Glossary of terms

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Adverse events

An adverse event is an effect other than that for which an agent or drug is intended. Adverse events are unfavourable results caused by the agent/drug. Groups of drugs that produce similar positive results generally also have similar adverse events. Adverse events are all unexpected events reported during a clinical study, regardless of the treatment, and not necessarily related to the medication or the placebo applied. By definition adverse events can even occur before the first medication has been taken.

Antidepressant drugs

Drugs that prevent or relieve depression (see depression treatment).

Anxiety

An unpleasant emotional state that consists of responses, both psychological and physiological, to unreal or imagined danger. Anxiety often results from unrecognised conflict in the mind. The symptoms can be physiologically, such as: increased heart rate, altered respiration rate, sweating, trembling, weakness and fatigue; or psychologically such as feelings of impending danger, powerlessness, apprehension and tension.

Anxiety disorders (also see social anxiety disorder – SAD)

Anxiety disorders are serious medical illnesses that fill people's lives with overwhelming anxiety and fear. Unlike the relatively mild, brief anxiety caused by a stressful event such as a business presentation or a first date, anxiety disorders are chronic i.e. build up over a long period of time, and will often increase in severity if not treated.
Anxiety disorders can be further divided into: panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, specific phobias, and generalised anxiety disorder. Each anxiety disorder has its own distinct features, but they are all characterised by excessive, irrational fear and dread.
Anxiety disorders are often under-diagnosed and under-treated. Far from being the exception, co-morbidity is the norm for patients with social anxiety disorder (SAD). The co-morbidity with depression is high and people suffering from an anxiety disorder are often not diagnosed before seeking treatment for the depression.

Anxiety treatment – anxiolytic drugs

Effective treatments for each of the anxiety disorders exist (sometimes combined with psychotherapy), and include: benzodiazepines, monoamine oxidase inhibitors (MAOIs), beta-blockers, and antidepressants (TCAs, MAOIs and SSRIs – see individual descriptions). SSRIs are effective treatments for anxiety disorders. Due to their high tolerability, the non-sedating effect and few adverse events, SSRIs are widely used and can help many patients with anxiety to lead productive and fulfilling lives.

Bipolar disorder

An illness in which the patient goes back and forth between opposite extremes in mood; the most notable bipolar disorder is manic-depressive disorder, which is characterised by extreme highs and lows in mood.

Baseline

When patients start in a clinical study it is important to have their initial (baseline) values for various measures (of e.g. rating scales, laboratory values, vital signs, weight) to compare with those from a later stage of the study.

Blinding

Clinical studies are often blinded; meaning that patients and/or their doctors do not know which treatment under investigation the individual patient is receiving.

CGI – Clinical Global Impression Scales

The Clinical Global Impression scale consists of two subscales: the Clinical Global Impressions–Improvement Scale (CGI-I), and the Clinical Global Impressions – Severity Scale (CGI-S) – see specific descriptions.

CGI-I – Clinical Global Impressions – Improvement Scale

Clinical Global Impressions – Improvement scale (CGI-I) evaluates a patient’s total improvement from baseline (when pharmacological therapy is commenced) on a 7-point scale regardless of whether the improvement is related to the study product. The assessor rates the patient from 1 (very much improved) to 7 (very much worse).

CGI-S – Clinical Global Impressions – Severity Scale

The Clinical Global Impression – Severity (CGI-S) scale evaluates a patient’s severity of disease on a 7-point scale based on the investigator’s total clinical experience with those patients. The assessor rates the patient from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

Citalopram

Citalopram belongs to the group of SSRIs, and is one of the most selective SSRIs currently available. Citalopram is used in treating depressive and anxiety disorders and is effective and well tolerated both in short-term and in long-term treatment.

Comorbidity

The presence of co-existing diseases.

Compliance

Compliance describes the behaviour of patients when they follow the recommendations and rules given by their treating physician (e.g. taking a medication as prescribed). In general, compliance is 50% among people with a chronic disease, irrespective of disease, treatment, or age.

