The timing and Severity of the withdrawal syndrome will differ depending on the specific substance and its pharmacokinetics and pharmacodynamics. For example, withdrawal from shorter-acting substances that are rapidly absorbed and that have no active metabo— lites (e.g., triazolam) can begin within hours after the substance is stopped; withdrawal from substances with long—acting metabolites (e.g., diazepam) may not begin for 1—2 days or longer. The withdrawal syndrome produced by substances in this class may be charac- terized by the development of a delirium that can be life-threatening. There may be evi- dence of tolerance and withdrawal in the absence of a diagnosis of a substance use for long periods of time at prescribed and therapeutic doses. However, ICD-10-CM codes only allow a diagnosis of sedative, hypnotic, or anxiolytic withdrawal in the presence of comorbid moderate to severe sedative, hypnotic, or anxiolytic use disorder.
The time course of the withdrawal syndrome is generally predicted by the half—life of the substance. Medications whose actions typically last about 10 hours or less (e.g., loraz- epam, oxazepam, temazepam) produce withdrawal symptoms within 6—8 hours of de- creasing blood levels that peak in intensity on the second day and improve markedly by the fourth or fifth day. For substances with longer half—lives (e.g., diazepam), symptoms may not develop for more than 1 week, peak in intensity during the second week, and de- crease markedly during the third or fourth week. There may be additional longer-term symptoms at a much lower level of intensity that persist for several months,
The longer the substance has been taken and the higher the dosages used, the more likely it is that there will be severe withdrawal. However, withdrawal has been reported with as little as 15 mg of diazepam (or its equivalent in other benzodiazepines) when taken daily for several months. Doses of approximately 40 mg of diazepam (or its equivalent) daily are more likely to produce clinically relevant withdrawal symptoms, and even higher doses (e.g., 100 mg of di- azepam) are more likely to be followed by withdrawal seizures or delirium. Sedative, hyp- notic, or anxiolytic withdrawal delirium is characterized by disturbances in consciousness and cognition, with visual, tactile, or auditory hallucinations. When present, sedative, hypnotic, or anxiolytic withdrawal delirium should be diagnosed instead of withdrawal.
The prevalence of sedative, hypnotic, or anxiolytic withdrawal is unclear.
Seizures and autonomic instability in the setting of a history of prolonged exposure to sed- ative, hypnotic, or anxiolytic medications suggest a high likelihood of sedative, hypnotic, or anxiolytic withdrawal.
Other medical disorders. The symptoms of sedative, hypnotic, or anxiolytic with- drawal may be mimicked by other medical conditions (e.g., hypoglycemia, diabetic keto- acidosis). If seizures are a feature of the sedative, hypnotic, or anxiolytic withdrawal, the differential diagnosis includes the various causes of seizures (e.g., infections, head injury, poisonings).
Essential tremor. Essential tremor, a disorder that frequently runs in families, may erroneously suggest the tremulousness associated with sedative, hypnotic, or anxiolytic withdrawal.
Alcohol withdrawal. Alcohol withdrawal produces a syndrome very similar to that of sedative, hypnotic, or anxiolytic withdrawal.