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McDonagh M, Peterson K, Carson S, et al. Drug Class Review: Atypical Antipsychotic Drugs: Final Update 3 Report [Internet]. Portland (OR): Oregon Health & Science University; 2010 Jul.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Drug Class Review: Atypical Antipsychotic Drugs

Drug Class Review: Atypical Antipsychotic Drugs: Final Update 3 Report [Internet].

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Appendix AScales used to assess efficacy and adverse events

The following narrative briefly describes each of the most commonly used assessment scales and summarizes methods of scoring and validation. The subsequent table lists abbreviations for all assessment scales noted in this review. The references cited here are listed at the end of this appendix.

Population-Specific Scales

Autism

The Aberrant Behavior Checklist (ABC),1 irritability subscale is rated by the parent or primary caretaker. The 15-item scale includes questions about aggression, self-injury, tantrums, agitation, and unstable mood on a scale of 0 to 45, with higher scores indicating greater severity.

The Children’s Psychiatric Rating Scale (CPRS)2 is a 63-item scale developed by the Psychopharmacology Branch of the National Institute of Mental Health to rate childhood psychopathology. Each item is rated from 1 (not present) to 7 (extremely severe). Four factors have been derived from the items: Autism Factor (social withdrawal, rhythmic motions/stereotype, abnormal object relations, unspontaneous relation to examiner, underproductive speech), Anger/Uncooperativeness Factor (angry affect, labile affect, negative and uncooperative), Hyperactivity Factor (fidgetiness, hyperactivity, hypoactivity), and Speech Deviance Factor (speech deviance, low voice).

Bipolar I Disorder

The Young Mania Rating Scale (YMRS) is an 11-item, clinician-administered interview scale designed to quantify the severity of mania. Clinicians select from 5 grades of severity specific to each item when making YMRS ratings. YMRS total scores range from 0 to 60. Clinical trials of individuals with Bipolar I Disorder generally required scores equal to or greater than 20 for enrollment and specified scores equal to or below 12 as representing symptomatic remission. One validity study reported high correlations between the YMRS and the Petterson Scale (r=0.89, P<0.001), the Beigel Scale (r=0.71, P<0.001), and an unspecified, 8-point global rating scale (r=0.88, P<0.001).3

Dementia

The BEHAVE-AD4 assesses 25 behaviors in the following 7 areas: paranoid and delusional ideation, hallucinations, activity disturbances, aggressiveness, diurnal rhythm disturbances, affective disturbance, and anxieties and phobia. Caregivers rate the presence and severity of each item over the preceding 2 weeks on a 4-point scale (0=not present; 1=present; 2=present, generally with an emotional component; 3=present, generally with an emotional and physical component). The maximum score is 75.

The NPI5 assesses the following 12 behavioral disturbances common to dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and appetite and eating abnormalities. The frequency and severity of each behavior is determined by a series of questions posed to the caregiver. Severity is graded 1, 2, or 3 (mild, moderate, or severe) and frequency is rated on a scale of 1 through 4 (1=occasionally, less than once per week; 4=very frequently, once or more per day or continuously). The maximum score for each domain is 12 (frequency multiplied by severity). The total score is the sum of the individual domain scores, for a maximum possible score of 144. Some trials in patients with dementia used the NPI-Nursing Home Version (NPI-NH), which has been validated for use in nursing homes.

The CMAI6 assesses the frequency of up to 29 agitated behaviors: pacing or aimless wandering; inappropriate dress or disrobing; spitting (usually at meals); cursing or verbal aggression; constant unwarranted requests for attention or help; repetitive sentences or questions; hitting (including self); kicking; grabbing onto people; pushing; throwing things; strange noises (weird laughter or crying); screaming; biting; scratching; trying to get to a different place (for example, out of the room or building); intentional falling; complaining; negativism; eating or drinking inappropriate substances; hurting self or other (for example, with a cigarette or hot water); handling things inappropriately; hiding things; hoarding things; tearing things or destroying property; performing repeated mannerisms; making verbal sexual advances; making physical sexual advances; and general restlessness. Caregivers administer the scale after receiving training. The frequency of each behavior is scored with reference to the previous 2 weeks on a 7-point scale (1=never, 2=less than one time per week, 3=one to 2 times per week, 4=several times per week, 5=once or twice per day, 6=several times per day, 7=several times per hour). The maximum possible score is 203.

Disruptive Behavior Disorders

The Nisonger Child Behavior Rating Form7 was developed for children with developmental disabilities. The Parent version has two positive/social subscales (Compliant/Calm and Adaptive/Social) comprising 10 items. It has 66 Problem Behavior items that score onto 6 subscales: Conduct Problem, Insecure/Anxious, Hyperactive, Self-Injury/Stereotypic, Self-Isolated/Ritualistic, and Overly Sensitive.

The Rating of Aggression against People and/or Property (RAAP)8 is a global rating scale of aggression that is completed by a clinician. It is scored from 1 (no aggression reported) to 5 (intolerable behavior).

