Toxicology of Antidepressant Drugs: Tricyclic Antidepressants

Animal Toxicity General Toxicology The LD 50 values for a number of tricyclic antidepressants, when administered to mice and rats in single oral or parenteral doses, are listed in Table Acute LD50 valuesa of some tricyclic antidepressants. Acute poisoning by tricyclic antidepressants usually leads to symptoms of central excitation followed at the higher and lethal dose levels by central inhibition. The symptomatology includes muscular weakness, twitching, stupor, respiratory disorders, ataxia, and tonic-clonic convulsions. Table Acute LD50 valuesa of some tricyclic antidepressants Imipramine Doxepine Nortriptyline Viloxazine Maprotiline Mouse i.v. p.o. 35 666 15- 20 148-178 26 327 60 1000 31 660- 900 Rat i.v. p.o. 22 625 13- 19 346-460 22 502 60-77 2000 38- 52 760-1050 a The values given are for LD50, single administration, in mg/kg body weight It is evident from Table Acute LD50 valuesa of some tricyclic antidepressants or from the reports of Pluviage () and of Ueki et al. () that no major differences in the acute toxicity of tricyclic antidepressants are apparent. Information on animal studies relating to the tolerance of tricyclic antidepressants Read more […]

Multiple Drug Use Epidemiology, Correlates, and Consequences

The initial focus is on the conceptual issues essential to the understanding of multiple drug use. This is followed by a discussion of the developmental nature of multiple drug use and the various strategies that have been designed to measure multiple use. The third section of the paper contains a review of the extent of multiple drug use in various segments of society with data from the Monitoring-the-Future surveys of high school seniors, the National Survey on Drug Abuse, and the Treatment Outcome Prospective Study of drug abuse treatment clients. The conclusion is that multiple drug use is pervasive. The next section deals with several consequences associated with multiple drug use: automobile accidents, delinquency, and emergency room visits. The final section outlines some of the prevention and treatment implications of multiple drug use from a public policy perspective. In a study of the effects of a single drug upon behavior, the implications are manifold. Dosage levels, modes of administration, baseline states, the expectations of the subjects and of the investigators, the environment in which the drug is taken — all these variables, and others as well, make human psychochemical studies difficult and complex. Read more […]

Drug Impairment Reviews: Opiates and Minor Tranquilizers

STUDY: Gordon, N.B. Reaction Times of Methadone-Treated Heroin Addicts. Psychopharmacologia, 16:337-344. 1970. Site: Rockefeller University and Yeshiva University, New York City, New York. Subjects: The subjects were divided into six groups. Groups 1 and 3 both had been maintained for at least 1 year on methadone for the treatment of heroin addiction. Group 1 had 18 males whose average age was 32.5 years; group 3 had 9 females whose average age was 33.5 years. Group 2 consisted of 20 unpaid male volunteers who did not use drugs; they averaged 32.5 years. The participants in groups 4 and 5 had recently withdrawn from narcotic drugs. The 20 males in group 4 averaged 31.5 years and had withdrawn 14 days earlier. The 19 males in group 5 averaged 30 years and had withdrawn 4 days earlier. Group 6 consisted of 9 females whose average age was 23 years. They were paid volunteers from the nonprofessional hospital staff, and did not use drugs. Method: Measurements were taken under controlled laboratory conditions; urines were tested (details were not given) for drugs to assure conformity to group. Variations of reaction time were tested in a button-pressing situation: (a) simple reaction time (one of six stimuli); (b) Read more […]

History of Drug Exposure as a Determinant of Drug Self-Administration

The purpose of this paper is to review how a drug’s effectiveness in initiating and maintaining self-administration can be influenced by a subject’s past experience with drugs. Drug self-administration by humans and laboratory animals is considered an instance of operant behavior (), controlled by the subject’s genetic constitution, past history, and the current circumstances of drug availability (of Skinner, 1938). The influence of history of drug exposure on current drug-maintained behavior may be controlled, in turn, by the particular drugs and doses employed and the conditions under which the drug is administered. This discussion will focus on the ways in which a history of drug exposure can control later drug self-administration in laboratory animals. Effects of history of drug exposure on initiation of drug self-administration In order to study drug self-administration by laboratory animals, an experimenter must set up a situation in which subjects are exposed to some contingency between the occurrence of a specific response and delivery of a particular drug. For many drugs, no explicit behavioral or pharmacologioal history is necessary for the drug to maintain behavior. In one initial study, for example, Read more […]

Usefulness of Propoxyphene Napsylate for Maintenance Treatment of Narcotic Addiction

Recently several studies have examined the use of propoxyphene napsylate (Darvon-N) in the detoxification and maintenance of narcotic addicts. Tennant () reported that three programs in Los Angeles had succeeded in detoxifying 280 heroin addicts with propoxyphene napsylate, while maintaining 92 others on an outpatient basis for periods up to 240 days. In a doubleblind detoxification study comparing propoxyphene napsylate and methadone, he found that propoxyphene patients were more likely than methadone patients to be opiate abstinent at one month followup (). However, in this doubleblind study, Tennant found propoxyphene to be less effective than methadone in suppressing withdrawal complaints. He also noted side effects from propoxyphene, such as mild visual hallucinations, slurring of speech and seizurelike symptoms (). Jasinski () reported that propoxyphene napsylate used in maximum non toxic doses (about 1200 mg per day) produced narcotic-like activity equal to that of only 20 to 25 mg of subcutaneously administered morphine, or 10 mg of orally administered methadone. Again, he found that propoxyphene napsylate doses greater than 700 mg produced disturbing side effects in many subjects. This paper will report Read more […]

