Liverpool University Neuroleptic Side Effect Research Articles

Somatic symptoms in schizophrenia: Association with socio-demographic and clinical characteristics, disability and quality of life.

There is lack of research on somatic symptoms in schizophrenia. We aimed at finding prevalence and types of somatic symptoms in patients with schizophrenia and assessed their association with socio-demographic and clinical characteristics. We assessed somatic symptoms using Patient Health Questionnaire-15 (PHQ-15) in 93 patients with schizophrenia diagnosed on ICD10-DCR. Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms, WHO Disability Assessment Schedule 2.0, WHO Quality of Life (BREF) Hindi version and Liverpool University Neuroleptic Side-Effect Rating Scale were used to assess psychopathology, disability, quality of life and side effects. Significant somatic symptoms (n ≥5 on PHQ-15) were present in 62 (67.7%) patients with schizophrenia. Forty three (69.4%) had mild (n = 5-9 on PHQ-15), 17 (27.4%) had moderate (n = 10-14 on PHQ-15), and only 2 (3.2%) had severe (n = ≥15 on PHQ -15) somatic symptoms. Mean somatic symptoms score on PHQ-15 was 7.28 (± 3.83); 96.8% reported feeling tired, 76.3% had constipation or diarrhoea, 67.7% trouble in sleeping, 61.3% nausea or indigestion, 52.7% back pain and 51.6% headache. Patients with somatic symptoms were older in age, had longer duration of illness and treatment, and had more negative symptoms. They had higher disability and poor quality of life especially in physical domain. Somatic symptoms are common in patients with schizophrenia and are associated with chronicity, refractoriness and negative symptoms, significant disability and poor quality of life. Thus during routine clinical practice, somatic symptoms should be assessed and managed in these patients.

Improving Medication Adherence in Convalscent Psychiatric Out-Patients Exposed to Psychotomimetic Medications in South-West, Nigeria: The Role of Medication Literacy and `Therapeutic Relationships.

Medication adherence is a growing concern to clinicians and healthcare providers in psychiatric communities, mounting evidence of the prevalence of non-adherence have been significantly associated with undesirable health outcomes and burdensome healthcare expenditure. This study examined medication adherence in psychiatric patients exposed to psychotomimetic medications and how therapeutic relationship predicts the level of medication adherence. This study was a cross-sectional survey design. Snowballing sampling technique was used to select psychiatric out-patients. The total number of participants for this study was thirty-six (36), males (65%) and females (35%). Majority of participants were between the ages of 31-50 years. Participants responded to Morinsky Medication Adherence Scale (α=0.91), Liverpool University Neuroleptic Side-Effect Scale (α= 0.89), and Therapeutic Relationship Scale (patient version) (α=0.71). Three hypotheses were formulated and tested using multiple regression analysis. Results of the multiple regression indicate that psychotomimetic side-effects inversely predicted medication adherence among psychiatric patients exposed to psychotomimetic drugs [β = .35, p <0.01]. Also, the outcome of the results indicated that therapeutic relationship was a significant predictor of medication adherence among psychiatric patients exposed to psychotomimetic drugs [β = .40, p <0.01]. Therefore, it was recommended that therapeutic relationship should be an integral part of the modalities in psychiatric treatment and to adopt best practices by effectively communicating with patients about the importance of adhering to treatment plans; and provide medication support services to patients and family caregivers. This helps to improve, build a sustainable therapeutic relationship (nurse-patient) through empathy and professional intimacy that facilitates diagnosis accuracy, and desired health outcome.

The impact of side effects on schizophrenia and bipolar disorder patients' adherence to prescribed medical therapy.

Our study aims to investigate how antipsychotic drugs' side effects impact schizophrenia and bipolar disorder patients and how this affects their adherence to prescribed medical therapy. The study sample consists of 47 bipolar disorder and 45 schizophrenic patients. Data were collected using the Medication Adherence Rating Scale (MARS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The mean total LUNSERS scores showed that bipolar disorder patients had more significant side effects compared with schizophrenic patients (P < .05). There was a moderate negative correlation between the mean MARS scores and mean LUNSERS scores of bipolar disorder patients (P < .05). Nursing care actions and strategies should be planned and implemented to promote adherence to treatment.

