sign in sign up
<<
Home , Alcohol detoxification, Ataxia, Magnesium

Treatment of Withdrawal

Hugh Myrick, M.D., and Raymond F. Anton, M.D.

Appropriate treatment of alcohol withdrawal (AW) can relieve the patient’s discomfort, prevent the development of more serious symptoms, and forestall cumulative effects that might worsen future withdrawals. Hospital admission provides the safest setting for the treatment of AW, although many patients with mild to moderate symptoms can be treated successfully on an outpatient basis. Severe AW requires pharmacological intervention. Although a wide variety of medications have been used for this purpose, clinicians disagree on the optimum medications and prescribing schedules. The treatment of specific withdrawal complications such as and seizures presents special problems and requires further research. KEY WORDS: AOD withdrawal syndrome; treatment method; inpatient care; outpatient care; symptom; disease severity; alcohol withdrawal agents; drug ; delirium tremens; AODR (alcohol and other drug related) seizure; patient assessment; cormorbidity; treatment cost; ; adrenergic receptors; special populations; literature review

ymptoms of alcohol withdrawal Clinical Features of Delirium tremens (DT’s), the most (AW) may range in severity from Alcohol Withdrawal intense and serious syndrome associated Smild to massive convulsions with AW, is characterized by severe (e.g., withdrawal seizures). Mild AW The symptoms of AW reflect overac- agitation; ; disorientation; per- can cause pain and suffering; severe tivity of the autonomic , sistent hallucinations; and large AW can be life-threatening. The goals a division of the nervous system that increases in heart rate, breathing rate, of AW treatment are to relieve the helps manage the body’s response to pulse, and blood pressure. DT’s occur patient’s discomfort, prevent the occur- stress. The of in approximately 5 percent of patients rence of more serious symptoms, and AW typically appear between 6 and undergoing withdrawal and usually forestall cumulative effects that might 48 hours after heavy alcohol con- appear 2 to 4 days after the patient’s worsen future withdrawals. Withdrawal sumption decreases. Initial symptoms last use of alcohol. treatment also provides an opportu- may include headache, tremor, sweat- nity to engage patients in long-term ing, agitation, anxiety and irritability, treatment. and , heightened HUGH MYRICK, M.D., is an assistant This article explores the manage- sensitivity to light and sound, disori- professor of and RAYMOND F. ment of AW and co-occurring con- entation, difficulty concentrating, ANTON, M.D., is a professor of psychia- ditions, evaluates different treatment and, in more serious cases, transient try at the Medical University of South settings and medications, and addresses hallucinations. These initial symptoms Carolina, Department of Psychiatry, considerations in treating special of AW intensify and then diminish Center for Drug and Alcohol Programs, populations. over 24 to 48 hours. Charleston, South Carolina.

