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Home , Typical antipsychotic

TITLE: Depot Atypical : A Review of the Clinical Effectiveness and Safety

DATE: 8 December 2010

CONTEXT AND POLICY ISSUES

Medication adherence in patients with psychiatric disorders such as and is often suboptimal and can be a major barrier to treatment success.1,2 One means of increasing medication adherence is through the use of depot injections of medications, which can be administered at extended intervals (for example, every four weeks).1 Long-acting formulations may be beneficial to those patients who have recurrent relapses that can be attributed to failure to adhere to treatment or patients who prefer this route of administration.1,3

Antipsychotic medications can be categorized as typical or first generation and atypical or second-generation.4 Atypical antipsychotics have some advantages over the typical antipsychotics. In terms of efficacy in schizophrenia, for example, atypical antipsychotics have a more favourable impact on negative symptoms, such as flattened affect, reduced thought and speech productivity, inability to experience pleasure, and decreased initiation of goal-directed behavior, and cognitive impairment, than typical agents.3 Further, atypical antipsychotics tend to have more favourable side effect profiles in that they carry a lower risk of extrapyramidal side effects and than the typical agents.3,4

Both typical (for example, , , flupenthixol and ) and agents ( and ) are available in Canada as long- acting or depot formulations that are injected intramuscularly (IM).5-9 Long-acting risperidone (LAR) is approved for use in Canada in schizophrenia and bipolar disorder,6 whereas long-acting paliperidone injection is approved for use in schizophrenia.5 This report reviews the evidence of comparative clinical effectiveness and harms associated with the use of atypical and typical antipsychotics in schizophrenia and bipolar disorder. As well, evidence of the risks and benefits of depot atypical antipsychotic use in different age groups is reviewed. This information could be helpful in informing formulary decisions with regards to antipsychotic depot injections and in individual patient management.

Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report.

Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH.

Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions.

RESEARCH QUESTIONS

1. What is the comparative clinical effectiveness and safety of depot atypical antipsychotics compared with depot typical antipsychotics for patients with schizophrenia or bipolar disorder?

2. What is the evidence for varying clinical effectiveness and safety of depot atypical antipsychotics in patients with schizophrenia or bipolar disorder of varying ages?

KEY MESSAGE

In patients with schizophrenia, limited evidence, mainly from non-randomized studies, was inconclusive with regard to the comparative clinical effectiveness and safety of 1) atypical and typical depot antipsychotics and 2) atypical depot antipsychotics in older and younger adults. No evidence was identified for patients with bipolar disorder, so no conclusions can be made with respect to this population.

METHODS

A limited peer reviewed literature search was conducted using the following bibliographic databases: PubMed and the Cochrane Library (2010, Issue 11). Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, and non-randomized studies. Where possible, retrieval was limited to the human population. The search was limited to English language documents published between January 01, 2005 and November 11, 2010. Grey literature was obtained through health technology agency websites and a focused Internet search. Internet links were provided, where available.

HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessments, systematic reviews and meta-analyses are presented first. These are followed by randomized controlled trials (RCTs) and non-randomized studies.

SUMMARY OF FINDINGS

No relevant health technology assessments, systematic reviews and meta-analyses were identified. One relevant RCT10 and four relevant non-randomized studies11-14 in patients with schizophrenia were identified by the literature search. Three studies involved comparisons between typical and atypical antipsychotic depot injections,10-12 while two studies compared outcomes of treatment with an atypical antipsychotic in different age groups.13,14 No relevant comparative studies in bipolar disordered were identified. A description of scales used to measure outcomes can be found in the appendix.

