Frederick J. Dunner

Serial dexamethasone suppression test results during antidepressant therapy: relationship to diagnosis and clinical change.

Thirty-two outpatients with major depression of mild to moderate severity were given a 1 mg dexamethasone test (DST) after 1 week of placebo. Those who failed to show a response to placebo began a 6-week course of desipramine treatment. Severity ratings and the DST were repeated during biweekly visits. DST results robustly validated Winokurs familial subtyping and the primary/secondary distinction only when multiple results were considered. The use of multiple DSTs doubled the sensitivity of this test to primary depression and to familal pure depressive disorder without affecting specificity. Based on these data, a single abnormal DST result is considerably more meaningful than a single normal one. This finding may have particular importance to outpatients.

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 studys 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 maina (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.

A placebo-controlled trial of valproate in tardive dyskinesia.

Carroll BJ (1979): Prediction of treatment outcome with lithium. Arch Gen Psychiatry 36:870. Evrard JL, Banman P, Peru R, et al (1978): Lithium concentration in saliva, plasma and RBC of patients given lithium acetate. Acta Psychiatr Scand 58:67. Mendels J, Frazer A (1974): Alteration in cell membrane activity in depression. Am J Psychiatry 131:1240. Mendels J, Frazer A (1973): Intracellular lithium concentration and clinical response: Towards a membrane theory of depression. J Psychiatr Res 10:9. Naylor GJ, McNamee liB, Moody JP (1971): Changes in erythroeytic sodium and potassium on recovery from a depressive illness. Br J Psychiatry 118:212. Naylor G J, Dick DAT, Dick EG (1976): Erythroeytic membrane cation carrier relapse rate of manic depressive illness and response to lithium. Psychol Med 6:257.

Relationship of free nortriptyline levels to therapeutic response

ABSTRACT– The relationship between the free plasma concentration of nortriptyline and therapeutic reponse 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.

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.

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.

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.

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.