Genetic Polymorphisms Associated With Constipation and Anticholinergic Symptoms in Patients Receiving Clozapine.

Clozapine impairs gastrointestinal motility owing to its anticholinergic and antiserotonergic properties. This commonly leads to constipation and potentially to more severe complications such as bowel obstruction and ischemia. The aim of this study was to determine whether genetic variations in the genes encoding muscarinic and serotonergic receptors (CHRM2, CHRM3, HTR2, HTR3, HTR4, and HTR7) explain the variations in incidence of constipation and anticholinergic symptoms during clozapine treatment. Genes associated with opiate-induced constipation were also included in this analysis (TPH1, OPRM1, ABCB1, and COMT). Blood samples from 176 clozapine-treated, Finnish, white patients with schizophrenia were genotyped. Constipation and anticholinergic symptoms were rated using the Liverpool University Neuroleptic Side Effect Rating Scale self-report questionnaire. In total, 192 single-nucleotide polymorphisms (SNPs) were detected and grouped to formulate a weighted genetic-risk score (GRS). No significant associations between individual SNPs or GRSs and constipation or laxative use were observed. A GRS of 19 SNPs in CHRM2, CHRM3, HTR3C, HTR7, ABCB1, OPRM1, and TPH1 was associated with anticholinergic symptoms in a generalized linear univariate model, with body mass index, clozapine monotherapy, and GRS as explaining variables (permuted P = 0.014). Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002). Two GRSs are able to predict the risk of anticholinergic symptoms in patients receiving clozapine and possibly an increased risk of gastrointestinal hypomotility.

F225. LEVODOPA AUGMENTATION OF ANTIPSYCHOTICS FOR THE TREATMENT OF NEGATIVE SYMPTOMS IN SCHIZOPHRENIA

BackgroundNegative symptoms (i.e., motivation deficits and diminished emotional expression) are prevalent in schizophrenia and consistently linked with functional impairment for affected individuals. Despite advances in psychopharmacology for schizophrenia, there remain no effective treatments for these negative symptoms. Older literature, however, suggests that levodopa in conjunction with antipsychotic treatment can have beneficial effects for patients with schizophrenia. While supporting the safety and potential efficacy of dopamine augmentation, these studies did not evaluate effects within specific symptom domains, particularly negative symptoms. This open-label pilot study was conducted to evaluate the preliminary efficacy and safety of levodopa augmentation of antipsychotics for the treatment of negative symptoms.MethodsTen stable outpatients with schizophrenia between the ages of 18 and 60 were enrolled. All were treated with stable atypical antipsychotic monotherapy for at least eight weeks, and had a minimum total score of 30 on the Scale for the Assessment of Negative Symptoms (SANS). Participants were treated with adjunctive open-label levodopa/carbidopa, with dose titration to levodopa 300mg TID over 38 days as tolerated, and dose maintenance for the remainder of the eight-week trial. Baseline assessments consisted of the SANS, Scale for the Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Calgary Depression Scale for Schizophrenia (CDSS), MATRICS Consensus Cognitive Battery (MCCB), and Quality of Life Scale (QLS) for community functioning. Treatment side effects were evaluated with the Simpson Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), UKU side effect rating scale (UKU), Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Barratt Impulsiveness Scale (BIS). Participants were reassessed on measures of psychosis and side effects weekly for the first four weeks, and every two weeks thereafter. The SANS and CGI were repeated at weeks 4 and 8, with the MCCB and QLS re-administered at week 8. Statistical analyses included the intent-to-treat sample (i.e., participants who received at least one dose of study medication) and consisted of linear mixed models for change in SANS total score (our primary outcome), and change in other clinical and side effects measures as a result of treatment.ResultsEnrolled participants (eight male and two female) had a mean age of 37.2 years. Seven participants completed the study, with three participants dropping out. The mean final dose of levodopa for study completers was 835.7 mg (SD 170.1). Levodopa augmentation resulted in a significant improvement in negative symptoms, with a mean SANS reduction for study completers of 15.3 (SD 5.7). This equated to a mean SANS improvement of 25.5% (range 17% to 57%), with 43% of study completers experiencing > 20% improvement in SANS score. Notably, significant improvement in negative symptoms emerged after the first four weeks of treatment. There was no significant change in positive symptoms, nor other clinical outcomes or side effect measures.DiscussionOur findings suggest that levodopa augmentation of antipsychotics may be an effective and well-tolerated treatment for negative symptoms in schizophrenia. These findings, however, need replication in larger randomized controlled trials. With the dearth of available treatments for negative symptoms, levodopa augmentation may represent a novel pharmacologic strategy to address this critical unmet therapeutic need for schizophrenia.