Health technology assessments No literature identified

Systematic reviews and meta-analyses No literature identified

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Randomized controlled trials

Comparison of Typical and Atypical Antipsychotic Depot Injections

A 2006 open-label RCT compared the efficacy of long-acting risperidone (LAR) injection (n=57) and zuclopenthixol IM (n=58) in individuals with schizophrenia and a comorbid substance use disorder.10 Individuals between the ages of 18 and 65 years old, with schizophrenia and comorbid substance use disorders were eligible for inclusion in the study. Individuals with organic, neurologic or other psychotic disorders were excluded, as well as those with clinically relevant abnormalities in baseline laboratory tests. Patients were recruited while in hospital, and allocated alternately to the two treatment arms, a method of randomization that is considered inappropriate.15,16 No information was provided about initial dosages or dosage titration. It was stated, however, that the risperidone group received an average of 47.2 mg per 15 days of (LAR) and 3.4 mg daily of oral risperidone, while the zuclopenthixol group received 200 mg of zuclopenthixol-depot every 21 days and 15 mg per day orally. It was not clear if all patients were on combinations of injectable and oral antipsychotics. Patients also participated in a psychotherapeutic program, and were followed for a total of six months. Outcomes included substance use based upon urine screening results, symptoms of schizophrenia (Positive and Negative Syndrome Scale – PANSS) and (Extrapyramidal Symptom Rating Scale – ESRS). The clinical global impression (CGI) scale and the Udvaig for klinisike (UKU) Side Effect Rating Scale were also described as outcome measures; however, data for these outcomes were not reported. Outcome assessors were blinded to treatment status.

Baseline characteristics were similar between groups and no statistically significant differences were observed.10 In total nine participants dropped out of the study, six treated with zuclopenthixol depot and three treated with LAR. Only those patients with complete data were included in the analysis. After six months of follow-up, the average number of urine tests that were positive for substances of abuse was 8.67 ± 3.0 in the LAR injection group and 10.36 ± 3.1 in the zuclopenthixol depot group (p=0.005). For the PANSS, positive and general symptoms did not differ between treatments; however, negative symptoms were lower in the LAR injection group (18.80 ± 8.71) than in the zuclopenthixol depot group (23.81 ± 7.40; p=0.008). The total PANSS score was also lower in the LAR injection group (64.93 ± 19.9 versus 74.03 ± 20.9; p=0.02), as were scores on the ESRS (1.24 ± 0.3 versus 2.85 ± 1.1; p=0.05). The authors of the study concluded that LAR injection was more effective than zuclopenthixol depot injection for the management of symptoms related to schizophrenia and in reducing substance use.

Limitations to this study10 include the open-label design and questionable method of randomization. Selective outcome reporting may have been an issue as results were not presented for all outcomes described in the methods section. The dosage titration was not entirely clear. Approximately 37% of individuals who were eligible for inclusion declined to participate. The reasons for declining were not reported. This could impact the generalizability of the study results as the authors indicated that those with the most severe disease may have been more likely to decline. As well, it is not clear if the results of this study would be generalizable to patients with schizophrenia without substance use disorders or those who could not be managed as outpatients.

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Non-randomized studies

Comparison of Typical and Atypical Antipsychotic Depot Injections

A 2010 study compared the effectiveness of LAR injection (n=122) and zuclopenthixol (n=31) and (n=43) depot injections in patients with schizophrenia, schizoaffective disorder or delusional disorder through retrospective review of electronic patient records.11 The study setting was described as “routine clinical practice.” Records were reviewed for the period of February 2002 to October 2008. Outcomes included the CGI-S (Clinical Global Impression – Severity) and CGI-I (Clinical Global Impression – Improvement) scales assessed three to five months following initiation of treatment, time to treatment discontinuation and time to hospitalization following initiation of treatment with the long-acting antipsychotic.

The percent improvement in CGI-S scores after three to five months of treatment was not statistically significant between the three groups (LAR=25%; zuclopenthixol=33%; flupentixol=36%; p=NS).11 As well, the percent of patients who had improved based on CGI-I scores (rated as minimally improved, moderately improved, much improved or very much improved) was not statistically significant between the three groups (LAR=74%; zuclopenthixol=74%; flupentixol=72%; p=NS). Average treatment duration was similar in the three groups (LAR=16.4 months; zuclopenthixol=17.1 months; flupentixol=13.6 months; p=NS). Time to discontinuation as a result of inefficacy was longer with zuclopenthixol (51 months) than LAR (44 months) or flupentixol (46 months). Time to discontinuation as a result of adverse effects was 50 months in the LAR group, 51 months in the zuclopenthixol group and 36 months in the flupentixol group. Time to hospitalization was longer with zuclopenthixol (43 months) than LAR (26 months) or flupentixol (31 months). P-values or 95% confidence intervals for these comparisons were not reported. The authors concluded that none of the three depot injections was clearly superior and that there is continued need for treatment alternatives with depot antipsychotic injections.

