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 ability of antidepressant drugs, electroconvulsive treatment (ECT), or lithium chloride (LiCl), to modify prolactin secretion in the rat was studied. Chlorimipramine, citalopram, fluoxetine, imipramine and zimelidine potentiated the low dose 5-hydroxytryptophan (5-HTP)-induced increase in prolactin secretion, suggesting inhibition of serotonin (5-HT) uptake by these drugs. Amitriptyline, doxepin, iprindole, mianserin and trazadone inhibited the prolactin stimulating effects of high doses of 5-HTP and quipazine, suggesting that these drugs have 5-HT receptor blocking properties. Tandamine inhibited only 5-HTP-induced increase in prolactin secretion. Chronic administration of imipramine, potentiated the effect of low dose 5-HTP significantly more than an acute dose. Amitriptyline, produced similar inhibition of the 5-HTP-induced increase in prolactin secretion after both acute and chronic administration. The ability of bupropion and mazindol to inhibit alpha-methylparatyrosine-induced prolactin secretion, and of nomifensine to inhibit reserpine-induced prolactin secretion, is consistent with other evidence that these agents are indirect dopamine (DA) agonists. Desipramine, acutely, had no effect on any of the above paradigms but after chronic administration, potentiated the effect of low dose 5-HTP on prolactin secretion. Nortriptyline had no effect on prolactin secretion after acute or chronic treatment. ECT for 10 days did not affect the ability of a 5-HT agonist or d-amphetamine to modify prolactin secretion. However, chronic, but not acute, treatment with LiCl markedly enhanced the prolactin response to 5-HT agonists and reserpine while shifting the dose response curve for d-amphetamine and apomorphine to the right. These results are discussed in light of current theories of the role of 5-HT and DA in depression.
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PMID:Effect of antidepressants, lithium and electroconvulsive treatment on rat serum prolactin levels. 697 60

Nineteen patients with L-DOPA treated parkinsonism involving depressive symptoms, the therapeutic effect of nortriptyline was compared to placebo in a controlled trial. The depressive and neurological symptoms were evaluated by rating scales. Nortriptyline had a clinical significant effect with regard to the depressive symptoms, whereas the neurological parameters were unchanged. The authors suggest the depression in Parkinson's disease to be of both reactive and endogenous origins.
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PMID:Anti-depressive treatment in Parkinson's disease. A controlled trial of the effect of nortriptyline in patients with Parkinson's disease treated with L-DOPA. 701 Aug 75

Depression is a common, but treatable, source of suffering, excess disability, and caregiver strain in late life. It is important to take a long-term view of the treatment of late-life depression because of the high risk for relapse, recurrence, and chronic illness. Elderly patients with medical and neurological illness or bereavement-related depressions also merit greater attention. Recent data highlight several important caveats: (a) the role of medical and psychosocial factors in the course of major depression; (b) variability in etiology, clinical presentation, and treatment response; (c) need for additional studies of syndromal and subsyndromal depression in primary and long-term care facilities, particularly in patients > 75 years of age; and (d) importance of continuation and maintenance treatment to maintain quality of life and to lower the risk for chronic illness. Nortriptyline, desipramine, and the newer selective serotonin reuptake inhibitors (SSRIs), paroxetine and sertraline, are preferred pharmacotherapy for short-term and long-term treatment. The newer SSRIs should be further studied in controlled trials of elderly depressed patients, including those > 75 years and those with medical or neurological illness. Psychotherapy also appears to be of major importance in successful outcome but, as does pharmacotherapy, merits further controlled investigation in both short- and long-term clinical trials.
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PMID:Treatment of depression in late life. 799 26

The prevalence of depression in the elderly suggests that a substantial number of older patients will be treated with an antidepressant medication such as one of the tricyclics, trazodone, fluoxetine or lithium. The physiological changes that accompany aging raise the possibilities of altered pharmacokinetics, patterns of efficacy and adverse effect profiles. The literature addressing the subject of antidepressant use in the elderly has not provided a clear, consistent picture of how these drugs behave in this population in comparison with younger patients. Particularly in the case of the tricyclic antidepressants (TCAs), a large degree of interindividual variation in drug clearance (CL) confounds attempts to find differences attributable to age per se. Study design, however, is also a problem in that very few investigators include a young control group, choosing instead to compare their data with previously reported outcomes. Designations of statistical significance and positive correlation also differ among investigators, and the clinical significance of any finding is not always addressed. The available data suggest that imipramine CL is reduced in the elderly and that amitriptyline CL may be reduced. Desipramine CL does not appear to be affected by age, although decreased renal function in the elderly may lead to accumulation of the hydroxylated metabolite, the clinical importance of which is not known. Nortriptyline is the most thoroughly studied TCA in the elderly. CL seems decisively lower only in elderly patients with concurrent medical illness. The hydroxylated metabolite probably accumulates with diminishing renal function. Not enough data are available on doxepin to make a conclusion. Trazodone CL is diminished somewhat in elderly men. Lithium CL appears to diminish with the declining renal function associated with aging. Fluoxetine data are sparse. Available data do not show any decrease in CL of the parent drug; more information is needed on the metabolite norfluoxetine. Although knowledge of CL changes with aging can help the clinician more accurately achieve the desired steady-state concentration of a drug during long term therapy, much work is still needed to evaluate the relationships among drug concentrations at steady-state, efficacy and adverse effects in the elderly.
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PMID:Clinical pharmacokinetics of antidepressants in the elderly. Therapeutic implications. 847 Oct 78

