Ellen A. Ovson, M.D., F.A.S.A.M.Medical DirectorBradford Health Services, Madison, Alabama

“If the patient be in the prime of life and if from drinking he has trembling hands, it may be well to announce beforehand either delirium or convulsions”

Hippocrates circa 400 BC

BAC 20 mg% to 99 mg%Loss of muscular coordinationChanges in mood, personality, and behavior

BAC 100 mg% to 199 mg%Neurologic impairment

Prolonged reaction timeAtaxia IncoordinationMental impairment

BAC 200 mg% to 299 mg%Marked ataxiaNausea and vomiting

BAC 300 mg% to 399 mg%HypothermiaSevere dysarthriaAmnesiaStage I anesthesia

BAC 400 mg% to 799 mg%Alcoholic comaProgressive obtundationDecreased respirationDecreased blood pressureDecreased body temperatureUrinary incontinence or retentionReflexes markedly decreased or absent

BAC 600 mg% to 800 mg%Often fatalDeath may occur from loss of airway protective reflexes (obstruction from flaccid tongue)Pulmonary aspiration of gastric contentsProfound CNS depression

SupportivePrimary goals

Prevent respiratiory depressionProtect airway (prevent aspiration)

Survival is probable with respiratory and cardiovascular supportIV glucose and thiamine (alcohol impairs glucogenesis)

Emesis / gastric lavage not indicated (EtOH rapidly absorbed)Charcoal does not absorb alcoholEnhancement of elimination has no roleHemodialysis is effective, but rarely indicated since treatment is supportive onlyNo effective antagonist (flumazenil not effective)Agitation best managed non-pharmacologically

Rate of metabolism follows zero order kineticsIndependent of time and concentration of the drugElimination occurs at a rate of 15 to 20 mg/dl/hr

Begins 6 to 24 hrs after last drinkOnset sometimes before BAC reaches 0Early symptoms include anxiety, sleep disturbance, vivid dreams, anorexia, nausea, and headachePhysical signs include tachycardia, elevation of blood pressure, hyperactive reflexes, sweating, and hyperthermiaTremor of hands/or tongue, 6 to 8 cycles/sec (exaggeration of normal physiologic tremor on EMG)

Seizures may occur, typically within 48 hrsDelirium tremens may begin 48 to 72 hrs after last drink, preceded by symptoms of early withdrawal

Profound sympathetic hyperactivity (tachycardia, hypertension, fever, diaphoresis)Mortality rate 1% to 5%, increases with delayed diagnosis, inadequate treatment, and concurrent medical illness

Effect of alcohol exerted through GABASedation, muscle relaxation, increased seizure thresholdChronic alcohol exposure leads to adaptive suppression of GABA activityAbstinence produces sudden relative deficiency in GABA activity resulting in anxiety, increased psychomotor activity, and predisposition to seizures

Alcohol inhibits sensitivity to autonomic adrenergic systemsChronic alcohol uptake results in upregulationDiscontinuation of alcohol results in rebound overactivity of central and peripheral noradrenergic systemsIncreased sympathetic autonomic activity from the locus ceruleus contributes to tachycardia, hypertension, tremor, diaphoresis, and anxiety

In mild withdrawal, may experience perceptual distortions of visual, auditory, or tactile nature (too bright, too loud, pins and needles)Frank hallucinations may develop in severe withdrawal

Visual hallucinations are most common and frequently involve animalsAuditory hallucinations begin as unformed sounds (clicks or buzzing) and may progress to voices

Often friends and relatives, often accusatoryTactile hallucinations may involve bugs crawling on the skin

In milder cases of withdrawal, the patient’s sensorium is otherwise clear and the patient retains insight that the hallucinations are not realIn more severe withdrawal, this insight may be lost

Generalized major motor seizuresMay occur singly or in a burst of several seizures over a few hoursOnset is usually 8 to 24 hours after last drink and may occur before BAC zeroFewer than 3% progress to status epilepticus (but alcohol involved in 25% of status epilepticus)

Seizures peak 24 hours after last drink, corresponding with EEG abnormalities (increased amplitude, photomyoclonic response, and spontaneous paroxysmal activity)EEG changes transient

Risk of seizures appears to be genetically influencedIncreased risk in those with prior history of withdrawal seizuresIncreased risk in those undergoing concurrent sedative-hypnotic withdrawal

Kindling effect Increased risk of seizures as an individual undergoes repeated withdrawals

