Behaviors, Vol. 11, pp. 135-140, Printed in the USA. All rights reserved.
Copyright 0 1986 Pergamon Journals Ltd
LITHIUM COMPLIANCE IN ALCOHOLIC MALES: A SIX MONTH FOLLOWUP STUDY BARBARA J. POWELL,? ELIZABETH C. PENICK,* BARRY I. LISKOW,? AUDREY S. RICE,* and WILLIAM McKNELLYt t Veterans Administration Medical Center, Kansas City, Missouri and *Kansas University Medical Center, Kansas City, Kansas Abstract-One hundred alcoholic patients were followed at monthly outpatient clinics for 6 months. Half were assigned low to moderate doses of lithium carbonate and half to chlordiazepoxide (10 mg tid) (active placebo). Drinking behavior and medication compliance were monitored at monthly clinics. After 6 months 52% of the lithium and 44% of the chlordiazepoxide patients were medication compliant. Of the 48% remaining in the lithium group, 14% did not return for a single visit while 14% came only once. Twenty percent came to clinic regularly; however they had never taken the medication as assigned. Of the 56% noncompliant chlordiazepoxide patients, 16% did not attend a single clinic; 24% came only once or twice and the remaining 16% attended clinics regularly although they were never medication-compliant. Drinking days and the percentage of patients reporting abstinence for one or more months were determined for medication compliant patients and for patients who attended clinic regularly but who did not take medication. Data were analyzed by KruskalWallis one way analysis of variance tests. While lithium and chlordiazepoxide compliant patients tended to report fewer mean drinking days per month (4.6 and 4.8 respectively) than the non-medication group (6.9) these differences were not significant; however, compared to 44% in the non-medication group, 60% of the lithium patients and 58% of the chlordiazepoxide patients reported having significantly more months of abstinence (p < .05). These results do not show that lithium is differentially efficacious in reducing alcohol consumption.
In recent years, investigators have reviewed the use of lithium carbonate in reducing alcohol consumption (Kline & Cooper, 1979; McMillan, 1981). Uncontrolled clinical reports attest to the efficacy of lithium treatment with alcoholics (Fries, 1969; Flemenbaum, 1974; Young & Keeler, 1977; Reilly, 1978), however only a few controlled studies have confirmed the prophylactic treatment of alcoholism using lithium (Kline, Wren, Cooper, Varga, & Canal, 1974; Merry, Reynolds, Bailey & Coppen, 1976; Peck, Pond, Becker & Lee, 1981). A major problem in assessing the effectiveness of any drug in the treatment of alcoholism is that of compliance. Moreover, it is well documented that treatment dropouts and noncompliance are characteristically high in alcoholic populations (Sellers, Cappell & Marshman, 1979). In reviewing studies of lithium’s effectiveness with alcoholics, it has been noted that even in the controlled studies the reported differences between lithium and placebo disappear when treatment dropouts are included in the analyses (Sellers, Naranjo & Peachey, 1981). The present report which is taken from a larger study’ reports on the medication compliance of alcoholics selected by pre-screening measures and the presence or absence of another co-existing psychiatric disorder. Patients were assigned to either lithium carbonate or chlordiazepoxide and were followed as outpatients monthly for 6 months. This work was supported by the Veterans Administration Medical Research Service. Requests for reprints should be addressed to: Barbara J. Powell, Ph.D., Veterans Administration Medical Center (151), 4801 Linwood Boulevard, Kansas City, Missouri 64128. ‘Powell, B.J. Efficacy of lithium in the treatment of alcoholic subgroups. Merit Review Study funded by the Medical Research Service, Veterans Administration, 1977-1981. 135
Subjects The patients were 100 alcoholic males drawn from the medical, psychiatric and alcohol treatment units at the Kansas City VAMC. Their mean age was 41.4 years (SD 10.81; range 21-60). Seventy-seven percent were Caucasian; 23% Black; 3 % had less than 8 years of education; 63% had finished high school and 34% reported 13 or more years of education. The socio-economic status of the majority (82%) was lower middle to lower class. Thirty percent were married, 58 percent were divorced, separated or widowed, and 12% were never married. Sixty-eight percent were employed, actually seeking work, or retired at entry into the treatment program. Procedure An initial screening was done on 314 patients to select those with (a) no serious physical handicap that