Mark Taylor

Mortality in schizophrenia: a measurable clinical endpoint

Over the last five years, large data sets on mortality in schizophrenia have been published which have established mortality as a measurable clinical endpoint. Four issues need clarification: whether mortality rates are declining, what the causes of death are, the effects antipsychotic treatments have on mortality and whether these data inform as to how mortality may be reduced in the future. A PubMed search was carried out to identify relevant publications. The search strategy was conducted as a review focusing predominantly on data since 2006. A large number of retrospective epidemiological and prospective studies have been published on mortality rates and causation in schizophrenia, predominantly from 2006—2009. Data suggest that the mortality gap with the general population increased from the 1970s but may have peaked in the mid-1990s. The main causes of mortality are suicide, cancer and cardiovascular disease, with evidence that cancer mortality rates are similar to cardiovascular mortality rates. Mortality causation is dependent upon age of the cohort, length of follow up and type of study. Antipsychotic treatments reduce mortality when compared with no treatment and atypical antipsychotics do not appear to increase cardiovascular mortality and morbidity compared with conventionals; further research is required for any definitive conclusion.

Impact of risperidone long acting injection on resource utilization in psychiatric secondary care

Risperidone long acting injection (RLAI) is the only long acting atypical antipsychotic available in the UK. Its impact on NHS resource use has not been widely studied. This review of medical records was conducted to quantify the impact of RLAI on NHS psychiatric secondary care resource use, primarily in terms of episodes of inpatient hospital care 12 months before and 12 months after RLAI initiation. Data on number of hospitalizations and hospital bed days were collected retrospectively, from patient notes and hospital databases in four acute psychiatric units in the UK for all individuals with a diagnosis of schizophrenia or schizoaffective disorder who were prescribed RLAI more than 12 months previously. Data were collected on 100 individuals (58 male) with a mean age 40.8 years (range 19—70). The median duration of illness before RLAI initiation was 12 years (range six months to 43 years). There were 62 admissions in the 12 months pre-RLAI, falling to 22 admissions in the 12 months post-RLAI. Number of admissions, we argue, offer a more reliable indicator of the impact of treatment than total hospital bed days in this type of study. In this study there were 40 fewer admissions in the 12 months after RLAI was initiated compared with the previous 12 months. This is important as readmission is a good proxy measure of relapse, and adherence to medication is known to be a key factor in relapse prevention.

Should long-acting (depot) antipsychotics be used in early schizophrenia? A systematic review

Background: The relapse rate after a first episode of schizophrenia is high, often due to non-adherence with medication. Long-acting injections of antipsychotics (LAI) are used to promote adherence to medication. Objective: To review the literature on the use of LAIs in first-episode and early schizophrenia. Method: A systematic electronic search of all original data containing peer-reviewed studies published in English using EMBASE, MEDLINE, Cochrane and PsychINFO from the onset of records. Reference lists from retrieved articles were examined for further relevant studies. Results: Ten studies were identified: two cohort studies; three randomised controlled trials; and five open studies. These studies, although limited, demonstrated the effectiveness of LAI in early schizophrenia. Seven of the 10 studies had risperidone long-acting injection as the only LAI. Conclusion: LAIs may be useful in the treatment of early schizophrenia in terms of symptom control and relapse reduction, particularly if chosen by the patient or when medication adherence is a priority. There is a need for a large-scale, randomised controlled trial comparing oral and LAI antipsychotics to assess long-term outcomes.

How to compare doses of different antipsychotics: A systematic review of methods

BACKGROUNDnThe ability to calculate equivalent dosage is important when comparing or switching between doses of different antipsychotics in the treatment of schizophrenia. It is also necessary when designing antipsychotic comparator trials which control for dosage.nnnMETHODnA systematic review to identify and critically evaluate the methods available for the estimation of antipsychotic dose equivalence was conducted. Electronic searches were carried out using Medline and PubMed and additional information was requested from pharmaceutical companies. The identified methods were evaluated against specific criteria regarding scientific rigour, quality of source data underpinning the method, clinical applicability and utility.nnnRESULTSnEleven articles were identified that described methodologies for antipsychotic dose equivalence. Seven of these referred to calculated methods, including chlorpromazine equivalence, maximum dose and daily-defined dose, and relied on an evidence base from both fixed and flexible dosing data. The remaining four described consensus methods which were based on the knowledge and experience of experts. Chlorpromazine was used as the standard comparator drug in the majority of the calculated equivalence studies, whereas risperidone was used for most consensus methods.nnnCONCLUSIONSnComparison of methods for calculating antipsychotic dose equivalence suggests that different methods yield different equivalencies and the evidence is not sufficiently robust for any of these to be considered as a gold standard method. Thus, choice of method may introduce bias, either an over or underestimate of equivalent dosage, when designing head-to-head, antipsychotic, fixed-dose trials. Consequently, clinical trial reports should routinely include justification of the choice of method for calculating dose equivalence.