Delirium tremens generally appears 72 to 96 hours after last drink

Marked tachycardia, tremor, diaphoresis, fever

Global confusion; disorientation to place and time; may become absorbed in a separate psychic realityHallucinations frequent, may have no insight, and therefore may be very frightening

Marked psychomotor activity may developSevere agitation in some casesPersistent low level motor activity in others

Severe disruption in sleep-wake cycle is common; absence of clear sleep for days

Duration is variable, 2 to 3 days in most studiesMay last few hoursMay last several days (report of confusion lasting 50 days before clearing)

Amount of daily intake and duration of heavy drinking have not been correlated consistently to the risk of severe withdrawal

BAC >300 mg% on presentation at higher risk of DT’sWithdrawal seizure at presentation increases risk of DT’sOlder patients at higher risk of confusion and delirium, may not involve severe autonomic manifestations of classic DT’s

CIWA, and shortened version CIWA-Ar are most extensively studiedDocumented reliability, reproducibility, and validity<9 indicates mild withdrawal, 10 to 18 indicates moderate withdrawal, and >18 suggests severe withdrawalHigh scores are predictive of seizures and delirium

ASAM Clinical Practice Guidelines (1997) reviewed literature on pharmacologic management of withdrawal Evidence indicated that the cornerstone of pharmacologic management of withdrawal is the use of benzodiazepines

Pharmacologically cross tolerant with alcohol Produce the similar effect of enhancing GABA-induced sedationAdministration of benzodiazepines alleviates the acute deficiency of GABA activity that occurs with sudden cessation of alcohol

All are similarly efficatious in reducing signs and symptoms of withdrawal

Longer acting agents (diazepam and chlordiazepoxide) may be more effective in preventing seizuresLonger acting agents may provide a smoother withdrawal courseLonger acting agents may pose a risk for oversedation in the elderly and those with liver disease (shorter acting agents, lorazepam or oxazepam may be preferable).

Rapid acting agents (diazepam, lorazepam, and alprazolam) offer more prompt control of symptomsRapid acting agents demonstrate greater abuse potential

Not as extensively studiedSize of studies not adequate to draw conclusions regarding efficacy in reduction of seizures and deliriumBenzodiazepines offer greater margin of safety with lower risk of respiratory depression as well as overall lower risk of abuse

“Phenobarbital, a long acting barbiturate, still is used by some programs, as it is long-acting, has well-documented anticonvulsant activity, is inexpensive, and has low abuse potential.”

Fixed ScheduleMedication administered in fixed amounts at scheduled times for five to seven daysHowever, many patients can go through withdrawal with only minor symptoms and need little or no medication

Symptom-triggered therapyPatient is monitored with structured assessment scale and given medication only when symptoms cross a threshold of severityStudies demonstrate as effective as fixed-dose regimen, but significantly less medication used and significantly shorter duration of detoxFacilitates delivery of large amounts of medication to patients with rapidly escalating symptoms, thus reducing undertreatment with fixed-dose schedule

In certain patients, such as those with severe coronary artery disease, fixed-dose may be used to prevent development of even minor withdrawal symptomsIn patients with a history of alcohol withdrawal seizures, fixed-dose may be used since seizures usually occur early in the course of withdrawal

Any detox regimen should allow for individualization with a mechanism to provide for large amounts of medication rapidly if needed.

Benzodiazepines should be administered orally or intravenouslyLorazepam provides good intramuscular and sublingual absorption

Beta blockers and alpha adrenergic agonists are effective in ameliorating symptoms by reducing autonomic manifestations of withdrawalNo demonstrated efficacy in reducing seizures or deliriumDelirium is a rare side effect of beta blockersReduction in autonomic symptoms may mask progression of withdrawal and hinder reliability of withdrawal scales

Carbamazepine used in Europe for alcohol withdrawalEqual efficacy to benzos for patients with mild to moderate withdrawalWithout toxicity over 7 day course of tx, less psychiatric distress, faster return to work, no impairment of learning, no abuse potentialPrevents withdrawal seizure in animal studiesStudies of adequate size to demonstrate efficacy in preventing withdrawal seizures or delirium not yet available

Antipsychotics are less effective than benzodiazepines to prevent deliriumActually lead to increase rate of seizureWidely used for agitation in withdrawalShould never be used except in conjunction with benzodiazepines

Magnesium generally normal at onset of withdrawal, drops as withdrawal progresses, normalizes as symptoms subsideOnly one randomized trial of magnesium during alcohol withdrawal documentedNo difference in severity of withdrawal or rate of seizures, regardless of magnesium correction Oral magnesium supplementation is without riskRoutine magnesium administration no longer recommended