might prevent them from attending followup clinics; (b) no sign of moderate-to-severe brain dysfunction; (c) no evidence of a psychotic episode and/or drug abuse; (d) no more than three previous hospitalizations for any psychiatric disorder (including alcoholism); and (e) willingness to return to monthly outpatient clinics. One hundred twenty nine patients failed to meet the initial screening requirements, thus leaving 185 patients for a second stage screening. In a second screening, patients were given the Psychiatric Diagnostic Interview (PDI) to (a) confirm the diagnosis of alcoholism, and (b) to classify patients into one of four alcohol subgroups of interest; Depression, Mania, Anti-Social Personality and Alcoholism only. The Psychiatric Diagnostic Interview (PDI) (Othmer, Penick, & Powell, 1981) is a structured criterion referenced interview based on the descriptive, syndromatic model of psychiatric diagnosis. The PDI is an elaboration and operationalization of diagnostic criteria proposed by Feighner et al. (Feighner, Robins, Guze, Woodruff, Winokur & Munoz, 1972) and is compatible with corresponding DSM-III diagnoses. The instrument has excellent discriminate validity (Powell, Penick, & Othmer, 1985) and is compatible with the NIMH Diagnostic Interview Schedule (Robins, Helzer, Croughan, & Ratcliff, 1981) for comparable disorders (Weller, Penick, Powell, Othmer, & Rice, 1985). The PDI determines systematically whether an individual is suffering or has ever suffered from any of 18 psychiatric syndromes: organic brain syndrome; alcoholism; drug abuse; mania; depression; schizophrenia; anti-social personality; hysteria/somatization/Briquet Syndrome; anorexia nervosa; obsessive-compulsive syndrome; phobic disorder; panic attack disorder; mental retardation; homosexuality; transsexuality; polydrug abuse; schizo-affective disorder; manic-depressive disorder. It can be administered by trained technicians and consists of relatively simple questions that have been tested in a variety of clinical and nonclinical settings. A “Yes/No” format is used in judging and scoring items as positive or negative. The interview functions as a “guided conversation” in which spontaneity and symptom elaboration are encouraged. Questions are arranged by syndrome and each syndrome is reviewed independently. Age of onset is determined for all positive syndromes, as well as the age when symptoms were last experienced. For purposes of this study, the subgroups were defined as follows: alcoholism only, positive on the PDI only for the syndrome of alcoholism; depressed alcoholic, positive on the PDI for alcoholism and depression but no other disorders; manic alcoholic, positive on the PDI for alcoholism and mania but no other disorders; antisocial afcohofic, positive on the PDI for alcoholism and anti-social personality but no other disorders. Once a patient had met the entry criteria, agreed to participate in the study, and had signed the consent form, he was given a complete medical examination including a
Lithium compliance in alcoholic males
standard lithium workup. If the medical findings contraindicated lithium treatment, the patient was dropped from the study. Nine patients were excluded because of medical considerations, leaving 100 patients in the study proper: 59 with alcoholism only, 20 with alcoholism and depression, 9 with alcoholism and mania and 12 with alcoholism and anti-social personality. Patients were told that by chance they would be assigned to one of two medications, lithium or chlordiazepoxide, both of which have been shown to be helpful to some individuals who abuse alcohol. Consenting patients were asked to return to monthly clinics so that their medication, drinking behavior and general physical and psychological state could be monitored. Patients were randomly assigned to a lithium or chlordiazepoxide treatment condition. Drug treatment was initiated while the patients were on inpatient status. While assigment to drug condition was random, the design was essentially that of an open clinical trial in that patients knew which drug they were to be taking. The chlordiazepoxide group received 10 mg. t.i.d. At this dosage, the drug was considered an “active” placebo. Men in the lithium condition received between 600-1500 mg per day. This dosage was determined for a given individual from his inpatient blood levels. Blood levels typically averaged .4 and .8 ml/eq on these low to moderate dosages of lithium. Upon discharge from inpatient status, patients were scheduled to return to monthly outpatient clinics in order that drug levels and drinking behavior could be monitored and project staff could determine if the patient needed crisis counseling or any other services. Drinking days were assessed by using a monthly calendar and asking patients to specify the days on which they did and did not drink. Every effort was made to establish a strong, trusting relationship between patient and project staff. This was considered an extremely important factor in encouraging and maintaining medication compliance. RESULTS
