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Biomedical subjects

F J Dunner

Publications and source records attributed to F J Dunner.

At least 19 recordsLinked to original sources

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

Clinical effectiveness of oral and parenteral rapid neuroleptization.

A random assignment, double-blind, placebo-controlled evaluation was used to compare the effectiveness of rapid parenteral injections of fluphenazine hydrochloride with that of oral doses of the same drug in 16 patients with acute psychotic illnesses. Doses of fluphenazine hydrochloride were much higher in the parenteral neuroleptization group than in the oral administration group during the acute phase, although oral doses were equivalent during the continuation phase. The rate of improvement was not different for the two groups, but the rate of extrapyramidal side effects was higher in the parenteral neuroleptization group. The results suggest that rapid parenteral neuroleptization for the acute treatment of psychosis offers more risks than benefits.

Acute Disease

The utility of a single-point dosing protocol for predicting steady-state lithium levels.

Two methods for predicting steady-state serum lithium level were compared prospectively in in-patients suffering from affective disorder. A single-point prospective administration model that required a single 24-hour serum lithium level, following a test dose produced statistically similar predictions of the observed steady-state lithium levels as did a model that required 12- and 36-hour levels. However, the latter two-point method produced significantly more accurate predictions from clinical interpretation. Although the two-point approach is preferable, the single-point method is clinically acceptable if its limitations of accuracy are taken into consideration.

Adult

Pharmacologic probes of neurotransmitter systems in tardive dyskinesia: implications for clinical management.

Despite the plethora of clinical drug trials in tardive dyskinesia, few consistent findings have emerged. One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems (dopamine, norepinephrine, acetylcholine, serotonin, GABA) in one specific population of tardive dyskinesia patients. This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia; each drug probed one of four neurotransmitter systems. The intra- and interpatient responses are analyzed and the implications of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed.

5-Hydroxytryptophan

Relationship of free nortriptyline levels to therapeutic response.

The relationship between the free plasma concentration of nortriptyline and therapeutic response was examined. Eighteen depressed inpatients were treated for 21 days with steady state total nortriptyline plasma concentrations between 50-150 ng/ml. Steady state free nortriptyline concentrations were measured. The therapeutic nortriptyline response was measured by administering the Hamilton and the Carroll Rating scales at day zero and day 21. Statistical relationships between free levels of drug and clinical response were found to be insignificant. Qualitative assessment of the data suggest that free serum levels of nortriptyline in excess of 10 ng/ml may have an inhibitory effect on clinical response.

Adolescent

Variable clinical response to choline in tardive dyskinesia.

Tardive dyskinesia is widely believed to be a state of relative hyperdopaminergic and hypocholinergic imbalance in the striatum of patients chronically treated with neuroleptics. However, not all patients with tardive dyskinesia respond to cholinergic drugs, which theoretically should restore the balance and improve the symptoms. We report a controlled, double-blind, crossover study of choline chloride in 11 patients with persistent tardive dyskinesia. Seven patients showed partial or minimal improvement, while two did not change and two deteriorated. The results are discussed in the light of other similar findings in the literature, and the implications for pharmacological subtypes of tardive dyskinesia using cholinergic probes are explored.

Acetylcholine

Prospective evaluation of two lithium maintenance dose schedules.

A prospective method for recommending lithium carbonate maintenance doses for patients requiring the drug either prophylactically or for acute mania has been previously described. Of 18 patients who required prophylactic lithium levels between 0.40 and 0.89 mEq/liter, the maintenance dose equation achieved the predefined therapeutic range in 15 (83%) cases. Of 20 patients requiring lithium concentrations between 0.90 and 1.30 mEq/liter for the treatment of acute mania, 17 (85%) attained the therapeutic range after receiving the recommended maintenance dose. The authors discuss the factors that limit the usefulness of this prospective dosing protocol.

Adult

The impact of psychopharmacology education on prescribing practices.