Schizophrenia

The Positive and Negative Syndrome Scale (PANSS) is a 30-item instrument designed to assess schizophrenia symptoms. Each item is rated using a 7-point severity scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate-severe, 6=severe, 7=extreme). The PANSS is administered by qualified clinicians using combinations of unstructured, semistructured, and structured interview strategies. The PANSS is composed of three subscales, a 7-item Positive Scale, a 7-item Negative Scale and a 16-item General Psychopathology Scale. The PANSS Total Score ranges from 30 to 210. The PANSS also provides a method of assessing relationships of positive and negative syndromes to one another and to general psychopathology. High correlations between the PANSS Positive Syndrome Scale and the Scale for the Assessment of Positive Symptoms (SAPS) (r=0.77, P<0.0001), the Negative Syndrome Scale and the Scale for the Assessment of Negative Symptoms (SANS) (r=0.77, P<0.0001), and the General Psychopathology Syndrome scale and the Clinical Global Impressions Scale (CGI) (r=0.52, P<0.0001) supports the scale’s criterion-related validity.9

Scales for General Use

Extrapyramidal Side Effect Scales

The Barnes Akathisia Scale (BAS) is a tool used for diagnosis of drug-induced akathisia.10 The BAS consists of items that assess the objective presence and frequency of akathisia, the level of an individual’s subjective awareness and distress, and global severity. The objective rating is made using a 4-point scale (0=normal limb movement, 1=restlessness for less than half the time observed, 2=restlessness for at least half of the time observed, 3=constant restlessness). The BAS subjective component consists of two items, both rated using 4-point scales. One is Awareness of Restlessness (0=absent, 1=non-specific sense, 2=complaints of inner restlessness, 3=strong desire to move most of the time) and the other is Distress Related to Restlessness (0=none, 1=mild, 2=moderate, 3=severe). The BAS Global Clinical Assessment of Akathisia is rated using a 6-point scale (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe).

The Simpson Angus Scale (SAS) is composed of 10 items and used to assess pseudoparkinsonism. Grade of severity of each item is rated using a 5-point scale. SAS scores can range from 0 to 40. Signs assessed include gait, arm-dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. In more than 1 randomized controlled trial of bipolar I disorder,11 treatment-emergent parkinsonism was defined as a SAS score of greater than 3 at any time following a score of 3 or less.

The Abnormal Involuntary Movement Scale (AIMS) is composed of 12 items and used to assess dyskinesia. Items related to severity of orofacial, extremity, and trunk movements, global judgment about incapacitation, and patient awareness are rated using a 5-point scale (0=none to 4=severe). Two items related to dental status are scored using “yes” or “no” responses. Overall AIMS scores range from 0 to 42. Randomized controlled trials of atypical antipsychotics in bipolar I disorder populations defined treatment-emergent dyskinesia as, “a score of 3 or more on any of the first 7 AIMS items, or a score of 2 or more on any two of the first 7 AIMS items.” 11, 12

The Extrapyramidal Symptom Rating Scale (ESRS) was designed to assess frequency and severity of parkinsonism, dyskinesia, akathisia, and dystonia.13 The ESRS involves a physical exam and 12 questionnaire items that assess abnormalities both subjectively and objectively. Most of the items focus on features of parkinsonism.

Depression Scales

The 17 items of the Hamilton Depression Rating Scale (HAM-D) are designed to measure symptoms of depression. Each item is rated using a 5-point scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating). Scores ranging from 10 to 13 suggest mild depression; 14–17, mild to moderate; and >17, moderate to severe.14 A 21-item version of the Hamilton Depression Rating Scale (HAMD-21) is also available. The HAMD-21 includes the following additional items: “diurnal variation”, “depersonalization and derealization”, “paranoid symptoms”, and “obsessional and compulsive symptoms”. It is the HAMD-21 that is most commonly used in randomized controlled trials of atypical antipsychotics. One randomized controlled trial of bipolar I disorder identified a HAMD-21 score of at least 20 as indicating moderate to severe depression.15

The Montgomery-Asberg Depression Rating Scale (MADRS) is another instrument extensively used in psychopharmacological research to assess severity of depressive symptoms.16 The MADRS has 10 items, each rated using a 7-point severity scale. Scores range from 0 to 60. MADRS, HAM-D, and CGI appear to be highly correlated (r>0.85, P<0.0001), with the best cut off for severe depression being 31 on MADRS (sensitivity 93.5%, specificity 83.3%).16 One study of patients with bipolar I depression limited enrollment by requiring a score of at least 20 on the MADRS. 17

Other Scales

The Brief Psychiatric Rating Scale (BPRS) is a 16-item scale designed to assess treatment change in psychiatric patients.18 The severity of each item is rated using a 7-point scale (1=not present, 2=very mild, 3=mild, 4=moderate, 5=moderately severe, 6-severe, 7=extremely severe). BPRS ratings are made using a combination of observations of and verbal report from patients. BPRS scores range from 16 to 112. This review includes numerous randomized controlled trials that assessed efficacy of atypical antipsychotics in schizophrenia or bipolar I disorder populations using the BPRS, generally as a secondary endpoint.