After six months in the study, overall patient compliance could be grouped as follows: 1. medication compliance (taking medication as prescribed for at least three of the six months); 2. clinic attendance compliance (attending three or more scheduled clinics but not compliant to medication); 3. minimal clinic compliance (attending one or two scheduled clinics and not compliant to medication) and 4. dropouts (failure to return to any of the scheduled followup clinics). The percent of patients by type of compliance from each drug group is presented in Figure 1. As noted, approximately half (52%) of the patients in the lithium group were medication compliant with slightly lower (44%) though comparable compliance among the chlordiazepoxide patients. Even though not compliant to medications, 18% of all patients, regardless of group assignment, made fairly regular visits. Fourteen and 24 percent of the patients in the lithium and chlordiazepoxide groups respectively had minimal compliance, returning for only one or two clinic visits. As noted, the number of drop-outs (14 and 15%) from each group was essentially the same, with attrition rates comparable to those reported by others (Kline et al., 1974; Merry et al., 1976; Peck et al., 1981). The drinking days and reported months of abstinence for the medication compliant
( N-50 Fig. 1.
( N=50) of patients
in each drug group
and type of compliance.
lithium and chlordiazepoxide patients were compared to those patients who returns to the clinic but who had never taken their assigned medication. Since only 24% of the patients had perfect attendance at all of the six scheduled clinics, some assumptions had to be made regarding drinking behavior during the month preceding missed appointments. With this in mind the data were calculated in two different ways: (a) data from missed appointments were ignored, and drinking information was averaged only for patients who actually attended the clinic, and (b) patients who missed appointments were assumed to be drinking and to have had the maximum number of drinking days for the missed appointment month, i.e., 30. These data were analyzed using the KruskalWallis one way analysis of variance procedure (Siegel, 1956). The results of these analyses are summarized in Table 1. As noted from the table, several patients from each group had perfect attendance and also reported being totally abstinent for the 6 months study period. Differences in the number of reported drinking days among the three groups were not significant regardless of how drinking during missed appointment months was handled. A significantly higher percent of abstinent months was reported by patients in both medication groups than by those not on medication (p < .05). This significance was found even when patients who missed appointments were considered as drinking (p < .Ol).
The results of this study do not support a differential effect of lithium in reducing drinking days over a 6 month period; however, a higher percentage of patients on lithium reported abstinent months than did the non-medication group. Patients in the chlordiazepoxide condition reported even greater abstinence than those on lithium, suggesting that patients who take their medication are more likely to be abstinent as well. Alternatively, patients who start to drink may stop their medication. Of additional interest to this study was the diagnostic subtype of patients and their medication compliance. The compliance of patients with uncomplicated alcoholism
Lithium compliance in alcoholic males
Drinking Days and Percent of Patients Abstinent for at Least One Month among the Three Groups over the Six Month Study Period Lithium (N = 26)
Mean Number of Drinking Days Per Month when . . . missed appointments are ignored missed appointments are counted’ Percent Reporting Abstinence for at Least One Month when . . missed appointments are ignored missed appointments are counted’ Patients Attending Six Clinics and Abstinent
Chlordiazepoxide (N = 22)
Clinic (N = 19)
‘In this highly conservativeanalysis, patients missing an appointment were assigned
day score of 30.