The authors describe a pharmacology education program on the psychiatry service of a Veterans Administration medical center. The program, directed by a clinical pharmacist, includes weekly lectures to medical students and weekly psychopharmacology review rounds for psychiatric residents that are also attended by staff psychiatrists. To determine the impact of the psychopharmacology review rounds on prescribing practices, the authors conducted a retrospective chart review of psychopharmacologic treatment methods before and after the rounds were instituted. The review compared prescribing practices in the two periods and focused particularly on changes in practices related to multiple daily dosages, polypharmacy, prophylactic anticholinergics, and drug use in alcohol withdrawal. The review demonstrated that the teaching effort resulted in a use of psychotropic medications that was more in line with recommendations in the literature.

Adult

Prediction of lithium maintenance doses using a single point prediction protocol.

Conflicting reports regarding the utility of a previously described single point prediction dosing method for lithium prompted the present study's reexamination of the relationship between a single point lithium concentration and the lithium maintenance dose. Seventeen informed, adult patients with affective illness were studied. The relationship between their 24-hour lithium concentration after a test dose and the maintenance dose was significant, hence confirming earlier reports. In addition, more confident relationships were noted when steady state range concentrations for lithium prophylaxis (0.41 to 0.89 mEq/liter) and for treatment of acute mania (0.9 to 1.27 mEq/liter) were analyzed separately. Maintenance dose predictive equations were generated for these lithium steady state ranges from a 24-hour single point level after a 1200-mg test dose. The clinical usefulness of the new relationships observed for maintenance dose prediction must await prospective testing.

Adult

Dexamethasone suppression testing of alcoholics.

Fourteen (33%) of 43 men hospitalized for alcohol abuse showed abnormal cortisol levels at 4 pm, 17 hours after administration of 1 mg of dexamethasone (median, five days after admission). Most (but not all) of these nonsuppressors showed multiple signs of alcoholic physical deterioration; there may be more than one mechanism by which alcohol abuse can lead to an abnormal result of this test. Suppressors and nonsuppressors reported similar alcohol consumption, symptoms of depression, and occurrence of depression among close relatives. Only two patients (5%) showed abnormal cortisol levels at 8 am, nine hours after administration of dexamethasone. These results suggest that, as a screen for primary depressive illness among recently abstinent alcohol abusers, the 4 pm cortisol level is not specific enough, but the 8 am level might be useful in patients who have no alcoholic relatives.

Adult

Serotonin precursor effects in tardive dyskinesia.

In an attempt to determine the role of serotoninergic mechanisms in the pathophysiology of tardive dyskinesia, the serotonin precursor 5-hydroxytryptophan (5HTP) with carbidopa, a peripheral decarboxylase inhibitor, were given in a double-blind crossover design to seven patients with longstanding tardive dyskinesia. In the five patients who completed the study, there was no change in dyskinetic movements. Most of the patients had worsening of psychotic symptoms with 5HTP. The data suggest that serotonin precursors have no therapeutic effects in tardive dyskinesia. The implications for the role of serotonin in the pathophysiology of tardive dyskinesia are discussed.

5-Hydroxytryptophan

A longitudinal survey of side effects in a lithium clinic.

The cross-sectional and longitudinal patterns of lithium side effects were surveyed in a prospective 12-month study. The use of other psychotropic medication (antidepressants, neuroleptics) in addition to lithium was associated with a higher frequency of complaints. The presence of noneuthymic mood was not associated with changes in the incidence of side effects. Persistent side effects were not related to current age, age at onset of illness, severity of illness, or duration of lithium therapy. The chronicity of lithium therapy was not specifically associated with the presence or absence of any of the 23 side effects surveyed.

Age Factors

Lithium kinetics in single daily dosing.

The feasibility of single daily dosing of lithium carbonate was tested in eight recurrent manic-depressives being treated with lithium prophylaxis. The patients received their entire 24-h maintenance dose at 8:00 p.m. for 12 consecutive days. The suitability of single daily dosing was determined by comparing 1) lithium through levels; 2) lithium kinetic parameters of half-life, clearance, and volume of distribution; and 3) renal function parameters of serum creatinine, creatinine clearance, and mean 24-h urine output during the initial divided daily dosage trial and the subsequent single daily dosage trial. The observation of no significant changes in either serum half-lives or renal lithium clearance levels supports the conclusion that the average steady-state lithium serum concentration (Cpss) is unchanged by conversion to single daily doses. No significant changes were observed in either serum creatinine or creatinine clearance. However, a significant decrease in the 24-h urine output was noted on the single daily dose.

Adult