a) persons with major depression are more likely to smoke and to have difficulty when they try to stop;
b) smokers with past major depression experience withdrawal symptoms, in particular depressed mood, more severely than do nondepressed persons; and
c) when they manage to succeed in stopping, persons with a depression history are at increased risk of experiencing severe states of depression, including full-blown major depression.

In a follow-up study of 126 treatment successes in a 10-week cessation program, the authors found that the proportion of new major depression was significantly greater among subjects who had a history of either recurrent or single major depression, compared with subjects without that history (30%, 16%, 2%, respectively, p<.001). This effect remained statistically significant after controlling for possible compounding due to age, gender, baseline Fagerstrom Score, depressed mood at baseline, depressed mood at end-of-treatment, and withdrawal symptom score at end-of-treatment. The only other predictor of post-cessation major depression was patients' reports of persistently elevated withdrawal symptoms. An examination of the duration of risk for post-cessation depression suggested that it could last from a few weeks to several months after cessation. Information from eight patients who experienced severe depressions within two weeks of stopping smoking and nine patients who experienced a new major depressive episode within three months of successfully completing a ten-week cessation program is presented in detail. When compared with the total subject pool, the post-cessation "casualties" were found to be predominantly female, and to have previous history of depression. These clinical findings indicate the importance of ascertaining the patient's psychiatric history at the start of smoking cessation treatment. Further work is needed to determine: other risk factors for new major depression following smoking cessation, the latency of its onset, its effect on the resumption of smoking, as well as the efficacy of psychological (such as supportive counseling), or pharmacological (such as buproprion or nicotine replacement therapy) cessation treatments for enhancing the ability to stop smoking or prevent the occurrence of post-cessation depression among depression-prone smokers. Growing literature indicating strong associations between nicotine dependence and other substance use disorders raises related questions regarding the influence of smoking cessation on the course of those co-morbid conditions. While there has been abundant work and information about the physical consequences of smoking and smoking cessation, it is clear that research efforts on the psychiatric aspects are just beginning. Lirio S. Covey, Ph.D. Department of Psychiatry, Columbia University New York State Psychiatric Institute Editor's Note: The Covey, L. article may be read in : The Journal of Addictive Disease, Vol 17, No. 1, 1998, pp. 35-46. Covey, L.S., Glassman, A.H., and Steiner, F. A Preliminary Investigation of Lamotrigine for Cocaine Abuse in HIV-Seropositive Patients Although a large number of psychotropic agents have been investigated for the treatment of cocaine addiction, none clearly demonstrated efficacy in clinical trials. This lack of success has pointed out the need to evaluate agents that possess mechanisms of action different from those hitherto investigated, which have been primarily dopaminergic or monamingeric in activity, e.g., anti-depressants such as desipramine, or stimulants, such as maxindol. This study was a preliminary investigation of lamotrigine, a novel anticonvulsant medication. Neurochemical studies suggest that lamotrigine indirectly decreases release of glutamate, a widely occurring excitatory amino acid (EAA). Agents that modulate EAA system have been the subject of recent attention in the addictions, because they may have two benefits: protecting against cocaine-related neurotoxicity, and decreasing cocaine use. A number of studies suggest that cocaine is neurotoxic and that this toxicity may be glutimate-medicated. The implications of lamotrigine's glutimate inhibiting properties for reducing cocaine-medicated neurotoxicity is supported by a number of preclinical studies; for example, in the rat lamotrigine has been found to protect against presumptive glutamate-medicated phenomena such as neurological deficits following ischemia,1,2 as well as kainic acid neurotoxicity.3 Lamotrigine's potential utility as a treatment agent for cocaine abuse stems from research into glutamatergic control of dopamine release.cf., 4,5 Findings suggest that EAA antagonists decrease the ability of cocaine to elevate extracellular dopamine levels in the striatum,6 as well as cocaine-stimulated extracellular dopamine levels in the nucleus accumbens. Because dopamine is thought to be central to the rewarding effects of cocaine,7 this raises the possibility that these effects may be reduced by lamotrigine, through glutamate inhibition. An agent that both decreases cocaine use and is potentially neuroprotective may have clinical utility for a wide variety of chronic cocaine abusers. However, these properties may be of particular relevance to the subpopulation of HIV-seropositive cocaine abusers, who may be at heightened risk for neurological damage from the additive or synergistic neurotoxic effects of cocaine use and HIV-disease. This study therefore had two primary goals: (1) to conduct a preliminary evaluation of lamotrigine's efficacy for cocaine addiction, based on urine toxicology screens and self-reported drug use; and (2) to explore lamotrigine's effects on cognitive functioning by administering a neuropsychological assessment battery pre- and post-treatment. Participants were 18 (11 male; 7 female) treatment refractory HIV-seropositive patients enrolled in an inner-city methadone maintenance program. All subjects met DSM-IV criteria for cocaine dependence. Patients had been using opiates for 15.2 (+7.3) years and cocaine for 13.3 (+6.7) years. The target dose of lamotrigine for this study was 300 mg/day. We began by employing a six-week induction schedule, recommended for lamotrigine in the treatment of epilepsy. After the first 8 patients, the schedule was halved to three weeks, in order to explore whether the target dose could be attained more rapidly, yielding a longer period of time for patients to be maintained on the full dose in a standard three month study. This change offered the opportunity to compare the treatment outcomes of patients assigned to these two induction schedules. Patients in the standard induction group (n=8) reached full dose week 6; patients in the accelerated induction group (n=10) reached full dose in week 3. The context in which lamotrigine was investigated comprised daily opiate-agonist treatment (methadone or buprenorphine), case management, and twice weekly manual-guided psychosocial group therapy (Risk Reduction Therapy) (Avants SK, unbpulished manual). Results and Conclusion Two patients in the accelerated induction group were discontinued from the study due to pronounced rash. No patients in the standard induction group was discontinued from treatment due to medication side-effects, although one patient in this group left the study for reasons unrelated to the test medication. Results showed a significant decrease in percent of cocaine positive urine screens, severity of drug-related problems, self-reported cocaine craving and days using cocaine only in the standard induction lamotrigine group. There were no changes in the accelerated induction group-patients in this group continued to use high rates of cocaine. Three of seven patients in the standard induction group were abstinent in the last week of the study; none of the accelerated patients were abstinent. Neuropsychological assessments showed that pre-treatment 70% of patients were impaired on one-third or more of the nine neuropsychological tests; all patients were impaired on at least one test. Post-treatment, verbal fluency increased for all patients, and there was a decrement in psychomotor speed in the standard induction group, which may be related in initiation of cocaine abstinence. There were no other decreases in cognitive functioning. Findings from this study suggest that further investigation of lamotrigine, titrated on a standard induction schedule, is w Arthur Margolin, Ph.D
Research Scientist Yale University
School of Medicine
Substance Abuse Center
New Haven, CT

