WHO Pharmaceuticals Newsletter 2003, No. 01
(2003; 12 pages) View the PDF document
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Open this folder and view contentsREGULATORY MATTERS
Open this folder and view contentsSAFETY OF MEDICINES
Open this folder and view contentsDRUGS OF CURRENT INTEREST
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View the documentDrugs of Abuse: Problems of Data Collection, Definitions and Liability Assessment
View the documentEVENTS & ANNOUNCEMENTS
 

Drugs of Abuse: Problems of Data Collection, Definitions and Liability Assessment

Tokuo Yoshida, Quality Assurance and Safety: Medicines, Essential Drugs and Medicines Policy, WHO

The 1969 WHO Expert Committee Report on Drug Dependence defines drug abuse as a ‘persistent or sporadic excessive drug use inconsistent with or unrelated to acceptable medical practice’. Drugs of abuse are controlled internationally by the United Nations. WHO, within this system, determines the abuse liability (likelihood of abuse) and therapeutic usefulness of psychoactive substances and proposes their addition to, removal from or transfer to appropriate lists of controlled substances. Since 1949, through its Expert Committee on Drug Dependence, WHO has reviewed more than 400 substances. WHO is also involved in the process of developing guidelines to improve the prescribing of controlled drugs, with the aim of preventing dependence and abuse.

Abuse liability assessment requires relevant data. Despite recent methodological advancement in laboratory studies, actual abuse is often hard to predict based only on laboratory test results in both animals and humans. Epidemiological data, however, are very scarce. Only a small number of countries with adequate resources have a data collection system in place for abused drugs, through information collected via drug abusers seeking treatment. Surveys for measuring drug abuse are expensive and not possible in countries with resource restraints. In these prevailing conditions of limited and scarce drug-abuse data, information from the WHO Collaborating Centre for International Drug Monitoring in Sweden has been of significant value. This centre, popularly known as the Uppsala Monitoring Centre (the UMC) maintains an adverse drug reactions database of therapeutic drugs from as many as 70 countries from around the world. WHO Adverse Drug Reaction Terms (WHO-ART) such as drug abuse, drug dependence, withdrawal syndrome etc make this facility sensitive enough to detect dependence liability in therapeutic use.

However, in spite of the obvious advantages, data interpretation and reporting of abuse related ADR data are not without complications. Confusion in terminology is rather common; the most frequent of confusions is about the relationship between withdrawal syndrome and drug dependence. The modern definition of drug dependence requires neither withdrawal nor tolerance, since an individual can become dependent on a drug without necessarily developing tolerance or demonstrating withdrawal symptoms upon discontinuation of the drug. However, excessive emphasis on this can lead to the opposite misconception that withdrawal is unrelated to dependence. When an individual has difficulty in managing the need for repeated doses of the drug to feel good or to avoid feeling bad, the person is considered "dependent" on the drug. Therefore, severe withdrawal can (but not always) lead to dependence.

The SSRIs (Selective Serotonin Reuptake Inhibitors) provide a useful case-study in understanding issues of dependence liability assessment for drugs acting on the central nervous system. It is stated that, although withdrawal reactions may occur on stopping therapy, the available pre-clinical and clinical evidence do not suggest that SSRIs cause dependence (EMEA/CPMP/2775/99). How-ever, such a conclusion may only be drawn after a careful review of the significant number of ‘drug dependence’ reports for SSRIs received by the ADR monitoring system and, not on the basis of the terminology discussion that withdrawal reactions by themselves are insufficient to imply dependence.

The use of a different term discontinuation syndrome to replace the conventional expression withdrawal syndrome is adding more confusion to this debate. However, whether the reactions are called discontinuation syndrome or withdrawal syndrome, the terminology would have no influence on the person's need for repeated doses of the drug. Rather, it is the severity of the reactions to drug discontinuation that will determine the need for repeating the doses of the drug to avoid feeling bad. This example indicates the need for continued efforts to clarify the meaning of key terms used in pharmacovigilance.

 

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