Alexander Panickacheril John

Prevalence and nature of antipsychotic polypharmacy among inpatients with schizophrenia spectrum disorders at an Australian mental health service

Objective: Though antipsychotic polypharmacy (APP) is widely utilised in many clinical settings for the treatment of people with schizophrenia, the extent of this practice varies considerably between different regions, countries and clinical settings. Studies from Australasia exploring the prevalence and factors associated with APP are sparse and have yielded inconsistent results. Methods: We conducted a systematic retrospective audit of the medical records of all admissions in 2010 in the adult wards of a metropolitan public mental health service in Western Australia, having a diagnosis of schizophrenia or schizoaffective disorder. We analysed the rates of APP use, and its association with selected demographic and clinical variables. Results: The prevalence of APP among our sample of 229 patients was high, at 43.2%. APP was associated with a longer hospital stay (p = 0.033) and voluntary admission (p = 0.027); but APP was not significantly related to: age, gender, diagnosis and treatment by different psychiatrists. Conclusions: Substantial difference exists between everyday clinical practice and recommendations of practice guidelines of schizophrenia, regarding the use of APP. Prospective studies from different settings exploring the relevant clinical, patient, prescriber and system-related issues are warranted, to comprehend the rationale behind high utilisation of APP in clinical practice.

Antipsychotic polypharmacy is not associated with reduced dose of individual antipsychotics in schizophrenia.

to agents associated with weight gain. This fact is suggested by the baseline weight of nearly 200 lb. Thus, in the naturalistic setting, it seems that the greatest weight gain may occur in antipsychotic-naive patients and is limited in patients who have already gained a significant amount of weight. This same phenomenon may have also limited weight gain in the asenapine group. Two individuals gained 10 lb (7.1% of initial body weight) and 16 lb (9.4% of initial body weight) each in less than 1 month. These subjects were discontinued from the asenapine when the weight change was noted and are included in the analysis. In registrational trials, 15% of subjects gained more than 7%of their bodyweight. The 2 subjects who gained more than 7% of their body weight comprise 10%of our sample,which reflects the findings of the registrational trials. In the original registrational trials, the observed weight gain in bipolar patients in 3 weeks of acute treatment with asenapine monotherapy was 2.86 lb. We found that patients treated with asenapine gained an average of 5.8 lb over 7.6 months. In addition, there was no significant difference in the weight gain compared with treatment with other SGAs. Therefore, our results suggest that naturalistic experience with asenapine reflects data obtained in the registrational trials.

Successful implementation of a cognitive remediation program in everyday clinical practice for individuals living with schizophrenia

Objective: This article evaluates the feasibility and benefits of implementing cognitive remediation interventions in everyday clinical practice among individuals living with schizophrenia. Method: We retrospectively assessed short-term cognitive and occupational outcomes of 89 consecutively admitted people with schizophrenia at a public mental health service. A computerized cognitive remediation program was offered at the facility as an integral component of psychosocial treatments. Data of service recipients who had completed the Brief Assessment of Cognition in Schizophrenia (BACS; Keefe et al., 2004) on admission and discharge were included for evaluating outcomes. Results: Thirty-seven service recipients did not participate (nontrainee), 18 completed less than 20 hr (incomplete trainee), and 34 completed more than 20 hr of cognitive remediation (completed trainee). Whist a variety of factors affected involvement, lack of interest was the predominant reason voiced for nonparticipation. Repeated measures analysis of variance did not reveal significant Group × Time interaction. Exploratory contrasts showed statistically significant improvement within the completed trainee group from baseline to discharge on the BACS composite score, list learning, and token motor task. Logistic regression analysis indicated that although improved cognition predicted enhanced employment outcome, there was no significant difference among the 3 groups. Conclusions and Implications for Practice: Cognitive remediation interventions were accepted by a sizable proportion of people with schizophrenia admitted to an inpatient clinical treatment and rehabilitation facility. Promising improvement in cognitive function among those who completed the training suggests the need for methodologically rigorous research exploring the feasibility and benefits of cognitive remediation programs at everyday clinical settings.

Occurrence of stuttering priapism on low dose of quetiapine.

