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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychiatric research has made remarkable advances in understanding the pathophysiology of depressive illnesses. Biologic depressions are now understood as neurotransmitter deficiency diseases. Certain forms of depression are treated with tricyclic antidepressant drugs, which increase the amount of available neurotransmitters. Complicating the clinical picture, however, is the problem of wide variability of levels of tricyclic drugs in the plasma of persons receiving the same dosage. Another problem is the apparent linear dose-response relationship of imipramine hydrochloride and its sister compound desipramine hydrochloride while amitriptyline and nortriptyline follow an inverted U-shaped dose-response curve. However, with newer, more sophisticated diagnostic methods, combined with monitoring of tricyclic drug levels in plasma, therapeutic efficacy can approach 90 percent. Available neurotransmitters also can be increased using monoamine oxidase (MAO) inhibitors. Although MAO inhibitors have been less popular than the tricyclic drugs, recent clinical research tends to support their efficacy. Distinct individual differences in the rate of metabolism of MAO inhibitors have been found. New methods are being devised to detect these differences and monitor directly the effects of these drugs. One of these methods, platelet MAO inhibition, shows some clinical promise. Tricyclic drugs and MAO inhibitors have recently been joined by lithium carbonate, which shows notable efficacy in removing acute manic-depressive symptoms as well as preventing their return during maintenance treatment. Its utility in treating cyclic depressions without mania is now being explored by researchers.
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PMID:Recent advances in antidepressant drug treatment. 39 Aug 88

A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression.
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PMID:Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients. 39 42

1. The first part of the paper is devoted to a critical review on the possible relationships between depression and monoamine oxidase. 2. This study describes the results of an investigation of MAO-activity in depression, using new approaches and methodology. This methodology was developed because the literature data indicated that a) previous results are difficult to compare because of varying methods and diverse target populations used; b) previous methodological deficiencies do not allow to draw definite conclusions about the relationship between MAO-activity and depression. 3. The present investigation selected 35 psychiatric patients according to clearly defined diagnostic criteria (20 endogenous depressive, 10 neurotic depressive, and 5 manic patients) matched to 25 healthy control-subjects. 4. The Michaelis-constant (Km), the maximum reaction speed (Vmax), and the 50% enzyme inhibition by tranylcypromine (IC50) of platelet-MAO were determined during and after recovery from the depressive or manic episode using 3 substrates (tyramine, tryptamine, and phenylethylamine). 5. The present investigation, in contrast to conventional methodology, utilized three different substrates at different concentrations. Significant correlations were demonstrated for the Vmax-values of each of the three substrates, whereas the Km and the IC50 (tranylcypromine)-values varied for each substrate. 6. The results show that there were no differences between the characteristics of the platelet-MAO in depressive or manic patients and those of normal subjects. Furthermore, treatment with tricyclic antidepressants had no effect on MAO-activity. A previous investigation indicated that the MAO-properties in human brain tissue were similar to that in human platelets.
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PMID:Depression and monoamine oxidase. 40 Oct

1. In humans, norepinephrine (NE) has been postulated to be involved in the regulation of mood and behavior and to be altered in patients with manic-depressive illness. 2. Recent methodological advances have made possible a more direct assessment of central noradrenergic activity by the accurate measurement of the small amounts of NE and of the enzyme responsible for the conversion of dopamine to NE, dopamine-beta-hydroxylase (DBH), found in cerebrospinal fluid (CSF). 3. Cerebrospinal fluid samples were obtained from depressed patients both before and after treatment with two monoamine oxidase-inhibiting antidepressant drugs, clorgyline and pargyline. 4. Patients were rated twice daily by nursing staff on a modified 15-point scale for severity of global depression and anxiety. Patients were also rated using the Hamilton depression rating scale. 5. High negative correlations were observed between the drug-related changes in CSF NE and the changes in depression ratings on both the global ratings (r = -.95, p less than .001) and the Hamilton rating scale (r = -.81, p less than .01). Changes in NE were also highly correlated with changes in global anxiety ratings (r = -.85, p less than .01) calculated on the basis of changes from baseline for each measurement. Drug-related changes in CSF DBH similarly showed negative correlations with clinical response (r = -.79, r = -.38, r = -.68 respectively). In contrast, no significant correlations were found when drug-related changes in CSF MHPG were compared to changes in clinical state.
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PMID:The central noradrenergic system and affective response to MAO inhibitors. 40 Oct 4

