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)

The major complications of therapy in PD are motor, autonomic and psychiatric. Motor complications may be associated with altered striatal bioavailability of levodopa, and may in part respond to changes in timing of drug administration, redistribution of dietary protein and the use of controlled-release preparations. Since long-term complications seem to be associated with higher cumulative doses of levodopa, the early use of adjunctive agents such as deprenyl and/or dopamine agonists is encouraged. Autonomic effects include impaired bladder and bowel function, impotence and postural hypotension. If conservative measures are ineffective, pharmacotherapy with domperidone, fludrocortisone, indomethacin or adrenergic agents may be required. Depression in PD is associated with decreased levels of noradrenaline and 5-HT and responds to tricyclic antidepressants. Drug-induced psychosis reflects stimulation of mesolimbic-cortical dopamine receptors. Alternatives include reduction of medication, the use of atypical neuroleptics (which may act at novel subtypes of the dopamine receptor) and electroconvulsive therapy.
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PMID:Prevention and management of late stage complications in Parkinson's disease. 157 55

Neuropsychiatric symptoms are a frequent feature of advancing Parkinson's disease (PD). The reported prevalence of depression varies greatly between different studies but there is general consensus that between 40 and 50% of patients will be affected. Depression may antedate motor manifestations of Parkinson's disease and is usually of moderate or mild intensity. However, depression is of major impact on the quality of life in PD patients according to a recent survey. Drug-induced psychosis is one of the major therapeutic challenges in Parkinson's disease and may occur in up to 6% in otherwise uncomplicated de novo patients when first receiving dopaminergic therapy. It increases in frequency, in advanced disease and particularly in patients with dementia where up to 22% may be affected. There is an amazing lack of controlled clinical trials assessing the effects of antidepressants in clinical trials including more than 20 patients and assessing efficacy of antidepressants specifically in the context of mood changes in Parkinson's disease. A comprehensive literature search yielded only a total of 17 articles of which a majority included less than 20 patients and/or did not use valid depression ratings. The only randomized controlled trial was conducted more than 20 years ago using nortryptiline while no controlled trials were available on the use of serotonin reuptake inhibitors. Studies assessing the antidepressant action of dopaminergic therapies are few and inconclusive. Thus, while tricyclic antidepressants or SSRIs are widely used in clinical practice, there is still a need for controlled clinical trials proving their efficacy specifically in parkinsonian depression. Three randomized controlled trials are now available assessing the efficacy of the atypical neuroleptics clozapine and olanzapine in the treatment of drug-induced psychosis. While clozapine is of proven efficacy at least in the short-term management of this complication without negative impact on the motor symptoms, olanzapine in currently used doses of 2.5 to 15 mg/d seems to aggravate motor symptoms with lesser effect on psychosis compared to clozapine. Currently, clozapine is the atypical neuroleptic of choice for the treatment of drug-induced psychosis in Parkinson's disease.
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PMID:Treatment options for depression and psychosis in Parkinson's disease. 1169 83

The pathological hallmark of Parkinson's disease (PD) is a degeneration of the dopamine (DA) producing cells in the substantia nigra and the ventral tegmentum, resulting in a dopamine deficiency in the dopaminergic projection areas with defective functioning of specific cortico-subcortical extrapyramidal circuits. Depending on which circuits (;motor', ;association' or ;limbic') are involved, and on the extent of the accompanying noradrenergic, serotonergic and cholinergic detrition in PD, dysfunction may result in motor deficits, mood disturbances or cognitive deficits, sometimes proceeding to dementia. Drug-induced psychosis occurs in approximately 15-20% of patients treated with dopaminergic agents. In PD, mainly nigrostriatal dopamine (A9) is depleted, leading to progressive motor dysfunction with subtle cognitive disturbances. As a rule, the neuropsychological deficit in PD might be described as the inability to switch cortical behavioral programmes in situations requiring the internal regulation of behavior. In daily life, in most patients these deficits do not become manifest, due to the abundance of external information to guide behavior. When the ability to use environmental information or external cues is lost as well, significant cell loss in the ventral tegmental area, with reduced DA-innervation of the mesocorticolimbic regions and the nucleus accumbens, must be suspected. This leads to clinically overt defects not only in the ;motor' but also in the ;limbic' and ;association' circuits. In addition to more severe cognitive disturbances or even dementia, this may also lead to mood disorders and drug-induced psychosis. Depression then occurs as the cortical modulation of limbic activity has become deficient, leading to emotional reactions disproportionate to the thoughts that evoke them. The proposed mechanism of psychosis in PD is that cortical sensory input is misinterpreted, leading to misperceptions (hallucinations) or false beliefs about reality due to a reduced ;signal-to-noise' ratio by insufficient processing of relevant information.
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PMID:Mental dysfunction in Parkinson's disease. 1859 Oct 98

On a day in November, the body of a 31-year-old man was found near a swimming lake with two open and partly emptied fish tins lying next to him. Further investigations showed that the man had been allergic to fish protein and suffered from severe depression and drug psychosis. Already some days before the suicide, he had repeatedly asked for fish to kill himself. Although the results of the chemical and toxicological examinations were negative, the autopsy findings and histological tests suggest that death was caused by an anaphylactic reaction.
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PMID:Suicide of a man with known allergy to fish protein by ingesting tinned fish. 2389 84