Course and Natural History - Disorders of Sedative–Hypnotics

Course and Natural History

Once a diagnosis of sedative–hypnotic dependence is manifested it is unlikely that a patient will be able to return to controlled, therapeutic use of sedative–hypnotics. All sedative–hypnotics, including alcohol, are cross-tolerant, and physical dependenceand tolerance are quickly re-established if a patient resumes use of sedative–hypnotics.

If after sedative–hypnotic withdrawal the patient has an-other primarily psychiatric disorder, such as generalized anxiety disorder (GAD), panic attacks, or insomnia, alternate treatment strategies other than sedative–hypnotics should be used if pos-sible. Definitive diagnosis of a psychiatric disorder during early abstinence is often not possible because protracted withdrawal symptoms may mimic anxiety disorders, and disruption of sleep architecture for days to months after drug withdrawal is ex-tremely common.

If the sedative–hypnotic dependence has developed sec-ondary to stimulant or alcohol use, primary treatment of the chemical dependence should be a priority. Often the symptom that was driving the sedative–hypnotic use disappears after the patient is drug abstinent.

Detoxification

Three general strategies are used for withdrawing patients from sedative–hypnotics, including benzodiazepines. The first is to use decreasing doses of the agent of dependence. The second is to substitute phenobarbital or some other long-acting barbiturate for the addicting agent, and gradually withdraw the substitute medication. The third, used for patients with a dependence on both alcohol and a benzodiazepine, is to substitute a long-acting benzodiazepine, such as chlordiazepoxide, and taper it during 1 to 2 weeks.

The pharmacological rationale for phenobarbital substitu-tion is that phenobarbital is long-acting and little change in blood levels of phenobarbital occurs between doses. This allows the safe use of a progressively smaller daily dose. Phenobarbital is safer than the shorter-acting barbiturates; lethal doses of pheno-barbital are many times higher than toxic doses, and the signs of toxicity (e.g., sustained nystagmus, slurred speech and ataxia) are easy to observe. Finally, phenobarbital intoxication usually does not produce euphoria or behavioral disinhibition, so most patients view it as a medication, not as a drug of abuse.

The withdrawal strategy selected depends on the particular benzodiazepine, the involvement of other drugs of dependence, and the clinical setting in which the detoxification program takes place. The gradual reduction of the benzodiazepine of depend-ence is used primarily in medical settings for dependence arising from treatment of an underlying condition. The patient must be cooperative, must be able to adhere to dosing regimens, and must not be abusing alcohol or other drugs.

Substitution of phenobarbital can also be used to withdraw patients who have lost control of their benzodiazepine use or who are polydrug-dependent. Phenobarbital substitution has the broadest use for all sedative–hypnotic drug dependencies and is widely used in drug treatment programs.

Stabilization Phase

The patient’s history of drug use during the month before treat-ment is used to compute the stabilization dose of phenobarbital. Although many addicts exaggerate the number of pills they are taking, the patient’s history is the best guide to initiating phar-macotherapy for withdrawal. Patients who have overstated the amount of drug that they have taken will become intoxicated during the first day or two of treatment. Intoxication is easily managed by omitting one or more doses of phenobarbital and re-ducing the daily dose.

To compute the initial daily starting dose of phenobarbi-tal, the patient’s average daily use of each sedative–hypnotic is estimated. Next, the patient’s average daily sedative–hypnotic dose for each drug is converted to its phenobarbital withdrawal equivalent by multiplying the average daily dose by the drug’s phenobarbital conversion constant shown in either Table 44.2 or 44.3. Finally, the phenobarbital withdrawal equivalences for each drug are added together. In any case, the maximum daily pheno-barbital dose is limited to 500 mg/day. The total daily amount of phenobarbital is divided into three doses per day.

Before receiving each dose of phenobarbital, the patient is checked for signs of phenobarbital toxicity: sustained nystag-mus, slurred speech, or ataxia. Of these, sustained nystagmus is

the most reliable. If nystagmus is present, the scheduled dose of phenobarbital is withheld. If all three signs are present the next two doses of phenobarbital are withheld, and the daily dosage of phenobarbital for the next day is halved.

If the patient is in acute withdrawal and has had, or is in danger of having withdrawal seizures, the initial dose of pheno-barbital is administered by intramuscular injection. If nystagmus and other signs of intoxication develop after 1 to 2 hours after the intramuscular dose, the patient is in no immediate danger from barbiturate withdrawal. Patients are maintained with the initial dosing schedule of phenobarbital for 2 days. If the patient has nei-ther signs of withdrawal nor phenobarbital toxicity (slurred speech, nystagmus, unsteady gait) phenobarbital withdrawal is begun.

Withdrawal Phase

Unless the patient develops signs and symptoms of phenobarbi-tal toxicity or sedative–hypnotic withdrawal, phenobarbital is decreased by 30 mg/day. Should signs of phenobarbital toxicity develop during withdrawal, the daily phenobarbital dose is de-creased by 50% and the 30 mg/day withdrawal is continued from the reduced phenobarbital dose. Should the patient have objec-tive signs of sedative–hypnotic withdrawal, the daily dose is in-creased by 50% and the patient is restabilized before continuing the withdrawal.