38 Alcohol Health & Research World Treatment of Alcohol Withdrawal

Seizures occur in up to 25 percent role in , disturb- source to prevent precipitation of of withdrawal episodes, usually beginning ances may to severe and even Wernicke syndrome by depletion of within the first 24 hours after cessation life-threatening metabolic abnormalities. reserves. of alcohol use. For more detail on the A causal relationship has been postu- signs and symptoms of AW, see the lated between low levels article by Trevisan et al., pp. 61–66. and the occurrence of seizures or delir- Treatment Settings for ium. Although such an association has not been verified, magnesium suppl- Supportive Care for ments may help improve general with- Patients with AW can be treated safely Alcohol Withdrawal drawal symptoms. and effectively either within a hospital Some alcoholics exhibit or clinic (i.e., inpatient treatment) or Certain medical disorders that com- deficiencies, presumably because of on an ambulatory basis (i.e., outpatient monly co-occur with alcoholism can poor dietary habits as as from treatment). Although studies have exacerbate symptoms of AW or com- alcohol-induced changes in the digestive compared the effectiveness of outpa- plicate its treatment. The purpose of tract that impair the absorption of tient versus inpatient detoxification, supportive care is to treat such disorders into the bloodstream. Two no specific criteria have been rigor- and to remedy nutritional deficiencies. dietary factors of particular importance ously tested. Patients with AW should be subject to in AW are folic acid and thiamine. a , with particular Folic acid plays a role in the synthesis emphasis on detecting conditions such of the cell’s genetic material and mat- Outpatient Treatment as irregular heartbeat (i.e., ), uration of certain blood cells. Folic acid Before the 1980’s, AW was generally inadequate heart function (i.e., con- deficiency can lead to changes in blood treated in an inpatient setting. Today, gestive heart failure), liver disease cells, including a form of anemia. Patients most detoxifications take place on an (e.g., ), pancreatic undergoing AW should be adminis- outpatient basis. In a review of pub- disease (i.e., alcoholic ), tered an oral formula lished studies, Abbott and colleagues infectious diseases (e.g., tuberculosis), containing folic acid for a few weeks. (1995) concluded that fewer than 20 bleeding within the digestive system, Thiamine plays an essential role in percent of patients undergoing AW and nervous system impairment. the body’s energy metabolism. Thiamine require admission to an inpatient unit. Vital signs (e.g., heartbeat and blood deficiency in alcoholics is a factor in In addition, more than 70 percent of the development of Wernicke syn- pressure) should be stabilized and participants undergoing outpatient disturbances of water and nutritional detoxification complete the program. balances corrected. In most studies, 50 percent of the The presence of water in the blood The symptoms patients continued in alcoholism treat- and within cells is essential for the ment after outpatient detoxification. performance of physiological processes of AW reflect Most importantly, this review found and to maintain both heart and overactivity of the no reports of serious medical compli- function. Some patients undergoing cations among AW outpatients except AW may require intravenous fluids to autonomic that one patient suffered a seizure correct severe dehydration resulting nervous system. after the start of detoxification. from vomiting, , sweating, No specific criteria exist for deciding and fever. Conversely, many AW patients which patients could benefit from may retain excess water in their blood outpatient detoxification. Practical and tissues. In these patients, intra- drome, a condition characterized by considerations suggest that candidates venous administration of liquid may for outpatient treatment should exhibit overload the heart’s ability to pump severe confusion, abnormal gait, and of certain eye muscles. In addi- only mild to moderate AW symptoms, blood, leading to heart failure. In most no medical conditions or severe psy- cases, water can be maintained tion, Wernicke syndrome can progress to an irreversible . All patients chiatric disorders that could complicate by oral administration of fluids. the withdrawal process, and no past Alcoholics are often deficient in being treated for AW should be given 100 milligrams (mg) of thiamine as history of AW seizures or DT’s. In , or “” (e.g., mag- soon as treatment begins and daily addition, candidates for outpatient nesium, , and ). during the withdrawal .1 Supplies detoxification should have a sober Because these substances play a major of thiamine stored in the body are significant other to serve as a reliable support person. Ambulatory AW 1 limited even in the absence of alco- A dose of 100 mg thiamine is equivalent to that patients should report to their treatment available in the highest potency nonprescription holism. Therefore, thiamine should vitamin B complex supplements. By contrast, always be administered before giving center daily so that the clinician can the daily requirement is approximately 1.5 mg. an alcoholic patient glucose as an energy reassess the patient’s symptoms, the

