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Forty of 42 patients (95%) completed the trial, of whom 23 (58%) responded to treatment. Highly significant improvement was documented on measures of depression, reversed neurovegetative symptoms, and somatic symptoms. Response was significantly correlated with severity of depression (pre-MAOI score on the Hamilton Rating Scale for Depression), severity of a composite score of anergic and reversed neurovegetative features, and low levels of improvement during initial imipramine/interpersonal psychotherapy. Of patients who met criteria for proposed subforms of anergic or atypical depression, 67% (18/27) responded (p less than .05); 77% (17/22) of patients who scored above the mean on the composite measure of anergic and reversed neurovegetative features responded (p less than .01).
To identify the factors that influence response to treatment of vesical instability.
These results support the distinction between early-onset and late-onset dysthymic disorder.
Sixty out-patients with different nosological types of depression were assigned at random to three different treatment groups and were treated under double-blind conditions for 6 weeks. Two groups received diclofensine in capsules of either 15 or 25 mg, and a third group received capsules with imipramine 25 mg. The dosage schedule provided an initial dose of 2 capsules/day which was to be gradually increased up to a maximum dose of 9 capsules/day. The daily mean dosages actually given over the entire trial period were 64.0 mg diclofensine for group I, 97.6 mg diclofensine for group II, and 102.9 mg imipramine for group III. All treatment groups showed a good improvement of the patients' clinical states within the 6-week period, but the imipramine-treated patients improved more slowly than the diclofensine-treated patients. This was demonstrated by the mean total scores of the Hamilton Depression Rating Scale (HDRS). Evaluation of different factors of the HDRS yielded differences between the two drugs in favour of diclofensine for the factor 'inhibition' from the end of week 1 until the end of week 3 and for the factor 'somatic complaints' during week 3. Side effects were - dose dependently - less frequent, less severe, and lasted shorter in the diclofensine-treated patients than in the imipramine-treated ones. The most frequently reported side effects in the diclofensine-treated patients were dry mouth, insomnia, dizziness, and agitation. In the imipramine group side effects were mainly dry mouth, tremor, dizziness, and sleepiness. In conclusion, this study shows an impressively faster onset of efficacy of diclofensine over imipramine, a finding which should be replicated by further studies.
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The Bmax of [3H]imipramine (IMI) binding has been reported to be reduced in platelets of depressed untreated patients as compared with normal controls. However, it has also been suggested that this difference could be related to the failure to take into account seasonal variations in the binding parameters for [3H]IMI recognition sites in platelets. For this reason, [3H]IMI binding was studied throughout 1 year in platelet membranes from 11 control volunteers, with blood samples collected once a month. The Bmax and Kd values of [3H]IMI binding showed no significant variation throughout the 12-month period of the study. These results indicate that in the control population, the platelet [3H]IMI binding parameters remain stable, and that the decrease in Bmax observed in depressed untreated patients reflects a genuine difference, which may be considered to be a biological marker in depression.
Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 micrograms/l, with concentrations above 500 micrograms/l in 11 cases. The serum amitriptyline concentration remained high for 3-4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 micrograms/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidepressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60-500 micrograms/l) but not high (greater than 500 micrograms/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
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In the presence of 10(-6) M atropine, 5-HT induced a positive chronotropic and inotropic effect in isolated guinea-pig atrium preparation. Both propranolol, a beta-adrenoceptor blocker, and imipramine, a 5-HT uptake inhibitor, did not affect the response induced by 5-HT, indicating that a tyramine-like mechanism is not involved. The positive chronotropic effect of 5-HT was mimicked by several 5-HT3 receptor agonists. N omega-Methyl-5-HT, reported to have a high affinity for 5-HT1B recognition sites, was found to act as a 5-HT3 receptor agonist with higher efficacy. The other 5-HT receptor agonists tested did not produced any responses. The positive chronotropic effect of 5-HT was inhibited by various 5-HT3 receptor antagonists, such as tropisetron, granisetron, ondansetron, cisapride and zacopride, but it was unaffected by various 5-HT receptor antagonists which are not selective for 5-HT3 receptor. Thus, the positive chronotropic response to 5-HT is a direct effect, and it was suggested to be mediated by 5-HT3 receptor subtype with rather an atypical profile.