Stuttering priapism, a distinct category of ischaemic priapism, is characterised by intermittent prolonged penile erections that persist beyond or are unrelated to sexual stimulation (Morrison and Burnett, 2012). Ischaemic priapism can be a rare and idiosyncratic adverse effect of antipsychotics (Sood et al., 2008). It has been suggested that antipsychotics with lower affinity for α1 receptors have reduced potential to cause priapism, and less than a dozen cases of priapism have been reported with quetiapine (Maakaron et al., 2013). Furthermore, the majority of these patients were on higher dosage of quetiapine. We report a case of stuttering priapism which occurred abruptly with 25 mg of quetiapine. A 27-year-old Caucasian single man with no history of coagulopathy, perineal injury or other significant medical conditions or substance abuse presented at a suburban mental health clinic with repeated episodes of painful penile erections after taking 25 mg of quetiapine for anxiety. He was also on duloxetine 60 mg which was initiated 2 weeks previously for obsessive ruminations. Priapism occurred an hour after taking the first dose of quetiapine, and over the next 4 weeks, he had five similar episodes lasting from 2 to 6 hours. No interventions were required to achieve detumescence, and he did not discuss the symptoms with others until his next psychiatric follow-up. Results of blood investigations were unremarkable. Quetiapine was ceased, but duloxetine was continued at the same dosage. There were no further episodes of priapism during next 3 months of follow-up. Quetiapine is widely used in clinical practice and often at relatively lower dosages for anxiety, insomnia and other symptoms. Priapism is not uniquely associated with quetiapine and has been reported as an idiosyncratic adverse effect with typical and atypical antipsychotics and with other psychotropics (Sood et al., 2008). While blockade of α1 receptors with antipsychotics has been proposed by some authors to explain its aetiology, the genesis of ischaemic priapism is likely to be much more complex, with various neural, endothelial, vascular and molecular factors playing a significant role (Morrison and Burnett, 2012). Although in this patient priapism did not recur after quetiapine was ceased, a synergistic role for duloxetine cannot be completely discounted. Psychiatric patients often under-report significant sexual and other adverse effects for a variety of reasons, and our report illustrates the need to be vigilant about monitoring for rare but devastating side effects such as priapism.

The Assessment of Motor and Process Skills as a measure of ADL ability in schizophrenia

Abstract Background: Functional impairments in schizophrenia are substantial, complex, and persistent. Objective measurement of ADL ability, functional capacity and performance is needed for effective intervention planning and outcome evaluation. Objective: To evaluate ADL ability in people with schizophrenia using the Assessment of Motor and Process Skills (AMPS) and to determine the utility of using the AMPS to predict levels of assistance required for successful community living. Method: In a retrospective audit, AMPS ADL measures of a consecutive sample of 64 people with schizophrenia admitted to a mental health facility were compared with normative data and with recommended “cut-off” measures for competency to live independently in the community. Results: Substantial difficulties were measured in both ADL motor (mean z = –1.5) and ADL process ability (mean z = –2.1). AMPS ability measures did not predict problems with independent living for 62.5% of the patients. Conclusion: People with schizophrenia admitted to an inpatient rehabilitation facility experienced significant difficulty performing ADL tasks. AMPS is a useful measure of ADL ability but should be used in conjunction with measures of functional performance in order to plan interventions and supports for people with schizophrenia that reflect the complexity of factors affecting community functioning.

