Positive and Negative Syndrome Scale(PANSS, Scale used to measure efficacy)

Introduction

What is PANSS?

PANSS (Positive and Negative Syndrome Scale) is a scale used to measure the severity of schizophrenia.

The PANSS measures the severity of positive symptoms, negative symptoms, and general psychopathology symptoms. The severity of the symptoms is measured and scored in a relatively short interview (45-50 minutes).

The score is also determined based on reports from family members and staff of the patient’s hospital. The higher the score, the more severe the illness.

Use of PANSS in Clinical Trials

In clinical trials using PANSS, participants are measured in PANSS scores both before the drug is administered and weeks after the drug has been administered.

Naturally, scores are lower after the medication is administered, so the difference between before and after can be used to determine the degree of improvement in severity. The larger the difference(the greater the decrease), the more effective the drug is.

Before I write more about the values of drug efficacy in another article, such as Difference from placebo, 95% confidence interval, Effect size, and p-value, let me explain a little about PANSS.

Total Score, Positive Score, Negative Score, General Psychopathology Score

As mentioned above, the PANSS measures the severity of positive symptoms, negative symptoms, and general psychopathology symptoms.

To measure the severity of “positive symptoms,” there are seven items on the Positivity Scale. The severity of each of the seven items, including “delusions” and “hallucinations,” is scored. (A list of all the items can be found in the latter part of this article.)

Each item is scored on a seven-point scale (1-7). A score of 1 is given for no symptoms, and a score of 7 for the most severe.

That is to say, the total PANSS positive score is scored between a minimum of 7 and a maximum of 49 points. The higher the score, the more severe the symptoms.

The “negative symptoms” are similarly scored on a seven-point scale for each of the seven items. PANSS negative scores are also scored from 7 to 49 points in total.

The “generale psychopathology symptoms” is similarly scored on the 16 items of the General Psychopathology Scale.The PANSS general Psychopathology score is scored between 16 and 112 points in total.

The scores for the 7 items on the positive scale, the 7 items on the negative scale, and the 16 items on the general psychopathology scale, are combined to produce the PANSS total score.

In other words, the PANSS total score is between 30 and 210.

PANSS Scores in an Actual Research

In one PANSS-based study, 101 schizophrenic patients were tested and the average score came out as follows.

PANSS positive score Average = 18.20 points
PANSS negative score Average = 21.01 points
PANSS general psychopathology score Average = 37.74 points
PANSS total score Average = 76.95 points

PANSS Scores and Severity

In general, the PANSS total score determines the severity of schizophrenia as follows

58 points mildly ill
75 points moderately ill
95 points markedly ill
116 points severely ill 

In the study using the PANSS above, the mean PANSS total score for the 101 schizophrenic patients was 76.95, so it appears that the 101 patients were moderately ill on average.

PANSS Scores and Drug Efficacy

To familiarize you with the PANSS score, here are some reference values I found.

According to the percentage reduction of the PANSS total score that a drug induces at the time of administration, the drug is evaluated as follows.

Large improvement
40% reduction in 1 week
45% reduction in 2 weeks
51% reduction in 4 weeks
53% reduction in 6 weeks

Minimal improvement
19% reduction in 1 week
23% reduction in 2 weeks
26% reduction in 4 weeks
28% reduction in 6 weeks

For example, suppose that after 6 weeks, a drug reduces the PANSS total score by 53%. The drug would then be effective enough to dramatically improve a severely ill patient(116 points) to mild symptom severity(58 points). The drug is rated as a large improvement agent.

A drug that reduces PANSS total score by only 28% after 6 weeks would not even reduce a severely ill patient(116 points) to a moderate level of symptom severity(75 points). The drug is evaluated as a drug that provides only minimal improvement.

PANSS Score Reduction with Lumateperone

Here is one specific example of how much a drug under development in a clinical trial reduced a patient’s PANSS score.

For example, let’s look at the case of lumateperone 42mg. Lumateperone 42mg was administered to 148 of the study participants. It was administered for 4 weeks.

Prior to lumateperone administration, the mean PANSS total score for those 148 patients was about 90 points. The positive score was about 26, the negative score was about 21, and the general psychopathology score was about 43.

A total score of 90 points means that, on average, the patients were markedly ill before the administration of lumateperone.

4 weeks after lumateperone administration, the mean PANSS total score had decreased to approximately 74.4, the positive score to approximately 21.2, the negative score to approximately 19.6, and the general psychopathology score to approximately 35.3.

Lumateperone administration reduced the PANSS total score by 15.6 points to moderate symptom severity(75 points), a 17% reduction, which was less than minimal improvement.

Even with only this amount of improvement (score reduction) in 4 weeks, a statistically significant improvement over placebo would seem to warrant marketing approval.

