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

This article reviews critically the present status of lithium in the treatment and prophylaxis of manic-depressive illness compared to the two anticonvulsant drugs, carbamazepine and valproic acid. Lithium is used successfully in the prophylaxis and treatment of manic-depression. The mechanism by which it exerts its effects is still not very clear. There is much evidence to indicate that lithium may exert its therapeutic action by interfering with the metabolism of phosphoinositides which play an important role in synaptic transmission. Because of lithium's narrow therapeutic/toxic ratio, blood concentration monitoring is crucial. Published data suggest that, compared to lithium, carbamazepine is similar in its relative specificity in treating mania. It is often faster in achieving its antimanic effects and best established as an alternative for patients not responding or intolerant to lithium. Carbamazepine is a good substitute for lithium when severe renal problems exclude the use of lithium. The therapeutic profile of valproic acid in manic-depression, although less extensively studied, appears to be similar to that of carbamazepine. As carbamazepine, it seems to be best indicated in patients with rapid cycles. Whereas lithium inhibits myo-inositol monophosphatase, carbamazepine shows a stimulating effect and valproic acid has no effect on this biochemical target. The implication of the inositol pathway in the pathogenesis of adverse effects, such as neurotoxicity and dermatological irritation, is discussed. A further understanding of this pathway is important for the future development of new lithium-like compounds in order to maximize the therapeutic benefits without the adverse effects.
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PMID:Lithium therapy in the treatment of manic-depressive illness. Present status and future perspectives. A critical review. 883 46

Bipolar disorder is characterised by recurrent episodes of mania and depression. The major objective of long term treatment is to reduce the frequency of these episodes. Lithium is the most widely recommended drug for this purpose, having been shown in controlled clinical trials to be more effective than placebo in reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical practice is less than that predicted from these trials. A major cause of relapse is noncompliance, largely due to intolerance to adverse effects such as perceived mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9 mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms, which if unchecked can cause brain damage and even death. The anticonvulsant drugs carbamazepine and valproic acid (sodium valproate) are potential alternatives to lithium. Patients who relapse frequently despite lithium may benefit from the addition of one of these agents, although formal clinical trial evidence of the efficacy of such combination treatment is lacking. Antipsychotics, administered as a depot formulation, can reduce the likelihood of relapse in patients with frequent manic episodes, especially if associated with poor compliance. Psychological treatment and patient education have been shown to improve outcome, and should be made more widely available to all patients with bipolar disorder.
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PMID:Long term treatment of bipolar disorder. 909 68

Hormones of the thyroid axis have been used to treat patients with any of several mental illnesses. However, in recent decades interest has focused almost exclusively on depression, though thyroid hormones, mainly thyroxine (T4), are used with lithium in rapid cycling bipolar disorder, a condition in which depression and mania rapidly alternate. In depression L-triiodothyronine (T3) has been used in preference to T4 because of its rapid onset and offset of action. In women starting treatment, T3 hastens the onset of therapeutic action of standard antidepressant drugs. It fails to do so in depressed men, who anyway respond faster than women to standard antidepressants. Standard drugs fail to produce satisfactory improvement in one-quarter to one-third of depressed patients. Then, in both men and women, T3 converts about two-thirds of drug failures to successes in rapid fashion. Lithium, which has antithyroid properties, produces a similar conversion rate. The majority of depressed patients are grossly euthyroid, but many show one or another subtle change in thyroid axis activity. However, the thyroid state of patients has not been matched systematically with their response to thyroid hormone augmentation. It seems likely that a tendency toward hypothyroidism can predispose to depression, but when depression occurs in a euthyroid patient, the thyroid axis is often invoked in the process of restitution.
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PMID:Novel uses of thyroid hormones in patients with affective disorders. 893 85

Recent years have seen the introduction of several new antidepressants, many of which have selective effects on serotonin (5-HT) pathways. In most patients these drugs are as effective as traditional tricyclic antidepressants and are somewhat better tolerated. In the most severe depressive disorders, however, drugs such as clomipramine, that produce potent inhibition of both 5-HT and noradrenaline reuptake may be more effective. Lithium is increasingly used in the treatment of resistant depression but its role in the short-term management of mania is less certain because of the increased risk of relapse on sudden discontinuation. In the treatment of mania and prophylaxis of bipolar disorder, carbamazepine and valproate are alternatives to lithium. In dementia, the cholinesterase inhibitor, tacrine, produces worthwhile improvement in about 40% of patients able to tolerate adequate doses. There is concern about adverse effects of antipsychotic drugs in patients with dementia, particularly those with Lewy body disease.
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PMID:Advances in psychopharmacology: mood disorders and dementia. 894 56

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.
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PMID:Management of the depressive component of bipolar disorder. 916 51

