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Divalproex sodium to treat concomitant substance abuse and mood disorders
Journal of Substance Abuse Treatment 18 (2000) 371–372
Brief report
Divalproex sodium to treat concomitant substance abuse and mood disorders Marc Hertzman, M.D.* Department of Psychiatry, University of Maryland, 20 Courthouse Square, #217, Baltimore, MD 20852, USA Received 27 August 1998; accepted 20 July 1999
Abstract A retrospective chart review of psychiatric outpatients selected for a combination of alcohol (or other substance abuse) and mood disorders. A subgroup of patients treated with divalproex sodium diminished their substance abuse during the period of treatment for their disorders. This pilot study suggests that prospective, systematic research on divalproex sodium for dual diagnosis is warranted. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Divalproex; Mood; Substance abuse
1. Introduction In the face of alcohol, and other substance abuse, it is often hard to tell, even with the best of histories, whether mood disorders are primary or secondary. Also, such patients may experience periods of irritability, anger, excitation, and even aggression. It can be difficult to distinguish intoxication and withdrawal effects from hypomania under these circumstances. Recently, valproate is being tested as a possible mood stabilizer in the face of concomitant substance abuse disorders (Brady et al., 1995; 1996). The rationale for this is as follows: anticonvulsants may reduce membrane and brain instability in the face of substance abuse, which can alter the likelihood of possible seizures and other sources of brain confusion (Roy-Byrne et al., 1989). The compounds demonstrated to have utility in bipolar disorder may also be appropriate to treat mood disorders that are secondary to substance abuse, although this is not yet well-established. At the very least, the safety of these compounds to smooth out withdrawal, and related anxiety syndromes has been demonstrated in small studies (Brady et al., 1995; Halikas et al., 1992). The present study is a retrospective outcome analysis from clinical records, of valproate, used to treat presumptive mood disorders in an unselected series of outpatients with concomitant substance abuse disorders. The outcome
* Corresponding author. Tel.: 301-912-2911; fax: 301-912-2820.
measure was a single one, the reduction of the “subjective maximum” substance use. 2. Methods The sample consists of 46 consecutive patients who were treated with valproate for mood disorders and displayed concomitant substance abuse. They were taken from an outpatient psychiatric practice’s records, for approximately 1 year. The practice consists of largely Caucasian, blue-collar workers from a similarly constituted suburban county near Baltimore, Maryland. The demographic characteristics of the sample are: 25 male, 21 female; ages 15 to 61, mean age ⫽ 35.6 years. Valproate level was drawn in 15 cases, mean level ⫽ 35.3 mcg/mL. Diagnoses of mood disorders, primarily “bipolar” or “mood disorder NOS,” as well as substance abuse, were made according to criteria from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria by the examining and treating psychiatrist. The “subjective maximum” substance use is presented to the patient through the following sequence of questions: “Sometimes, when people are feeling depressed, or ‘hyper’ and irritable, they can’t drink [use _____ drug] as much as they usually would. Has this happened to you any time lately?” The usual answer to this question [which is generally to be ignored] is, “I don’t drink [use _____ drug] very much.” The interviewer then asks, “But when you do, at this time, how much can you manage before you have to stop?”
0740-5472/00/$ – see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S 0740-5472(99)00 0 8 0 - X
372
M. Hertzman / Journal of Substance Abuse Treatment 18 (2000) 371–372
To whatever number of drinks [drug usages] is given, the interviewer then asks, “What happens if you have one more?” The highest number given is considered the “subjective maximum.” The rationale for using this number is that there is general agreement that most studies underestimate alcohol and other drug use. Also, this single number is relatively easily obtained, in a disarming manner. 3. Results Of the 46 subjects, 24 showed a reduction in alcohol or other substance use, 2 showed a change in their usage, no subjects increased usage, l was in denial at follow-up and could not be evaluated. For the remaining 19 subjects, there was inadequate information to make an assessment. Although the original intent of the study was to crosscorrelate demographics, diagnosis, and outcome of treatment of mood disorders, the strength of the substance abuse reduction result essentially precluded any data “spread,” in order to measure such relationships. 4. Discussion This preliminary, retrospective study can be interpreted several ways, depending upon the assumptions one makes. If one assumes that (a) increases in usage are at least as likely as decreases, the result is highly significant, and demonstrates a very strong relationship between the prescription
of valproate, and the reduction of alcohol and other substance use, at least over a period of weeks to several months. If one assumes (b) the worst, for example, that all missing information represents subjects who increased their usage, the result is, at worst, that valproate had no effect one way or the other. The limitations of the study also include a strong homogeneity of sample for such a retrospective study. A single psychiatric practitioner was involved, and it is not clear how well these results may generalize to other practices; or what the limitations of self-study may impose upon the data collection and interpretation. Nevertheless, the possible reduction of alcohol and other substance use is encouraging, and the results suggest the need for prospective study designs to confirm the outcome.
References American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC: Author. Brady, K. T., Malcolm, R., & Ballenger, J. C. (1996). Anticonvulsants in substance abuse disorders. Psychiatric Annals 27, S488–S491. Brady, K. T., Sonne, S. C., Anton, R., & Ballenger, J. C. (1995). Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study. Journal of Clinical Psychiatry, 56, 118–121. Halikas, J. A., Ross, D., Crosby, R. D., & Carlson, G. (1992). Valproate in the treatment of cocaine addiction: a preliminary report. Annals of Clinical Psychiatry 4, 65–66. Roy-Byrne, P. P., Ward, N. G., & Donnelly, P. J. (1989). Valproate in anxiety and withdrawal syndromes. Journal of Clinical Psychiatry 50(3), 44–48.
