Twenty-nine hospitalized patients suffering acute exacerbations of schizophrenia were treated for 2 weeks with fixed daily oral doses of haloperidol prospectively calculated to achieve a haloperidol plasma concentration of either 8-18 ng/ml or 25-35 ng/ml. Reduced haloperidol as well as haloperidol concentrations were assayed to determine if the former enhanced the predictability of response. Wee 2 haloperidol plasma concentrations were negatively correlated to clinical response as measured by the percentage change in the BPRS score from baseline (r = -0.43, P less than 0.05). In contrast, week 2 plasma concentrations of reduced haloperidol, total haloperidol (haloperidol + reduced haloperidol), and reduced haloperidol/haloperidol ratio did not correlate with the change in the BPRS score. Chi-square analysis concluded that patients with ratios greater than one were no less likely to be treatment responders (less than 25% improvement in BPRS from baseline and week 2 BPRS less than 55) than those with ratios less than one. Although these data lend additional support to reports of a curvilinear relationship between haloperidol plasma concentration and clinical response, they also suggest that reduced haloperidol plasma concentrations are of no value in predicting treatment response.

Acute Disease↗

PubMed1990

A comparison of the effect of fluoxetine and trazodone on the cognitive functioning of depressed outpatients.

Tricyclic antidepressants with clinically significant amounts of anticholinergic activity can adversely affect memory and cognitive functioning. The study evaluated the effect of two non-anticholinergic antidepressants, fluoxetine and trazodone, on immediate and short-term memory in clinically depressed outpatients. The results of this study demonstrated that neither drug affected the depressed patients' cognitive skills as measured by the Guild memory test (digit span and paired associations) during their treatment and recovery. The only factor that was useful in predicting an improvement in cognitive functioning was the change in the measures of depression (Hamilton Rating Scale for Depression and Clinical Global Impression) with time.

Depressive Disorder↗

PubMed1990

Haloperidol plasma levels and acute clinical change in schizophrenia.

Twenty-five inpatients with acute exacerbations of schizophrenia (by Research Diagnostic Criteria) or schizoaffective disorder underwent a prospective haloperidol dosing procedure and were assigned fixed doses chosen to yield a distribution of haloperidol plasma levels above and below a hypothesized upper therapeutic limit of 18 ng/ml. Changes in Brief Psychiatric Rating Scale scores after 1 week of treatment were negatively correlated with haloperidol plasma levels, and the statistically optimum cutoff point fell near the predicted 18 ng/ml. Plasma level/response relationships over the subsequent 3 weeks were weaker but patients with higher plasma levels had consistently less improvement.

Adult↗

PubMed1990

A report of trazodone-associated laboratory abnormalities.

A 6-week multicenter, double-blind, controlled study comparing the therapeutic efficacy of two antidepressant drugs, trazodone and fluoxetine, was conducted. The hematocrit, hemoglobin, red blood cell count, serum cholesterol, serum calcium, and serum albumin levels were all significantly decreased after six weeks of trazodone treatment. Similar findings were not obvious for the fluoxetine treatment group. Trazodone caused the development of a pseudoanemia in 36% of the trazodone treatment patients compared with 20% of the fluoxetine treatment patients. The anemia was not regarded as clinically significant. Of the decreases in the patients' chemistries, only the decrease in cholesterol could not be reconciled.

Double-Blind Method↗

PubMed1990

Illicit anabolic steroid use: a controlled personality study.

The illicit use of anabolic steroids for strength and cosmetic reasons appears to be an increasing problem. Although alcohol and drug abuse have been associated with increased risk for personality psychopathology, the personality correlates of illicit anabolic steroid abuse are unknown. To determine whether personality psychopathology is common among anabolic steroid users, we evaluated a series of illicit anabolic steroid users and compared them with a group of age-matched alcoholics and 2 control groups. Anabolic steroid users were found to have increased risk for personality psychopathology compared with community controls. The risk appeared to be partially explained by a group membership effect. Additionally, similar to the alcoholic group, illicit anabolic steroid users also demonstrated significant antisocial traits.

Adolescent↗

PubMed1990

Triazolam--an "abused drug" by the lay press?

For the second time in the past ten years adverse reports in the lay press have questioned the safety of triazolam. Anecdotal reports of central nervous system adverse reactions can be separated into four general categories: (1) delirium in psychiatric patients; (2) delirium in geriatric patients; (3) withdrawal reactions; and (4) anterograde amnesia. Of the four, the amnesia reactions are regarded as serious enough by the Food and Drug Administration that it is requiring hypnotic drug manufacturers to revise the labeling of temazepam and flurazepam along with triazolam to emphasize the potential for this class of drugs to cause traveler's amnesia.

Amnesia↗

PubMed1990

Pharmacokinetic protocol for predicting plasma haloperidol concentrations.

The accurate prediction of steady-state plasma haloperidol concentrations was successfully accomplished by obtaining two blood samples following a 20 mg test dose (kinetic method). Prediction of steady-state concentrations on the basis of a mg/kg/day dosage (dose method), although equally precise, generated significantly less information concerning the variance between observed and predicted haloperidol plasma concentrations. Both predictive methods were less precise when the daily doses exceeded 0.47 mg/kg/day. Fifty percent (6/12 patients) of the haloperidol plasma concentrations were underpredicted if this threshold was exceeded. This finding may suggest the possibility of dose-dependent pharmacokinetics with haloperidol in some patients.