AlcoholNo controlled trials comparing ethyl alcohol to benzos or placeboIV administration requires very close monitoringNumerous adverse effectsUse is discouraged by addiction specialists

PhenytoinRecent studies failed to demonstrate efficacy of preventing recurrent withdrawal seizuresBenzos are extremely effective in preventing withdrawal seizures, and the addition of phenytoin does not lead to improved outcomesUse of phenytoin in withdrawal has been largely abandoned

ThiamineThiamine deficiency may lead to Wernicke’s disease and the Wernicke-Korsakoff syndrome

Acute onsetTriad:

Mental disturbanceGlobal confusion, apathetic state, memory impairment

Paralysis of ocular movementsSixth nerve palsy: weakness or paralysis of abduction, invariably bilateral, rarely symmetric

AtaxiaGait and stance

Neurologic emergency Treated with immediate administration of thiamine, 50 mg IV and 50 mg IMDelay in thiamine administration increases risk of permanent memory impairment

Administration of IV glucose may exhaust reserve of B vitamins resulting in acute precipitation of Wernicke’s diseaseIV solutions containing glucose should always be accompanied with administration of thiamine in the alcoholic patient

Ocular palsy responds to thiamine administration within hoursGait and cognition improve more slowly

As apathy, drowsiness, and confusion recede, a permanent defect in retentive memory and learning known as Korsakoff’s psychosis may persist

Patients with symptoms of Wernicke’s disease, those to receive IV glucose solution, and those at high risk of malnutrition should receive initial dose of thiamine parenterally

Not all seizures in alcoholics are due to withdrawalAlcoholics are at higher risk for seizures unrelated to withdrawalCareful history of temporal relationship of alcohol use to the seizure should be taken, diagnosis of withdrawal seizure should be assumed only is there is a clear history of marked reduction or cessation of drinking 24 to 48 hours preceding the seizure

All patients with first seizure should be admitted for observation and evaluation Neurologic exam and brain imaging as a minimum; EEG and lumbar puncture may be appropriatePrevious history of withdrawal seizures with clear history of withdrawal seizure may not require full evaluation

If seizure is generalizedIf no focal deficit on examIf no history of head traumaIf no suspicion of meningitis

Then, additional testing has a very low yield and may be safely omitted

Increased risk of seizures for 6 to 12 hours post seizureSecond seizure occurs in 1 of 4Parenteral rapidly acting benzodiazepine indicated, followed by oral detox regimenPhenytoin no more effective than placebo at preventing recurrent seizuresSince seizure increases risk for DT’s, admission for treatment with benzos is safe and reasonable approach

Older studies indicated mortality ~30%Current studies reflect ~1% mortalityAdequate sedation and meticulous medical care often necessitate ICU admit

Management of fluid / electrolytes in midst of marked autonomic hyperactivityOften delirium arises in medically ill patient in whom alcohol dependence was unrecognizedHigh index of suspicion for infection; may be masked by fever, tachycardia, and confusion

Cross tolerant sedative-hypnotics reduce mortality, but have not been shown to reverse the delirium or reduce its duration

Goal is to sedate to a point of light sleep, thus controlling agitation and preventing behavior risking harm to self or staff, and allowing staff to provide supportive medical careIV benzodiazepines provide rapid controlMassive doses (hundreds, even thousands mg of diazepam) may be required to control agitationRespiratory support must be available

Reports of continuous infusion of short-acting agents, but existing evidence suggests no more effective than bolus dosing of longer-acting agentsBenzodiazepines may be supplemented with neuroleptic to manage agitation, but neuroleptics must never be used alone due to effect on seizure threshold

Management of withdrawal is only the first- and at times most easily achieved- step toward the primary goal of treating the patient’s underlying addiction to alcoholDevelopment of a plan to engage the patient in treatment is a critical component of withdrawal

Medical detoxification first, if applicableGroup therapyIndividual therapyExperiential therapyTwelve Step facilitationLength of stay, regardless of level of care, correlates directly with rate of sobriety.Monitoring and accountability enhance that rate.

Sedative-hypnotic medications decrease excitement, exert a calming effect, and facilitate sleep.Among the most widely prescribed drugs in the U.S.Sedative-hypnotics stimulate the inhibitory neurotransmitters in the GABA receptors.Although all sedative-hypnotics are stimulating at low doses, their primary effect is to decrease CNS function.