Histaminergic gene polymorphisms associated with sedation in clozapine-treated patients

Sedation is a common adverse effect of clozapine treatment, which may be partly related to clozapine binding to histamine receptors in the central nervous system. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the histaminergic system are associated with sedation in clozapine-treated patients. The study population comprised 237 clozapine-treated, Finnish, Caucasian patients that were diagnosed with schizophrenia and 176 were genotyped using Illumina HumanCoreExome-12 BeadChip. Sedation levels were assessed using self-rating questions from the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The relationships between 55 different SNPs in the histaminergic system and adverse sedation effects were examined. SNPs were analyzed separately, and in groups, to formulate a genetic risk score (GRS). A permutation test was performed to avoid type I errors. Eight linked SNPs (r2 = 1) in the HNMT gene were also associated with sedation according to the GLM, adjusted for age, gender and BMI (false-discovery-rate-adjusted p = 0.013). An association on a trend level between a GRS of four different SNPs (recessive histamine N-methyltransferase HNMT rs2737385, additive histamine receptor H1 rs1552498, dominant HRH1 rs17034063 and recessive amine oxidase, copper containing 1 AOC1 rs6977381) and sedation was found (permuted p-value = 0.066) in a generalized linear model (GLM) incorporating age, gender and body mass index (BMI; adjusted R2 = 0.22). Polymorphisms in genes encoding histamine receptors or enzymes related to histamine metabolism may explain individual variation in sedative effects experienced during clozapine treatment.

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability.

The objective of this study was to compare patients' attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including medication tolerability; assessment of side effects, efficacy and quality of life made by blinded raters; and additional objective side-effect data including changes in weight and key blood parameters.

Adjunctive memantine in clozapine-treated refractory schizophrenia: A one-year extension study

IntroductionIn a recent 26-week placebo-controlled, crossover trial (n = 52) we found significant positive effects on verbal and visual memory, and negative symptoms in clozapine-treated patients with refractory schizophrenia.ObjectivesIn this 1-year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.AimsTo evaluate the persistence of improvements in cognitive functioning and symptoms of memantine add-on therapy to clozapine in schizophrenia.MethodsCompleters of the first trial who experienced a beneficial effect of memantine after 12 weeks continued memantine for one year. Primary endpoints were change from baseline to 26 weeks treatment and 26 weeks to 52 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Secondary endpoints were change on the Health of the Nation Outcome Scales (HoNOS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).ResultsOf 32 completers who experienced a beneficial effect of memantine 23 patients continued memantine for one year. Memory improvement was sustained, verbal recognition memory improved even further between t = 26 weeks and t = 52 weeks. Continued treatment with memantine add-on to clozapine was associated with significantly improved PANSS positive, negative and overall score, CGI-S and HoNOS scores.ConclusionsIn the extension phase the positive effect of memantine add-on therapy on verbal memory sustained and positive, negative and overall symptoms of schizophrenia, clinical global status and psychosocial functioning significantly improved. Memantine was well tolerated without serious adverse effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Rating scales to measure side effects of antipsychotic medication: A systematic review.

Many patients experience side effects during treatment with antipsychotics. This article reviews the clinical use and psychometric characteristics of rating scales used to assess side effects in patients treated with antipsychotics. A systematic literature search was performed using the electronic databases PubMed and Embase, with predefined search terms. In total, 52 different scales were used in the 440 articles retrieved. For multiple side effects measured with one scale, the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale for Clinicians was used the most, whereas the Liverpool University Neuroleptic Side Effect Rating Scale had the best psychometric characteristics (Cronbach's α 0.81 and test-retest reliability 0.89). The Simpson Angus Scale was used the most to rate extrapyramidal side effects, although the Maryland Psychiatric Research Center scale had the best characteristics (Cronbach's α 0.80, test-retest reliability 0.92 and inter-rater reliability 0.81-0.90). The Arizona Sexual Experience Scale was used the most to assess sexual dysfunction, but the Antipsychotics and Sexual Functioning Questionnaire and the Nagoya Sexual Functioning Questionnaire had the best characteristics. This review will help researchers and clinicians make a purpose-oriented choice of which scale to use. CRD42014013010.

