Richard I. H. Wang

Rating the presence and severity of opiate dependence.

The means for rating dependence to narcotic drugs and determining the severity of physical dependence is examined, using the administration at 0.8 mg naloxone intramuscularly and assessing the severity of dependence mainly by the presence and time of appearance of withdrawal signs. Responses were studied in 75 patients with drug abuse problems. Naloxone or saline was administered double blind and at random. In methadone‐ and opiate‐dependent sub;ects, net withdrawal scores after naloxone differed significantly from those after saline. In nonopiate‐dependent patients, there was no significant difference between net scores after naloxone and after saline. The results at the investigation were confirmed by a crossover study in which naloxone and saline were administered to 4 patients with suspected opiate dependence.

Crossover and Parallel Study of Oral Analgesics

Abstract: Ten years ago, analgesics were studied using crossover designs. In recent years, analgesics have been studied only in parallel designs primarily because biostatisticians do not like crossover studies. The advantages of crossover studies are numerous: (1) patients serve as their own control; (2) there is less variability of responses among patients; and (3) a smaller number of patients is needed to provide statistically significant data. As long as crossover of treatment medications does not occur within 4 to 6 hours, the problem of carryover effect of the previous medication is insignificant or negligible. Two studies will be presented. One is a crossover study of Percodan with and without naloxone to placebo. The other is a parallel study comparing the effects of propoxyphene with naloxone to those of propoxyphene alone. The results of these studies reaffirm the value of the crossover method of evaluating analgesics.

The oral analgesic efficacy of bicifadine hydrochloride in postoperative pain.

Abstract: The analgesic efficacy of 75 and 150 mg bicifadine hydrochloride was compared to 650 mg aspirin and placebo in a double‐blind, single‐dose study. Oral doses were administered to 100 patients suffering from moderate to severe postoperative pain. Significant analgesic activity was demonstrated with 650 mg aspirin and 150 mg bicifadine as compared to 75 mg bicifadine or placebo. No significant treatment difference was found between 75 mg bicifadine and placebo. Side effects were minor and did not interfere with the course of therapy.

A Brief Self-Assessing Depression Scale

The Wang-Self-Assessing Depression Scale (SADS) was devised to provide a brief self-rating form for measuring depressive symptomatology. The present study compares the SADS with the Zung Self-Rating Depression Scale (SDS) to assess reliability and relative ease of completion. Ninety-three ratings on each scale were obtained from a subject group that included normal volunteers and patients with differing degrees of depression. The paired t-test showed no significant difference between mean SDS scores and mean SADS scores for normal volunteers or subjects rated at any of the four depression levels. Positive correlation was demonstrated between tsds scores and SADS scores for depressed and normal subjects. The period of time required to complete the Wang SADS was found to be significantly shorter than for the Zung SDS, while the number of errors and requests for additional assistance were significantly lower. It was felt that these differences would constitute an advantage in the clinical use of the Wang SADS for diagnosing, evaluating, and monitoring the progress of depressed inpatients and outpatients.

The Hypnotic Efficacy of Triazolam

In a double-blind cross-over study, triazolam, a substituted benzodiazepine, was compared to flurazepam and to placebo for their hypnotic activities and side-effects. Twenty adult male patients with histories of insomnia requiring nightly hypnotic medication received placebo, 0.5 mg triazolam, 1.0 mg triazolam, 15 mg flurazepam, or 30 mg flurazepam on five consecutive nights, according to a randomized schedule. As a hypnotic medication, triazolam was found to be thirty to sixty times as potent as flurazepam, on a weight basis. In the therapeutic dosages given, triazolam demonstrated significant activity in prolonging the duration and increasing the depth of sleep, and in reducing the number of times of waking. Patient satisfaction with triazolam was good. The side-effects reported by some subjects were mild and did not interfere with the course of administration. A slightly higher incidence of side-effects was reported following 0.5 mg of triazolam than after 1.0 mg of the drug.