Depression (see background document on depression)

Depression is a serious illness that can impair all aspects of a person's life, including personal relationships, performance at work and enjoyment of leisure activities, and is associated with a variety of other diseases (comorbidity) and has a high risk of suicide (up to 15%). Symptoms are not identical in all patients but often include: irritability, feeling of guilt and/or helplessness and anxiety, difficulties in sleeping, withdrawal from interpersonal contact as well as physical symptoms such as headache There are a number of different forms of depression, the most common being major depression, dysthymia, and bipolar disorder (also called manic-depressive illness). Depression affects approximately 10–15% of the population at some time during their life.

Depression treatment – antidepressive therapy

Several types of medicine have been developed to treat depression, including tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin re-uptake inhibitors (SSRIs). Antidepressant therapy should preferably include treatment of the acute episode of depression and long-term treatment to consolidate the therapeutic response and prevent relapse. Current guidelines recommend at least a 6-month course of maintenance treatment regardless of the therapeutic class.

DESS – Discontinuation Emergent Signs and Symptoms

The DESS is a 43-item checklist designed to assess possible events that emerge following discontinuation of drug use, also known as withdrawal symptoms. The DESS is a clinician-rated checklist that is used to evaluate signs and symptoms possibly associated with discontinuation or interruption of treatment.

Drop-out rate

The drop-out rate represents the proportion of patients who leave a clinical study prior to the last schedules visit. All patients in clinical studies participate voluntarily and can choose to leave a clinical study at any time and for any reason, without explanations needed and without prejudice regarding their future treatment. However, the reasons often given are inconvenience (moving further away, changing job, etc.), feeling a lack of efficacy or intolerable adverse events. The patient can be withdrawn by the investigator for safety reasons, due to lack of efficacy or because they no longer meet the criteria in the protocol, for example, by becoming pregnant.

Dysthymia

A mood disorder characterised by depressed feeling (sad, blue, low, down in the dumps) and loss of interest or pleasure in one’s usual activities and in which the associated symptoms have persisted for more than two years but are not severe enough to meet the criteria for major depression. Also known as depressive neurosis.

Efficacy

Strength, effectiveness. The ability of a drug to control or cure an illness. Efficacy should be distinguished from activity, which is limited to a drug’s immediate effects on the cause of the disease. How efficacy is to be assessed in clinical studies is defined in the study protocol and is typically determined by comparison of an initial baseline score with one or more scores at predefined time in the study.

Efficacy assessments

In clinical studies, efficacy can be assessed by various methods, as defined in the study protocol. In clinical studies in psychiatry rating scales are frequently used either as interviews or as self-rating scales by the patient. These may include one or more of the following: MADRS, HAMD, CGI, SDS etc. (see individual descriptions).

Enantiomer

In nature, compounds with the same molecular formula can exist as non-superimposable mirror images of each other, known as enantiomers. Often one isomer exerts an active effect whilst the other is inactive. The mixture of the isomers is referred to as a racemic mixture or racemate.

Escitalopram

Escitalopram is the active S-enantiomer of the SSRI citalopram. In spite of the fact that SSRIs, including citalopram, have been established as an effective and safe treatment, further improvements in the class of SSRIs have been developed. Escitalopram offers a unique mode of action resulting in superior effficacy. Escitalopram is used for short-term and long-term treatment of depression and anxiety disorders and escitalopram is even better than citalopram with respect to onset of symptom and overall effect.

Generalized Anxiety Disorder (GAD)?

GAD is a disorder causing an individual to experience constant worrisome and unreasonable thoughts and stresses over routine daily activities for several months. People with GAD always anticipate the worst. The disorder is often accompanied by physical symptoms such as fatigue, trembling, muscle tension, headache and nausea.