Delayed Initiation of Clozapine Continues to Be a Substantial Clinical Concern

About 20% to 30% of people with schizophrenia fail to respond satisfactorily to trials with 2 or more antipsychotics given at adequate dosage for 4 to 6 weeks each and are considered as having treatment-resistant schizophrenia (TRS). People with TRS have increased prevalence of smoking, substance abuse, criminal behaviour, functional impairment, psychiatric hospitalisation, impaired quality of life, and 3 to 11 times higher health care costs compared with those who are responsive to treatment. Clozapine is the only medication with worldwide regulatory approval for managing TRS and has demonstrated superior efficacy over typical and atypical antipsychotics, with approximately 40% of patients responding adequately. However, treatment with clozapine is not effective for a significant proportion of people with TRS, and there is emerging concern that delayed initiation of clozapine could be associated with suboptimal response. Nielsen et al., researching Denmark’s nationwide databases, opined that each previous antipsychotic trial reduced the likelihood of response to clozapine by 8% to 11% and that one-third of the patients had 4 or more antipsychotics prior to commencing clozapine. Another study from Denmark suggested that while nearly 25% of people with TRS who were treated with clozapine showed moderate to substantial functional improvement, each year of delay was associated with a 15% decrease in the chance of functional improvement among females. Promisingly, based on best available evidence, many recent revisions of clinical practice guidelines for schizophrenia, including that of the Canadian Psychiatric Association, have recommended that TRS should be identified early and that, once established, treatment with clozapine should not be delayed. Theoretically, in many patients, TRS could be diagnosed as early as 3 months from onset of psychosis and clozapine introduced. However, while the pathway from evidence generation to its synthesis and guideline development is robust and well developed, the route for the dissemination of these guidelines into clinical practice is much more arduous and poorly researched. With regard to the pharmacoepidemiology of clozapine, both the rate of its use and the timing of its usage are clinically relevant. While there has been research interest in the past 2 decades on the area of underutilisation and low prescription rates of clozapine, attempts to synthesise and analyse the data on the delayed initiation of clozapine have been much more limited. In this context, we reviewed the literature on the time taken for patients with schizophrenia to be commenced on clozapine in clinical practice and highlight the complex issues surrounding the delayed initiation. We searched the PubMed, PsycINFO, Embase, and Ovid MEDLINE databases up to December 2017 using the search terms clozapine in combination with initiation or start or commence or first episode psychosis or early psychosis or early schizophrenia. The search resulted in a total of 3371 studies. The 3 authors independently screened and reviewed the abstracts available in the English language and identified 10 relevant studies. The authors reviewed the full text of these studies and through crossreferencing identified an additional article. The findings are summarised in Table 1. Research focussed on this area has been somewhat limited and predominantly from Western countries. Furthermore, many methodological issues confounded these studies. None of them were prospective, data collation was

PM444. Effectiveness of Integrating Cognitive Remediation Program into Everyday Clinical Practice of Schizophrenia at Psychiatric Rehabilitation Settings

