Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.
 ...
PMID:The effects of lithium therapy on thyroid and thyrotropin-releasing hormone. 982 58

Patients receiving antidepressant monotherapy may be partially or totally resistant to treatment in 10 to 30 percent of cases. In patients who have experienced only partial treatment results, the clinician should first consider optimizing antidepressant dosage or lengthening therapy. Antidepressant drug substitution should generally be reserved for use in patients who haven't responded at all (nonresponders). Combining two or more antidepressants is generally not recommended, as this approach may obscure adequate monotherapy evaluation and lead to significant adverse effects or drug-drug interactions. Use of electroconvulsive therapy is recommended in patients with psychotic and severe refractory depression. Augmentation therapy is often efficacious in patients who exhibit a partial antidepressant response. Lithium and thyroid hormone have been the most extensively studied augmentative agents but, more recently, pindolol and buspirone have also been used for this purpose.
 ...
PMID:Practical management of treatment-resistant depression. 986 79

Augmentation therapy is used for those situations where a patient's depression is either treatment-resistant, or partially and/or insufficiently responsive to treatment. It also may be used to attempt to induce a more rapid treatment response. Using drugs together may increase the risk of adverse effects, through potentiation of existing adverse effects or alterations in plasma concentrations of the drug. It is important that clinicians are aware of potential risks of augmentation therapy. Lithium augmentation of a tricyclic antidepressant is relatively well tolerated and the dangers are no greater than using these medications on their own. There are also no reports of serious adverse events when lithium is added to a monoamine oxidase inhibitor. With lithium augmentation of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) therapy there have been case reports of the development of a central serotonin syndrome, and thus caution must exercised. A serious concern when using a tricyclic antidepressant to augment an SSRI is the effect of the SSRI on the cytochrome P450 system and the resulting significant increase in tricyclic antidepressant blood concentrations. Augmentation with thyroid hormones appears to be well tolerated and effective. Case reports and open studies indicate that augmentation with buspirone and the psychostimulants, carbamazepine and valproic acid (valproate sodium) is effective and results in minimal adverse effects. However, there is no empirical evidence supporting these results. Recent work supports the tolerability and efficacy of pindolol augmentation. Considerable caution should be exercised when combining psychotropic drugs. The practitioner should only do so with a full knowledge of the compounds involved and their pharmacological properties.
 ...
PMID:Risk of adverse events with the use of augmentation therapy for the treatment of resistant depression. 988 89

Lithium carbonate at the dose level of 1.1 g/kg was administered in diet to normal (18% protein), low-protein- (LP; 8%) and high-protein (HP; 30% diet)-fed rats for a period of 1 mo. The LP diet resulted in a significant decrease in the hepatic levels of zinc, iron, copper, manganese, calcium, and serum levels of calcium and sodium. The HP diet caused a marked decrease in copper and calcium levels in liver, but an increase in potassium levels in serum was observed. Lithium treatment to normal rats led to a significant reduction in the hepatic contents of zinc, copper, potassium, calcium, and serum contents of potassium and sodium, whereas an elevation in serum contents of calcium was noticed. Administration of lithium to protein-deficient rats increased the hepatic concentration of manganese and serum concentration of calcium and the levels almost reached the normal limits. On the other hand, there was a marked depression in potassium contents in the serum of LP- as well as HP-fed rats following lithium treatment when compared to LP and HP groups, respectively.
 ...
PMID:Effect of lithium on hepatic and serum elemental status under different dietary protein regimens. 1020 56

The aim of this short review was to collate the data involving the effects of lithium alone, or in combination, with antidepressant drugs in several animal models of depression. It has been shown that lithium administration reduced immobility in the mouse forced swimming test when given 30 min, but not 45 min, before testing. Further studies indicated that this activity was probably a result of an activity on serotonin (5-HT) 1A and 1B receptor subtypes. Lithium treatment has been shown to reverse helpless behaviour in the learned helplessness model of depression after chronic treatment (30 days), where lithium was administered in the drinking water. Further studies showed that acute (5 days) administration of lithium failed to reverse behavioural deficits. In the olfactory bulbectomised rat model of depression, several immunological and enzymatic functions have been shown to be altered and these changes are regularised by antidepressant treatment as well as lithium administration for 15 days. Hypokinesia (reduced locomotor activity) is a phenomenon observed following immobilisation stress in rats. This behavioural deficit was attenuated by lithium together with a wide range of antidepressant drugs used in the treatment of unipolar depression at non-stimulant doses. In addition, a single administration of lithium slightly inhibited midbrain raphe lesion-induced muricidal behaviour (25%); however, repeated treatment (5 days) significantly attenuated this behavioural deficit. Lithium treatment has also been shown to reverse behavioural and biochemical deficits induced by reserpine together with those induced by acute administration of single intracerebroventricular (i.c.v.) dose of the Na, K-ATPase-inhibiting compound, ouabain. Long-term studies of lithium augmentation have not been performed, so that no clear recommendations for the duration of this therapy can be made. The points raised in this short review endorse the commencement of such studies.
 ...
PMID:The effect of lithium administration in animal models of depression: a short review. 1039 5