HAMA – Hamilton Anxiety Scale

The HAMA was developed to quantify the severity of symptoms of anxiety and is widely used to evaluate anxiety in clinical studies.

The Hamilton Anxiety Scale consists of 14 items, each defined by a series of symptoms; 1) anxious mood, 2) tension, 3) fears, 4) insomnia, 5) intellectual, 6) depressed mood, 7) somatic complaints: muscular, 8) somatic complaints: sensory, 9) cardiovascular symptoms, 10) respiratory symptoms, 11) gastrointestinal symptoms, 12) genitourinary symptoms, 13) autonomic symptoms, and 14) behaviour at interview.

Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (very severe). The sum (total score) indicates the severity of anxiety; less than 12 is normal, 18 mild anxiety (and the lowest threshold at which medication is usually prescribed), 25 moderate anxiety, and 30 severe anxiety.

HAMD – Hamilton Rating Scale for Depression

The Hamilton Rating Scale for Depression exists in two versions rating either 17 or 24 items typical for depressive patients. Both sub-scales are used to measure the severity of depressive symptoms. The clinician marks the severity of symptoms based on an interview with the patient, including assessment on the basis of specific statements, content, tone, facial expressions, and gestures of the patient during the interview. The symptoms are scored from 0 to 2, 3 and 4 (the higher the score the more severe the depression); a total score of 10–13 indicates mild depression; 14–17 mild to moderate depression and more than 17 moderate to severe depression.
The 17-item HAM-D scale consists of the following items: 1) depressed mood, 2) feelings of guilt, 3) suicide, 4) insomnia early, 5) insomnia middle, 6) insomnia late, 7) work and activities, 8) retardation, 9) agitation, 10) anxiety psychic, 11) anxiety somatic, 12) somatic symptoms gastrointestinal, 13) somatic symptoms general, 14) genital symptoms, 15) hypochondriasis, 16) loss of weight, and 17) insight.
The 24-item HAM-D scale consists of all the items in the 17-item HAM-D scale plus: 18) diurnal variation, 19) depersonalisation and derealisation, 20) paranoid symptoms, 21) obsessional and compulsive symptoms, 22) helplessness, 23) hopelessness, and 24) worthlessness.

Incidence

This is the number of new cases of a disease or condition in the total population at risk measured over a given time interval.

Isomer

One of two or more molecules that have the same chemical formula but have a different chemical construction or arrangement of their atoms – often they are mirror images of each other.

LSAS – Liebowitz Social Anxiety Scale

The Liebowitz Social Anxiety Scale is a clinician-administered (interview) scale to evaluate the wide range of social situations within the last 7 days that are typically difficult for individuals with social phobia. The LSAS includes 24 items, 13 describing performance situations and 11 items describing social interaction situations. Each item is rated for fear (0 to 3 = none, mild, moderate, severe) and avoidance (0 to 3 = never, occasionally, often, usually). Thus, the LSAS provides an overall social anxiety severity rating, and scores on 4 subscales: 1) performance fear, 2) performance avoidance, 3) social fear, and 4) social avoidance. Total scores for fear and avoidance as well as total LSAS scores are achieved by summing of the scores.

MADRS – Montgomery and Aasberg Depression Rating Scale

The Montgomery and Aasberg Depression Rating Scale, the MADRS, is a tool for evaluating the effect of an antidepressive treatment. The MADRS consists of 10 items that are all core symptoms of the depressive episode and measures the severity of the depressive episode for the previous 7 days. The MADRS ratings are based on a clinical interview with the patient beginning with general questions about symptoms and gradually becoming more detailed to allow for a precise rating of depression severity.

The symptoms rated are: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each symptom is rated on a scale from 0 (no signs of depression) to 6 (severe symptoms), and the sum (the total score, 0-60), indicates the severity of the depression. A score of 0-6 indicates no depression, 7-21 mild depression, 22-29 moderate depression, and equal to or more than 30, severe depression.
One of the strengths of this depression scale is the high inter-rater reliability, meaning that different raters performing an interview will obtain similar results.

