Double-blind comparison of the side-effect profiles of daily versus alternate-day dosing schedules in lithium maintenance treatment of manic-depressive disorder.

The side-effect profiles of daily vs. alternate-day lithium carbonate dosing schedule were compared in a double-blind study of 50 manic-depressive patients. Following a 3-month period on daily lithium maintenance treatment the patients were randomly allocated to daily or alternate-day lithium dosing aiming at maintaining the same 12-h serum concentration as prior to allocation (median 0.7 mmol/l). The daily and alternate-day median lithium doses were 700 mg and 1200 mg, respectively. There was no significant correlation between changes in the side-effect scores on the UKU side-effect rating scale and lithium dosing schedule (ordinal logistic regression), although analysis revealed a trend in favour of alternate-day dosing with respect to polyuria/polydipsia and diarrhoea (loose stool). The study thus lends no support to the hypothesis that lithium-related side-effects can be diminished by extending the interval between lithium doses from 1 to 2 days.

Urinary excretion of albumin and transferrin in lithium maintenance treatment: daily versus alternate-day lithium dosing schedule.

Urinary excretion of albumin and transferrin was determined by means of sensitive immunochemical methods in 40 manic-depressive patients prior to and following 6 months of daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 700 mg in the daily treatment group and 1200 mg in the alternate-day group, the corresponding median 12-h serum lithium concentration being 0.6 mmol l-1 and 0.7 mmol l-1, respectively. Urinary excretion of albumin and transferrin was significantly elevated in the lithium-treated patients as compared to a control group (Mann-Whitney). The change in urinary albumin:creatinine and transferrin:creatinine ratios between allocation and 6 months of treatment did not correlate significantly with the lithium dosing schedule (multiple linear regression), but did correlate with total lithium carbonate dose. In conclusion, the study provides no evidence of any difference in glomerular function (permeability) in the daily and alternate-day lithium dosing schedules, and lends no support to the hypothesis that alternate-day treatment diminishes the effect of lithium on renal function.

Lithium prophylaxis of manic-depressive disorder: daily lithium dosing schedule versus every second day.

The prophylactic efficacy of lithium carbonate given every second day versus daily intake was compared in a double-blind study including 50 manic-depressive patients. The patients met the DSM-III-R criteria for bipolar disorder or depressive disorder; according to ICD-8 the patients fulfilled criteria for manic-depressive disorder: All patients had experienced at least 3 episodes of mania or major depression, and all had been euthymic for at least 4 months. The median doses of lithium carbonate given were 800 mg/day or 1200 mg/every second day corresponding to median 12-h serum lithium concentrations of 0.6 mmol/l or 0.7 mmol/l, respectively. Manic or depressive relapse was defined as DSM-III-R criteria for mania or major depression, and a score > or = 10 on the Bech-Rafaelsen Mania Scale or the Bech-Rafaelsen Melancholia Scale, respectively. The two treatment schedules were allocated at random. Using the Cox proportional hazard model for statistical analysis, the lithium dosing schedule of every second day did not maintain its prophylactic efficacy against recurrent episodes of manic-depressive disorder. The risk of relapse increased 3 times when the interval between intake of lithium was extended from 1 to 2 days.

Agreement in psychiatric assessment.

In 103 schizophrenic patients we investigated the extent of practice needed in the use of the Brief Psychiatric Rating Scale (BPRS) to enable its reliability to be assessed. The agreement level of the 7 raters was analysed. Generally, the lowest mean agreement found was for the negative symptoms of the BPRS schizophrenia subscale. A high degree of agreement was attained both for the positive symptoms of the BPRS schizophrenia subscale and for the symptoms of the depression--and of the mania subscale. The degree of disagreement observed was due to both individual differences in assessment ability and the rating procedure. These results indicate that it is necessary to state the degree of agreement achieved in studies in which several raters are taking part.

Effect of amitriptyline on the thyrotropin response to thyrotropin-releasing hormone in endogenous depression.

Patients with endogenous depression whose depressive episodes were clinically resolved after electroconvulsive therapy were divided into two groups: one in which patients remained well (n = 16) and another in which patients relapsed within 6 months (n = 11). Treatment with amitriptyline for 3 weeks did not affect the median thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) in recovered patients, whereas that in relapsed patients was significantly enhanced. The data suggest that amitriptyline affects the TSH response to TRH differently in stably recovered and relapsed patients. If this effect is maintained beyond the 3-week period studied, treatment with amitriptyline will invalidate the predictive value of the TRH test.

Dexamethasone suppression test, TRH test and Newcastle II depression rating in the diagnosis of depressive disorders.

The dexamethasone suppression test (DST), the thyrotropin releasing hormone (TRH) test and the Newcastle II depression rating (NII) were compared with the clinical diagnosis and evaluated in 61 patients fulfilling the criteria of an affective disorder according to the DSM-III classification. A statistically significant correlation between clinical diagnosis and DST as well as NII, but not between clinical diagnosis and TRH test, was found. There was no correlation between DST and the severity of depression according to the Hamilton depression rating. The nosographic and the diagnostic specificities and sensitivities for the DST, TRH test and NII and DST and NII, a nosographic sensitivity of 50% and a nosographic specificity of 84% were found. Correspondingly, the diagnostic sensitivity was 43% and the diagnostic specificity was 88%. The DST and the TRH test were found of no value in the prediction of the response to antidepressive treatment. Mainly because of a low diagnostic sensitivity the NII, the DST and the TRH test are of limited value in the diagnosis of depressive disorders.