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.
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PMID:Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation. 937 52

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

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. 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 and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. 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:Conventional and new antidepressant drugs in the elderly. 1072 80

Research on treatment-resistant depression in the elderly has been limited, and recommendations for clinical management have often been extrapolated from studies using nongeriatric patients. This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline after failing to respond to an adequate trial of a serotonin reuptake inhibitor. Seven (70%) of the patients responded to the addition or substitution of nortriptyline. All seven of the responders have remained on nortriptyline for maintenance therapy, none of whom have experienced recurrence of their depression after an average treatment duration of 1 year. Response to nortriptyline occurred in about 4 weeks in most patients. The mean daily dose of nortriptyline was 54 mg, and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients. No patients developed significant electrocardiogram changes. Nortriptyline, possibly due to its different mechanism of action, may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to serotonin reuptake inhibitors.
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PMID:Nortriptyline in geriatric depression resistant to serotonin reuptake inhibitors: case series. 1128 13

A patient in stage 3-4 of the Unified Parkinson's Disease Rating Scale (UPDRS), or in stage 4-5 of Hoehn and Yahr staging scale, or a patient with 0-50% activities of daily living scale of Schwab and England is considered a Late Parkinson's Disease (LPD) patient. The prevalence of disturbed sleep in Parkinson's Disease (PD) was found to vary according to an objective rating, from 60 to 98%. The factors predicting the quality of life in PD patients are: depression, sleep disturbances and dependence. The present article proposes the insertion of the following items as a chapter in a revised UPDRS based on updated knowledge in sleep arousal disturbances in PD. V. SLEEP-AROUSAL DISTURBANCES: Sleep disturbances 43. Light fragment sleep (LFS) 44. Sleep-related breathing disorders (SRBD) 45. Restless legs-periodic leg movements during sleep (RLS-PLM) 46. REM behavioral disorders (RBD) 47. Sleep-related hallucinations (SRH) 48. Sleep-related psychotic behavior (SRPB) Arousal disturbances 49. Sleep attacks (SA) 50. Excessive daytime sleepiness (EDS). Approaching the treatment of disturbed sleep in LPD means postponement of the institutionalization of the LPD patient, allowing the spouse or the caregiver a quiet nights sleep. This approach consists of three steps, each one of major importance. (1) Correct diagnosis based on detailed anamnesis of the patient, of the spouse or of the caregiver; a one week recording on a symptom diary (log) by the patient or the caregiver; excluding co morbidities. Then choosing the most appropriate sleep test, if necessary: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), actigraphy or video-PSG. This first step allows the diagnosis of one of the above mentioned sleep-arousal disturbances. (2) The non-specific therapeutic approach consists of: (a) checking the sleep effect on motor performance: beneficial, worse or neutral. (b) Dopaminergic adjustment is necessary due to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. L-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio-physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.
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PMID:Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS. 1148 77

Depression is associated with increased cardiovascular mortality in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate variability (HRV) or heart period variability has been linked to sudden death in patients with cardiac disease as well as in normal controls. Recent studies have shown decreased vagal function in cardiac patients with depression as well as in depressed patients without cardiac illness. In this study, we compared 20 h awake and sleep heart period nonlinear measures using quantification of nonlinearity and chaos in two groups of patients with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of treatment with paroxetine or nortriptyline. Patients received paroxetine, 20-30 mg/day or nortriptyline targeted to 190-570 nmol/l for 6 weeks. For HRV analysis, 24 patients were included in the paroxetine treatment study and 20 patients in the nortriptyline study who had at least 20000 s of awake data. The ages of these groups were 60.4 +/- 10.5 years for paroxetine and 60.8 +/- 13.4 years for nortriptyline. There was a significant decrease in the largest Lyapunov exponent (LLE) after treatment with nortriptyline but not paroxetine. There were also significant decreases in nonlinearity scores on S(netPR) and S(netGS) after nortriptyline, which may be due to a decrease in cardiac vagal modulation of HRV. S(netGS) and awake LLE were the most significant variables that contributed to the discrimination of postparoxetine and postnortriptyline groups even with the inclusion of time and frequency domain measures. These findings suggest that nortriptyline decreases the measures of chaos probably through its stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Nortriptyline was also associated with a significant decrease in nonlinearity scores, which may be due to anticholinergic and/or sympatholytic effects. As depression is associated with a strong risk factor for cardiovascular mortality, one should be careful about using any drug that adversely affects cardiac vagal function.
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PMID:Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate. 1242 59


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