Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population.

We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.

Substance abuse and HIV infection.

This chapter reviews the associations between substance use, comorbid psychiatric disorders, and HIV risk behaviors; the prevalence of substance use disorders among HIV-positive individuals in treatment settings; the medical, psychiatric, and substance abuse treatment of individuals with substance use disorders and HIV infection; and finally, HIV risk reduction among substance abusers.

Stimulant psychosis: symptom profile and acute clinical course.

Nineteen patients seen at a psychiatric emergency service with amphetamine- or cocaine-induced psychotic disorder were assessed with structured interviews, chart review, and blood and urine testing. All had a predominance of positive symptoms from the Positive and Negative Syndrome Scale (PANSS). However, some subjects had substantial Negative Scale scores (26%), bizarre delusions (95%), and Schneiderian hallucinations (63%), mimicking a broad range of schizophrenic symptoms. Several PANSS scores were correlated with treatment intensity: Positive score with seclusion hours, General Psychopathology and Negative scores with hospitalization length, and General Psychopathology score with neuroleptic dose. Presenting symptoms may help in treatment planning.

Utility of routine drug screening in a psychiatric emergency setting.

OBJECTIVE: The study determined whether dispositions from an urban psychiatric emergency service would differ between patients who received a mandatory urine drug test and those who may or may not have had a test based on the attending psychiatrist's clinical judgment. The accuracy of clinicians' suspicion of substance use among mandatorily screened patients was also examined. METHODS: A total of 392 consenting patients presenting to an urban psychiatric emergency service were randomly assigned to a mandatory-screen group (N=198) or a usual-care group (N=194). Physicians ordered screens based on clinical judgment. Additional screens were performed without physicians' knowledge for patients in the mandatory-screen group for whom no screen was ordered. Demographic and clinical information, results of drug screens, and information about dispositions were collected from clinical charts or hospital databases. RESULTS: No difference in dispositions was found between the mandatory-screen group and the usual-care group. Survival analysis did not reveal a difference between the two groups in length of stay in inpatient psychiatric units. As for accuracy of physicians' suspicion of substance use, positive drug screens were recorded for 10.2 percent of the 198 patients in the mandatory-screen group who did not admit drug use or for whom physicians did not expect drug use. A total of 39.3 percent of the patients who were suspected of use and 88.2 percent of those who admitted use had positive drug screens. Only 20.8 percent of patients who denied substance use had positive screens. CONCLUSIONS: Routine urine drug screening in a psychiatric emergency service did not affect disposition or the subsequent length of inpatient stays. The results do not support routine use of drug screens in this setting.

Patterns of substance use among patients in an urban psychiatric emergency service.

Data from patients visiting an urban psychiatric emergency service in California were examined to document incidence and patterns of substance use and ethnic differences among users. A total of 392 patients were randomly assigned to receive a drug screen (N = 198) or to receive usual care (N = 194). Forty-four percent of the mandatorily screened patients had positive screens for any substances: 37 percent were positive for any drugs, and 7 percent were positive for alcohol only. Cocaine was present in 62 percent of the drug-positive screens. Blacks were two and a half times more likely than whites to have positive screens for drugs and five times more likely to have positive screens for cocaine.

Sulfonium salts as derivatizing agents. 3. Quantitation of the cocaine metabolite benzoylecgonine in urine using gas chromatography with ion-pair extraction/on-column alkylation.

Recent studies have demonstrated the utility of quantitative assays for benzoylecgonine in assessing the efficacy of cocaine-dependence-treatment programs to determine if the amount of cocaine consumed has been reduced. We describe a simple gas chromatographic method for determining benzoylecgonine concentrations in urine. BZE is extracted from urine as an ion pair with tri-n-propylsulfonium ion. Injection into the heated injection port of the gas chromatograph results in thermal conversion of the ion pair to the n-propyl ester of BZE. Using the structural analogue of BZE, m-toluylecgonine, as the internal standard, the analysis is carried out on a (5% phenyl)methylpolysiloxane capillary column with nitrogen-phosphorus detection. There was a good correlation between BZE concentrations determined by gas chromatography-mass spectrometry and concentrations determined by the method described in this paper. Application to cocaine-dependence-treatment programs is discussed.

Medication adherence strategies for drug abusers with HIV/AIDS.

