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Drug withdrawal is a physiologic response to an effectively lowered drug concentration in a patient tolerant to the drug in question. Withdrawal results in a predictable constellation of symptoms that are reversible if the drug is reintroduced. Withdrawal is a phenomenon of altered neurochemistry, and the central nervous system (CNS) is the most consequential target. Under normal conditions, the CNS maintains a balance between excitation and inhibition. Although such balance can be achieved by several means, excitation is constant and actions occur through removal of inhibitory tone.1

Clinicians may encounter withdrawal symptoms as the primary reason for hospitalization or as a consequence of hospitalization when interruption of drug use occurs, either intentionally or unintentionally.

Withdrawal syndromes are well known to occur in hospitalized patients, particularly those admitted in intensive care units (ICUs). Up to 20% of pediatric ICU patients who receive sedative infusions of opioids or benzodiazepines experience withdrawal symptoms.2 A case series examining pediatric ICU patients who received infusions of both fentanyl and midazolam noted that 50% exhibited withdrawal symptoms. In a representative study of children in critical care units who receive fentanyl sedation,3 it was recognized that avoidance of oversedation and appropriate medication tapering may reduce the incidence of drug withdrawal in hospitalized children.4,5

In recent decades, overuse and abuse of prescription opioids have been epidemic in North America, Europe, and Australia. Opioid withdrawal has become a recognized issue associated with prescription opioid abuse.6

This chapter focuses on syndromes associated with withdrawal from the following classes of agents: ethanol, sedative-hypnotics such as benzodiazepines and barbiturates and gamma hydroxybutyrate (GHB), opioids, and selective serotonin reuptake inhibitors (SSRIs).


The onset, progression, duration, and severity of withdrawal symptoms depend on the patient’s degree of tolerance and the half-life of the drug involved. In general, drugs with shorter half-lives produce withdrawal symptoms sooner after discontinuation, and the symptoms tend to be more severe (Table 170-1).

TABLE 170-1Expected Onset and Duration of Withdrawal Symptoms by Agent in Children


Ethanol withdrawal is one of the most common withdrawal syndromes in the general population, behind those of nicotine and caffeine, but is extraordinarily rare in children. Pediatric alcohol withdrawal only rarely occurs in neonates born to alcohol abusing mothers. The neonatal alcohol withdrawal syndrome is multifaceted and should be considered a spectrum. The ...

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