In Conclusion (Four Efficacy Values)

In clinical trials, the magnitude of reduction in PANSS scores with developmental drugs is further compared to the magnitude of reduction in PANSS scores with placebo.

Then, “Difference from placebo” is calculated. The “95% confidence interval” is also calculated.

“Difference from placebo” is divided by “Standard deviation” to calculate “Effect size”.

The “p-value” is calculated to determine whether there is a statistically significant improvement over placebo, i.e., whether the trial is a success or a failure.

These four calculated efficacy values are described in the following article.
How to Judge the Efficacy of an Investigational Drug for Schizophrenia(coming soon!)

Appendix 1: Positive and Negative Symptoms

I am a little late in writing this, but for those of you who have never heard of the three symptoms: positive symptoms, negative symptoms, and general psychopathology symptoms, I will briefly explain them in case you have not heard of them. For more details, please see the list in Appendix 2.

Positive symptoms are symptoms such as hallucinations, delusions, and thought disorder. Perceptions, feelings, and thoughts are disturbed by an inability to perceive reality correctly.

Positive symptoms are typical symptoms that characterize schizophrenia. Symptoms are particularly intense during the acute phase of the illness.

Negative symptoms refer to symptoms such as decreased motivation, flat emotions, decreased thinking, and social withdrawal.

Some perceptions do not elicit feelings and do not lead to motivation. The patient’s thinking becomes impoverished and he/she does not want to communicate with others. These symptoms are particularly problematic during the maintenance and stable phases.

General psychopathology symptoms refers to other symptoms associated with schizophrenia in addition to positive and negative symptoms. They include anxiety, unnatural thought content, and impaired judgment.

Appendix 2: Interview items

Below are the items for the positive score, the items for the negative score, and the items for the genaral psychopathology score.

POSITIVE SCALE (P)

P1. DELUSIONS – Beliefs which are unfounded, unrealistic and idiosyncratic.
Basis for rating – Thought content expressed in the interview and its influence on social relations and behaviour.

P2. CONCEPTUAL DISORGANISATION – Disorganised process of thinking characterised by disruption of goal-directed sequencing, e.g. circumstantiality, loose associations, tangentiality, gross illogicality or thought block.
Basis for rating – Cognitive-verbal processes observed during the course of interview.

P3. HALLUCINATORY BEHAVIOUR – Verbal report or behaviour indicating perceptions which are not generated by external stimuli. These may occur in the auditory, visual, olfactory or somatic realms.
Basis for rating – Verbal report and physical manifestations during the course of interview as well as reports of behaviour by primary care workers or family.

P4. EXCITEMENT – Hyperactivity as reflected in accelerated motor behaviour, heightened responsivity to stimuli, hypervigilance or excessive mood lability.
Basis for rating – Behavioural manifestations during the course of interview as well as reports of behaviour by primary care workers or family.

P5. GRANDIOSITY – Exaggerated self-opinion and unrealistic convictions of superiority, including delusions of extraordinary abilities, wealth, knowledge, fame, power and moral righteousness.
Basis for rating – Thought content expressed in the interview and its influence on behaviour.

P6. SUSPICIOUSNESS/PERSECUTION – Unrealistic or exaggerated ideas of persecution, as reflected in guardedness, ad distrustful attitude, suspicious hypervigilance or frank delusions that others mean harm.
Basis for rating – Thought content expressed in the interview and its influence on behaviour.

P7. HOSTILITY – Verbal and nonverbal expressions of anger and resentment, including sarcasm, passive-aggressive behaviour, verbal abuse and assualtiveness.
Basis for rating – Interpersonal behaviour observed during the interview and reports by primary care workers or family.

NEGATIVE SCALE (N)

N1. BLUNTED AFFECT – Diminished emotional responsiveness as characterised by a reduction in facial expression, modulation of feelings and communicative gestures.
Basis for rating – Observation of physical manifestations of affective tone and emotional responsiveness during the course of the interview.

N2. EMOTIONAL WITHDRAWAL – Lack of interest in, involvement with, and affective commitment to life’s events.
Basis for rating – Reports of functioning from primary care workers or family and observation of interpersonal behaviour during the course of the interview.

N3. POOR RAPPORT – Lack of interpersonal empathy, openness in conversation and sense of closeness, interest or involvement with the interviewer. This is evidenced by interpersonal distancing and reduced verbal and nonverbal communication.
Basis for rating – Interpersonal behaviour during the course of the interview.

N4. PASSIVE/APATHETIC SOCIAL WITHDRAWAL – Diminished interest and initiative in social interactions due to passivity, apathy, anergy or avolition. This leads to reduced interpersonal involvements and neglect of activities of daily living.
Basis for rating – Reports on social behaviour from primary care workers or family.