Brief report
Divalproex sodium to treat concomitant substance abuse and mood disorders Marc Hertzman, M.D.* Department of Psychiatry, University of Maryland, 20 Courthouse Square, #217, Baltimore, MD 20852, USA Received 27 August 1998; accepted 20 July 1999
Abstract A retrospective chart review of psychiatric outpatients selected for a combination of alcohol (or other substance abuse) and mood disorders. A subgroup of patients treated with divalproex sodium diminished their substance abuse during the period of treatment for their disorders. This pilot study suggests that prospective, systematic research on divalproex sodium for dual diagnosis is warranted. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Divalproex; Mood; Substance abuse
1. Introduction In the face of alcohol, and other substance abuse, it is often hard to tell, even with the best of histories, whether mood disorders are primary or secondary. Also, such patients may experience periods of irritability, anger, excitation, and even aggression. It can be difficult to distinguish intoxication and withdrawal effects from hypomania under these circumstances. Recently, valproate is being tested as a possible mood stabilizer in the face of concomitant substance abuse disorders (Brady et al., 1995; 1996). The rationale for this is as follows: anticonvulsants may reduce membrane and brain instability in the face of substance abuse, which can alter the likelihood of possible seizures and other sources of brain confusion (Roy-Byrne et al., 1989). The compounds demonstrated to have utility in bipolar disorder may also be appropriate to treat mood disorders that are secondary to substance abuse, although this is not yet well-established. At the very least, the safety of these compounds to smooth out withdrawal, and related anxiety syndromes has been demonstrated in small studies (Brady et al., 1995; Halikas et al., 1992). The present study is a retrospective outcome analysis from clinical records, of valproate, used to treat presumptive mood disorders in an unselected series of outpatients with concomitant substance abuse disorders. The outcome
* Corresponding author. Tel.: 301-912-2911; fax: 301-912-2820.
measure was a single one, the reduction of the “subjective maximum” substance use. 2. Methods The sample consists of 46 consecutive patients who were treated with valproate for mood disorders and displayed concomitant substance abuse. They were taken from an outpatient psychiatric practice’s records, for approximately 1 year. The practice consists of largely Caucasian, blue-collar workers from a similarly constituted suburban county near Baltimore, Maryland. The demographic characteristics of the sample are: 25 male, 21 female; ages 15 to 61, mean age ⫽ 35.6 years. Valproate level was drawn in 15 cases, mean level ⫽ 35.3 mcg/mL. Diagnoses of mood disorders, primarily “bipolar” or “mood disorder NOS,” as well as substance abuse, were made according to criteria from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria by the examining and treating psychiatrist. The “subjective maximum” substance use is presented to the patient through the following sequence of questions: “Sometimes, when people are feeling depressed, or ‘hyper’ and irritable, they can’t drink [use _____ drug] as much as they usually would. Has this happened to you any time lately?” The usual answer to this question [which is generally to be ignored] is, “I don’t drink [use _____ drug] very much.” The interviewer then asks, “But when you do, at this time, how much can you manage before you have to stop?”
0740-5472/00/$ – see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S 0740-5472(99)00 0 8 0 - X
372
M. Hertzman / Journal of Substance Abuse Treatment 18 (2000) 371–372
To whatever number of drinks [drug usages] is given, the interviewer then asks, “What happens if you have one more?” The highest number given is considered the “subjective maximum.” The rationale for using this number is that there is general agreement that most studies underestimate alcohol and other drug use. Also, this single number is relatively easily obtained, in a disarming manner. 3. Results Of the 46 subjects, 24 showed a reduction in alcohol or other substance use, 2 showed a change in their usage, no subjects increased usage, l was in denial at follow-up and could not be evaluated. For the remaining 19 subjects, there was inadequate information to make an assessment. Although the original intent of the study was to crosscorrelate demographics, diagnosis, and outcome of treatment of mood disorders, the strength of the substance abuse reduction result essentially precluded any data “spread,” in order to measure such relationships. 4. Discussion This preliminary, retrospective study can be interpreted several ways, depending upon the assumptions one makes. If one assumes that (a) increases in usage are at least as likely as decreases, the result is highly significant, and demonstrates a very strong relationship between the prescription
of valproate, and the reduction of alcohol and other substance use, at least over a period of weeks to several months. If one assumes (b) the worst, for example, that all missing information represents subjects who increased their usage, the result is, at worst, that valproate had no effect one way or the other. The limitations of the study also include a strong homogeneity of sample for such a retrospective study. A single psychiatric practitioner was involved, and it is not clear how well these results may generalize to other practices; or what the limitations of self-study may impose upon the data collection and interpretation. Nevertheless, the possible reduction of alcohol and other substance use is encouraging, and the results suggest the need for prospective study designs to confirm the outcome.
References American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC: Author. Brady, K. T., Malcolm, R., & Ballenger, J. C. (1996). Anticonvulsants in substance abuse disorders. Psychiatric Annals 27, S488–S491. Brady, K. T., Sonne, S. C., Anton, R., & Ballenger, J. C. (1995). Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study. Journal of Clinical Psychiatry, 56, 118–121. Halikas, J. A., Ross, D., Crosby, R. D., & Carlson, G. (1992). Valproate in the treatment of cocaine addiction: a preliminary report. Annals of Clinical Psychiatry 4, 65–66. Roy-Byrne, P. P., Ward, N. G., & Donnelly, P. J. (1989). Valproate in anxiety and withdrawal syndromes. Journal of Clinical Psychiatry 50(3), 44–48.