Construction and validation of the My Medicines and Me Questionnaire for assessment of the self-reported side effects of psychotropic medication.

We aimed to construct and assess the psychometric properties of the My Medicines and Me Questionnaire (M3Q), a self-report side-effect questionnaire for mental health patients. Thirty individuals taking a psychotropic medication completed the M3Q side-effect checklist along with the Liverpool University Neuroleptic Side Effect Rating Scale. Thirty healthy comparison individuals also completed the M3Q checklist. Data were analyzed using factorial analysis. Psychometric evaluations including validity and reliability testing were carried out on the questionnaire's checklist. The original 54-item checklist of the M3Q was shortened to include only those items found to be significant in the factorial analysis. The revised 32-item checklist of the M3Q was found to be valid and reliable. The M3Q is a simple, valid and reliable questionnaire that can be used routinely in clinical practice for detecting bothersome side effects of a range of psychotropic medications. This will provide a platform for improved communication between the clinician and the patient.

Factors associated with subjective side-effects during clozapine treatment

Objective: Clozapine is associated with subjectively unpleasant or clinically serious side-effects, which may affect treatment adherence. The aims of the study were to explore the association of clozapine+ norclozapine serum concentration and other factors with subjective side-effects in schizophrenia patients. Methods: In this cross-sectional study, 237 patients with a diagnosis of schizophrenia, schizo-affective or other non-organic psychoses completed the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), a self-report scale measuring side-effects of antipsychotics and a clinical questionnaire. Clozapine+ norclozapine serum concentration of 190 patients was measured. Of the patients 80 (33.7%) were on antipsychotic combination therapy. Results: Higher clozapine+ norclozapine concentrations were associated with the depression–anxiety factor of LUNSERS and antipsychotic combination treatments were associated with sympatichotonia–tension factor. Younger patients reported sedation more often than older patients. Conclusion: According to the present results, high clozapine concentrations were associated with depression–anxiety symptoms, but the causality remains unknown.

CYP1A2polymorphism −1545C &gt; T (rs2470890) is associated with increased side effects to clozapine

BackgroundCytochrome P450 1A2 gene (CYP1A2) polymorphisms have been suggested to be associated with increased side effects to antipsychotics. However, studies on this are scarce and have been conducted with either various antipsychotics or only in small samples of patients receiving clozapine. The aim of the present study was to test for an association between the CYP1A2 −1545C > T (rs2470890) polymorphism and side effects in a larger sample of patients during long-term clozapine treatment.MethodsA total of 237 patients receiving clozapine treatment completed the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) assessing clozapine-induced side effects. Of these patients, 180 completed the questionnaire satisfactorily, agreed to provide a blood sample, and were successfully genotyped for the polymorphism.ResultsThe TT genotype of CYP1A2 polymorphism −1545C > T (rs2470890) was associated with significantly more severe side effects during clozapine treatment (p = 0.011). In a subanalysis, all seven types of side effects (sympathicotonia–tension; depression–anxiety; sedation; orthostatic hypotension; dermal side effects; urinary side effects; and sexual side effects) appeared numerically (but insignificantly) more severely among TT carriers. In addition, use of mood stabilizers was more common among patients with the TT genotype (OR = 2.63, p = 0.004).ConclusionsThis study has identified an association between the CYP1A2 polymorphism −1545C > T (rs2470890) and the occurrence of more severe clozapine side effects. However, these results should be regarded as tentative and more studies of larger sample sizes will be required to confirm the result.