N5. DIFFICULTY IN ABSTRACT THINKING – Impairment in the use of the abstract-symbolic mode of thinking, as evidenced by difficulty in classification, forming generalisations and proceeding beyond concrete or egocentric thinking in problem-solving tasks.
Basis for rating – Responses to questions on similarities and proverb interpretation, and use of concrete vs. abstract mode during the course of the interview.

N6. LACK OF SPONTANEITY AND FLOW OF CONVERSATION – Reduction in the normal flow of communication associated with apathy, avolition, defensiveness or cognitive deficit. This is manifested by diminished fluidity and productivity of the verbal interactional process.
Basis for rating – Cognitive-verbal processes observed during the course of interview.

N7. STEREOTYPED THINKING – Decreased fluidity, spontaneity and flexibility of thinking, as evidenced in rigid, repetitious or barren thought content.
Basis for rating – Cognitive-verbal processes observed during the interview.

GENERAL PSYCHOPATHOLOGY SCALE (G)

G1. SOMATIC CONCERN – Physical complaints or beliefs about bodily illness or malfunctions. This may range from a vague sense of ill being to clear-cut delusions of catastrophic physical disease.
Basis for rating – Thought content expressed in the interview.

G2. ANXIETY – Subjective experience of nervousness, worry, apprehension or restlessness, ranging from excessive concern about the present or future to feelings of panic.
Basis for rating – Verbal report during the course of interview and corresponding physical manifestations.

G3. GUILT FEELINGS – Sense of remorse or self-blame for real or imagined misdeeds in the past.
Basis for rating – Verbal report of guilt feelings during the course of interview and the influence on attitudes and thoughts.

G4. TENSION -Overt physical manifestations of fear, anxiety, and agitation, such as stiffness, tremor, profuse sweating and restlessness.
Basis for rating – Verbal report attesting to anxiety and thereupon the severity of physical manifestations of tension observed during the interview.

G5. MANNERISMS AND POSTURING – Unnatural movements or posture as characterised be an awkward, stilted, disorganised, or bizarre appearance.
Basis for rating – Observation of physical manifestations during the course of interview as well as reports from primary care workers or family.

G6. DEPRESSION – Feelings of sadness, discouragement, helplessness and pessimism.
Basis for rating – Verbal report of depressed mood during the course of interview and its observed influence on attitude and behaviour.

G7.MOTOR RETARDATION – Reduction in motor activity as reflected in slowing or lessening or movements and speech, diminished responsiveness of stimuli, and reduced body tone.
Basis for rating – Manifestations during the course of interview as well as reports by primary care workers as well as family.

G8. UNCOOPERATIVENESS – Active refusal to comply with the will of significant others, including the interviewer, hospital staff or family, which may be associated with distrust, defensiveness, stubbornness, negativism, rejection of authority, hostility or belligerence.
Basis for rating – Interpersonal behaviour observed during the course of the interview as well as reports by primary care workers or family.

G9. UNUSUAL THOUGHT CONTENT – Thinking characterised by strange, fantastic or bizarre ideas, ranging from those which are remote or atypical to those which are distorted, illogical and patently absurd.
Basis for rating – Thought content expressed during the course of interview.

G10. DISORIENTATION – Lack of awareness of one’s relationship to the milieu, including persons, place and time, which may be due to confusion or withdrawal.
Basis for rating – Responses to interview questions on orientation.

G11. POOR ATTENTION – Failure in focused alertness manifested by poor concentration, distractibility from internal and external stimuli, and difficulty in harnessing, sustaining or shifting focus to new stimuli.
Basis for rating – Manifestations during the course of interview.

G12. LACK OF JUDGEMENT AND INSIGHT – Impaired awareness or understanding of one’s own psychiatric condition and life situation. This is evidenced by failure to recognise past or present psychiatric illness or symptoms, denial of need for psychiatric hospitalisation or treatment, decisions characterised by poor anticipation or consequences, and unrealistic short-term and long-range planning.
Basis for rating – Thought content expressed during the interview

G13. DISTURBANCE OF VOLITION – Disturbance in the wilful initiation, sustenance and control of one’s thoughts, behaviour, movements and speech.
Basis for rating – Thought content and behaviour manifested in the course of interview.

G14. POOR IMPULSE CONTROL – Disordered regulation and control of action on inner urges, resulting in sudden, unmodulated, arbitrary or misdirected discharge of tension and emotions without concern about consequences.
Basis for rating – Behaviour during the course of interview and reported by primary care workers or family

G15. PREOCCUPATION – Absorption with internally generated thoughts and feelings and with autistic experiences to the detriment of reality orientation and adaptive behaviour.
Basis for rating – Interpersonal behaviour observed during the course of interview.

G16. ACTIVE SOCIAL AVOIDANCE – Diminished social involvement associated with unwarranted fear, hostility, or distrust.
Basis for rating – Reports of social functioning primary care workers or family