This paper describes two clinical techniques aiming to improve adherence to medications for HIV/AIDS in methadone maintenance patients. The first technique, providing on-site dispensing of antiretroviral medications, enhanced medication adherence but did not produce enduring effects beyond the time of the intervention. To develop a more long-lasting intervention, the programme is experimenting with more individualized medication management, in which a staff member provides assessment and problem solving to help improve medication adherence. Clinical and practical issues are presented--including each technique's aims, screening and recruitment of participants, description of the technique, staff and administrative support issues, and research results. The paper aims to assist staff in drug treatment programmes to implement interventions that can increase adherence to medications for HIV/AIDS.

Buprenorphine and naloxone interactions in methadone maintenance patients.

Buprenorphine is undergoing clinical trials for the treatment of opiate addiction. Although the abuse liability of sublingual buprenorphine is low, reports of intravenous abuse have appeared. This study describes the physiologic and subjective effects of intravenously administered buprenorphine and naloxone given alone and in combination to methadone-maintained patients (40-60 mg/day). On four separate occasions at least 1 day apart, 6 subjects were administered either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg naloxone in combination, or placebo. One male subject quit the experiment after three sessions because of excessive opiate withdrawal. Buprenorphine produced no significant physiologic or subjective effects. Naloxone produced marked opiate withdrawal symptoms. Buprenorphine in combination with naloxone produced characteristic physiologic and subjective opiate antagonist-like symptoms and signs. The parenteral abuse potential of the buprenorphine and naloxone combination is discussed.

Measurement properties of quantitative urine benzoylecgonine in clinical trials research.

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.

Psychiatric morbidity, illicit drug use and adherence to zidovudine (AZT) among injection drug users with HIV disease.

This study describes the relationship between the need for psychiatric consultation, illicit drug use, and zidovudine (AZT) adherence in HIV-infected injection drug users (IDUs) in methadone maintenance treatment (MMT). The treatment records of 57 IDUs in MMT who had been prescribed AZT between May and August of 1991 were reviewed. Those who required psychiatric consultation (P+, N = 46, 81%) were compared with those who did not require psychiatric consultation (P-, N = 11, 19%) on adherence to AZT treatment (using the mean corpuscular volume [MCV] as a biological marker), on recent illicit drug use, and on CD4 lymphocyte (T cell) count changes from the beginning to the end of AZT treatment. The P+ subjects were less likely than P- subjects to adhere to AZT treatment: fewer in the P+ group had an MCV outside of the normal range, and P+ subjects had a lower average monthly increase in MCV since the beginning of AZT treatment. Recent illicit drug use and CD4 lymphocyte count changes from the beginning to the end of AZT treatment did not show group differences. Psychiatric morbidity among HIV-infected IDUs in MMT is common, and may contribute to poor adherence to AZT treatment. Psychiatric screening and adherence-enhancing interventions should be targeted to IDUs entering drug treatment programs.

A controlled trial of fluoxetine in crack cocaine dependence.

This controlled study tested the efficacy of the selective serotonergic reuptake inhibitor fluoxetine in the out-patient treatment of primary crack cocaine dependence. Thirty-two subjects were randomly assigned, 16 in each group, to placebo or fluoxetine, 40 mg/day, in a double-blind controlled trial over a 12-week period. Outcome measures included quantitative urine benzoylecgonine concentration, self-reports of cocaine use and craving, and treatment retention. Subjects assigned to fluoxetine were retained in treatment significantly longer than those on placebo: a median of 11 weeks compared to 3 weeks (logrank test, P < 0.001). Because of the poor retention in the placebo group, between-groups comparisons of outcome were limited to the first 6 weeks of treatment. No differences in cocaine use or craving were found between the two groups over weeks 1 to 6. The significant improvement in retention associated with fluoxetine may support further study of this medication in the treatment of cocaine dependence.

Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care.

Twenty-seven HIV-infected methadone maintenance patients who demonstrated problems adhering to zidovudine (AZT) were randomly assigned to a group that received eight weeks of weekday supervised therapy and dispensing of AZT or a group that received usual care of the clinic. Adherence was assessed by self-report, erythrocyte mean corpuscular volume (MCV), Medication Event Monitoring Systems (MEMS), and pill counts. Subjects in the intervention group demonstrated significantly higher MCV levels during the intervention period than usual care subjects, with similar but non-significant trends for the three other adherence measures. MEMS percent indicated significant group differences on weekdays, but not weekend days. There were no differences at a one-month follow-up. Results suggest supervised therapy and dispensing may be an effective strategy for improving AZT adherence, but only while provided. Further research is needed to establish the effects of larger and longer lasting interventions.

Fluoxetine for cocaine dependence in methadone maintenance: quantitative plasma and urine cocaine/benzoylecgonine concentrations.

