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WHO Expert Committee on Drug Dependence – WHO Technical Report Series, No. 915 – Thirty-third Report
(2003; 31 pages) [French] [Spanish] View the PDF document
Table of Contents
View the document1. Introduction
View the document2. Scheduling criteria
Open this folder and view contents3. Critical review of psychoactive substances
Open this folder and view contents4. Pre-review of psychoactive substances
View the document5. Terminology used in reporting abuse-related adverse drug reactions
View the document6. Other matters
View the documentAcknowledgements
View the documentReferences
View the documentAnnex Terminology used in reporting abuse-related adverse drug reactions
 

Annex Terminology used in reporting abuse-related adverse drug reactions

The Expert Committee on Drug Dependence (ECDD) has been instrumental in developing appropriate terminology to aid understanding of the phenomena of drug dependence and abuse. At its thirteenth meeting (1), ECDD had already proposed using drug dependence to replace the terms drug addiction and drug habituation. This proposal was accepted globally during the 1970s.

However, the ICD-10 (2) employed certain technical terms that were slightly different from the conventional terms, such as withdrawal state instead of withdrawal syndrome or abstinence syndrome. This led to the question of whether ICD-10 was entirely consistent with the definition of drug dependence worked out by the ECDD during the 1960s. At its twenty-eighth meeting (3) the Committee discussed this question and concluded that there was no inconsistency between the definition of drug dependence adopted by this Committee and the diagnostic guidelines for dependence syndrome developed by WHO in conjunction with ICD-10. This clarification has apparently reduced the conceptual confusion, at least among drug abuse researchers and treatment experts. However, in the area of postmarketing surveillance, which involves a much broader range of health professionals, conceptual confusion is still commonplace. Such confusion is particularly common with regard to the meaning of closely-related terms, as outlined below.

Drug addiction and drug dependence

Although the term drug addiction was eliminated from the technical terminology of WHO many years ago, it is still widely used as a general term. For example, the word addictive is commonly used to mean dependence-producing. Where drug addiction is used as a technical term it seems to refer to severe cases of dependence. However, as there is no internationally accepted definition of addiction, it is impossible to be certain in what way addiction differs from dependence.

Drug abuse and drug dependence

From the above-mentioned definition of drug abuse, it is clear that acceptable medical use of the drug, whether or not it results in drug dependence, is not drug abuse. There are situations in which treatment with a dependence-producing drug needs to be continued, even after the patient has become dependent on it. In this case, drug dependence may be reported as an adverse drug reaction, but not as drug abuse. In this connection, it is also useful to stress that dependence liability alone is not sufficient reason for proposing the international control of a psychoactive drug. It is the abuse liability (likelihood of abuse) of the drug that must be considered. It is necessary to make the distinction between the abuse of a psychoactive substance which tends to result in the deterioration of an individual’s physical, psychological and social functioning, and its therapeutic use which is intended to improve any or all of these. It is also known that not all dependence-producing drugs are abused (e.g. caffeine is dependence-producing but it is seldom abused).

Drug abuse and drug maladministration

Drug abuse is defined as “persistent or sporadic excessive drug use inconsistent with or unrelated to acceptable medical practice”. Thus, the intentional use of excessive doses, or the intentional use of therapeutic doses for purposes other than the indication for which the drug was prescribed, is drug abuse. Misuse and non-medical use are synonyms of drug abuse. However, inappropriate prescribing (e.g. indiscriminate prescribing of antibiotics) or medication errors, if accidental or unintended, should not be classified as drug abuse. Such an inappropriate use of the drug should rather be considered as drug maladministration. Drug maladministration can cause many adverse reactions and it is a drug safety problem requiring an appropriate response, but it can rarely be a consequence of the normal therapeutic use of a drug. It is therefore difficult to imagine a situation in which drug maladministration needs to be reported to the adverse drug reaction database; it has to be addressed as a separate safety issue.