Vol. 22, No. 1, 1998 39 occurrence of medical complications, with mild withdrawal symptoms may Pharmacological and ongoing treatment effectiveness. benefit from supportive care alone. In Management the context of nonpharmacological Inpatient Treatment therapy, supportive care consists of Pharmacological treatment is most providing patients with a quiet envi- frequently employed in moderate to Inpatient detoxification provides the ronment, reduced , limited severe AW. Although more than 150 safest setting for the treatment of AW, interpersonal interaction, nutrition medications have been investigated because it ensures that patients will be and fluids, reassurance, and positive for the treatment of AW, clinicians carefully monitored and appropriately encouragement. disagree on the optimum medications supported. Compared with outpatient Supportive care does not prevent and prescribing schedules. The follow- facilities, inpatient clinics may provide hallucinations or seizures. In fact, ing review describes some medications better continuity of care for patients although more than two-thirds of a that have been recognized as potential who begin alcoholism treatment while of outpatients experiencing mild treatments for AW. in the hospital. In addition, inpatient AW successfully completed detoxifica- detoxification separates the patient tion using social support alone, 8 per- Benzodiazepines from alcohol-related social and envi- ronmental stimuli that might increase cent had to be referred to an emergency Benzodiazepines (BZ’s) are a class of the risk of relapse. room and 2.5 percent required inpa- medications widely prescribed Despite the lack of research-based tient admission (Whitfield et al. 1978). to treat anxiety, insomnia, and seizures. criteria, certain factors suggest that a However, Shaw and colleagues (1981) Especially in North America, BZ’s are patient should receive inpatient treat- found supportive care sufficient treat- considered by research studies and ment (see textbox). These factors ment for 75 percent of inpatients with consensus reports to be the medications include a history of significant AW no psychiatric or medical problems. of choice to treat AW (American Psy- symptoms, high levels of recent drink- Although these studies suggest that chiatric Association Task Force 1989; ing, a history of withdrawal seizures or a nonpharmacological approach to Institute of Medicine 1990; Anton and DT’s, and the co-occurrence of a serious treating AW may work for most patients, Becker 1995; Moskowitz et al. 1983). medical or psychiatric illness (Ballenger the data do not provide specific guid- Early controlled trials with BZ’s and Post 1978; Brown et al. 1988). ance on the selection of treatment types. emphasized multiple daily dosing In addition, supportive care may be according to a fixed schedule (Kaim et Cost Comparison more costly, because a greater amount al. 1969). For inpatients in severe AW, of nursing care may be required dur- a loading procedure has been recom- The choice of treatment setting for ing nonpharmacological AW treatment. mended (Sellers et al. 1983). In this alcohol detoxification has important Until controlled studies of adequate treatment strategy, 10 mg or more of cost implications. Hayashida and duration and numbers of patients are (Valium®) or another long- colleagues (1989) found outpatient studied, the role of pharmacological lasting BZ is administered every hour alcohol detoxification to be considerably treatment of patients with AW symp- until either the symptoms are suppressed less costly than inpatient treatment toms will continue to be debated. ($175 to $388 versus $3,319 to $3,665, The most disturbing and perhaps respectively). To some extent, the higher controversial issue regarding nonphar- Relative Indications cost of inpatient treatment reflects the macological treatment of AW is the for Inpatient Alcohol occurrence of more severe symptoms concern that failure to medicate may Detoxification of AW as well as more co-occurring lead to alcohol-induced toxicity to medical problems among hospitalized nerve cells (i.e., neurotoxicity), which • History of severe withdrawal patients compared with ambulatory symptoms patients. However, the safety, efficacy, may increase the patient’s susceptibil- and cost-effectiveness of outpatient ity to seizures following repeated • History of alcohol withdrawal detoxification suggest an important withdrawals (i.e., kindling) (for fur- seizures or delirium tremens role for this setting in the treatment ther discussion of kindling, see the • Multiple past detoxifications of mild to moderate AW. article by Becker, pp. 25–33) (Ball- enger and Post 1978). Therefore, • Concomitant medical or although some withdrawal episodes psychiatric illness Nonpharmacological may appear to be mild enough to • Recent high levels of alcohol Management be treated without medications, consumption this approach may have long-term • Lack of reliable support network While most clinicians agree that severe deleterious consequences for patients • Pregnancy AW requires pharmacological treatment, who experience future withdrawal studies suggest that some patients episodes.