Early death in those previously hospitalised for mental healthcare in Scotland: a nationwide cohort study, 1986–2010

Objectives To compare the mortality in those previously hospitalised for mental disorder in Scotland to that experienced by the general population. Design Population-based historical cohort study using routinely available psychiatric hospital discharge and death records. Setting All Scotland. Participants Individuals with a first hospital admission for mental disorder between 1986 and 2009 who had died by 31 December 2010 (34u2005243 individuals). Outcomes The main outcome measure was death from any cause, 1986–2010. Excess mortality was presented as standardised mortality ratios (SMRs) and years of life lost (YLL). Excess mortality was assessed overall and by age, sex, main psychiatric diagnosis, whether the psychiatric diagnosis was ‘complicated’ (ie, additional mental or physical ill-health diagnoses present), cause of death and time period of first admission. Results 111u2005504 people were included in the study, and 34u2005243 had died by 31 December 2010. The average reduction in life expectancy for the whole cohort was 17u2005years, with eating disorders (39-year reduction) and ‘complicated’ personality disorders (27.5-year reduction) being worst affected. ‘Natural’ causes of death such as cardiovascular disease showed modestly elevated relative risk (SMR1.7), but accounted for 67% of all deaths and 54% of the total burden of YLL. Non-natural deaths such as suicide showed higher relative risk (SMR5.2) and tended to occur at a younger age, but were less common overall (11% of all deaths and 22% of all YLL). Having a ‘complicated’ diagnosis tended to elevate the risk of early death. No worsening of the overall excess mortality experienced by individuals with previous psychiatric admission over time was observed. Conclusions Early death for those hospitalised with mental disorder is common, and represents a significant inequality even in well-developed healthcare systems. Prevention of suicide and cardiovascular disease deserves particular attention in the mentally disordered.

Glasgow Antipsychotic Side-effects Scale for Clozapine — Development and validation of a clozapine-specific side-effects scale

OBJECTIVEnThe authors developed and validated a clozapine-specific side-effects scale capable of eliciting the subjectively unpleasant side-effects of clozapine.nnnMETHODSnQuestions from the original Glasgow Antipsychotic Side-effects Scale (GASS) were compared to a list of the most commonly reported clozapine side-effects and those with a significant subjective burden were included in the GASS for Clozapine (GASS-C). The original authors of the GASS and a group of mental health professionals from the UK and Ireland were enlisted to comment on the questions in the GASS-C based on their clinical experience. 110 clozapine outpatients from two sites completed the GASS-C, the original GASS and a repeat GASS-C. Statistical analyses were performed using SPSS for Windows version 19.nnnRESULTSnThe GASS-C was shown to have construct validity, in that Spearmans correlation coefficient was 0.816 (p<0.001) with the original GASS, whilst Cohens kappa coefficient was >0.77 (p<0.001) for one question and >0.81 (p<0.001) for remaining relevant questions. GASS-C was also shown to have strong test-retest reliability, in that Cronbachs alpha coefficient was >0.907 (p<0.001), whilst Cohens kappa coefficient was >0.81 (p<0.001) for 12 questions and >0.61 (p<0.001) for the remaining four questions.nnnCONCLUSIONnThe GASS-C is a valid and reliable clinical tool to enable a systematic assessment of the subjectively unpleasant side-effects of clozapine. Future research should focus on how the scale can be utilised as a clinical tool to improve real-world outcomes such as adherence to clozapine therapy and quality of life.

Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate.

Objectives: In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. Method: The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan–Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Conclusions: Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time.

Socioeconomic status and prescribing for schizophrenia: analysis of 3200 cases from the Glasgow Psychosis Clinical Information System (PsyCIS)

Aims and method To investigate whether socioeconomic status influenced rates of depot medication prescribing, polypharmacy (more than two psychotropic medications), newer (second-generation) antipsychotic prescribing and clozapine therapy. Postcodes, Scottish Index of Multiple Deprivation (SIMD) categories and current medication status were ascertained. Patients in the most deprived SIMD groups (8-10 combined) were compared with those in the most affluent SIMD groups (1-3 combined). Results Overall, 3200 patients with ICD-10 schizophrenia were identified. No clear relationship between socioeconomic status and any of the four prescribing areas was identified, although rates of depot medication use in deprived areas were slightly higher. Clinical implications Contrary to our hypothesis, there was no evidence that patients with schizophrenia within NHS Greater Glasgow and Clyde who live in more deprived communities had different prescribing experiences from patients living in more affluent areas.

A stitch in time: 3-monthly long-acting injectable paliperidone palmitate in schizophrenia:

journals.sagepub.com/home/tpp 231 Depot antipsychotic medication, often referred to as long-acting injections (LAIs), are an important treatment option for mental health problems such as schizophrenia and bipolar disorder.1,2 They were designed over 50 years ago to promote adherence to maintenance antipsychotic medication, but arguably remain stigmatized and underused.3 Table 1 compares oral formulations with LAIs.

Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early discontinuation. APP had no adverse outcomes on assigned CGI improvement or mean end-point severity ratings for RLAI and zuclopenthixol decanoate.