Anxiety and depression are among the most common conditions cited by those seeking treatment with complementary and alternative therapies, such as exercise, meditation, tai chi, qigong, and yoga. The use of these therapies is increasing. Several studies of exercise and yoga have demonstrated therapeutic effectiveness superior to no-activity controls and comparable with established depression and anxiety treatments (e.g., cognitive behavior therapy, sertraline, imipramine). High-energy exercise (i.e., weekly expenditure of at least 17.5 kcal per kg) and frequent aerobic exercise (i.e., at least three to five times per week) reduce symptoms of depression more than less frequent or lower-energy exercise. Mindful meditation and exercise have positive effects as adjunctive treatments for depressive disorders, although some studies show multiple methodological weaknesses. For anxiety disorders, exercise and yoga have also shown positive effects, but there are far less data on the effects of exercise on anxiety than for exercise on depression. Tai chi, qigong, and meditation have not shown effectiveness as alternative treatments for depression and anxiety.
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Lithium is the established standard in the long-term treatment of bipolar disorder, but several new drugs have been assessed for this indication. We did a network meta-analysis to investigate the comparative efficacy and tolerability of available pharmacological treatment strategies for bipolar disorder.
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The preliminary results of wall-incorporated antireflux valve are encouraging. It is technically simple and easy. It is not time consuming and requires a shorter ileal segment than that required for the intussuscepted valve. Staples are not used. The vascular pedicle is not manipulated. The wall-incorporated valve is suitable for the normal, dilated, or short ureter. Despite limited clinical experience, the valve may provide a reliable technique for reflux prevention in bladder substitutes.
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Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.
In the learned helplessness model, rats that received bilateral microinjection of HSV-CREB into the dentate gyrus showed significantly fewer escape failures in the subsequent conditioned avoidance test than those injected with control vector (HSV-LacZ). In contrast, microinjection of HSV-CREB in either the CA1 pyramidal cell layer of hippocampus or the prefrontal cortex did not produce an antidepressant response. In the forced swim test, CREB expression in the dentate gyrus resulted in a significantly shorter immobility time than those injected with HSV-LacZ.
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Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients. In a six-week, double-blind multicenter comparison of alprazolam, imipramine hydrochloride, and placebo in the treatment of 723 patients with depression, the two active drugs were statistically more effective than placebo. Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. Anticholinergic side effects were reported most often by patients receiving imipramine, while drowsiness was the only side effect reported most often in the alprazolam group. The Feighner Diagnostic Criteria and prestudy and poststudy intercenter conferences with videotaped patient interviews ensured interrater reliability.
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The activity of some metabolizing enzymes was assessed in the liver microsomes of Acomys cahirinus, mice and rats. The enzymatic studies were followed by the determination of cerebral level of apomorphine (APO), imipramine (IMI) and its metabolite desipramine (DMI) of animals treated with a single dose of APO or IMI. It was found that the level of cytochrome P-450 and the activity of IMI demethylase and glucuronyltransferase in the liver microsomes of rats was significantly higher than those in the liver microsomes of Acomys and mice. The brain levels of APO, IMI and DMI were different in investigated species and IMI and DMI levels in the brain of Acomys, mice and rats corresponded to the activity of IMI demethylase in the liver microsomes of these species.
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Relationship between the chronic and excessive exposure to glucocorticoids and the development of psychiatric disorders, including depression, has been described in the literature. We decided to investigate whether a combination of agents with antidepressant activity (i.e., imipramine, ketamine, and Zn(2+)) may influence/reverse the depressogenic effect of dexamethasone therapy. The antidepressant-like effect was assessed by the forced swim test in adult mice. The inhibitory activity of dexamethasone was dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64 μg/kg) given as a single injection increased immobility time, whereas 16 μg/kg/day of dexamethasone administered repeatedly (for 14 days) induced a significant alteration in animal behavior. Both the acute or sub-chronic administration of the active doses of imipramine (10 mg/kg), Zn(2+) (30 mg/kg), and ketamine (30 mg/kg), and the combinations of their per se inactive doses reversed the inhibitory activity of dexamethasone (16 μg/kg/day) administered for 14 consecutive days. Whereas a single injection of an inhibitory dose of dexamethasone (64 μg/kg) was not able to abolish the antidepressant effect of imipramine (5 mg/kg), Zn(2+) (10 mg/kg), and imipramine-Zn(2+) combination (2.5 and 5 mg/kg, respectively) given once a day for 14 consecutive days. Our findings indicate that the chronic dexamethasone injection procedure has some potential as an animal model of depression and they further support the theory of interplay between glutamatergic neurotransmission and the chronic or excessive exposition to glucocorticoids.