The majority of cases of central diabetes insipidus are still pathogenetically unclear (idiopathic). Atherosclerotic cholesterol emboli might be partly responsible for some of these idiopathic cases. A 54-year-old woman with known aortic valve stenosis and a history of a transitory ischemic attack presented with sudden-onset polyuria and polydipsia of up to eight l/d, which had started acutely with headaches. She had been treated with lithium for 3 years because of cyclothymic depression. Plasma sodium was in the upper normal range (142-148 mmol/l). Hypertonic saline infusion during lithium therapy revealed a normal threshold of thirst and resetting of vasopressin secretion (osmotic threshold > 300 mosmol/l), whereas vasopressin reserve was normal. Lithium withdrawal led to an even greater delay of vasopressin release upon hypertonic saline infusion (> 310 mosmol/l). Pituitary function tests revealed a normal anterior pituitary function. MR imaging of the hypothalamo-hypophyseal region showed a normal hypothalamic region and a highly intensive neurohypophyseal signal in the T1-weighted image. The patient responded well to desmopressin. We suggest that in this rare case clinical symptoms as well as biochemical findings like impairment of AVP release might be related to a minor structural hypothalamic damage by a vascular lesion, caused, for example, by an atheromatous (cholesterol) embolism in the hypothalamic region responsible for integration of osmoreceptor function and AVP-secretion. The patient's atherosclerosis and aortic stenosis might be responsible for this event.
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PMID:Atherosclerosis, aortic stenosis and sudden onset central diabetes insipidus. 928 11

Depending on its intensity and duration, nutritional deficiency can disrupt the structure and function of the nervous system of humans and other mammals, with consequences more or less devastating for the whole organism, particularly in the early postnatal life, when body growth is very rapid and the need for proteins, calories and other nutrients is greatest. In this review, electrophysiological data are presented regarding the use of the phenomenon of cortical spreading depression (CSD) to study effects of malnutrition on the brain. Several conditions of clinical importance and that are known to alter brain function are shown also to influence CSD features in experimental animals. Some of these conditions, (e.g., pharmacological manipulation of neurotransmitter systems, dietary treatment with Lithium, acute hyperglycemia, hypothyroidism, aging and environmental stimulation) decrease CSD susceptibility, while other conditions increase it, as, for example, systemic reduction of extracellular chloride levels, deprivation of REM-sleep, acute hypoglycemia, treatment with diazepam, consumption of ethanol and malnutrition. Particular emphasis is laid on the effect of early environmental enrichment on CSD in normal and malnourished animals. Our results suggest that such effect is more evident in the malnourished brain, as compared to the well-nourished one. The data also show that malnutrition alters the brain responsivity to some CSD-facilitatory or inhibitory agents. The underlying mechanisms to explain the observed effects are discussed.
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PMID:Malnutrition and brain function: experimental studies using the phenomenon of cortical spreading depression. 939 8

1. In this article some of the most important and tolerated drugs in the elderly are reviewed. 2. Tricyclic antidepressants have to be used carefully because of their important side effects. Nortriptyline and desipramine appear to be the best tolerated tricyclics in old people. 3. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose. 4. MAO inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy and the last generation drugs (reversible MAO inhibitors), such as moclobemide, seem to be very successful. 5. Lithium is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients due to its side effects. 6. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide, or drug-resistant forms.
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PMID:Antidepressant drugs in the elderly. 952 61

Lithium is one of the most studied agents used to augment the pharmacologic effect of antidepressant drugs, particularly in refractory depression. We reviewed 22 case reports, 22 open trials, 5 open comparison studies, and 9 placebo-controlled studies of lithium augmentation and 6 studies in which antidepressants were added to, or coadministrated with, lithium. The efficacy of the augmentation therapeutic strategy is supported by these analyses, involving 969 patients. The optimal dose and the most effective blood levels of lithium are unclear, but a reasonable strategy would be to start with low doses (600-900 mg/day) and, if necessary, to increase the doses to obtain a level in accordance with the usual therapeutic range of blood levels (0.8-1.2 mEq/L). Some patients respond quickly, but others need a long and combined treatment; it is thus advantageous to prescribe lithium for at least 3 to 6 weeks. Despite the fact that the mechanism of action of lithium augmentation is still unknown, all refractory depressed patients can potentially be treated by lithium augmentation, particularly bipolar patients, to obtain full prophylactic effect as soon as possible.
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PMID:The use of lithium to augment antidepressant medication. 963 46

Lithium remains a first-line approach for the treatment of acute mania and the prophylactic management of manic-depressive illness, yet the underlying neurobiological mechanisms remain as yet undefined. In this paper we critically examine the accumulated preclinical and clinical evidence for the action of lithium in the brain and suggest areas that may be most productive for future investigation, i.e., membrane transport systems, neurotransmitter receptor regulation, second messenger generating systems, protein kinase C (PKC) regulation, and gene expression. In their experimental design, preclinical investigations have often jeopardized the physiologic relevance of their studies by a relative lack of attention to issues such as therapeutic concentrations, acute versus chronic exposure, and a lack of adequate cation and/or psychotropic controls. Future studies should account for the established prophylactic efficacy of lithium, the higher risk for relapse into mania after abrupt discontinuation, the ability of lithium to stabilize recurrent depression associated with unipolar disorder, and the efficacy of lithium in the treatment of refractory major depressive disorder in the presence of an antidepressant. Studies of the action of lithium in receptor mediated phosphoinositide signaling in the brain over the past several years have opened up heuristic lines of investigation that stem from lithium's uncompetitive inhibition of the enzyme inositol monophosphatase. Subsequent studies involving regulation of inositol transport, PKC isozymes and activity, and the expression of the major PKC substrate MARCKS (myristoylated alanine-rich C-kinase substrate) have offered potential avenues for understanding the complexity of the action of long-term lithium in the brain. These studies will offer us a better understanding of the neuroanatomical sites of action of lithium and together with ongoing clinical investigations using brain imaging in patients with manic-depressive illness a more complete understanding of the pathophysiology of this disease.
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PMID:Neurobiology of lithium: an update. 967 36


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