Lithium augmentation in antidepressant-resistant patients.
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Antidepressive Agents↗
Biomedical subjects
F G Souza
Publications and source records attributed to F G Souza.
The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder.
Thyroid and adrenal function was assessed in euthymic bipolar patients, stable on prophylactic lithium for at least 1 year, before and after lithium discontinuation in a randomised double-blind placebo-controlled trial. All hormonal measurements were within the reference range, but a significant increase (P less than 0.001) in plasma thyroxine (T4) levels and a decrease (P less than 0.01) in TSH levels were observed 1 month after lithium withdrawal; cortisol concentrations showed a non-significant decrease in the same period. No relationship could be demonstrated between the magnitude of the change in hormone levels and the probability of relapse of manic symptoms. In the second part of this study, inositol was added for 11 days to the diets of bipolar patients being treated with prophylactic lithium and normal controls. No modification was shown in T4 and TSH in either group before or after inositol administration. Inositol did not alleviate other side-effects such as tremor and thirst in the patient group. This result suggests that short-term dietary inositol is not equivalent to lithium withdrawal and is of no value in reducing hormonal and other adverse effects of lithium prophylaxis.
Adult↗
Lithium treatment and prophylaxis in unipolar depression: a meta-analysis.
Meta-analysis was used to establish the efficacy of lithium in acute treatment and prophylaxis of depressive illness from existing published clinical trials. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method and the Pearson product-moment correlation coefficient. Some benefit from lithium, compared with other treatments, emerged from trials of acute treatment. Lithium was clearly superior to placebo in the acute treatment of bipolar depressed patients. In controlled studies of lithium prophylaxis over five months to three years, an impressive effect was found for lithium when compared with placebo. For uncontrolled studies there was a similar-sized effect, corresponding to an improvement in the rate of favourable outcome from 35% for placebo to 70% with lithium treatment. The comparison of lithium with other antidepressants in prophylaxis showed no conclusive advantage for lithium in unipolar illness. There is no reason to doubt the efficacy of lithium in the prophylaxis of unipolar depressive illness.
Antidepressive Agents↗
Lithium augmentation in antidepressant-resistant patients. A quantitative analysis.
A quantitative analysis was used to examine the efficacy of lithium augmentation in the acute treatment of depressed patients resistant to a standard trial of an antidepressant. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method. Only controlled trials were included in order to minimise bias in method. A highly statistically significant effect for lithium augmentation was found, the pooled odds ratio being 0.146 and its 95% confidence interval 0.05-0.44 (i.e. the odds of remaining ill are reduced by between 56% and 95% with the use of lithium treatment). While these results support the case for lithium augmentation in treatment-resistant depression, there remains considerable uncertainty over the duration of treatment necessary to see and sustain the treatment response.
Antidepressive Agents↗
The efficacy of lithium in prophylaxis of unipolar depression Evidence from its discontinuation.
Forty unipolar patients satisfying DSM-III criteria for major depression who discontinued lithium therapy were retrospectively compared with 105 similar patients who continued the drug and served as a control group. The time to readmission from starting lithium was compared while both groups were still on lithium, and after discontinuation in one group and further continuation in the control group. The progressive increase in the probability of recurrence over two years was the greatest after discontinuation of lithium. For the patients who eventually discontinued lithium, the cumulative probability of recurrence in two years was 0.08 on lithium and 0.58 after stopping it. The probability of recurrence was unchanged over the duration of the study for patients who continued to take lithium. There was no evidence of a lithium withdrawal syndrome within three months of stopping the drug. The results support the view that the everyday clinical use of lithium as prophylaxis is beneficial in unipolar depression.
Bipolar Disorder↗
Isolation and characterization of human brain aminopeptidase which hydrolysis enkephalin-containing peptides.
A human brain aminopeptidase, which hydrolyses low molecular weight enkephalin-containing peptides (ECPs), was purified to apparent homogeneity from the homogenate of human brain. The enzyme purification involved DEAE-cellulose chromatography and preparative polyacrylamide gel electrophoresis. The purified aminopeptidase hydrolyses only the Tyr1-Gly2 bond of enkephalines and of ECPs. The rate of hydrolysis of Met-enkephalin and Leu-enkephalin was higher than the rate of hydrolysis of ECPs containing 7 to 13 aminoacid residues. Large ECPs such as peptide E and beta-endorphin were not hydrolysed. The molecular weight of this enzyme is about 100,000 daltons, as determined by gel filtration on Sephadex G-200 and by polyacrylamide gel electrophoresis in presence of sodium dodecyl sulfate. The enzyme has an isoelectric point of pH 4.9, is activated by dithiothreitol (DTT) and inhibited by puromycin, bacitracin, p-mercuryacetate, Zn++, Cu++ and Ni++. The optimum pH for enzyme activity is 7.5.
Amino Acids↗