Those associated with severe withdrawal states include: methaqualone, glutethimide, phenobarbital, and short-acting benzodiazepines such as alprazolam and triazolam.Those with less severe clinical withdrawal include: meprobamate, diazepam, chlordiazepoxide, and lorazepam.

Mild to Moderate toxicity: slurred speech, ataxia, and incoordinationIn older adults, there may be a paradoxical agitated confusion and even delirium.Severe toxicity: stupor and comaWith older non-BZD agents, toxicity may progress leading to respiratory arrest or cardiovascular collapse.Overdose on the older agents may be associated with a variety of agent-specific manifestations, such as the bullous lesions (barb blisters) with barbiturates.

With the older sedative-hypnotic agents, tolerance may develop to the therapeutic effects, but not their lethal effects; therefore, the therapeutic index decreases.Toxicity and overdose thus occur with only small increases over the individual’s regular intake.

On the other hand, benzodiazepines virtually never lead to death when ingested by themselves.A lethal dose has not been established for any of the benzodiazepines.The few reported deaths involved short-acting, high potency BZDs such as alprazolam and triazolam, or administration of BZDs IV.Inappropriate administration of chlordiazepoxide by the IM route can lead to erratic absorption, producing respiratory compromise.

Despite their safety, BZDs continue to be a major cause of overdose when ingested with other agents.Mixed overdoses – such as those in combination with alcohol, major tranquilizers, antidepressants, or opiates – can be fatal.

Assessment and maintenance of the airway and, when required, ventilatory support are the cornerstone in managing overdose.Many BZDs slow gut motility and some – such as phenobarbital, meprobamate, glutethimide, and ethchlorvinyl – can form concretions in the stomach. Therefore, gastric lavage is effective, provided that the patient has an active gag reflex or is mechanically ventilated.

Gastric lavage with 1.0 g/kg of activated charcoal, alongwith a dose of cathartic, should be given, followed by repeated doses of activated charcoal at 0.5-1.0 g/kg every 2-4 hours; alternatively, the charcoal may be administered by slow continuous nasogastric infusion.Some agents have extensive enterohepatic circulation and repeated doses of charcoal have been shown to speed their elimination.

Alkalinization of the urine may be helpful in eliminating phenobarbital, but forced diuresis has not been shown to be helpful with any of the agents.Flumazenil is a competitive antagonist with very weak agonist properties at the BZD receptor; thus it can reverse the effects of BZDs, but not alcohol or other sedative-hypnotic agents.

Flumazenil’s primary indication is the reversal of short-acting BZDs, such as midazolam, after medical procedures.It may also be used when BZDs have been ingested alone in overdose.

Flumazenil is administered by slow IV titration, not exceeding 1 mg, with monitoring for the recurrence of sedation.Flumazenil is very short-acting; therefore signs of sedation may return in 50-60 minutes.

The use of flumazenil has been associated with seizures and cardiac arrhythmias, especially when it is administered rapidly in large amounts and in patients who have ingested a sedative-hypnotic in combination with a substance capable of causing seizures (i.e., tricyclics).

Patients who are physiologically dependent on BZDs are at high risk of seizures when given flumazenil. Thus, flumazenil is not part of the standard “coma cocktail” (thiamine, glucose, and naloxone) because it causes rapid BZD withdrawal.

Sedative-hypnotic withdrawal can occur with both high- and low-dose use.The withdrawal syndrome resembles that of acute alcohol withdrawal syndrome in many ways due to both binding to the GABA receptor.The withdrawal syndrome is most likely to occur following discontinuation of a low dose of at least 4-6 months or a high dose for 2-3 months.Time course and severity of withdrawal of determined by (1) dose, (2) duration of use, and (3) duration of drug action.

Vital SignsTachcardiaHypertensionFeverCentral Nervous SystemAgitationAnxietyDeliriumHallucinationsInsomniaIrritabilityNightmaresSensory disturbancesTremor

EarsTinnitusGastrointestinalAnorexiaDiarrheaNauseaHigh-Dose (Severe) WithdrawalSeizuresDeliriumDeath

Withdrawal severity has been related to dose and duration of treatment.Latency to onset of withdrawal is related to the elimination half-life.Most frequents signs of W/D: anxiety, insomnia, restlessness, agitation, irritability, and muscle tensionLess frequent: nausea, diaphoresis, lethargy, aches and pains, coryza, hyperacusis, blurred vision, nightmares, depression, hyperreflexia, and ataxiaUncommon: psychosis, seizures, confusion, paranoid delusions, hallucinations, and persistent tinnitus

Four different etiologies of signs and symptoms of discontinuation: (1) symptom recurrence or relapse, (2) rebound, (3) pseudowithdrawal, and (4) true withdrawal.Symptom recurrence or relapse is characterized by recurrence of symptoms for which the BZD was prescribed and can occur over days or months after discontinuation.

