Robert A. Greenstein

Clinical Experience with Naltrexone

(1975). Clinical Experience with Naltrexone. The American Journal of Drug and Alcohol Abuse: Vol. 2, No. 3-4, pp. 365-377.

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder

Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy (7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 +/- 0.10 mEq/L, whereas in the muscle it was 0.50 +/- 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 +/- 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 +/- 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 +/- 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mEq/L.

Effects of Contingent Payment on Compliance with a Naltrexone Regimen

The effects of several schedules of payment on duration and patterns of compliance with a naltrexone regimen were examined. Patients were paid under contingencies based on either number of doses ingested or on a fixed time schedule. Reinforcement schedules based on number of doses ingested produced more consistent treatment-oriented behavior than a time-based schedule. Covariation between behavior and alternating contingencies (A-B-A) indicated that the schedules contributed to increased duration of treatment compared to previous noncontingent payment. The issue of using extrinsic reinforcers such as monetary payment to enhance compliance is discussed and additional procedures are suggested.

CLINICAL PHARMACOLOGY OF NARCOTIC ANTAGONISTS

Both naloxone and naltrexone are effective narcotic antagonists with minimal agonistic effects and a wide margin of safety. Naloxone is useful in the treatment of narcotic overdose and it is helpful in the quantification of physical dependence. Naltrexone is pharmacologically successful as an orally effective, long-acting antagonist but its clinical usefulness in the prevention of relapse is still being determined.

Naltrexone: A Short-Term Treatment for Opiate Dependence

The narcotic antagonist, naltrexone, was studied in 242 patients during a 6-year period. Although a large number of subjects discontinued naltrexone abruptly, treatment was related to a significant decrease in opiate and nonopiate drug use. Methods for improving retention during induction and maintenance are discussed and posttreatment outcome results are presented. The authors conclude that naltrexone may be a useful short-term treatment option for opiate dependence.

Conditioning in human opiate addicts.

Eight volunteers maintained on daily methadone participated in a classical conditioning procedure to determine which if any of the elements of narcotic withdrawal could be conditioned. The unconditioned stimulus was the injection of a small dose of naloxone. The unconditioned response was a brief precipitated withdrawal syndrome. The conditioning stimulus was a tone, odor, and injection of saline. Conditioning was successful in the pilot study in 5 of 8 subjects. The conditioned response consisted of tearing, yawning, lacrimation, systolic blood pressure increase, respiratory irregularities and subjective feelings of narcotic withdrawal sickness (nausea, muscle aches, chills). A second group of 8 subjects showed, in addition to the above, evidence of conditioning of heart rate, respiratory rate and skin temperature decrease. These laboratory findings support the clinical reports of a conditioned withdrawal syndrome and suggest ways to improve treatment results by detecting and extinguishing or modifying conditioned responses.

Suicidal Ideation in Veterans Receiving Treatment for Opiate Dependence

Abstract Persons with opiate use disorders, especially veterans. have a number of both chronic and acute indicators of risk for suicide, but are not typically screened for suicidal ideation on a routine basis, beyond initial evaluations. One hundred one veterans receiving treatment for opiate dependence at an urban VA medical center were screened for suicidal ideation. Over 24% reported some suicidal ideation. Current ideation was associated with severe chronic pain, ongoing problems with street drugs. firearm ownership, and with having recently enrolled in treatment. It was also associated with a variety of recent negative life events and mental health issues, especially depression, recurring troubling thoughts, hallucinations, loss of jobs, and conflicts with family members. Two veterans endorsing suicidal ideation required immediate hospitalization. The implications of these findings are discussed, and frequent screening for suicidal ideation among patients receiving treatment for opiate dependence is recommended.

SCHEDULED APPOINTMENTS AND PATIENT-STAFF COMPLIANCE

Studies of medication compliance have focused primarily on patient resistance to treatment, medication side effects, or the complexity of the medication regimen. This study of patient visits in a large psychiatric clinic found that, because of failure to schedule appointments or to notify receptionists of rescheduled appointments, physician noncompliance was as important as patient failure.

Chronic Vietnam PTSD and Acute Civilian PTSD A Comparison of Treatment Experiences

Many types of external trauma have been linked to the genesis of posttraumatic stress disorder (PTSD) and yet recent reports have focused almost exclusively on PTSD occurring in the Vietnam veteran (PTSD/veteran). The extent to which treatment experiences with PTSD/veteran can be generalized to other traumatized patients, for example, acute civilian populations, has not been investigated. Clinical observations comparing PTSD precipitated by a motor vehicle accident with PTSD/veteran suggested there were major differences between these two groups on the following variables: source of referral, age, sex, socioeconomic level, nature of stressor, timing of the stressor, character of the intrusive and avoidance symptoms, and treatment noncompliance behavior. These differences were of sufficient magnitude to call into question the feasibility, at this time, of constructing generalizations regarding PTSD utilizing only the PTSD/veteran population.

Applications of Human Behavioral Pharmacology to the Problems of Drug Addicts: A Brief Review

The work of Abraham Wikler (1973) over the past three decades has called attention to the importance of conditioned responses in the addictive process. Drugs act as powerful forces in shaping behavior, both by their direct pleasant effects (positive reinforcement) and by their effects in relieving withdrawal symptoms (negative reinforcement). Wikler theorized that the environmental cues which have been repeatedly paired with drug-induced states may become conditioned stimuli. He observed that former addicts who are free of drugs often develop tearing and yawning (opiate withdrawal signs) when they discuss drugs in group therapy. He and others subsequently showed that withdrawal signs could become conditioned in animals (Wikler and Pescor, 1967; Goldberg and Schuster, 1970). More recently, conditioned withdrawal has been demonstrated in humans (O’Brien et al, 1975; O’Brien et al, 1977). These conditioned withdrawal responses are thought to be partly due to simple pairing of pharmacological withdrawal with environmental cues, and partly due to pairing of environmental stimuli with the body’s homeostatic mechanisms adapting to the onset of drug effects (Wikler, 1973; Siegel, 1974). Eventually the environmental stimuli themselves can elicit the adaptative response and this can be perceived as withdrawal.