There are several limitations to this study.11 The CGI scores were assigned following retrospective review of records by psychiatrists. In other words, the scores were not assigned and recorded at the time of care by the attending psychiatrist. Approximately 30% of patients received other antipsychotics, so it is not clear what impact this might have on the observed outcomes. There were differences at baseline in symptoms severity between the three treatment groups, with the flupentixol group being the least severe. These differences could affect the study outcomes as well. The lack of randomization in the study design can create potential for bias and confounding. The dosages of the three depot injections were not reported, which limits the ability to assess whether they were therapeutically equivalent or to assess generalizability. Since this population was mainly middle-aged and white, it is not clear if the results would be generalizable to other populations.

A 2009 retrospective chart review compared outcomes of 68 outpatients with schizophrenia or schizoaffective disorder who used typical antipsychotic depot injections (n=46) or LAR injection (n=22).12 The typical antipsychotic depot injections included in the study are flupenthixol decanoate, zuclopenthixol decanoate and fluphenazine. Patients who were treated between June 1, 2000 and June 1, 2008 were eligible for inclusion, regardless of co-morbid conditions (psychiatric or medical). All patients were over the age of 18. Measures of clinical effectiveness, adverse effects, and duration of treatment were obtained from patient charts. Clinical measures included the PANSS and the CGI-S. No information was provided about the dosages of the

Depot Atypical Antipsychotics 4

antipsychotics, but co-intervention with other psychiatric medications was common in both groups, particularly with oral atypical agents.

A larger proportion of the LAR injection group was male (82% versus 61%) and had comorbid psychiatric conditions (41% versus 20%), but these differences did not reach statistical significance.12 The average treatment duration was 20.4 ± 9.9 months for the typical depot group and 15.2 ± 8.12 months for the LAR depot group (p=0.02). At the time of the review, 41.3% of the typical depot group and 9.1% of LAR injection group had discontinued treatment (p=0.02). The proportion of patients who experienced an adverse effect was higher in the typical depot group (65.2%) compared with the LAR injection group (36.4%; p=0.02). The percentage decreases in total PANSS score, PANSS-positive, PANSS-general perceptions, and CGI-S were statistically significant in both groups, while the percent decrease in PANSS-negative was only statistically significant in the LAR injection group. Differences in the magnitude of change in the typical depot and LAR injection groups were not statistically significant. The authors concluded that both typical and LAR injections improved the symptoms of schizophrenia, but that duration of treatment was superior with typical depots, while the adverse effects experienced with LAR depot was superior.

Limitations to this study12 include the lack of randomization and subsequent potential for bias and confounding, lack information about dosage of the medications, baseline differences between groups, the use of oral atypical antipsychotics in the 54% of typical depot group and differences between groups in the use of co-interventions (a larger proportion of the LAR group took antidepressants than the typical depot group: 22.7% versus 4.3%; p=0.02). These factors make the results of this study difficult to interpret, compromise the internal validity of the study and may limit its generalizability.

Comparison of Atypical Antipsychotic Depot Injections in Varying Age Groups

A 2008 study explored predictors of continuation of treatment with LAR injection in 211 patients with schizophrenia.13 All patients who received care from a United Kingdom health services trust consecutively initiated on treatment with LAR injection between over a one-year period were included in the cohort, which was followed for three years. Treatment was initiated with 25 mg of LAR injection every two weeks. A Cox proportional hazard regression model was used for the analysis.

