The term 'dependence' has come to be used interchangeably with 'addiction' (to mean uncontrolled drug-seeking behaviour). 1 Inevitably this has led to some unfortunate confusion. 1 This choice of language was made in the Diagnostic and Statistical Manual of Mental Disorders 3rd revised edition (DSM-III-R) because the term 'addiction' was thought to be pejorative while the word 'dependence' was thought more neutral. 1 However, the original usage of 'physical dependence' (or physiological dependence) referred to 'physiological adaptation that occurs when medications acting on the central nervous system are ingested with rebound when the medication is abruptly discontinued'. 1 The FDA clarified the definition of this term in 2019: 'Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug'. 2 The FDA also made the distinction from addiction clear:
Physical dependence is not synonymous with addiction; a patient may be physically dependent on a drug without having an addiction to the drug. Tolerance, physical dependence, and withdrawal are all expected biological phenomena that are the consequences of chronic treatment with certain drugs. These phenomena by themselves do not indicate a state of addiction.
The National Institute on Drug Abuse (NIDA) statement on this issue is consistent with this interpretation:
Dependence means that when a person stops using a drug, their body goes through 'withdrawal': a group of physical and mental symptoms that can range from mild (if the drug is caffeine) to life-threatening … Many people who take a prescription medicine every day over a long period of time can become dependent; when they go off the drug, they need to do it gradually, to avoid withdrawal discomfort. But people who are dependent on a drug or medicine aren't necessarily addicted. 3
The Diagnostic and Statistical Manual of Mental Disorders, 5th revised edition (DSM-V) also identifies this issue: 4
'Dependence' has been easily confused with the term 'addiction' when, in fact, the tolerance and withdrawal that previously defined dependence are actually very normal responses to prescribed medications that affect the central nervous system and do not necessarily indicate the presence of an addiction.
With benzodiazepines, both physical dependence and addiction are possible. Misuse means taking a medication in a manner or dose other than prescribed: for example, taking the drug for a legitimate medical complaint for which the drug was not prescribed. 5, 6 Abuse means taking a medication to experience euphoria or for recreational purposes. 6 Addiction (synonymous with a substance use disorder) involves compulsive use of a drug, craving the drug, impaired control over drug-taking and use despite harm or negative consequences - an isolated episode of misuse or abuse is not sufficient to entail a diagnosis of addiction. 6 The majority of people who use benzodiazepines and z-drugs are taking them as prescribed by their clinician, without addiction or abuse. Only 2% have benzodiazepine use disorders (i.e. addiction), while 17.1% have misused benzodiazepines (once or more). 7 However many people taking the medication as prescribed will be physically dependent on the drug through the expected physiological process of adaptation. This means that when they stop the drug they will experience withdrawal.
A failure to appreciate this difference (which may seem merely semantic) can lead to real-life consequences. For example, people who have difficulty stopping their medications because of withdrawal effects can be accused of addiction or abuse. Requests for re-instatement to manage withdrawal effects can be characterised as 'drug seeking behaviour', and therefore refused. As the withdrawal syndrome from benzodiazepines can include seizures and occasionally be life-threatening, this response can have catastrophic consequences. Additionally, mis-diagnosis of physical dependence as addiction can lead to inappropriate management. This includes sending people to 12-step addiction-based detoxification and rehabilitation centres that focus on psychological aspects of compulsive use rather than physiological aspects of withdrawal, leading to unnecessary harms in the form of too rapid tapering regimens and consequent social and professional consequences (if people have addiction listed on their medical record).
The FDA in its 2020 boxed warning on benzodiazepine dependence and withdrawal took pains to highlight this issue: 'Physical dependence is the body's adaptation to repeated use of a drug, resulting in withdrawal reactions when the medicine is abruptly discontinued or the dose is significantly reduced. Dependence may lead some individuals to continue using the medicine to avoid symptoms of withdrawal.' 8 Moreover, the FDA's review of cases of severe withdrawal found that 'dependence and subsequent withdrawal symptoms developed even when the benzodiazepine was prescribed for therapeutic use'. 8
This chapter deals with patients who are using benzodiazepines and z-drugs as prescribed; those with addiction issues are beyond the scope of the current textbook. Such patients will need support for the behavioural aspects of addiction that are not relevant to people with physical dependence.