40 Alcohol Health & Research World Treatment of Alcohol Withdrawal

or the patient becomes excessively that BZ’s are “suitable agents for alco- been shown to kindling in sedated. Often only 1 to 2 days of med- hol withdrawal.” All BZ’s appeared cells. Third, antiseizure medications ication are required under this regimen. equally effective in treating AW symp- do not appear to have abuse potential. Other studies have assessed the need toms. The Working Group also found Fourth, these medications have been for BZ administration based on the that the dose of medication should be used to treat mood and anxiety disor- severity of the patient’s symptoms. individually tailored to suit the symp- ders, which share some symptoms These assessments have employed a tom severity of each patient. The with AW, including depression, irri- standard AW scale called the Clinical authors recommended that patients tability, and anxiety. Fifth, antiseizure Institute of Withdrawal Assessment with moderate to severe AW symptoms medications are generally not as sedat- for Alcohol, revised (CIWA-Ar) (Saitz be treated pharmacologically. Pharma- ing as BZ’s and therefore allow the et al. 1994). Such studies have found cological treatment should also be patient to engage more quickly in that when the overall dose of BZ’s is administered to patients with a history alcoholism treatment programs. reduced, patients suffer less unwanted of withdrawal seizures or in those with In Europe, the antiseizure medica- sedation and are therefore able to partic- comorbid medical illnesses. tions (Tegretol®) and ipate more readily in other treatment valproic acid (Depakene® and others) activities. Clearly, the CIWA-Ar is a use- Adrenergic Medications have been used successfully to treat ful instrument for quantifying AW as well AW for many years. However, these as for guiding the need for medication. Adrenergic receptors are specialized medications have rarely been used in No single BZ appears to be supe- proteins on the surface of certain rior to other BZ’s for treating AW nerve cells. These receptors play an clinical settings in North America for (Moskowitz et al. 1983). The selection important role in the regulation of the the treatment of AW. This fact is attri- of a specific BZ for a specific patient autonomic nervous system and may butable in part to the reluctance of has primarily been made on the basis therefore be expected to influence the clinicians to abandon the safe and of clinical factors such as the patient’s occurrence and severity of some with- familiar BZ’s and because most rele- age; occurrence of prior seizures; and drawal symptoms. Studies show that vant research on the aforementioned the functional state of the liver, the medications that alter the function of medications has been conducted and primary site for the metabolism of BZ’s. adrenergic receptors significantly published outside the In patients with impaired liver func- improve symptoms of AW, especially (Malcolm et al. 1989). tion, longer lasting BZ’s may cause by reducing elevated pulse and blood problems, ranging from oversedation pressure (Saitz and O’Malley 1997). to incoordination (i.e., ) and No evidence indicates, however, that Treatment of Complicated confusion. Many alcoholics have liver these medications block delirium or Withdrawal damage and therefore require medica- seizures. Most reviewers have concluded tions that are rapidly metabolized. that adrenergic medications are of Recent clinical reviews have stressed value largely as adjuncts to BZ’s in the Delirium Tremens the value of short-acting BZ’s, such management of AW. These medications Because DT’s are more likely to occur as (Serax®) and also may be useful in outpatient settings, ® in patients who have co-occurring (Ativan ) (Gallant 1989). Lorazepam where the abuse liability of BZ’s by medical illnesses, the recognition and is readily metabolized and is shorter patients is difficult to monitor or prevent aggressive treatment of such illnesses acting than diazepam. O’Brien and and where AW symptoms are generally is paramount. The required treatment colleagues (1983) compared lorazepam less severe than among inpatient pop- and diazepam in patients with moderate ulations (Anton and Becker 1995). includes maintaining water and elec- AW and found both medications to trolyte balance, correcting metabolic disturbances, and administering med- be equally effective in alleviating AW Antiseizure Medications symptoms, although excessively low ication as appropriate. blood pressure occurred more commonly Although in most treatment settings The optimum pharmacological in the diazepam-treated patients. BZ’s are the drugs of choice for uncom- therapy for the treatment of DT’s is Recently, new practice guidelines plicated AW, nonsedating antiseizure somewhat controversial. Some clini- were developed by the American Society medications may represent desirable cians have used BZ’s to decrease of Medicine Working Group alternatives. There are several potential autonomic hyperactivity, the risk of on Pharmacological Management of advantages to using antiseizure medi- AW seizures, and agitation. Despite Alcohol Withdrawal (Mayo-Smith cations. First, seizures are one of the these beneficial effects, BZ’s may 1997). The Working Group reviewed most serious complications of AW, contribute to the aggressive and impul- data presented in 134 articles on the and the use of an antiseizure medica- sive behavior and confusion that are treatment of AW published between tion should decrease the probability elements of DT’s. In addition, with- 1966 and 1995. Based on the review of a patient experiencing a seizure. drawal delirium may develop and of data, the investigators concluded Second, antiseizure medications have persist despite administration of high