Variables Influencing Subjective Well-Being in Patients with Schizophrenia

Objectives : The purpose of this study was to analyze the relationship between subjective well-being and other clinical parameters such as sociodemographic and clinical variables, which include positive and negative symptoms, depressive symptoms, insight, and side effects. Methods : Fifty-one outpatients diagnosed with schizophrenia were recruited in this study. Subjective well-being was assessed using a self-rating scale, the Subjective Well-being under Neuroleptics-Short form (SWN-K). Sociodemographic variables were also evaluated and other evaluations were conducted using the Positive and Negative Syndrome Scale (PANSS), Calgary Depres- sion Scale for Schizophrenia (CDSS), Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Korean Version of the Revised Insight Scale for Psychosis (KISP), and Multidimensional Scale of Perceived Social Support (MSPSS). The relation- ship between subjective well-being and these clinical variables was assessed. Results : Education years and social support scores were positively correlated with the total SWN-K scores, but severity of illness, severity of depression, severity of side effect, and the scores on insight were negatively correlated. The stepwise multiple regression analyses indicated that the total SWN-K score of the patients with schizophrenia was associated with negative symptoms and in- sight. Conclusion : Better insight and more severe negative symptoms in patients with schizophrenia may be associated with worse subjective well-being. Results indicate that careful evaluation of subjective well-being is essential for proper management of pa- tients with schizophrenia. (Korean J Schizophr Res 2014;17:93-99)

A randomized controlled trial undertaken to test a nurse‐led weight management and exercise intervention designed for people with serious mental illness who take second generation antipsychotics

AimTo test the effect of a nurse-led intervention on weight gain in people with serious mental illness prescribed and taking second generation antipsychotic medication.BackgroundWeight gain and obesity has reached epidemic proportions in the general population with the prevalence of Metabolic Syndrome reaching 20–25% of the global population. People with serious mental illness are at even higher risk, particularly those taking second generation antipsychotic medication.DesignAn experimental randomized controlled trial was undertaken.MethodThe control group received a 12-week healthy lifestyle booklet. In addition to the booklet, the intervention group received weekly nutrition and exercise education, exercise sessions, and nurse support. Participants (n = 101) were assessed at baseline and 12 weeks. Data were collected between March 2008–December 2010. Seven outcome measures were used: body measurements included girth (cm), weight (kg), height (cm), and body mass index (kg/m2); questionnaires included the medication compliance questionnaire, the Drug Attitude Inventory, the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical Outcomes Study Short Form 36. Differences in primary outcome measures between baseline and 12 weeks follow-up were compared between intervention and control groups using standard bi-variate statistical tests. The study was conducted between 2008–2010.ResultsThe analysis of outcome measures for the control group (n = 50) and intervention group (n = 51) was not statistically significant. There was a mean weight change of −0·74 kg at 12 weeks for the intervention group (n = 51), while the control group (n = 50) had a mean weight change of −0·17 kg at 12 weeks.ConclusionThe results were not statistically significant.

Combination Treatment With Aripiprazole and Valproic Acid for Acute Mania

Despite the fact that combination treatment for patients with acute bipolar is prevalent in clinical practice, the outcomes of adjunct treatment with aripiprazole and a mood stabilizer have rarely been reported. The aim of this single-blind, randomized, controlled trial was to investigate treatment efficacy and safety of aripiprazole as an adjunct to valproic acid (Ari+Val), compared with haloperidol plus valproic acid (Hal+Val), in acute manic patients. Treatment efficacy was prospectively assessed for 8 weeks in 42 patients with acute mania using the Young Mania Rating Scale and the Clinical Global Impression-Severity of illness scale. Emergent adverse events were assessed by the Drug-Induced Extrapyramidal Symptoms Scale and the Liverpool University Neuroleptic Side Effect Rating Scale. Both Ari+Val and Hal+Val produced a high rate of response (85.7% and 92.9%, respectively) and remission (82.1% and 85.7%, respectively) after the 8-week trial. Changes in the Young Mania Rating Scale and the Clinical Global Impression-Severity of illness scale over the study period and time to remission and response were not significantly different between the 2 groups. Patients treated with Ari+Val showed significantly fewer extrapyramidal adverse events than those treated with Hal+Val (t = -2.048, F = 40, P = 0.048). However, significant weight gain was more prevalent in the Ari+Val group than the Hal+Val group (t = 2.055, F = 40, P = 0.046). Our findings suggest that both combination strategies with Ari+Val and Hal+Val are beneficial for acute manic episode. Although patients receiving Ari+Val showed fewer extrapyramidal symptoms than those taking Hal+Val, careful consideration of adverse events such as weight gain and sedation is warranted.