Physical (physiological) dependence and drug dependence

The ECDD (3) recommended against the use of the term physical (physiological) dependence for several reasons. Firstly, it noted that the distinction between physical (physiological) dependence and psychic (psychological) dependence was difficult to make in clinical situations. Such a distinction would also be inconsistent with the modern view that all drug effects are potentially understandable in biological terms. The term physical (physiological) dependence was also considered to be confusing because clinicians often interpreted the manifestation of withdrawal syndrome as evidence of both physical dependence and drug dependence. (This is not the case, as explained in more detail below.) Nonetheless, the term is still used to mean a state of adaptation evidenced by the manifestation of withdrawal syndrome upon discontinuation of the drug or the development of tolerance or both.

Drug dependence and withdrawal syndrome

The simplest explanation of drug dependence is “a state in which the individual has a need for repeated doses of the drug to feel good or to avoid feeling bad”. This is consistent both with general public understanding and with the more sophisticated definition of drug dependence used by the ECDD. The ICD-10 (2) emphasizes the loss of control over one’s drug-seeking behaviour as the core concept of drug dependence and sets out diagnostic guidelines for dependence syndrome with six check-points. Two of them concern withdrawal state and tolerance while the remaining four could be considered as different manifestations of the state of dependence itself. For a positive diagnosis of dependence syndrome, at least three of the six criteria must be observed. Thus, even when both tolerance and withdrawal occur, this is not sufficient to meet the requirement for dependence syndrome unless one of the remaining four criteria is met. Conversely, even when both withdrawal and tolerance are absent, an individual can still have dependence syndrome if three of the remaining four requirements are met.

It is therefore correct to say that withdrawal and tolerance are neither required nor sufficient for a positive diagnosis of dependence syndrome. However, excessive emphasis on this can lead to the misconception that withdrawal syndrome is unrelated to dependence. A withdrawal state or syndrome is one of the six criteria of which at least three must be met for a positive diagnosis of dependence syndrome to be made. In other words, when withdrawal syndrome exists, one-third of the requirement for a positive diagnosis of dependence syndrome is met. Therefore, the notion that withdrawal is unrelated to dependence is inconsistent with the ICD-10 diagnostic guidelines.

SSRIs are an example of how a conceptual confusion over terminology can affect proper reporting, interpretation and communication of adverse drug reactions related to dependence. To avoid the association with dependence, an increasing number of researchers have used a different term, discontinuation syndrome, instead of withdrawal syndrome. The number of hits for discontinuation syndrome in searches of the international medical literature began to increase, relative to the occurrence of withdrawal syndrome, in 1997 after a symposium on antidepressant discontinuation syndrome held in 1996. In fact, dependence syndrome has been reported to the Uppsala Monitoring Centre for all SSRIs through the same postmarketing surveillance systems, although there are significantly fewer reports of dependence syndrome than of withdrawal syndrome. Also, the proportion of reports of drug dependence in relation to the number of reports of withdrawal syndrome varies considerably between individual SSRIs from 26% for fluoxetine to only 1% for venlafaxine (according to the global adverse drug reaction database of the Uppsala Monitoring Centre as of June 2002) (see Table below).

Drug name

Withdrawal syndrome reports (ws)

Drug dependence reports (dd)

Ratio (%)dd/ws

Fluoxetine

419

109

26.0

Sertraline

631

69

10.9

Mirtazapine

17

1

5.9

Fluvoxamine

69

4

5.8

Nefazodone

83

4

4.8

Paroxetine

2380

91

3.8

Citalopram

107

3

2.8

Venlafaxine

1185

13

1.1

Three SSRIs are among the 30 highest-ranking drugs in the list of drugs for which drug dependence has ever been reported to the Uppsala Monitoring Centre database; a total of 269 reports had been received as of June 2002 (109 reports for fluoxetine, 91 for paroxetine and 69 for sertraline).

References

1. WHO Expert Committee on Addiction-Producing Drugs. Thirteenth report. Geneva, World Health Organization, 1964 (WHO Technical Report Series, No. 273).

2. The ICD-10 Classification of Mental and Behavioural Disorders. Clinical descriptions and diagnostic guidelines. Geneva, World Health Organization, 1992.

3. WHO Expert Committee on Drug Dependence. Twenty-eighth report. Geneva, World Health Organization, 1993 (WHO Technical Report Series, No. 836).

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