Major depression

A mental disorder characterised by the occurrence of one or more major depressive episodes and the absence of any history of manic episodes.

Manic depression

Alternating between attacks of mania and depression, also known as bipolar disorder.

Microdialysis

The microdialysis technique allows sampling of small quantities of biological fluids from discrete, closed compartments in the body, such as the brain. The samples can then be analysed to determine the concentrations of various drugs, chemicals and/or neurotransmitters. A major advantage of the technique is that it can be performed in vivo. An added advantage of this technique is that it also permits injection of drugs through the microdialysis probe to a specific area of interest. Thus, one can determine in preclinical experiments how a particular drug or treatment changes the neurochemistry in a particular brain region without the interference/modulation of the other brain regions or pharmacokinetic considerations.

Monoamine oxidase inhibitor (MAOI)

MAOIs interfere with the action of the enzyme monoamine oxidase, thereby slowing the breakdown of certain neurotransmitters, some of which possess physiological effects in the central nervous system thus affecting the mood.

Neurotransmitters

Neurotransmitters are substances that are released on stimulation from a neuron in the nervous system, and cross the synapse to either excite or inhibit the target cell and thereby transfer the impulse or message. Among the many substances that have the properties of a neurotransmitter are ,e.g., acetylcholine, noradrenaline, adrenaline, dopamine and serotonin.

Noradrenaline

One of the neurotransmitters in a part of the nervous system.

Obsessive compulsive disorder (OCD)

OCD is characterised by recurrent, persistent obsessions and/or compulsions. Obsessions are repetitive thoughts, intrusive ideas, or impulses that is experiences as inappropriate, intrusive, and unwanted. Compulsions are repetitive behaviours that the individual feels driven to perform, but generally recognises as senseless, in an effort to avoid or decrease the anxiety created by obsessions.

Onset of action

The time at which the effect of the treatment starts. When using citalopram the effect can be seen after 2 to 4 weeks, whereas with the next generation SSRI, escitalopram, symptom improvement is significant after one week.

Panic disorder (PD)

Anixety disorder is characterised by intense periods of fear and worry and panic attacks. Performance situation
A situation requiring an individual to undertake a particular task, e.g., going shopping, making a telephone call.

Placebo

A pharmacologically inactive drug formulation. In order to make an impartial evaluation of a new drug, some clinical studies are designed such that patients are given either the new drug or placebo to assess how patients respond to the active versus no pharmacological treatment.

Placebo effect

An effect that is usually, but not necessarily, beneficial that is attributable to an expectation that the treatment will have an effect. Patients participating in clinical studies regularly consult a physician (specialist or general practitioner) concerning their disease. This specialised care by participating in a study makes the patient feel safe, nursed and well treated which may result in a measurable clinical effect of placebo treatment, called the placebo effect.

Point prevalence

The proportion of the population that has the disease or symptom at the specific time considered.

Post-natal depression – see Post-partum depression

 

Post-partum depression

State of depression after giving birth. One in ten women suffer from post-partum depression. Symptoms can be fatigue, irritability, sleeplessness, loss of appetite and anxiety. Also called post-natal depression.
Prevalence
The proportion of the population that either has or has had the disease/symptom.

Psychotherapy

A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or non-verbal communication.

Racemate or racemic mixture

A racemic mixture comprises two enantiomers of the same compound, which are mirror images of each other.

Rating scales

Rating scales are frequently used to evaluate psychiatric patients. Different rating scales have been developed for different disorders, each with specific advantages. When used in clinical studies it is important that the same rater or assessor is used throughout the study whenever possible. For some scales, physicians rate the patients while for others study nurses are allowed to rate. In general for all scales, the higher the score, the more severe the disorder.
Various scales are referred to in this glossary and accompanying backgrounders: Clinical Global Impression Scales – improvement scale and severity scale (CGI-I and CGI-S); Hamilton Anxiety Scale (HAMA); Hamilton Rating Scale for Depression (HAMD); Liebowitz Society Anxiety Scale (LSAS); Montgomery and Ǻsberg Depression Rating Scale (MADRS); Sheehan Disability Scale (SDS).