A Review of Drug Abuse Data Bases: Treatment-Oriented Data Systems

Six treatment-oriented data systems were studied: 1. Drug Abuse Warning Network (DAWN) Purpose. Project DAWN is a Federal program jointly funded by the Drug Enforcement Administration (DEA) and the National Institute on Drug Abuse (NIDA). DAWN has been in existence since 1972 and was established to monitor the consequences of drug abuse using two indicators, emergency room visits and deaths. Respondents and Sampling. DAWN collects its information through episode reports provided by selected hospital emergency rooms, crisis centers, and medical examiners. In order to be eligible, emergency rooms must: Be open 24 hours per day; Be located in non-Federal short-term general hospitals (specialty hospitals, hospital units of institutions, and pediatric hospitals are excluded); and Have at least 1,000 patient visits to the emergency room per year. At the end of 1978, over 900 facilities were supplying data to the program. Reporting facilities are concentrated in 24 Standard Metropolitan Statistical Areas (SMSA’S) which are not randomly selected but are chosen to account for approximately 30 percent of the population of the U.S. in geographically diverse locations. Drugs Investigated. DAWN distinguishes Read more […]

WHO’s Response to International Drug Control Treaties

I should like to review briefly the activities undertaken by WHO since I last reported to you in Philadelphia June 1979: Scheduling Activities WHO’s recommendations to the Secretary-General of the UN regarding the control status of eight substances were reviewed by the 6th Special Session of the UN Commission on Narcotic Drugs in February 1980 in Vienna. Tilidine and Sufentanil were placed in schedule I of the 1961 Convention while Dextropropoxyphene was placed in schedule II of the same Convention. The Commission agreed with the recommendations of WHO that Phencyclidine continue to be controlled under schedule II of the 1971 Convention as it is needed in veterinary practices. It was also decided that three analogues of PCP (TEP, PHP or PCPY and PCE) be controlled under schedule I and Mecloqualone under schedule II of the 1971 Convention. In September 1980, WHO plans to review the status of a group of 9 substances (anorectics). These are: Phentermine Chlorphentermine Chlortermine Benzphetamine Mazindol Fenfluramine Amfepramone Phenmetrazine Phendimetrazine Phenmetrazine and Amfepramone are already controlled under schedule II and IV respectively of the 1971 Convention. Technical Cooperation Read more […]

Update on Naltrexone Treatment

Our group in Philadelphia has used naltrexone in the treatment of 201 narcotic addicts in 258 separate treatment episodes as of 1 July 1977. The antagonist treatment program is an important part of our overall multimodality program which includes methadone or propoxyphene maintenance treatment, inpatient detoxification, long-term therapeutic community, family, group, and individual therapies, and a variety of behavioral treatments. Narcotic antagonist treatment, of course, appeals only to those patients who are genuinely interested in becoming drug free. It is not nearly as popular as methadone treatment, but it occupies an important niche — amounting to 5-10 percent of our total patient population at some time in their treatment careers. Our narcotic antagonist patients are demographically similar to our other patients: mean age 27, 60 percent black, more than 95 percent male, and more than 95 percent veterans of military service. Our methods for detoxification from narcotics and institution of antagonist therapy have been reported elsewhere (2, 4); they are similar to those described by others. We use intravenous naloxone prior to the first naltrexone dose to detect residual physical dependence and thus reduce Read more […]

Outpatient Treatment and Outcome of Prescription Drug Abuse

Forty-six consecutive patients who voluntarily sought outpatient treatment for abuse of one or more prescription drugs were studied. Barbiturates, amphetamines, and diazepam were the most common drugs abused. Desired treatments by patients included counseling, medical withdrawal, or medical maintenance with the drug of abuse or a chemically related drug. Twenty-two (47.8 percent) patients left treatment and relapsed within one month; another eight (17.4 percent) patients relapsed between one and three months after entering treatment. Only 13 (28.3 percent) reported abstinence 90 days after entering treatment. This experience suggests that a wide range of medical, social, and psychologic resources are required to treat prescription drug abuse, and that long-term drug abstinence is difficult to achieve with all patients. Treatment of prescription drug abuse has dealt primarily with drug complications such as overdose, toxic reactions, and techniques for medical withdrawal. Other reports describe behavior patterns of prescription drug abuse and often refer to it as poly-drug abuse, since many persons frequently abuse more than one drug. Some reports emphasize the clinical complexity of poly-drug abuse and particularly Read more […]

Multimodality Treatment of Narcotic Addiction: Pharmacologic Therapies

Narcotic substitution The single therapy that has had the greatest impact on narcotic addiction appears to be methadone maintenance. Unlike drug-free approaches, it is acceptable to a large number of addicts (). It is medically safe, has minimal side effects and no toxicity when given to tolerant individuals, even for long periods of time (). Though the results of methadone treatment vary among programs, there is strong evidence that it provides a way to control narcotic addiction. Most patients who remain in methadone treatment have a marked decrease in heroin use, an increase in employment rates, and demonstrate improved personal adjustment (). At present there are approximately 80,000 people being treated with methadone in the United States (), but despite methadone’s wide applicability and effectiveness, it leaves much to be desired. It has been controversial since the beginning, and many aspects of methadone programs have been criticized (). One problem has been an inability to demonstrate that methadone treatment increases the long term cure rate for addiction. This is a disappointment, as many had hoped that the social rehabilitation obtained via methadone maintenance would lay the groundwork for successful Read more […]