Rebound is marked by the development of symptoms within hours to days of discontinuation that are qualitatively similar to the disorder for which the drug was precribed but more intense. Symptoms are of short duration and self-limited.

Pseudowithdrawal (over-interpretation of symptoms) may occur when expectations of withdrawal lead to the experiencing of abstinence symptoms.True withdrawal is marked by emergence of symptoms in an individual who is physically dependent on the drug. It can only be suppressed by reinstitution of the discontinued drug or another cross-tolerant sedative-hypnotic.

Considerable individual variation and variability exist among patients who discontinue BZDs.Any combination of sgs and sxs may be experienced with varying severity throughout the initial one to four weeks of abstinence.The clinical picture can consist primarily of subjective symptoms with few concurrently observable hyper-adrenergic signs or vital sign fluctuations.Discontinuation syndromes commonly occur in combination. For example, recurrence of anxiety and insomnia and the sgs and sxs of rebound and withdrawal overlap. Therefore, sorting out rebound from withdrawal is unnecessary (if not impossible!).

Prolonged withdrawal has been reported in a small proportion of patients following long-term BZD use.Sgs and sxs may persist for weeks to months following discontinuation and is characterized by its irregular and unpredictable course.Patients experience slowly abating, waxing and waning symptoms of insomnia, perceptual disturbances, tremor, sensory hypersensitivity, and anxiety.

BZD action in the CNS is mediated by the GABA-Benzodiazepine-Receptor Complex.GABA is the primary CNS inhibitory neurotransmitter.Activation of the GABA receptor induces the opening of a neuronal membrane-bound chloride channel, causing hyperpolarization.Chronic lorazepam use resulting in tolerance to the ataxia-inducing effects causes down-regulation (decreased receptor number, decreased GABA-receptor function, and diminished protein synthesis for GABA receptors).With abrupt discontinuation, GABA receptors are up- regulated with GABA-receptor complex function enhanced.

BZD pharmacokinetics determine the onset of discontinuation symptoms following chronic use, with the elimination half-life dictating the rate of decline of blood levels.Onset of action of W/D from short-acting BZDs (lorazepam, oxazepam, triazolam, alprazolam, and temazepam) occurs within 24 hours of cessation, with peak severity within 1 to 5 days.With long-acting BZDs (diazepam, chlordiazepoxide, and clonazepam), onset occurs within 5 days and withdrawal peaks at 1 to 9 days.

Duration of acute withdrawal can be as long as 7-21 days for short-acting and 10-28 days for long-acting BZDs.Withdrawal symptoms from short-acting BZDs are experienced as being more intense than those with long-acting drugs, and are of more rapid onset.Higher dose and longer duration place patients are greater risk for severe withdrawal.Beyond one year of continuous use, duration of use becomes a less important factor.Tolerance develops more rapidly to short-acting BZDs and withdrawal requires more aggressive medical attention.

Patients with chronic psychiatric disorders maintained on BZDs for more than 3-6 months will be physically dependent on the BZD.Numerous BZD discontinuation studies highlight the high (40-100%) prevalence of active concurrent psychiatric disorders.Most demonstrate a correlation between the patients’ degree of psychopathology and their withdrawal symptom severity and difficulty in discontinuing use.

Concurrent use/abuse of other substances complicates the clinical presentation in withdrawal.The percentage of alcoholics who regularly use BZDs ranges from 29-33%.Comorbid alcohol abuse and anxiety disorders occurs in 18-19%.Moderate alcohol use (>1 beer/day) is a more significant predictor of BZD withdrawal severity than half-life of the drug.Patients with high-dose BZD use who present for inpatient addiction treatment exhibit a high rate (70-96%) of concurrent dependence on other substances.

>20% of patients newly admitted to inpatient treatment reported using BZDs at least weekly; 73% of heroin users reported greater than weekly use; >15% of heroin users used BZDs daily. There is also a high rate of BZD use in methadone clinics. Studies of adult sons and daughters of alcoholics have shown increased propensity to develop dependence when exposed to alprazolam and diazepam. There also appears to be a linkage of paternal hx of alcoholism and severity of withdrawal from alprazolam.