Vol. 22, No. 1, 1998 41 doses of BZ and adequate control of indicates that adolescents with AW include causing less sedation, exhibiting minor AW symptoms (Hersh et al. 1997). require specialized treatment. For the less interaction with alcohol if both Antipsychotic medications, such as elder population, cumulative years of are used concomitantly, and producing (Haldol®), have been used drinking may lead to more severe antianxiety activity without abuse in low doses to treat DT’s. These agents withdrawal symptoms (Anton and liability. Additional information is lack the excessive sedation and low Becker 1995); the shorter acting BZ’s needed concerning the use of clinical blood pressure effects of BZ’s while may be preferable in treating this scales to quantitate drug effects in providing behavioral control. However, population, given the increased suscep- AW and clearer specifications on the antipsychotic medications can cause tibility to oversedation in the elderly. utility of supportive care in the treat- adverse effects, such as increased sus- Although pregnancy does not appear ment of AW. Furthermore, considerable ceptibility to seizures, increased rest- to increase the occurrence of major research is necessary to further eluci- lessness and agitation, and abnormal withdrawal symptoms, such symptoms date the role of pharmacotherapy in the muscular movements. Clearly, more may be fatal to both the mother and treatment of patients who have experi- specific guidelines are needed in the the fetus. In addition, medications enced multiple withdrawal episodes. ■ pharmacological treatment of DT’s used to treat AW may have adverse (Saitz and O’Malley 1997). effects on the fetus (e.g., congenital malformation). To prevent such risks, References Alcohol Withdrawal Seizures treatment with BZ’s should be limited to the minimum amount needed to ABBOTT, J.A.; QUINN, D.; AND KNOX, L. Ambu- AW seizures not related to DT’s (i.e., prevent major complications of AW. latory medical detoxification for alcohol. American Journal of Drug and 21(4): 549–563, primary AW seizures) usually subside (For a discussion of the fetal effects of 1995. with only supportive treatment. withdrawal during pregnancy, see the However, because up to one-third article by Thomas and Riley, pp. 47–53.) American Psychiatric Association Task Force. Treatment of Psychiatric Disorders. Washington, of patients with untreated primary The treatment of AW in the medi- DC: American Psychiatric Association, 1989. p. 187. seizures subsequently develop DT’s, cally ill can present a considerable all primary seizures should be treated. challenge. These patients are at a ANTON, R.F., AND BECKER, H.C. and pathophysiology of alcohol withdrawal. In: Evidence suggests that for patients higher risk of developing major with- Kranzler, H.R. Handbook of Experimental Pharm- who do not have a history of AW drawal symptoms and may progress to acology: Volume 114. The Pharmacology of Alcohol seizures, administration of BZ’s should more severe forms of AW, such as DT’s. Abuse. New York: Springer-Verlag, 1995. be sufficient to prevent such seizures Concurrent medical conditions should pp. 315–367.

(Rothstein 1973). not only be aggressively treated, but BALLENGER, J.C., AND POST, R.M. Kindling as a Controversy surrounds the use of should also be anticipated in patients model for alcohol withdrawal syndromes. British the antiepileptic medication undergoing AW who have been admit- Journal of Psychiatry 133:1–14, 1978. ® (Dilantin ) in the treatment of AW ted to the hospital for medical or BROWN, M.E.; ANTON, R.F.; MALCOLM, R.; seizures. Phenytoin does not appear surgical treatment. AND BALLENGER, J.C. Alcohol detoxification and to prevent the occurrence of primary withdrawal seizures: Clinical support for a kindling AW seizures. However, phenytoin hypothesis. Biological Psychiatry 23:507–514, 1988. may be useful in combination with a Conclusions GALLANT, D.M. Improvements in treatment of BZ for preventing an initial seizure in alcohol withdrawal syndromes. Alcoholism: Clinical patients who have a history of one or The treatment of patients exhibiting and Experimental Research 13:721–722, 1989. more seizures in their adult life, irre- AW has been varied and at times HAYASHIDA, M.; ALTERMAN, A.I.; AND MCLELLAN, spective of whether any of them were controversial. Although clinicians gen- T. Comparative effectiveness and costs of inpa- AW seizures (Anton and Becker 1995). erally agree that severe AW requires tient and outpatient detoxification of patients More studies are needed in this area, pharmacological intervention, a wide with mild-to-moderate alcohol withdrawal syn- particularly focusing on the efficacy variety of medications have been used. drome. New England Journal of Medicine 320(6): 358–365, 1989. of BZ’s and antiseizure medications, Further uncertainty exists among the such as carbamazepine and valproic treatment community when considering HERSH, D.; KRANZLER, H.R.; AND MEYER, R.E. acid, in the treatment and prevention pharmacological treatment of mild to Persistent delirium following cessation of heavy alcohol consumption: Diagnostic and treatment of AW seizures. moderate AW, including the preferred implications. American Journal of Psychiatry treatment setting (i.e., inpatient versus 154(6):846–851, 1997. outpatient). While extensive research Institute of Medicine. Prevention and Treatment Special Population Issues has been aimed at tackling such issues, of Alcohol Problems. Washington, DC: National a consensus has not yet been reached. Academy Press, 1990. pp. 268–269. Research has not been conducted to Directions for future research include KAIM, S.C.; KLETT, C.J.; AND POTHFELD, B. determine specific AW strategies for the continued search for non-BZ Treatment of the acute alcohol withdrawal state: adolescent, geriatric, pregnant, or treatments for AW. Desirable charac- A comparison of four drugs. American Journal of medically ill populations. No evidence teristics of such alternatives would Psychiatry 125:1640–1646, 1969.