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ERPs are described as a new dependent variable class allowing a dynamic exploration of cognitive activities. Attentional processes play a fundamental role in those activities. An original conception of attention is outlined. In this view, attention is considered as responsible of managing of different cognitive processes. The interest of attentional impairment assessment with ERPs particularly in psychiatric disorders such as depression is underlined. This is illustrated by Buchsbaum M.S. et al. (1988) study. These authors recorded EPs, during a continuous performance test, in 3 groups of depressive patients under amoxapine, imipramine or placebo. Results showed in the amoxapine group and enhanced N120 amplitude in midline and right parietal cortex. In normal subjects, an amplitude increase in those areas usually reflects a selective attention effect. Behavioral performance was improved in the amoxapine group compared to that of patients who received imipramine or placebo. This improvement as soon as 48 h after drug administration could be related to the higher amoxapine affinity for serotonin S2 receptors.
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Initial lithium-TCA treatment reduced depressive symptoms significantly more than TCA alone. The difference was evident from 1(st) week onward and persisted at 4 weeks.
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The objective of this investigation was to study the effect of different terpenes on IMH permeation in EtOH:W (2:1) system. Permeation studies of IMH were carried out with unjacketed Franz diffusion cells through rat skin. The flux of IMH with terpenes was found to be significantly higher than that in control (EtOH:W, 2:1) (P<0.05). Amongst all studied terpenes, menthol, terpineol, cineole and menthone were found to be effective permeation enhancers for IMH. It was found that the contribution of diffusivity in enhanced permeation of IMH was much higher in comparison to partitioning of IMH in skin with terpene treatment. Results of this study were explained with the help of H-bond breaking potential and self-association of terpenes. In order to elucidate the effect of terpenes on stratum corneum barrier FT-IR was used.
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SSRI and the SNRI reboxetine inhibit RWA at doses not suppressing LOC. RWA may represent a simple behavioral readout of positively motivated behavior that merits further attention for psychopharmacology.
Electroconvulsive therapy (ECT) is the most effective treatment in a variety of psychiatric syndromes (especially mood disorders). However one of its adverse effects is neurocognitive dysfunction. Declarative memory impairment after ECT is unquestionable and well investigated. There are only few ambiguous studies focused on nondeclarative and immediate memory changes during ECT.
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The present study was designed to investigate the central nervous system activity of terpene GABA (and piracetam) derivatives designated as BF-1, BF-2, BF-3, BF-4, BF-5, BF-6. We assessed their anticonvulsant activity in the two main mouse models of seizures (MES-test, PTZ-test), an antidepressant-like effect in the forced swim test (FST), as well as an influence on spontaneous locomotor activity. Our study demonstrated the strong anticonvulsant activity of (1S,3R,7R)-(-)-3,8,8-trimethyl-4-aza-bicyclo[5.1.0]acetate-5-one hydrochloride (compound BF-2) in the PTZ-test. Activity of BF-2 was equipotent to ethosuximide (380 mg/kg, po) in the PTZ-test, when used at a dose of 100 mg/kg, po. No neurotoxic effects were demonstrated by administration of all tested compounds. Moreover, BF-2, BF-3, BF-6 compounds significantly reduced the immobility time in FST at both doses (by 21-50%), while BF-5 induced a significant anti-immobility effect only when used at a dose of 100 mg/kg (by 39%). The compound BF-6 used at the dose of 30 mg/kg was the most active (50% reduction), and the effect was similar to the result obtained with classical antidepressant--imipramine. The motor stimulatory activity was demonstrated by BF-1 compound at the dose of 100 mg/kg with no effect at a lower (30 mg/kg) dose. On the other hand, the BF-3 at 30 mg/kg significantly decreased spontaneous activity during 30 min observation period, while no alteration in this activity during 6-min observation was detected. At present, it is not possible to indicate which mechanisms of novel, active terpene GABA derivatives are involved in the demonstrated antidepressant-like activity. Although further studies are needed to solve this issue, these data suggest a potential value of the examined terpene GABA derivatives.
