Withdrawal symptoms concepts

The APA defines substance dependence (addiction) as a cluster of symptoms indicating that the individual continues use of the substance despite significant substance-related problems. Evidence of tolerance and withdrawal symptoms are included in the list of symptoms, but neither tolerance nor withdrawal is necessary or sufficient for a diagnosis of substance dependence. Dependence (addiction) requires three or more of the symptoms, whereas abuse can be diagnosed when only one or two symj)-toms are present. The chronic, relapsing nature of dependence (addiction) fulfills criteria for a chronic disease, but because of the voluntary component at initiation, the disease concept is controversial. 

Attention has been drawrn previously to reports of withdrawal symptoms when certain benzodiazepine compounds were stopped (39 ). The question of whether benzodiazepine dependence occurs has remained unsettled. Difficulty has arisen because concepts of addiction have traditionally related to the clinical picture associated with withdrawal of narcotic compounds this is the problem of definition. The consideration of benzodiazepine dependence is particularly hampered because possible withdraw symptoms closely resemble the clinical features of anxiety for which the compoimd was given, leading to confusion between a withdrawal syndrome and a relapse of anxiety (41 ). This may well have led to an overacceptance of benzodiazepines as safe from dependency problems recognized in other minor tranquillizers. 

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

Others have proposed that the symptoms result from cellular water intoxication, itself a result of hyponatremia. The salutary but transient effect of mannitol administration is invoked in support of that concept. Hypertonic mannitol withdraws water from the intracellular space into the extracellular space, thereby at least temporarily restoring the sodium balance in the... 

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