Effects of orally administered delta‐9‐tetrahydrocannabinol in man

The etfects of Δ9‐tetrahydrocannabinol (Δ9‐THC) administered orally at 2 dose levels were studied in a group of 7 healthy young adult males. Each subiect was studied for 7 nights (2 drug, 5 placebo). Vital signs, subiective feelings, deep tendon reflexes, electrocardiogram, electroencephalogram, visual evoked responses, postural responses, time estimation and reaction time and sleep patterns were studied. At the doses studied, Δ9‐THC increased pulse rate, altered subjective feelings, and caused hyperreflexia and upset postural responses in the absence of visual cues. Some subjects also exhibited lowered oral temperature, changes in averaged visual evoked response, and alteration of sleep patterns.

Effect of chloroquine and phenobarbital on morphine glucuronidation and biliary excretion in the rat

Abstract The relationship between morphine glucuronidation and biliary excretion was studied in rats pretreated with saline (control), chloroquine (CQ) or phenobarbital (PB) by determining the conversion of morphine to morphine-3-glucuronide (MG) in vitro and the biliary excretion of intravenously administered morphine and MG in vivo . For the biliary excretion studies. 14 C-morphine or 14 C-MG was administered intravenously and excretion measured in anesthetized renal-ligated rats in which the common bile ducts were cannulated. The effect of PB treatment on the biliary excretion of morphine and MG was complex and it was found that: (1) PB pretretment did not alter the proportions of morphine and MG in bile; (2) the rate of biliary excretion of morphine (as MG) was decreased in PB-pretreated rats even though MG formation was increased in vitro ; (3) the plasma disappearance of 14 C after 14 C-morphine administration was also decreased by PB pretreatment; (4) the biliary excretion of administered MG was significantly decreased by PB pretreatment; and (5) the 14 C plasma disappearance after 14 C-MG administration was not changed by PB pretreatment. Several interpretations can be derived from these results. One possibility is that MG formation is not a rate-limiting step in the biliary excretion of morphine. An alternate interpretation would be that PB pretreatment may have an inhibitory effect on the biliary excretion of morphine and MG that is unrelated to metabolism. Chloroquine pretreatment produced only a slight effect on the biliary excretion of morphine and no effect on the biliary excretion of administered MG. Using studies in vitro , we could not demonstrate that CQ induced an increase in MG formation.

Reserpine and alpha-methyldopa in the treatment of tardive dyskinesia

Thirty inpatients with evidence of tardive dyskinesia secondary to antipsychotic medications participated in this double-blind, controlled, randomized study comparing reserpine, α-methyldopa and placebo. Reserpine at doses of 0.75–1.5 mg daily, or α-methyldopa at doses of 750–1,500 mg daily, produced a statistically significant improvement in tardive dyskinesia symptomatology compared to the results obtained with placebo.

The Clinical Analgesic Efficacy of Oral Nefopam Hydrochloride

The analgesic efficacy of 60 and 120 mg nefopam hydrochloride was compared to 650 mg aspirin and placebo in a double-blind single-dose study. Oral doses were administered to 120 patients suffering from acute postsurgical or fracture pain. All active medications demonstrated analgesic activity in comparison to placebo. Patients on 120 mg nefopam obtained the greatest degree of analgesia. Side effects were minor and did not interfere with the course of therapy. The incidence of side effects (sweating, nausea, and lightheadedness) was greater on 120 mg nefopam than on 650 mg aspirin).

Electrocardiographic changes simulating hypokalemia during treatment with lithium carbonate

Summary Electrocardiographic abnormalities simulating hypokalemia developed in two patients while receiving lithium carbonate therapy, in the face of normal serum electrolytes. Lithium carbonate is being used increasingly in acute and long-term management of manic depressive illness. The ECG changes reversed on discontinuation of the drug in the first, and on decreasing the dose in the second, case. Displacement of intracellular myocardial potassium by lithium may be the possible mechanism.