was compared with those who had mixed alcoholism or alcoholism plus an additional psychiatric disorder (i.e., anti-social personality, depression or mania). The latter groups were combined because of small cell sizes. The number of patients from the two sub-groups who were compliant to either lithium or chlordiazepoxide or who fell into the minimal and dropout groups were analyzed by the Chi Square statistic. Significantly more of the mixed alcoholics were found to be medication non-compliers (x2 = 6.78, p < .05). This result supports our findings regarding the importance of co-existing disorders in the treatment of alcoholics (Powell, Penick, Othmer, Bingham & Rice, 1982; Penick, Powell, Othmer, Bingham & Rice, 1984). The uncomplicated or “pure” alcoholic appears to be a better candidate for studies in which compliance is of importance than does his mixed counterpart. REFERENCES Feighner, J.P., Robins, E., Guze, S.B., Woodruff, R.A., Winokur, G., & Munoz, R. (1972). Diagnostic Criteria for use in psychiatric research. Archives of General Psychiatry, 26, 57-64. Flemenbaum, A. (1974). Affective disorders and ‘chemical dependence’: Lithium for alcohol and drug addiction? Diseases of the Nervous System, 35, 281-285. Fries, H. (1969) Experience with lithium carbonate treatment at a psychiatric department in the period 1964-1967. Acta. Psychiatrica Scandinavia, 44, 41-43. Kline, N.S. & Cooper, T.B. Lithium therapy in alcoholism. In D.W. Goodwin and C.K. Erickson (Eds.) (1979). Alcoholism and affective disorders. S.P. Medical and Scientific Books, New York. Kline, N.S., Wren, J.C., Cooper, T.B., Varga, E., & Canal, 0. (1974). Evaluation of lithium therapy in chronic and periodic alcoholism. American Journal of Medical Science, 268, 15-22. McMillan, T.M. (1981). Lithium and the treatment of alcoholism: A critical review. British Journal ofAddiction, 76, 245-258. Merry, J., Reynolds, C.M., Bailey, J., & Coppen, A. (1976). Prophylactic treatment of alcoholism by lithium carbonate. Lancet, 1, 481-482. Othmer, E., Penick, E.C., & Powell, B.J. (1981). Psychiatric Diugnostic Interview. Los Angeles: Western Psychologial Services. Peck, CC., Pond, S.M., Becker, C.E., & Lee, K. (1981). An evaluation of the effects of lithium in the treatment of chronic alcoholism. I Clinical results. Alcoholism, 5, 247-251.
Penick, E.C., Powell, B. J., Othmer, E., Bingham, SF., Rice, A.S., & Liese, B.S. (1984). Subtyping alcoholics by coexisting psychiatric syndromes: Course, family history, outcome. In Goodwin, D.W., S.A. (Eds.) Longitudinal Research in Alcoholism. Hingham, Van Duser, R.T., and Mednick, Massachusetts: Kluwer-Nijhoff Publishing Co. Powell, B.J., Penick, E.C., Othmer, E., Bingham, S.F., & Rice, A.S. (1982). Prevalence of additional psychiatric syndromes among male alcoholics. Journal of Chnical Psychiatry, 43, 404-407. Powell, B.J., Penick, E.C., & Othmer, E. (1985). Discriminate Validity of the Psychiatric Diagnostic Interview. Journal of Clinical Psychiatry, 46, 320-322. Reilly, P.D. (1978). Efficacy of lithium carbonate in alcoholism: Case studies. Rhode Island Medical Jour-
nal, 61, 86-91. Robins, L.W., Helzer, J., Croughan, J., & Ratcliff, D.S. (1981). NIMH Diagnostic Interview Schedule. Its history, characteristics and validity. Archives of GeneralPsychiatry, 38, 381-389. Sellers, E.M., Cappell, H.D., & Marshman, J.A. (1979). Compliance in the control of alcohol abuse. In R.B. Haynes, D.W. Taylor & D.L. Sackett (Eds.) Compliance in health care. Baltimore: The Johns Hopkins University Press, 223-243. Sellers, E.M., Naranjo, C.A., & Peachey, J.E. (1981). Drugs to decrease alcohol consumption. NewEngland Journal of Medicine, 305, 1255-1262. Siegel, S. (1956). Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill. Weller, R.A., Penick, E.C., Powell, B.J., Othmer, E., & Rice, A.S. (1985). Agreement between two structured diagnostic interviews: DIS and the PDI. Comprehensive Psychiatry, 26, 157-163. Young, L.D. & Keller, M.H. (1977). Sobering data on lithium in alcoholism. Lancet, 1, 144.