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The release of 3H-(-)-noradrenaline (NA) from rat vas deferens in vitro was examined under various experimental conditions. It was found that in normal and reserpinized vas deferens the release of NA evoked by (+)-amphetamine (5 X 10(-6) M) or low external Na+ (26 mM) was antagonized by imipramine methiodide and desipramine, inhibitors of the NA uptake, but was not dependent on the presence of Ca2+ in the medium and was not antagonized by the potent local anaesthetic agent bethoxycaine. The release evoked by veratridine in reserpinized tissue was antagonized by the uptake inhibitors but was in normal tissue only partially inhibited in presence of Ca2+ but almost completely in absence of Ca2+. The release by high K+ (117 mM)+low Na+ (26 mM) in normal tissue was dependent on the presence of Ca2+ and was antagonized by the muscarinic agonists carbacholine and metacholine and by high concentrations of desipramine. In the reserpinized vasa the corresponding release was not dependent on Ca2+ and was not antagonized by the muscarinic agents but was inhibited by high concentrations of desipramine.
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To characterise the 5-hydroxytryptamine (5-HT) receptor subtypes mediating contraction of the inferior alveolar artery. Additionally, to determine the role of cyclooxygenase products, nitric oxide, endothelium, monoamine oxidase and 5-HT uptake in modulating contraction of inferior alveolar arteries to 5-HT.
Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater.
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This report describes a middle-aged female who received imipramine for 7 days, developed severe cholestatic jaundice with features similar to primary biliary cirrhosis, and then improved clinically over the next 12 mo. Biochemical and histologic abnormalities persisted over a 14-yr period of follow-up, though subsequent administration of haloperidol may have influenced the long-term course. High levels of circulating immune complexes were also found 14 yr later, which raises questions about the relationship of primary biliary cirrhosis to drug-induced liver injury. A review of the literature on imipramine- and phenothiazine-related hepatic injuries reveals multiple similarities, and this case provides further evidence for a common hepatic reaction to the two drugs.
75 outpatients who presented to an affective disorder clinic received the dexamethasone suppression test (DST). Following 1 week observation, and following 1 week on low-dose imipramine HCl, all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of imipramine HCl (150-300 mg/day) over a minimum 3- to 5-week period. Of the 45 patients who required this trial and who received imipramine HCl for at least 3 weeks, there was no relationship between DST suppression or nonsuppression vs. clinical response to imipramine HCl. There was a statistically significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose imipramine HCl as opposed to nonsuppressors (positive DST).
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One hundred and fifty-two women undergoing mastectomy were randomly assigned to routine care or routine care plus monitoring by a specialist nurse. The nurse detected and referred 76% of her patients for psychiatric help. Only 15% of the routine care subjects that warranted help were referred. Twelve to eighteen months after surgery, morbid anxiety and depression were less common in the monitored (5% and 5%) than in the control (30% and 50%) group. This difference appeared to be due primarily to psychiatric treatment which included antidepressant medication, anxiolytic drugs, and supportive psychotherapy. Few affective disorders remitted without such treatment. In a further study, the effects of antidepressant medication plus cognitive therapy and cognitive therapy alone were compared. Both treatments alleviated depression in the short term but the improvement was sustained in the long term only in those given combined treatment.
The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine-resistant depression-model mice. In order to utilize GLP-2 as a clinical treatment tool for depression, we herein focused on the intranasal delivery that is non-invasive approach, because the i.c.v. administration is invasive and impractical. In the present study, we prepared a GLP-2 derivative containing cell penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS-CPPs-GLP-2) for the intranasal (i.n.) administration. PAS-CPPs-GLP-2 (i.n.) exhibited antidepressant-like effects in the forced-swim test (FST) and tail suspension test (TST) in naïve mice as well as adrenocorticotropic hormone (ACTH) treated-mice. However, PAS-CPPs-GLP-2 (i.v.) and the GLP-2 derivative containing CPPs without a PAS (CPPs-GLP-2) (i.n.) did not affect the immobility time in the mouse FST. Moreover, fluorescein isothiocyanate (FITC)-labeled PAS-CPPs-GLP-2 (i.n.), but not FITC-labeled CPPs-GLP-2 (i.n.) was distributed through the mouse brain after the FST session. These results suggest that PAS-CPPs-GLP-2 is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of major depression.