After three years of follow-up, 16% of patients remained on treatment with LAR injection. The most common reasons for discontinuation were lack of efficacy (36%), patient choice (37%) and adverse effects (21%).13 The regression model showed that each one-year increase in age was associated with a 3% decrease in the risk of discontinuing treatment, after adjusting for other variables in the model including dose, duration of illness and inpatient/outpatient status. The authors did not make any conclusions related to patient age and treatment safety or efficacy. The following limitations to the study were noted: lack of formal assessment of treatment response and lack of data on prior treatments and co-medications. Approximately 68% of participants in this study were inpatients, 81.5% of whom had schizophrenia, 7.1% had bipolar disorder and the remainder of which were categorized as having another psychiatric disorder. The majority of participants were black. Generalizability to other populations might be limited by these factors. As well, it is not clear if the same relationship with age would be expected if the entire study population had either schizophrenia or bipolar disorder.

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Data from a 2007 12-month open-label trial were used to compare the efficacy and adverse events associated with the use of LAR injection in young adults (n=66) in the early stages of schizophrenia or schizoaffective disorder to older patients (n=351).14 In this study, young adults were defined as being less than 25 years old for males and less than 30 years old for females. The study population included clinically stable outpatients or inpatients, with PANSS total scores ranging from 60 to 120 and good health at baseline. Patients with substance use disorders, history of tardive dyskinesia or neuroleptic malignant syndrome, ECG abnormalities or pregnancy were excluded. Patients were administered 25 mg or 50 mg of LAR injection every two weeks after an initial treatment period with oral risperidone, which continued for two to three weeks after the initial treatment with LAR injection. Outcomes were assessed every three months and included the PANSS and CGI-S. Remission of symptoms was also assessed as an efficacy measure. Patient reported outcomes included the 36-Item Short Form Health Survey (SF–36) and patient’s attitudes towards their medication. Adverse effects were assessed with the EPSR scale and with a 100-mm visual analog scale to assess pain of injection (0 mm=no pain to 100 mm=unbearable pain).

Aside from age and treatment duration, the two groups were similar at baseline.14 Sixty-four percent of the younger adults and 72% of the older adults completed the study and the two groups had similar reasons for discontinuing treatment which included withdrawal of consent, adverse effects, lack of efficacy, nonadherence and other reasons. The magnitude of the change in PANSS scores from baseline to the end of the 50-week follow-up was similar for younger and older adults (PANSS Total, PANSS-Positive, PANSS-Negative). The change from baseline in measures of disorganized thoughts, anxiety/depression, and uncontrolled hostility was similar between groups. In patients who were not in remission at baseline, remission was achieved in 28% and 25% of the younger and older adult groups, respectively. No data were presented for the CGI-S and VAS for older adults, so no comparisons between groups can be made for these outcomes. Among the younger adults, clinically significant improvements were observed for the social-functioning, role-emotional, physical-functioning, and role-physical domains of the SF-36, but the only significant difference between the two groups of younger adults was seen on the physical functioning domain (p=0.014). Over the course of the study, younger adults’ attitudes towards medications became less positive (mean change = -0.5) while they became more positive in the older adult group (mean change = + 1.0; p=0.017). The younger adults were described as reporting more adverse events on average, but no statistical comparisons were made. The proportion of younger adults experiencing , headache, hyperkinesia, rhinitis, depression, fatigue, nausea, and somnolence was larger than in older patients, but again no statistical comparisons were made. ESRS scores were described as similar between groups, but no data were presented. The authors concluded that the use of LAR injection was associated with clinical benefits in stable young adults with early schizophrenia.

Limitations to this study14 include its open-label design, a drop-out rate of 36%, lack of data on the duration of illness (which could potentially affect response), selective outcome reporting, and lack of information on co-medications. The exclusion of patients with a history of EPS and who used substances could potentially bias the study results and limit generalizability. The definition of used substances was not indicated. If, for example, nicotine was one of the substances that lead to exclusion, a large proportion of patients with schizophrenia would be excluded.