1. Arthur Margolin, s. Kelly Avants, Dominick DePhilippis, & Thomas R. Kosten. A preliminary investigation of lamotrigine for cocaine abuse in HIV-seropositive patients. The American Journal of Drug and Alcohol Abuse. 1998;24(1): 85-101.
2. Smith, S.E., and Meldrum, B.S., Cerebroprotective effect of lamotrigine after focal ischemia in rats. Stroke 26:(1) 117-121 (1995). Wiard, R.P., Dickerson, M.C., Beek, O., Norton, R., and Cooper, B.R., Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Stroke 26:(3)466-472 (1995).
3. McGreer, E.G., and Zhu, S.G., Lamotrigine protects against kainate but not ibotenate lesions in rat striatum. Neuroscience Letter 112:348-351 (1990).
4. McGinty, J.F. Introduction to the role of excitatory amino acids in the actions of abused drugs: a symposium presented at the 1993 annual meeting of the College on Problems of Drug Dependence. Drug and Alcohol Dependence 37:91-94 (1995).
5. Freed, W.J., Glutamatergic mechanisms mediating stimulant and antipsychotic drug effects. Neuroscience and Biohavioral Reviews 18:(1)111-120 (1994).
6. Moghaddam, R., and M.L., B., Glutamatergic antagonists attenuate ability of dopamine uptake blockers to increase extracellular levels of dopamine: Implications for tonic influence of glutamate on dopamine release. Synapse 18:337-342 (1994).
7. Beitner-Johnson, D., and Nestler, E.J. Basic neurobiology of cocaine: Actions within the mesolimbic dopamine system :[Clinician's Guide to Cocaine Addiction, Ed., T.R. Kosten & H.D. Kleber], Guilford Press, New York, 1992. Return to September/October Epikrisis Index

Steven J. Lash, Ph.D.
Clinical Psychologist
Salem Veterans Affairs Medical Center and Assistant Professor of Clinical Psychiatric Medicine
University of Virginia

1. Lash, S. J., & Blosser, S.L. (1998). Increasing adherence to substance abuse aftercare group therapy. Journal of Substance Abuse Treatment, 15, 1-6
2. Lash, S.J. (1998). Increasing participation in substance abuse aftercare treatment. American Journal of Drug and Alcohol Abuse, 24, 31-36
3. Lash, S.J., & Dillard, W. (1996). Encouraging participation in aftercare group therapy among substance-dependent men. Psychological Reports, 79, 585-586.

Author Notes: The author is a clinical psychologist at the Salem Veterans Affairs Medical Center and an associate professor of clinical psychiatric medicine at the University of Virginia. Reprints of the referenced articles and the treatment participation contract are available from him at: Substance Abuse Treatment Program (116A4), VAMC, Salem, VA 24153

Jointly Hosted by North Carolina Physicians Health Program UNC School of Medicine, Office of Continuing Medical Education
Embassy Suites Cary, North Carolina
October 2-4, 1998

In less than three days, you can have it all! Learn techniques to manage change and stress-the power of humor-a better marriage. Experience overcoming the ultimate stress. Compare insights about handling negative emotions in others and in yourself.

For more registration information call: (919)881-0585.

The retrospective cross-sectional study explored the associations of personality characteristics with parenting problems among 25 couples, one or both members of which were identified as alcoholics by virtue of their voluntary past completion of residential program for alcoholics. Most of them (90%) scored lower, indicating their more problematic parental attitudes and behaviors, on all four scales of the Adult-Adolescent Parenting Inventory (AAPI: inappropriate parental expectations of children, lack empathy for children's needs, value physical punishment, and parent-child role reversal) than average "normal" nonalcoholics, nonabusive adults. Such parenting problems were found to be very highly associated with clients' personality characteristics. For example, schizoid, schizotypal, histrionic, and passive aggressive characteristics (DSM-III--R-based) along with a few other personal characteristics of the couples, accounted for nearly all (90.2%, R2 =902) of their propensity to reverse roles with their children. Findings also suggested that the identified parenting problems among alcoholic couples are amenable to programmatic intervention: the longer couples had participated in aftercare programs offered by the treatment facility the more appropriate and empathetic was their parenting.

Wilfred Alexander Gallant, Ed.D., M.S.W., C.S.W., I.C.A.D.C., C.G.C.
Associate Professor, School of Social Work
University of Windsor
Windsor, ON., Canada

Editor's Notes: A complete research report of this study may be found in: Gallant, W., Gorey, K., Gallant, M., Perry, J., Ryan, P. (1998). The association of personality characteristics with parenting problems among alcoholic couples. The American Journal of Drug and Alcohol Abuse. 24(1); 119-129.