to DSM-IV criterias). The main outcome measure is sex- and age-adjusted Z scores of Body Mass Index (BMI).

BMI, sex- and age-adjusted BMI percentiles and BMI Z scores are significantly increased in schizophrenic adolescents after prescription of atypical antipsychotics (p= 0.025).

Despite the limited number of children included, this pilot study confirms a significant link between prescription of risperidone in early onset schizophrenia and increase of adjusted BMIZ scores. Clinicians and caregivers are to be aware of potential metabolic adverse effects of these medications. These findings suggest a regular health monitoring in adolescents treated with atypical antipsychotics, before and along the prescription.