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Limitations

There were five studies included in this rapid review, four of which were exclusively in schizophrenia or schizoaffective disorder. While one study included patients with bipolar disorder, these patients comprised just 7% of the study population. Thus, the evidence of the comparative effectiveness of atypical and typical antipsychotic injections in patients with bipolar disorder was lacking. Three studies provided data on comparative efficacy of typical and atypical antipsychotics, and two studies provided information on clinical effectiveness and harm in different age groups. One of the included studies was an RCT, while the rest were nonrandomized studies. Overall, the methodological rigor of the studies was not strong and the individual studies were subject to a number of limitations that could compromise their internal validity and generalizability as previously detailed. All of the studies included in this rapid review evaluated LAR injection, and no relevant studies of paliperidone IM injection were identified.

CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING:

For LAR injection, evidence from one RCT suggested that the efficacy of LAR injection was superior to zuclopenthixol in patients with schizophrenia and substance abuse disorders. Two nonrandomized studies that compared LAR to typical depot injections did not clearly demonstrate superior efficacy and safety of LAR. Two nonrandomized studies were identified that explored the association between age and outcomes of LAR injection in patients with schizophrenia. One study found that older patients were less likely to discontinue treatment, while the other study found differences between older and younger patients for improvement in physical functioning, but this was only one of many outcomes assessed in the study.

There is insufficient evidence regarding the comparative effectiveness of atypical and typical depot antipsychotics in patients with bipolar disorder to make any conclusions. Further, evidence regarding the comparative effectiveness of atypical antipsychotics in different age groups of patients with bipolar disorder was also insufficient to make any conclusions. Paliperidone depot injection was not evaluated in any of the included studies, so no conclusions about its effectiveness can be drawn.

The amount of evidence of the comparative safety and efficacy of atypical versus typical antipsychotics in patients with schizophrenia and bipolar disorder is limited. Further, there is a lack of methodological rigor in this body of evidence. These are factors that may be considered when making formulary decisions about antipsychotics or decisions about individual patient management. The evidence from the population with schizophrenia suggests that no single depot antipsychotic agent was clearly superior to the others in terms of efficacy and adverse effects.

PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca

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REFERENCES:

1. Chue P, Emsley R. Long-acting formulations of atypical antipsychotics: time to reconsider when to introduce depot antipsychotics. CNS Drugs. 2007;21(6):441-8.

2. Deeks ED. Risperidone long-acting injection: in bipolar I disorder. Drugs. 2010 May 28;70(8):1001-12.

3. Clinical practice guidelines: treatment of schizophrenia: III. Pharmacotherapy. Can J Psychiatry [Internet]. 2005 Nov [cited 2010 Nov 10];50(Suppl 1). Available from: https://ww1.cpa- apc.org/Publications/Clinical_Guidelines/schizophrenia/november2005/cjp-cpg-suppl1-05- pharmacotherapy.pdf

4. Jibson MD. Antipsychotic medications: classification and pharmacology. 2010 May [cited 2010 Nov 15]. In: UpToDate [Internet]. Version 18.2. Waltham (MA): UpToDate; c2005 - . Available from: http://www.uptodate.com Subscription required.

5. Janssen Ortho. Invega® Sustenna™ paliperidone palmitate: antipsychotic. 2010 Jul 21 [cited 2010 Nov 11]. In: e-CPS [Internet]. July 21, 2010. Ottawa (ON): Canadian Pharmacists Association; c2009 - . Available from: https://www.e-therapeutics.ca Subscription required.

6. Janssen Ortho. Risperdal® Consta® risperidone: antipsychotic. 2009 Dec 1 [cited 2010 Nov 11]. In: e-CPS [Internet]. December 1, 2009. Ottawa (ON): Canadian Pharmacists Association; c2009 - . Available from: https://www.e-therapeutics.ca Subscription required.

7. Canada Inc. Clopixol®/Clopixol-Acuphase®/Clopixol Depot®. 2009 Dec 1 [cited 2010 Nov 16]. In: e-CPS [Internet]. January 23, 2009. Ottawa (ON): Canadian Pharmacists Association; c2009 - . Available from: https://www.e-therapeutics.ca Subscription required.