Recovery

Persistent well being after the continuation treatment has been finalised. At present, treatment guidelines recommend at least 6 months of continuation treatment after full remission has been achieved. Therapy should generally be continued with the same drug and at the same dose, as when remission was achieved.

Recurrence

The return of symptoms and signs of a new episode of the disease after a period of full normalcy after treatment of any previous depressive episode. For a clinical study, a threshold will be defined where symptoms or signs of the disease are considered to have returned, i.e., recurred. In the case of the MADRS, this is defined as greater than 12.

Relapse

The return of symptoms and signs from the same episode of a disease after a period of improvement. For a clinical study, a threshold will be defined where symptoms or signs of the disease are considered to have returned, i.e., relapsed. In the case of the MADRS, this is greater than 12.

Remission

A reduction in severity or degree of a disease back to normalcy as defined for the specific measurement scale used. In the case of the MADRS, this is defined as less than or equal to 12.

Response

Response is defined as a measurable change. In clinical studies the change in MADRS total score from baseline is often used to quantify response, and is usually defined as at least a 50% reduction in the total score.

SDS – Sheehan Disability Scale

The SDS is a 3-item scale of impairment. The items address the impact of symptoms of social anxiety disorder (SAD) on three areas of functioning, namely, work, social and family within the last 7 days.

Serotonin (see also selective serotonin re-uptake inhibitor / SSRI)

Serotonin is a naturally occurring compound that is found in many living organisms. It is found in high concentrations in many body tissues, including the cells of the intestine, brain and central nervous system. Serotonin has many physiological properties, e.g., it stimulates smooth muscle movement in the intestines and serves as a neurotransmitter – transporting signals from one nerve cell to another or from a nerve cell to a muscle cell.

Selective serotonin re-uptake inhibitor – see SSRI

 

SF36 – The MOS 36-item Health Survey

The SF 36 is a comprehensive and very widely used survey tool designed to assess perceived health status. SF 36 includes one multi-item scale that assesses eight health concepts: 1) limitation in physical activities because of health problems, 2) limitations in social activities because of physical or emotional problems, 3) limitations in usual role activities because of physical health problems, 4) bodily pain, 5) general mental health (psychological distress and well-being), 6) limitations in usual role activities because of emotional problems, 7) vitality (energy and fatigue), and 8) general health perception.

Side effects – see adverse events

 

Social anxiety disorder (SAD)

SAD is characterised by an abnormal fear of situations in which a person may be exposed to the scrutiny of others. As a result, patients with this disorder avoid, or endure with intense anxiety, social or performance situations.
SAD exists as two distinct subtypes: generalised and non-generalised SAD. Generalised SAD is a highly familial, chronic condition in which patients fear both social and performance situations, whilst the non-generalised form is usually limited to fear of performance situations.

SSRI – selective serotonin re-uptake inhibitor

Selective serotonin re-uptake inhibitors (SSRIs) are used to treat depressive disorders and anxiety disorders. They work by specifically inhibiting the re-absorption of the neurotransmitter serotonin in the synapses in the brain, thereby increasing the serotonin level in the brain. Several SSRIs are on the market and they differ in respect to efficacy, adverse events, and/or tolerability.

Synapse

The synapse is the site at which an impulse is transmitted from one nerve cell to another electrically or chemically.

Tolerability

Tolerability is a specific property of a drug that illustrates the frequency and severity of adverse events; i.e. how an individual is able to tolerate a specific drug treatment.

Tricyclic Antidepressant (TCA)

Tricyclic antidepressants were discovered more than 50 years ago and block the re-uptake of serotonin, noradrenaline and a number of other neutransmitters.