The Clinical Global Impression Scale (CGI) consists of 3 items (Severity of Illness, Global Improvement, and Efficacy Index) designed to assess treatment response. A 7-point scale is used to rate Severity of Illness (1=normal to 7=extremely ill) and Global Improvement’ (1=very much improved to 7=very much worse). Efficacy Index is rated on a 4-point scale (from “none” to “outweighs therapeutic effect”). The Clinical Global Impressions Scale for use in bipolar illness (CGI-BP) is a modification of the original CGI and designed specifically for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness.19

Scales used to assess outcomes

ScaleAbbreviation
Aberrant Behavior ChecklistABC
Abnormal Involuntary Movement ScaleAIMS
Adverse effects checklist
Association for Methodology and Documentation in Psychiatry
Barnes Akathisia ScaleBAS
Bech Rafaelsen Melancholia ScaleBRMS
Behavioral Pathology in Alzheimer’s Disease Rating ScaleBEHAVE-AD
Benton Visual Retention TestBVRT
Brief Psychiatric Rating ScaleBPRS
Calgary Depression ScaleCDS
California Verbal Learning TestCVLT
Children’s Psychiatric Rating ScaleCPRS
Chemical Use, Abuse, and Dependence ScaleCUAD
Client Satisfaction Questionnaire-8CSQ-8
Clinical Global Impression ScaleCGI
Clinical Global Impressions-ImprovementCGI-I
Clinicians Global Impressions of ChangeCGI-C
Clinicians Global Impressions-Severity of Illness ScaleCGI-S
Coding Symbols for a Thesaurus for Adverse Reaction TermsCOSTART
Cohen-Mansfield Agitation InventoryCMAI
Consonant Trigram
Continuous Performance TestCPT
Controlled Ward Association Test of Verbal Fluency
Covi-Anxiety Scale
Delayed Recall Test
Diagnostic Interview Schedule III-RDIS-III-R
Digit Span Distractibility Test
Digit Symbol Substitution Test
Disability Assessment ScheduleDAS
Drug Attitude InventoryDAI-30
Drug-Induced Extrapyramidal Symptoms ScaleDIEPS
Dyskinesia Identification System Condensed User ScaleDISCUS
EuroQuol-Visual Analogue Scale
Extrapyramidal Symptom Rating ScaleESRS
Final Global Improvement RatingFGIR
Global Assessment of FunctioningGAF
Global Assessment ScaleGAS
Hamilton Rating Scale for DepressionHAM-D
Heinrichs-Carpenter Quality of Life Scale
Last Observation Carried ForwardLOCF
Level of Functioning Scale
Maryland Assessment of Social Competence
Medical Outcomes Study Short Form 36-Item Health Survey
Mini Mental State ExaminationMMSE
Montgomery-Asberg Depression Rating ScaleMADRS
Multnomah Community Ability ScaleMCAS
Munich Quality of Life Dimensions List
North American Adult Reading Test-RevisedNAART-R
Negative Symptom AssessmentNSA
Neuropsychiatric InventoryNPI
Nisonger Child Behavior Rating Form
Nurses Observation Scale for In-Patient EvaluationNOSIE
Occupational Functioning Assessment Scale
Overall Safety Rating
Paced Auditory Serial Addition TaskPASAT
Patient Global ImpressionPGI
Phillips Scale
Positive and Negative SyndromePANSS
Scale for Schizophrenia
Psychotic Anxiety Scale
Psychotic Depression Scale
Quality of Life ScalesQLS
Rating of Aggression Against People and/or PropertyRAAP
Repeatable Battery for the Assessment of Neuropsychological StatusRBANS
Role Functioning ScaleRFS
Scale for the Assessment of Negative SymptomsSANS
Scale for the Assessment of Positive SymptomsSAPS
Schneiderian Symptom Rating Scale
Simpson Angus Rating Scale for Extrapyramidal Side EffectsSAS, SARS
Simpson-Angus Neurologic Rating Scale
Slow-wave sleepSWS
Social Adjustment ScaleSAS-SM
Social Functioning ScaleSFS
Social and Occupational Functioning AssessmentSOFA
Social Verbal Learning TestSVLT
Stroop Color-Word Test
Subjective response to treatment scale
Subjective Well-Being Under Neuroleptics Scale
Trail Making TestTMT
Tremor, akathisia
UKU Side Effect Rating Scale
Verbal Fluency Categories
Verbal Fluency Letters
Verbal List Learning Immediate Test
Wechsler Adult Intelligence Scales - Maze TestWAIS
Wisconsin Card Sort TestWCST
World Health Organization – Quality of Life [Brief]WHO-QOL (BREF)
Young Mania Rating ScaleYMRS

Appendix A References

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Spearing MKPR, Leverich GS, Brandt D, Nolen W. Modification of the Clinical Global Impressions ((CGI) Scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Research. 1997;73(3):159–171. [PubMed: 9481807]
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.
Bookshelf ID: NBK50588

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