8. Lundbeck Canada Inc. Fluanxol®/Fluanxol Depot®. 2004 Oct 9 [cited 2010 Nov 11]. In: e- CPS [Internet]. September 10, 2004. Ottawa (ON): Canadian Pharmacists Association; c2009 - . Available from: https://www.e-therapeutics.ca Subscription required.

9. Bristol-Myers Squibb. Modecate® Concentrate. 2009 Jul 23 [cited 2010 Nov 11]. In: e- CPS [Internet]. July 23, 2009. Ottawa (ON): Canadian Pharmacists Association; c2009 - . Available from: https://www.e-therapeutics.ca Subscription required.

10. Rubio G, Martínez I, Ponce G, Jiménez-Arriero MA, López-Muñoz F, Álamo C. Long- acting injectable risperidone compared with zuclopenthixol in the treatment of schizophrenia with substance abuse comorbidity. Can J Psychiatry. 2006 Jul;51(8):531-9.

11. Shajahan P, Spence E, Taylor M, Daniel D, Pelosi A. Comparison of the effectiveness of depot antipsychotics in routine clinical practice. Psychiatrist. 2010;34(7):273-9.

12. Virit O, Altindag A, Bulbul F, Savas HA, Dalkilic A. Long-acting typical and atypical antipsychotics in treatment of schizophrenia: A retrospective comparison. Klinik

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Psikofarmakoloji Bulteni [Internet]. 2009 [cited 2010 Nov 11];19(2):119-27. Available from: http://www.psikofarmakoloji.org/pdf/19_2_5.pdf

13. Taylor DM, Fischetti C, Sparshatt A, Thomas A, Bishara D, Cornelius V. Risperidone long- acting injection: a prospective 3-year analysis of its use in clinical practice. J Clin Psychiatry. 2009 Feb;70(2):196-200.

14. Lasser RA, Bossie CA, Zhu Y, Locklear JC, Kane JM. Long-acting risperidone in young adults with early schizophrenia or schizoaffective illness. Ann Clin Psychiatry. 2007 Apr;19(2):65-71.

15. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1-12.

16. Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise JM. Appendix tables 4 and 5 [Internet]. In: An update review for the U.S. Preventive Services Task Force: evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis. Rockville (MD): U.S. Preventive Services Task Force; 2008 Feb [cited 2010 Nov 11]. Available from: http://www.uspreventiveservicestaskforce.org/uspstf08/bv/bvupaptab4-5.htm.

17. Clinical Global Impression (CGI) [Internet]. In: Guy W, editor. ECDEU Assessment Manual for . Rockville (MD): U.S. Department of Health, Education, and Welfare; 1976 [cited 2010 Nov 11]. Available from: http://www.servier.com/App_Download/Neurosciences/Echelles/CGI.pdf.

18. Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res. 2005 Jul 15;76(2-3):247-65.

19. Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale [Internet]. North Tonawanda (NY): Multi-Health Systems Inc; 2004. [cited 2010 Nov 11]. Available from: http://www.mhs.com/product.aspx?gr=cli&prod=panss&id=overview

20. Ware JE, Jr. SF-36® Health Survey Update [Internet]. Lincoln (RI): SF-36; 2003. [cited 2010 Dec 3]. Available from: http://www.sf-36.org/tools/sf36.shtml

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APPENDIX: Description of Instruments Used in the Included Studies

CGI: Clinical Global Impression Scale

The CGI is a rating system with three questions to asses severity of illness (CGI-S), improvement (CGI-I) and response to treatment (CGI-R).17

ESRS - Extrapyramidal Symptom Rating Scale

The ESRS is a scale that assesses the severity of drug-induced movement disorders, including , , , and tardive dyskinesia. 18.

PANSS – Positive and Negative Syndrome Scale

The PANSS is a scale that is used in clinical practice to measure the type of symptoms that a patient is experiencing. Five scale scores can be calculated: Positive Scale, Negative Scale, Composite Index, General Psychopathology Scale and the Supplemental Aggression Risk Profile19

SF-36 - Short-Form 36

The SF-36 is a health status measure that assesses eight dimensions of health including role- physical, physical functioning, bodily pain, vitality, social functioning, general health, role- emotional and mental health.20

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