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This article presents information on the clinical features and treatment of herpes zoster. This information will help clinicians diagnose and manage herpes zoster pain.
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The influence of the oral administration of different doses of citalopram (5, 15 and 45 mg/kg), imipramine (15, 30, 45 and 60 mg/kg), nortriptyline (15, 45 and 60 mg/kg) and amineptine (45 mg/kg) on stress-induced analgesia has been studied in anaesthetized rats. None of the administered antidepressants seem to have appreciable analgesic activity when analgesia is tested by the tail-immersion method. Citalopram, imipramine and nortriptyline, but not amineptine, increase the analgesia induced by inescapable footshock delivered continuously for 2 min to rats. Citalopram is the most potent drug. Our results support the suggested importance of 5-HT and noradrenaline terminals, but not those of dopamine, in the mediation of the stress-induced analgesia and seem to support the hypothesis that the analgesic activity of antidepressants is partially related to their modulating effects on the endogenously released opioid peptides involved in the endogenous pain inhibitory systems.
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A systematic literature search from 1967 to 1996 identified relevant pediatric studies that evaluated cardiovascular effects of TCAs.
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Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.
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Sertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged > or =60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.
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Plasma levels of tricyclic antidepressant drugs vary considerably between individuals receiving the same amount of drug. The bearing of this variation on the occurrence of subjective side effects was investigated in 40 psychiatric inpatients with depressive disorders. Plasma levels were determined before and during four weeks of treatment with nortriptyline 50 mg. three times a day and patients were rated for subjective side effects, the assessors being unaware of the plasma levels of the drug.Plasma levels varied widely between individual patients, but in any given patient the plasma level tended to be constant over a period of time. The side effects of nortriptyline diminished significantly with time and were in most cases absent during the fourth week of treatment. There was a significant positive correlation between plasma level of nortriptyline and subjective side effects.The steady-state plasma level of a drug which is metabolized is usually a more important determinant for its effect than dosage, since it reflects the amount of drug available for biological action. Very high plasma levels of nortriptyline should presumably be avoided, since there is no evidence that they are needed for therapeutic effect and they are potentially harmful.
An assay technique for measuring anticholinergic drugs in human serum based upon their inhibition of the specific binding of [3H]-quinuclidinyl benzilate to rat brain muscarinic receptors is described. The assay was validated by demonstrating a close correlation (r = 0.99) between serum levels of nortriptyline measured by the radioenzymatic assay and a GLC technique. The assay measures free anticholinergics, and under standard assay conditions, approximately 95% of benztropine is bound to serum protein. Marked variation in serum anticholinergic levels in patients receiving the same oral dose was observed, and in individual patients there was a non-linear relationship between increasing oral dose and serum anticholinergic levels. In a cross-sectional study of 109 patients receiving concurrently neuroleptics and anticholinergics, there was no correlation (r = 0.029) between serum neuroleptic levels measured by radioreceptor assay and extrapyramidal side effects (EPS). In the patients whose serum anticholinergic levels were also determined, there was a significant inverse correlation (r = 0.44) between anticholinergic levels of EPS. In this cohort of patients, there was no significant correlation between serum anticholinergic and serum neuroleptic levels (r = 0.16) and the ratio of serum anticholinergic to serum neuroleptic was a poor predictor of EPS (r = 0.26). The results suggest a marked variation in sensitivity of patients to the EPS-inducing of neuroleptics; nevertheless, the incidence of EPS decreases with increasing serum levels of anticholinergics. An optimal serum anticholinergic level of 10 pmole atropine equivalent per ml was associated with a low incidence of EPS and is relevant to drug action at the striatal muscarinic receptor.
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We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model.
Plasma levels of amitriptyline and nortriptyline were measured twice weekly in 62 patients treated for three weeks with i.m. amitriptyline 120 mg/day. In half the patients the ratio of amitriptyline to nortriptyline was under 1 and in the other half it was greater than 1. 30 of these 62 patients were clinically monitored with the Hamilton Rating Scale and the side effects of the drug were recorded. There was no correlation between plasma level of the drug and its side effects, but there was a statistically significant curvilinear correlation between the plasma levels of amitriptyline plus nortriptyline and nortriptyline alone, and the clinical effect. The practical value of this type of investigation was demonstrated by showing that patients whose drug plasma level was not in the therapeutic range, were clinically improved after adjustment of the dose. The plasma level of amitriptyline plus nortriptyline must lie between 60 to 220 ng/ml, and that of nortriptyline between 60 to 140 ng/ml, to obtain the best clinical effect. Associated treatments, age, weight and sex of patients, and the type of depression did not appear significantly to affect the plasma level of the drug.
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To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia.
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Parameters for the binding of perazine (PER), amitriptyline (AT) and nortriptyline (NT) to plasma and to single plasma proteins were determined by equilibrium dialysis. The highest affinity (K at least 10(5) M-1) and lowest capacity (first site 1 mol/mol) towards all three drugs was exhibited by alpha 1-acid glycoprotein (alpha 1-AGP). From the parameters, alpha 1-AGP was estimated to contribute 43% to total binding of PER and 49 and 31%, respectively, to AT and NT binding in samples with normal protein concentrations. Fractions bound to total lipoproteins would amount to 32% (PER), 40 (AT) and 52% (NT), respectively, while the contribution of albumin would range from 11% (AT) to 25% (PER). The extent of the binding to plasma was compared with that to single proteins and their mixtures. Binding to combinations of alpha 1-AGP, lipoproteins and albumin exceeded that to plasma with PER but not with AT and NT. This leads to the assumption that additional plasma constituents interfere with PER binding.
