The review by Nielsen and colleagues [1] makes some interesting points about the distinction between dependence and withdrawal reactions by comparing existing data on benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). In comparing the discontinuation syndromes described for both drug categories found in a systematic review of the literature, the authors conclude that the symptoms described are very similar and that referring to these symptoms as part of a dependence syndrome in the case of the benzodiazepines but not in the case of the SSRIs ‘does not seem rational’.

The authors also compare and contrast the definitions of Dependence over several iterations of the DSM and ICD as well as the WHO definition. They make the point that there was an important change in the DSM criteria from DSM-III to DSM-IIIR. In the DSM-III, withdrawal and tolerance symptoms figured much more prominently and were essential to making a diagnosis of Dependence. In the DSM-IIIR and IV, Dependence was described as a cluster of behavioral, cognitive and physiologic symptoms which include drug-seeking and pre-occupation with taking the drug.

The authors take issue with ‘general lack of research and evidence-based approach in the development of DSM’ criteria. I agree that the DSM process is less than ideal. Furthermore, the use of the term Dependence in the DSM to characterize the full spectrum of behaviors and physiologic changes that we know as addiction has led to a great deal of confusion. In particular, there has been confusion between physical dependence, characterized by tolerance and withdrawal, and DSM Dependence which refers to a much more complex pathologic state. The addition of behavioral and cognitive symptoms to the DSM definition of Dependence in DSM-IIIR was essential to capture the full spectrum of addictive disorders which, by multiple definitions, are characterized by cognitive symptoms and behaviors that lead to functional disruption. Because of the unfortunate use of the term Dependence in DSM parlance, it was necessary to create another diagnostic category, Withdrawal Reaction, to describe those symptoms that occur with abrupt cessation after chronic use of psychoactive substances, including the SSRIs.

The authors mention the strong financial ties between DSM-IV panel members and the pharmaceutical industry and suggest that this may have influenced the fact that DSM-IV makes a distinction between Dependence and Withdrawal Reactions. In fact, this distinction was made because some psychoactive drugs can produce physical dependence as characterized by tolerance and withdrawal, but not produce DSM Dependence. It is more likely that they avoided the use of the term physical dependence in this nomenclature because of potential confusion with DSM Dependence rather than because of pharmaceutical industry influence. The distinction between drugs that produce physical dependence and those that are associated with the full spectrum of addiction is an important one. I think the use of Dependence to characterize this full spectrum of behavioral, cognitive and physiologic symptoms in DSM is an unfortunate choice which will continue to contribute to confusion in the important distinction between physical dependence and addiction.

However, I disagree with the main premise of the review. The fact that there are withdrawal symptoms associated with the abrupt discontinuation of SSRIs and many other antidepressants is undisputable. The fact that these symptoms are similar to those that occur with abrupt discontinuation of the use of benzodiazepines is also true. The discontinuation symptoms associated with benzodiazepines, opiates or any other drug that has both therapeutic use and abuse potential could be a withdrawal reaction or a symptom of Dependence. The most appropriate term is a matter of context, not of the characteristics or severity of symptoms. If discontinuation symptoms occur in the context of a behavioral syndrome in which the procurement and use of a drug dominate an individual's motivation and normal constraints on behavior seem largely ineffective, this is DSM Dependence. Inherent in this definition is the overwhelmingly powerful motivation to obtain and self-administer the drug—it is focused on both the antecedent behavior and the consequences of use. As such, if an individual takes benzodiazepines as prescribed by a physician for a long period of time and experiences physical and cognitive symptoms following abrupt continuation, this would most appropriately be called a withdrawal reaction.

The reason that the discontinuation syndrome associated with SSRIs is not called Dependence is that it is not characteristically associated with the other features of addiction such as loss of control over use, dose escalation and functional impairment. While the authors cite some internet discussions in which individuals use the term addiction in describing their difficulties with withdrawal symptoms from SSRIs, preclinical studies, well-controlled trials and the surveillance techniques that are used to detect drug diversion all converge to support the fact that SSRIs and other antidepressants do not have abuse potential. For this reason, there is a good rationale to support the use of the term ‘Withdrawal Reaction’ in discussions about the discontinuation syndrome associated with cessation of SSRI use.


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