42 Alcohol Health & Research World Treatment of Alcohol Withdrawal

MALCOLM, R.; BALLENGER, J.C.; STURGIS, E.T.; abstinence syndrome. Current Therapeutic Research: SELLERS, E.M.; NARANJO, C.A.; HARRISON, M.; AND ANTON, R. Double-blind controlled trial Clinical and Experimental 34:825–831, 1983. DEVENYI, P.; ROACH, C.; AND SYKORA, K. Diaze- comparing carbamazepine to oxazepam treatment pam loading: Simplified treatment of alcohol ROTHSTEIN, L. Prevention of alcohol withdrawal of alcohol withdrawal. American Journal of Psychiatry withdrawal. Clinical Pharmacological Therapeutics 146:617–621, 1989. seizures: The roles of d-phenylhydantoin and 34:822–826, 1983. . American Journal of Psychiatry MAYO-SMITH, M.F. Pharmacological management 130:1381–1432, 1973. of alcohol withdrawal: A meta-analysis and evidence- SHAW, J.M.; KOLESAR, G.S.; SELLERS, E.M.; KAPLAN, H.L.; AND SANDORS, P. Development of optimal based practice guideline. Journal of the American SAITZ, R.; MAYO-SMITH, M.F.; ROBERTS, M.S.; Medical Association 278(2):144–151, 1997. REDMOND, H.A.; BERNARD, D.R.; AND CALKINS, treatment tactics for alcohol withdrawal: I. Assessment D.R. Individualized treatment for alcohol with- and effectiveness of supportive care. Journal of MOSKOWITZ, G.; CHALMERS, T.C.; SACKS, H.S.; Clinical Psychopharmacology 1:382–387, 1981. FAGERSTROM, R.M.; AND SMITH, H. Deficiences drawal: A randomized double-blind controlled trial. Journal of the American Medical Association of clinical trials of alcohol withdrawal. Alcoholism: WHITFIELD, C.L.; THOMPSON, G.; LAMB, A.; 272:519–523, 1994. Clinical and Experimental Research 7:42–46, 1983. SPENCER, V.; PFEIFER, M.; AND BROWNING- O’BRIEN, J.E.; MYER, R.E.; AND THOMAS, D.C. SAITZ, R., AND O’MALLEY, S.S. Pharmacotherapies FERRANDO, M. Detoxification of 1,024 alcoholic Double-blind comparison of lorazepam and of alcohol abuse: Withdrawal and treatment. Medical patients without psychoactive drugs. Journal of the diazepam in the treatment of the acute alcohol Clinics of North America 81(4):881–907, 1997. American Medical Association 239:1409–1410, 1978.

THE PHYSICIANS’ GUIDE TO HELPING PATIENTS WITH ALCOHOL PROBLEMS

This easy-to-follow manual provides primary care physicians and other health care professionals with guidelines on the use of screening and procedures for patients at risk for alcohol problems. The brief intervention procedures are designed for use in primary care settings during routine patient visits. Also available is the companion brochure for patients, “How to Cut Down on Your Drinking,” presenting tips for those whose doctors have advised them to reduce their alcohol consumption and are taking steps to follow that advice.

To order your free copies of the Physicians’ Guide and the patient brochure, write to: National Institute on Alcohol Abuse and Alcoholism, Publications Distribution Center, P.O. Box 10686, Rockville, MD 20849Ð0686. Fax: (202) 842Ð0418. Full text of both publications is available on NIAAA’s World Wide Web site at http://www.niaaa.nih.gov

Vol. 22, No. 1, 1998 43