The addition of lithium to the treatment regimens of previously nonresponding depressed patients has been repeatedly investigated in controlled studies. The authors undertook this meta-analysis to investigate the efficacy of lithium augmentation of conventional antidepressants. An attempt was made to identify all placebo-controlled trials of lithium augmentation in refractory depression. Only double-blind studies that involved participants who had been treated with lithium or placebo addition after not responding to conventional antidepressants were to be included in the meta-analysis. Further inclusion criteria were the use of accepted diagnostic criteria for depression and the use of response criteria based on the acceptable measurement of depression as an outcome variable. Studies were located by a search of the MEDLINE database, a search in the Cochrane Library, and an intensive search by hand of reviews on lithium augmentation. Nine of 11 placebo-controlled, double-blind studies were included in this meta-analysis. Aggregating three studies with a total of 110 patients that used a minimum lithium dose of 800 mg/day, or a dose sufficient to reach lithium serum levels of > or = 0.5 mEq/L, and a minimum treatment duration of 2 weeks, the authors found that the pooled odds ratio of response during lithium augmentation compared with the response during placebo treatment was 3.31 (95% confidence interval, 1.46-7.53). The corresponding relative response rate was 2.14 (95% confidence interval, 1.23-3.70), the absolute improvement in response rate was 27% (95% confidence interval, 9.8%-44.2%), and the number of patients needed to be treated to obtain one more responder was 3.7. Inclusion of six more studies that fulfilled inclusion criteria but which treated subjects with additional lithium for less than 2 weeks or with a lower lithium dose (total, 234 patients) resulted in even higher estimates. Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients who fail to respond to antidepressant monotherapy.
 ...
PMID:Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. 1077 Apr 84

The algorithms for the treatment of bipolar disorder are presented. Lithium is the first choice when treating acute mania. Other options are antipsychotics or mood stabilizers such as carbamazepine and valproate. Mood stabilizers (often in combinations) are drugs of choice for maintenance treatment. For the treatment of acute depression under lithium maintenance, increase doses of lithium or addition of antidepressants may be necessary.
 ...
PMID:Algorithms for the pharmacotherapy of bipolar disorder. 1056 Aug 97

Lithium is a difficult drug to use. Although it is effective in the management of mania, manic-depressive illness and recurrent depression, its unwanted effects are troublesome and the dose needs to be titrated against measurements of blood levels. With care, however, the risks can be minimized. Here we discuss lithium and approaches to optimize its use.
 ...
PMID:Using lithium safely. 1056 60

Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by glycogen synthase kinase 3beta (GSK-3beta) and inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] signalling. This article describes recent experiments in cell and developmental biology that advance our understanding of how lithium works and it presents new directions for the study of both depression and Alzheimer's disease (AD).
 ...
PMID:Lithium therapy and signal transduction. 1066 10

To evaluate whether lithium treatment has been overvalued and may be no longer as effective as formerly, we reviewed published reports on long-term lithium treatment (1970-1996) as well as analyzing its clinical effects on 360 patients with DSM-IV bipolar disorder who entered into lithium maintenance monotherapy after 1970. Neither reported recurrence rates nor average proportions of time ill nor patient improvement of 50% or more during lithium maintenance therapy in a stable clinic setting has changed significantly since the 1970s. Unfavorable results in some settings may reflect accumulation over time of patients with complex, less treatment-responsive illnesses. Lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders. Data evaluated herein did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently.
 ...
PMID:Does lithium treatment still work? Evidence of stable responses over three decades. 1157 37


<< Previous 1 2 3 4 5 6 7 8 9 10