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The purpose of this study was to summarize and compare the clinical success rates of extended-release venlafaxine, some selective serotonin reuptake inhibitors (SSRIs), and certain tricyclic antidepressants (TCAs). A meta-analytic approach was used to synthesize outcomes from published randomized controlled trials involving patients scoring > or =15 on the Hamilton Rating Scale for Depression (HAM-D) or > or =18 on the Montgomery-Asberg Depression Rating Scale (MADRS). Searches of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases were performed, as were searches of references from retrieved articles and reviews. Drugs included in the comparison were extended-release venlafaxine (venlafaxine-XR); the SSRIs citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the TCAs amitriptyline, imipramine, desipramine, and nortriptyline. Therapeutic success was defined as a 50% decrease in the HAM-D or MADRS score. Data were extracted by 2 independent evaluators, with differences resolved through consensus discussions. Weighted mean success rates were calculated for each drug class, using a random-effects model. The resulting data represent 44 trials with 63 study arms and 4033 patients with depression. Venlafaxine-XR demonstrated a 73.7% success rate, which was statistically significantly greater than that of the studied SSRIs (61.1%) and TCAs (57.9%) (P<0.001). Thus this meta-analysis of randomized controlled studies of patients with depression suggests that venlafaxine-XR is clinically superior in efficacy to SSRIs and TCAs. Venlafaxine-XR also had universally lower, though nonsignificant, dropout rates.
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Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11-14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed.
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1) For a large number of drugs, we do not yet know which cytochrome P-450 enzymes are involved in their metabolism; 2) For a large number of drugs, the consequences of a P-450 genetic polymorphism have yet to be determined; 3) Genetic polymorphism can lead to important potential clinical consequences for some opioids, anticonvulsants (phenytoin), benzodiazepines (diazepam), muscle relaxants (succinylcholine), antidepressants (imipramine, nortriptyline, venlafaxine), typical neuroleptics, alcohol, antihypertensives (propranolol, timolol), local anesthetics (procainamide), L-dopa, nicotine, and warfarin. Based on these results, factors for and against using genomic testing were reviewed.
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Subjects with depression may exhibit activation of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the response of basal hormone levels to antidepressant therapy.
Sixty per cent of the patients referred to two gastroenterological clinics and diagnosed as suffering from the irritable bowel syndrome (IBS), were found to have significant psychoneurotic morbidity on the basis of the General Health Questionnaire. A double-blind, completely randomised, placebo controlled comparison of treatment with a combined anxiolytic/antidepressant (Motipress) found a significantly better effect of Motipress than placebo on diarrhoea and abdominal pain. Detailed analysis of the results suggests that there is no direct relationship between psychoneurotic illness and IBS, but the presence of the former has an adverse effect on the short-term outcome of the bowel disorder.
Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the "soft signs" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life.
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ADRs reported with antidepressant treatment were categorised using their likely pharmacological basis; adrenergic, cholinergic, serotonergic and histaminergic. To identify genetic predictors of susceptibility to each group of ADRs, a candidate gene analysis was performed with data from 431 depressed patients (from a total sample size of 811 patients) enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, who were randomly allocated to receive treatment with escitalopram or nortriptyline. Data from 474 patients treated with citalopram or reboxetine in the GenPod project (total sample of 601 patients) were used for replication of significant findings.
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Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.
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It is recommended that children and adolescents on tricyclics receive an ECG at baseline and after each dose increase. Recommendations are made regarding ECG parameters and indications for cardiac consultation.
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On the basis of the present findings, it is tempting to speculate that an increase in brain energy metabolism by the antidepressant paroxetine, nortriptyline and venlafaxine could play a role in the mechanism of action of these drugs. These data corroborate with other studies suggesting that some antidepressants modulate brain energy metabolism.
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Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale.
The CORE study is the first multicenter, randomized controlled trial of continuation ECT in the relapse prevention of major depressive episodes. We successfully recruited a large number of severely depressed patients into a 6 month trial and used a method of reducing bias that might result from lack of blinding.
Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain.
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While there is a significant relationship between the CYP450 genotype and serum concentrations of escitalopram and nortriptyline, the genotypes are not predictive of differences in treatment response for either drug. Furthermore, differences in antidepressant serum concentrations are not associated with variability in treatment response.
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There is a significant pharmacokinetic interaction between diltiazem and nortriptyline, which is probably due to a reduction in the first pass clearance of nortriptyline, leading to an increase in its bioavailability.
The following methods were found to be more efficacious than placebo: tailored written advice, individual counselling, telephonic counselling, group courses, all forms of nicotine-replacement therapy, bupropion and nortriptyline. Acupuncture was not superior to placebo. It was not possible to draw any unequivocal conclusions about hypnotherapy. No randomised studies were found with respect to the 'Allen Carr method'. Rates of 12 months' continuous abstinence were as follows for those methods with proven efficacy: tailored advice: 7%, individual counselling: 16%, telephonic counselling: 7.5%, nicotine gum: 17%, nicotine patch: 13%, nicotine inhaler: 17%, nicotine tablets: 20%, bupropion: 17%, and nortriptyline: 24%. The success rates for nicotine tablets and nortriptyline were based on only 2 and 1 study respectively.
CVRF scores were generated with the Probability of Stroke Risk Profile. Subjects with the highest one-third of scores were designated High CVRF, and their baseline clinical presentation and treatment outcomes were compared with the remaining subjects.
The aim of this review is to assess the effectiveness of antidepressant medications in aiding long term smoking cessation. The drugs include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; selegiline; sertraline, tryptophan and venlafaxine.