BZD withdrawal should be avoided during acute medical and surgical conditions; continued BZD use rarely has a negative effect on the acute medical condition.Special consideration should be given to discontinuing BZDs in patients in whom the medical condition could be worsened by adrenergic and psychological stress factors.In general, patients with chronic medical conditions experience BZD withdrawal more severely than others.

The use of anxiolytics peaks between the ages of 50 and 65, with hypnotics most frequent in the oldest age range.Hepatic microsomal enzyme oxidase system (MEOs) efficiency decreases with age. Elderly patients’ elimination half-lives are two to five times slower than younger adults.Therefore, withdrawal in the elderly may be quite prolonged, especially with the long-acting BZDs.

Women are prescribed BZDs twice as often as men; hence, twice as many women as men are likely to become dependent.Female gender is also associated with increased withdrawal severity in patients undergoing tapered cessation of long-term, therapeutic BZD use. However, gender is not a factor in abrupt cessation.

Determine the reason the patient or referent is seeking evaluation of sedative-hypnotic use and/or discontinuation.Take a sedative-hypnotic history.Elicit a history of other alcohol or psychoactive drug use.Take a psychiatric history.Take a family history of substance use, psychiatric, and medical disorders.Take a current and past medical history.Take a psychosocial history.Perform a physical and mental status exam.Conduct a UDS.Complete an individualized assessment with differential diagnoses.Determine level of care for Detox and method.Obtain patient consent and initiate Detox.

BenzodiazepinesalprazolamchlordiazepoxideclonazepamclorazepatediazepamflurazepamlorazepamoxazepamtemazepamtriazolamBarbituratespentobarbitalsecobarbitalbutalbitalphenobarbitalNon-barbituratesPlacidylDoridenQuaaludeSoma

Dose Equivalent to 30 mg of Phenobarbital0.5-1251-27.51015210-151515

10010010030

500250300700

For dependent patients, there are two options for detoxification: tapering or substitution.Tapering is indicated for use in: (1) outpatient ambulatory setting, (2) patient with therapeutic-dose BZD dependence, (3) patients who are dependent only on BZDs, and (4) patients who can reliably present for regular clinical follow-up during and after detoxification.Tapering is done by decreasing the BZD dose on a weekly to every-other-week schedule. The rate should not exceed 5 mg diazepam (12.5 mg chlordiazepoxide or 15 mg phenobarb) or 10% of the starting dose per week, whichever is smaller. The first 50% of the taper is usually smoother, quicker, and less symptomatic. For the final 25-35%, the rate and dose should be cut in half.

Substitution and taper is indicated for those who are unable to tolerate the taper and those previously excluded from taper.Substitution is accomplished with a cross-tolerant long-acting BZD or Phenobarbital, with Phenobarbital having the advantage of less disinhibition and broad clinical efficacy.If hepatomegaly or elevated liver enzymes are a problem, then oxazepam may be substituted. Lorazepam could be used, but has higher abuse liability.

Calculate the equivalent dose of chlordiazepoxide, clonazepam, or phenobarbital using the Substitution Dose Conversion Table and divide into three to four daily doses.Provide prn doses of BZD until substituted drug reaches steady state.Gradually reduce the dose.

Sedative-hypnotic tolerance testing may be performed when the tolerance level is difficult to determine.Pentobarbital 200 mg is given PO q2 hours for up to 24-48 hours or until signs of intoxication appear; then total dose administered in divided by number of days to arrive at daily dose. Phenobarbital is then substituted with gradual taper.

Signs and symptoms of withdrawal are treated as needed with 30-60 mg phenobarbital every 1-4 hours.When the patient has received similar 24-hour phenobarbital doses for two consecutive days, the total is divided by 2 to arrive at the stabilizing dose.This dose is divided over the next 24 hours and then is tapered.

Carbamazepine has been studied as an adjunct to traditional detoxification. In one study, significantly more patients treated with carbamazepine were BZD-free at 5 weeks with less withdrawal severity reported.Sodium valproate also is effective in attenuating withdrawal.Propranol diminishes the severity of adrenergic symptoms, but should not be used alone.Clonidine is ineffective in treating BZD W/D.Buspirone is ineffective as well.Trazodone decreases anxiety in BZD-tapered patients.CBT has been shown to improve the rate of successful alprazolam discontinuation.

Prolonged BZD W/D is associated with sgs and sxs lasting weeks to months following discontinuation, probably as a result of long-term receptor site adaptation.Propranolol 10-20 mg qid is helpful in attenuating anxiety or tremors, as are sedating antidepressants for insomnia.

eovson@bradfordhealth.net