Cocaine abuse is a common clinical problem among opioid-dependent patients who are in methadone maintenance treatment. In an open prospective study, 16 DSM-III-R, cocaine-dependent, methadone maintenance treatment patients were treated with fluoxetine, at a mean dose of 45 mg/day for 9 weeks. Eleven subjects (69%) were infected with the human immunodeficiency virus. Cocaine use was significantly reduced by the end of treatment, although most subjects did not achieve abstinence. Comparison of intake to week 9 showed a significant decrease in self-reported cocaine use, craving, and quality of high. Actual cocaine use was measured by a quantitative analysis of cocaine and benzoylecgonine (BE) concentrations in plasma and urine. Median BE and cocaine concentrations in urine decreased significantly from intake to week 9 of fluoxetine treatment. This decrease would not have been detected if BE had been measured only qualitatively, as present or absent in the urine. Fluoxetine was well tolerated in combination with methadone and did not appear to alter methadone concentrations in plasma. Few adverse effects were noted. No subjects had to discontinue fluoxetine. Fluoxetine may be a promising treatment approach for cocaine abuse in methadone maintenance patients. Quantitative determination of exact cocaine and BE concentrations in biofluids may be a more accurate method of measuring cocaine use outcome than qualitative urinalysis.

HIV-infected intravenous drug users in methadone maintenance treatment: clinical problems and their management.

Infection with the human immunodeficiency virus (HIV) is a significant and growing problem among intravenous drug users (IVDUs), both from the standpoint of personal morbidity and public health concerns regarding spread of the virus. Most HIV-infected IVDUs are opioid addicts. The most common form of long-term treatment of opioid dependence is methadone maintenance treatment (MMT). MMT can therefore play an important role in both AIDS prevention and reduction of HIV-related morbidity through diminishing drug use, promoting a healthier life-style, and providing direct medical and psychiatric care. Attempts to manage patients with a triple diagnosis of drug abuse, medical, and psychiatric problems can pose significant clinical challenges, requiring the efforts of a multidisciplinary team. The management of HIV-infected patients in MMT is discussed and case examples from the MMT program of the San Francisco General Hospital Substance Abuse Services are presented to illustrate useful strategies in the care of these complicated patients.

Buspirone in drug users with AIDS or AIDS-related complex.

Anxiety is a prominent feature of human immunodeficiency virus (HIV)-related psychiatric disorders. Psychiatric disorders are associated with poor drug abuse treatment outcome in both healthy and HIV-infected drug users. While it is important to treat anxiety, the use of traditional antianxiety agents such as benzodiazepines can lead to adverse effects such as sedation and misuse, especially in patients with drug abuse problems. A retrospective chart review was employed to examine the use of buspirone in treating anxiety in intravenous drug users with acquired immune deficiency syndrome (AIDS) or AIDS-related complex who were receiving methadone maintenance treatment. All patients were opiate users, and most were also secondary users of other substances, including stimulants and alcohol. Of 17 patients who were started on buspirone, 14 remained on medication for more than 2 weeks. Of this latter group, all showed at least temporary improvement in one or more of the following areas: subjective reduction of anxiety, reduction of prescribed benzodiazepine use, or reduction in the number of urine tests positive for drugs of abuse, particularly morphine. Buspirone was well tolerated by all but three of these patients; there was no evidence of buspirone misuse. Given its favorable adverse effects profile, buspirone may be particularly useful in the treatment of anxiety in HIV-infected drug users.

Drug abuse, psychiatric disorders, and AIDS. Dual and triple diagnosis.

Substance abuse and psychiatric disorders commonly occur together. This form of dual diagnosis is notable because it complicates assessment and makes treatment more difficult for both psychiatric and drug abuse problems. Drugs can cause psychiatric disorders and can also be used as an attempt to "cure" them by self-medication. The spread of the human immunodeficiency virus (HIV) among drug users has added a third potential clinical problem, that of the acquired immunodeficiency syndrome, to the difficulties already presented by drug abuse and psychiatric disorders. Patients with this triple diagnosis pose challenges to primary care physicians as well as addiction medicine specialists or psychiatrists. Assessment should include a drug abuse history, preferably corroborated by others, evaluation of the mental state, and examination focusing on signs of drug abuse and HIV infection. Treatment should include the management of HIV disease, abstinence from drug abuse, and access to psychiatric care. New systems of health care service, including interdisciplinary case management, may be needed to manage patients with a triple diagnosis.