Prediction of relapse with the TRH test and prophylactic amitriptyline in 39 patients with endogenous depression.

The authors conducted a double-blind prospective study of 39 patients with unipolar endogenous depression who recovered after ECT. Thyrotropin (TSH)-releasing hormone (TRH) tests were performed before and after ECT. Patients were divided into three groups on the basis of their altered TSH response: Persistent remission was predicted for patients in group 1 (N = 15) and relapse was predicted for groups 2A (N = 13) and 2B (N = 11). Patients in groups 1 and 2A received placebo and those in group 2B received amitriptyline for 6 months. Fewer relapses occurred in groups 1 and 2B than in group 2A (p less than .05), showing that relapse can be predicted by the TRH test and prevented by amitriptyline.

Dexamethasone suppression test and TRH test in endogenous depression.

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.

The histamine test in schizophrenia.

The cutaneous response to intradermal injection of 50 micrograms of histamine was studied in nonmedicated schizophrenic patients, schizophrenic patients treated with neuroleptic drugs, nonschizophrenic patients receiving neuroleptics, and nonmedicated controls. The diminished response previously reported in schizophrenic patients was not reproduced. Thus, the histamine test does not appear to be useful in diagnosing schizophrenia.

Circadian variation of serum thyrotropin in endogenous depression.

The circadian variation of serum thyrotropin (thyroid-stimulating hormone; TSH) was studied in nine patients with endogenous depression before and after recovery. Depressed state did not appear to influence the pattern of TSH. When 2 mg of dexamethasone was administered, serum TSH was significantly reduced for 18 hours, whereafter the effect leveled off. The TSH response to thyrotropin-releasing hormone (TRH) was evaluated 25 hours after the administration of dexamethasone and the response was found to be unchanged.

Addition of L-tryptophan to electroconvulsive treatment in endogenous depression. A double-blind study.

The combination of electroconvulsive treatment (ECT) and i.v. L-tryptophan (T) was compared with ECT and saline in double-blind study comprising 20 patients with endogenous depression. No significant difference was found with regard to the number of ECT given nor in the rate of reduction of depressive symptoms. Except for a slight decrease of plasma total tryptophan in the palcepo group, no difference were found in plasma total and free tryptophan nor in the concentration of total tryptophan in the cerebrospinal fluid.

Thyrotrophin-releasing hormone (TRH) stimulation test in manic-depressive illness.

The thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH 200 microgram intravenously was studied in 19 patients with unipolar depression, 12 with bipolar depression, 14 with mania, and 5 with mixed manic-depressive illness. The TSH responses were decreased in all of these affective disorders compared to those found in 10 patients with reactive depression, 5 with reactive paranoid psychosis, 14 with neurotic depression, and 60 controls. The decrease of the TSH response in manics could not be accounted for by the effects of neuroleptic drugs. The TSH response in the groups with reactive depression, reactive paranoid psychosis, and neurotic depression, respectively, did not differ significantly from that found in controls. With the exception of a decrease in serum T3 level and free T3 index in the manics, no significant differences in serum T3 level or in free T3 and T4 indexes were found between the groups. Changes found in serum T4 level were due to changes in the thyroxine-binding proteins.

Prognostic value of thyrotropin-releasing hormone stimulation test in endogenous depression.

Thyrotropin-releasing hormone (TRH) stimulation tests were performed in 19 patients with endogenous depression before treatment and when they had apparently recovered following antidepressive treatment. An increase in the maximal serum thyrotropin (TSH) response to TRH of more than 2.0 muU/ml was found in all of ten patients who did not relapse, while such an increase was found in only one of nine patients who did relapse within 6 months. I. e., a correct prognosis was possible in 94.7% (95% confidence limits 74.0 - 99.9%). Through significant changes were found in serum thyroxin (T4), free T4 index, serum triiodothyronine (T3) and free T3 index, these findings were of no prognostic value.

Protirelin stimulation test and thyroid function during treatment of depression.

Thyroid levels were estimated in 15 patients with endogenous depressions. Before electroconvulsive treatment (ECT), serum thyroxine (T4) and free T4 index values were elevated (P less than .02). After recovery from depression, the levels were normal. Serum triiodothyronine (T3) and free T3 index were normal both before and after ECT. Serum thyrotropin (TSH) levels were also normal and not substantially altered by the ECT procedure. The mean maximal TSH response to protirelin (thyrotropin-releasing hormone) was diminished in the depressed patients and normal after recovery. In three patients, the increase in TSH response to protirelin after recovery did not occur and they relapsed within six months, while in seven patients with increased TSH response to protirelin after recovery only one relapse occurred. The disturbances in the free T4 index, T4, and the protirelin test may in some depressed patients resemble hyperthyroidism, but this condition can be excluded by means of serum, T3 and free T3 index.