Cognitive deficits (CD) in schizophrenia are recalcitrant to treatment as usual. Whilst there has been considerable interest in recent years for evaluating the efficacy of cognitive remediation (CR) programs in schizophrenia at research settings, scant attention has been paid to evaluate the effectiveness of CR programs at everyday clinical practice settings. Method: We evaluated retrospectively short-term cognitive, occupational and accommodation outcomes of consecutive patients with schizophrenia admitted over a 5 year period at a tertiary-care inpatient public psychiatric rehabilitation facility in Western Australia. The Brief Assessment of Cognition in Schizophrenia (BACS) was utilised to assess cognition. Patients were divided into 3 groups based on their participation in the neuroplasticity based auditory CR program of PositScience; those who did not participate (non-trainers), those who completed less than 20 hours of training (incomplete-trainers) and those who completed 20 or more hours of training (completetrainers). Results: The mean age of the patients was 32.1 years, 68.5% were males, nearly 80% had treatment-resistant illness, 65% were on clozapine and comorbidity was highly prevalent (72%). Thirtyseven patients were classified as non-trainers, 17 as incompletetrainers and 34 as completetrainers. The 3 groups did not differ in measured demographic and clinical parameters. Compared to their admission scores, completetrainers had significantly improved scores at discharge on verbal memory (p=0.012), motor speed (p=0.009) and the composite score (p=0.006). Furthermore, 24%, 22% and 36% of patients changed from unemployed to the employed group in the non-trainers, incomplete-trainers and complete-trainers groups respectively from admission to discharge. Conclusion: Our study demonstrates that CR program can be integrated effectively into the interventions provided for people with schizophrenia at public psychiatric rehabilitation settings. Significant improvements in cognitive and functional outcomes revealed in this study indicate the need for further translational research in the field of CR in schizophrenia. PM445 A family of primary familial brain calcification due to mutation in platelet-derived growth factor-B gene Teruo Hayashi, Giovanni Coppola, Andrea Legati, Tadashi Nishikawa Seiwakai Nishikawa Hospital, Japan Abstract Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by abnormal deposits of calcium in the basal ganglia and cerebellum. PFBC can present with a spectrum of symptoms resembling those seen in dementia and schizophrenia. Mutations in some genes have been found to cause PFBC: namely, the SLC20A2 gene that codes for the sodium-dependent phosphate transporter and the PDGFRB gene that codes for the platelet-derived growth factor (PDGF) receptor β. A recent study found that mutations of PDGFB, which encode the ligand peptide PDGF-B for the PDGF receptor β, also cause PFBC. Here we report the first Japanese family of PFBC carrying a mutation of PDGFB. CT scans revealed a symmetrical calcification over the basal ganglia in two members of the family. One family member complained auditory hallucination at 16 years old, and had been treated for schizophrenia. The other family member complained memory and gait disturbances in his late 60s. The mutation in PDGFB (c.445C>T, p.Arg149*) that causes the substitution of an arginine with a stop codon at amino acid 149 of the PDGF-B protein (p. Arg149*) was consistently detected in both cases. No mutations in SLC20A2 were detected. This finding indicates that the PDGF pathway plays a crucial role in pathogenesis of PFBC, and that dysfunction of the PDGF signaling may lead to psychiatric symptoms that are associated with dementia and/or schizophrenia.Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by abnormal deposits of calcium in the basal ganglia and cerebellum. PFBC can present with a spectrum of symptoms resembling those seen in dementia and schizophrenia. Mutations in some genes have been found to cause PFBC: namely, the SLC20A2 gene that codes for the sodium-dependent phosphate transporter and the PDGFRB gene that codes for the platelet-derived growth factor (PDGF) receptor β. A recent study found that mutations of PDGFB, which encode the ligand peptide PDGF-B for the PDGF receptor β, also cause PFBC. Here we report the first Japanese family of PFBC carrying a mutation of PDGFB. CT scans revealed a symmetrical calcification over the basal ganglia in two members of the family. One family member complained auditory hallucination at 16 years old, and had been treated for schizophrenia. The other family member complained memory and gait disturbances in his late 60s. The mutation in PDGFB (c.445C>T, p.Arg149*) that causes the substitution of an arginine with a stop codon at amino acid 149 of the PDGF-B protein (p. Arg149*) was consistently detected in both cases. No mutations in SLC20A2 were detected. This finding indicates that the PDGF pathway plays a crucial role in pathogenesis of PFBC, and that dysfunction of the PDGF signaling may lead to psychiatric symptoms that are associated with dementia and/or schizophrenia. PM446 The relationship between MMN and COMT Val108/158Met genotype in schizophrenia Sho Horikoshi,Tetsuya Shiga, Hiroshi Hoshino, Haruka Ochiai, Keiko Kanno-Nozaki, Kazuko Kanno, Haruka Kaneko, Itaru Miura, Hirooki

Successful evaluation of cognitive function and the nature of cognitive deficits among people with schizophrenia in clinical rehabilitation settings

Objectives: Despite possessing considerable relevance for planning and delivery of effective rehabilitation interventions, systematic evaluation of cognitive function is often ignored in clinical practice. This paper describes a successful method for measuring cognitive function and the nature of cognitive deficits (CD) in people with schizophrenia admitted to psychiatric rehabilitation services. Methods: Data on the cognitive functioning of consecutive patients with schizophrenia / schizoaffective disorder admitted during a 5-year period to a public in-patient rehabilitation facility was collated retrospectively and analysed. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive function. Results: It was possible to administer the BACS to 122 of 135 consecutive admissions. The mean composite score on the BACS was 1.8 standard deviations below the norm, and 43% had moderate or severe CD. The BACS sub-tests of list learning and symbol coding revealed more severe deficits. Conclusions: The study indicates that evaluation of cognitive function using brief instruments is feasible in psychiatric rehabilitation settings. Global and domain-specific CD were prevalent among people with schizophrenia. In view of the strong association of cognitive functioning with community functioning and rehabilitation outcomes, further studies exploring the feasibility and utility of routinely evaluating cognitive function are warranted.