Dose-Response Relationship, Drug↗

PubMed1989

Behavioral performance and seizure activity of lithium-intoxicated Sprague-Dawley rats treated with theophylline.

Male Sprague-Dawley rats were divided into four groups that were treated with various combinations of lithium, saline, and theophylline, i.e., saline/saline, saline/theophylline, lithium/theophylline, and lithium/saline. Neurobehavioral testing of cerebellar and neuromuscular functioning, and determination of the effect of the drug combinations on the animals' seizure threshold concluded that while theophylline increases lithium clearance, it does not exacerbate lithium neurotoxicity.

3-Mercaptopropionic Acid↗

PubMed1989

Serum fluoxetine and norfluoxetine concentrations and antidepressant response.

A high-performance liquid chromatography assay for fluoxetine and its major metabolite, norfluoxetine, was established. Serum concentrations of the two were measured in 13 depressed outpatients following a 6-week trial of the drug. No significant correlations were obvious between clinical improvement as measured by the Hamilton Rating Scale for Depression and the Clinical Global Impression scores and the serum concentrations of fluoxetine and its major metabolite, norfluoxetine, according to these initial pilot data.

Adult↗

PubMed1989

A comparative trial of fluoxetine versus trazodone in outpatients with major depression.

The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients. The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment. However, that difference was no longer apparent during the remainder of the study. The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone.

Adult↗

PubMed1988

Effect of meal frequency on fluid balance and behavior of ponies.

Twelve ponies were fed their total daily ration either as one large meal or divided into six small meals. Pre- and post-feeding behavior was recorded six times a day. Blood samples were taken for 30 min before and two hr after the meal. Plasma protein increased from 7.0 to a peak of 7.3 g/dl with small meals and from 7.3 to 8.1 g/dl with large meals, and returned to pre-feeding levels by 90 min post-feeding. Hematocrit rose from 33.3 to 34.1% with small meals and from 33.0 to 36.0% with large meals. These rapid and short-lived increases indicate a decrease in plasma volume. Plasma osmolality rose with feeding from 283 to 285 mosmoles/kg with small meals and from 281 to 288 mosmoles/kg with large meals. Water availability had no significant effect on blood changes. Digestibility and rate of passage were measured with chromic oxide, but there were no differences. Vocalizing (neighing) and walking occurred more often before than after feeding, while eating bedding and engaging in other oral behaviors were more frequent after feeding.

Animals↗

PubMed1988

The effects of intravenous theophylline infusion versus intravenous sodium bicarbonate infusion on lithium clearance in normal subjects.

Ten normal subjects ingested lithium carbonate (600 mg p.o. b.i.d.) for three 1-week intervals. At the end of each weekly interval, subjects' lithium clearances were randomly perturbed for 12 hours with the subject in a supine position by infusing either normal saline (308 mEq), sodium bicarbonate (350 mEq) in normal saline (308 mEq), or theophylline (mean = 14.0 micrograms/ml) in normal saline (308 mEq). Subjects were placed on a 200 mEq/day sodium diet during the lithium clearance perturbation stages of the study. When each patient's normal saline lithium clearance was used as a control, it was found that the theophylline produced a significantly greater % increase in lithium clearance than did the sodium bicarbonate. Theophylline infusions increased patients' individual lithium clearances by 51 +/- 52%, while sodium bicarbonate infusions increased lithium clearances by 0.6 +/- 33%. Theophylline infusions ought to be investigated as an alternative to hemodialysis in lithium intoxications requiring the immediate reduction of lithium concentrations.

Adult↗

PubMed1988

Benzodiazepine withdrawal: a review of the evidence.

In a recent series of controlled studies, investigators looked at what happened when benzodiazepines were discontinued. Despite methodological problems, these studies showed that rebound anxiety occurred in a substantial minority of patients after several weeks of drug use. Also, a withdrawal syndrome developed in nearly half of patients who used benzodiazepines for more than a year. In these studies, risk factors included dose, duration of use, elimination rate of the drug, and abruptness of discontinuation. Patients who are physically dependent on benzodiazepines may need help in stopping these agents. Physicians should advise gradual discontinuation and, along with emotional support, should consider the use of alternative medications for the control of symptoms.

Anti-Anxiety Agents↗

PubMed1988

The relationship of haloperidol concentrations to therapeutic response.

Data from pharmacokinetics studies that examined the relationship of haloperidol serum concentrations and therapeutic response in schizophrenic patients were reexamined utilizing the method of logistic regression analysis. A linear rather than a curvilinear relationship was obvious between serum haloperidol concentration and therapeutic response according to both the regression analysis and inspection of the distribution of the data. It was concluded that a serum haloperidol concentration in the range of 9 to 15 ng/ml was associated with a 30% decrease in the total Brief Psychiatric Rating Scale (BPRS) score. Haloperidol concentrations above these appear unlikely in the majority of patients to produce any additional reduction of symptoms. The BPRS psychosis factor finding suggested an analogous finding for serum haloperidol concentrations between 12 and 17 ng/ml. The analyses suggest that the probability of response to haloperidol seems to reach a point of diminishing return at concentrations of approximately 9 to 17 ng/ml. Serum concentrations above this limit do not appear to either decrease or increase the probability of response.

Adolescent↗