3,4-Dihydroxy-5-fluorophenylalanine, fluorodopa, was injected into rats in which unilateral lesions of the nigrostriatal pathway had been made. The rats rotated towards the side with the lesions, thus providing further evidence that fluoro-dopa is an analogue of dopa. [(18)F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A well-collimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of (18)F in the brain. Control animals accumulated (18)F continuously for 100 min. This accumulation represents net transport of [(18)F]fluoro-dopa from blood to brain, decarboxylation to [(18)F]fluoro-dopamine, storage, and degradation of [(18)F]fluoro-dopamine. alpha-Methyl-dopa, a competitive inhibitor of dopa transport and decarboxylation, prevented the accumulation of (18)F; reserpine, known to release stored intracerebral dopamine, discharged (18)F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of (18)F. These changes in the accumulation of intracerebral (18)F, after [(18)F]fluoro-dopa, were commensurate with the known action of the drugs used to induce them and demonstrate the use of a gamma-emitting precursor of a neurotransmitter to monitor simply, atraumatically, and externally the intracerebral metabolism of the transmitter in fully conscious primates. When applied to man, the same technique should be able to provide more conclusive evidence than is presently available for the role of catecholamines in schizophrenia and depression. It should also provide further insight into the natural history of nigrostriatal diseases and the action of drugs used in their treatment.
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PMID:[18F]fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine. 41 9

The blood platelets, which serious arguments permit one to consider as valid models of serotoninergic neurones, were studied in various types of depression and during treatment with antidepressor drugs. The modifications of several platelet parameters were analysed in particular. The level of hydroxyndoles (OH-5-tryptamine or 5-HT for example) is generally lowered. The uptake of 5-HT is also reduced with normalisation by antidepressor treatments; the fixation of mepacrine, sign of the passive uptake of bioamines, is modified in the same direction, especially, in our experience, in maniacs, with a rise during treatment with phenothiazines. Finally, among the platelet enzymes, monoamine oxidase has a reduced activity in bipolar depressed patients, certain maniac depressive psychosis, and endogenic melancholias. Other platelet parameters, (liberation or release, nucleotide levels, 5-HT bonds at membrane level, etc.) may provide in the future, interesting information. In spite of sometimes contradictory data, the platelet model may be of interest, especially from pharmacological point of view.
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PMID:[The platelet model applied to the study of depressive illness (author's transl)]. 44 12

In the last two decades, there has been rapid progress in the pharmacologic treatment of affective disorders. In Part I of this review, drugs mainly used for depression (tricyclic antidepressants and monoamine oxidase inhibitors) were discussed. Here, lithium carbonate, the most effective drug for manic-depressive illness (bipolar depression) is the focus. Its indications, mode of action, pharmacokinetics, dosage, and side effects are discussed. A section on drug interactions with lithium deals with the combination effect of lithium used with antidepressant and other psychotropic agents.
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PMID:Series on pharmacology in practice. 1. Drugs that alter mood. II. Lithium. 44 9

Data from double-blind, placebo-controlled trials of the monoamine oxidase (MAO) inhibitors show that phenelzine is clearly effective in neurotic or atypical depressives, but the findings concerning its effect in endogenous depressives are inconclusive. Although few controlled studies have been done with tranylcypromine, similar conclusions are warranted. Studies have contrasted MAO inhibitors and tricyclic antidepressants (TCAs) to gain further information about the type of patients likely to respond to MAO inhibitors. We believe that simply contrasting the relative efficacy of TCAs and MAO inhibitors is outdated. Neurotic or atypical depression is probably a heterogeneous syndrome, and delineation of subtypes responsive to specific antidepressants is needed. The implications of fast acetylation, selective MAO inhibitors, types MAOA and MAOB, and measures of platelet MAO inhibition are discussed in this article.
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PMID:Monoamine oxidase inhibitors. A review of antidepressant effectiveness. 45 92

Nomifensine is a tetrahydoisoquinoline antidepressant which is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or the recently introduced agents. Nomifensine resembles the tricyclic antidepressants in many of its pharmacological effects in animal models of depressive illness, but differs from them in that it strongly inhibits the re-uptake of dopamine as well as noradrenaline and is a relatively weak inhibitor of serotonin uptake. It has an overall efficacy comparable with that of imipramine and amitriptyline in depressive illness, but at dosages which have achieved a similar overall clinical improvement, nomifensine causes little or no sedation, fewer and milder anticholinergic side effects, and also appears less likely than these drugs to cause serious cardiotoxicity on overdosage. Nomifensine may aggravate the psychopathology of patients with schizo-affective disorders and intensification of the psychosis may require neuroleptic therapy. Nomifensine also has antianxiety activity, but its role in treating anxiety associated with primary depression has still to be clarified. Nomifensine appears to be well tolerated by the elderly.
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PMID:Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness. 47 72

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.
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PMID:Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate. 49 44


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