P-1103 - Patient attitudes, satisfaction, tolerability for conventional depot antipsychotics and risperidone long acting injection: a cross-sectional survey in community patients

Maintenance antipsychotic medication has a key role in the long term management of schizophrenia but in clinical practice its effectiveness is often reduced by poor adherence. Antipsychotic long acting injections (LAIs) can improve clinical outcomes in those who have adhered poorly with oral medication. To compare patients’ attitudes, satisfaction and tolerability to their currently prescribed LAI, either a FGA-LAI or risperidone long-acting injection (RLAI), which was the only SGA-LAI at the time of this research. Cross-sectional survey of a representative sample of patients prescribed a FGA-LAI (n = 39) or RLAI (n = 28) for a minimum of 6 months. Assessments comprised drug attitude inventory (DAI-30), tolerability measured by Liverpool university neuroleptic side effect rating scale (LUNSERS) and satisfaction with antipsychotic medication by the SWAM scale. The DAI-30 score for patients on FGA depots was 16.18 and RLAI was 14.43, which indicated positive attitudes in both the groups. This difference did not reach statistical significance (p = 0.491). Further analysis, based on both the LUNSERS and SWAM scales, did not find any significant difference in tolerability and patient satisfaction. There was no evidence of differences between FGA-LAIs and RLAI in terms of patient rated tolerability, attitudes and satisfaction. Both groups of patients had positive attitudes to their LAI and overall tolerability was good. This data is observational, and not from a randomised design, which may reflect selection bias. Randomised studies are needed to further investigate differences in tolerability and attitudes between specific LAIs.

Antipsychotic-Associated Mental Side Effects and Their Relationship to Dopamine D2 Receptor Occupancy in Striatal Subdivisions

We examined the relationship between antipsychotic-associated mental side effects and dopamine D2 receptor occupancy in striatal subdivisions using high-resolution positron emission tomography with [11C]raclopride to better characterize the neurochemical mechanism underlying these adverse effects. Twenty-one patients with schizophrenia receiving stable doses of antipsychotics and 24 age- and sex-matched healthy controls completed 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography scans with [11C]raclopride to measure D2 receptor binding potential (BP ND) in the striatum. The D2 receptor BP ND was obtained using a Logan plot, and receptor occupancy was calculated as the percentage reduction of receptor BP ND with drug treatment relative to baseline. The data obtained from age- and sex-matched healthy controls were used as an estimate of the patients' baseline, as previously proposed. Antipsychotic-associated mental side effects were measured with the Liverpool University Neuroleptic Side Effect Rating Scale. The whole striatal D2 receptor occupancy ranged from 54% to 95%. The analysis revealed that the Liverpool University Neuroleptic Side Effect Rating Scale score had significant positive associations with D2 occupancy in the precommissural dorsal caudate, postcommissural caudate, and ventral striatum. The results suggest that mental side effects of antipsychotics are associated with D2 receptor blockade in the associative and limbic subdivisions of the striatum, which are considered to play a crucial role in cognition and reward motivation.

Aripiprazole Versus Haloperidol in Combination With Clozapine for Treatment-Resistant Schizophrenia in Routine Clinical Care

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

Adverse effects of antipsychotic drugs: survey of doctors’ versus patients’ perspective

Almost no data are available on whether patients and doctors have similar or dissimilar opinions on the presence and level of distress due to antipsychotic adverse effects. The aim of this survey is to compare doctors' versus patients' perspective on the presence and level of distress due to antipsychotic adverse effects in a sample of patients under the care of the South-Verona mental health services. All patients exposed to antipsychotic drugs during a census period of 6months were identified. For each included subject, socio-demographic, clinical and treatment data were extracted. Patients' perspective on antipsychotic adverse effects was measured by means of the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The LUNSERS was similarly employed to measure doctors' perspective on antipsychotic adverse effects. During the recruitment period, 243 patients taking antipsychotic drugs were enrolled. The correlation between the total LUNSERS score reported by patients and doctors was very low (correlation coefficient 0.22, 95% confidence interval 0.15-0.30). On average, patients perceived more adverse effects and with a significant higher distress than doctors. Multivariate analyses found no factors simultaneously associated with both patient and doctor ratings of adverse effects. Our study suggests that doctors, researchers and health care providers should increasingly consider patient and doctor perspectives as two complementary dimensions that may provide different insights in the evaluation of antipsychotic drugs. Integrating different points of view may represent a way to develop a better therapeutic alliance that might decrease the likelihood of nonadherence.