All groups (clomipramine [n=9], fluoxetine [n=10], placebo [n=11]) showed a significant improvement after 12 weeks of treatment. There were significant differences between the fluoxetine and placebo groups in some ratings of anxiety severity and impairment. No significant differences were observed between clomipramine and placebo groups or between fluoxetine and clomipramine groups.
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A controlled study comparing salbutamol (6 mg/day) to clomipramine (150 mg/day), both given by intravenous infusion, was performed on depressed inpatients (10 per group). The symptomatology was evaluated by two blind observers at days 0, 5, and 15 using the Hamilton Rating Scale. Both treatments were effective on the overall symptomatology but the onset of action of salbutamol was more rapid.
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A double-blind, randomized trial of oral vs intravenous clomipramine hydrochloride pulse-loading dosing regimens was conducted. After a two-week drug-free assessment period, 22 inpatients with a diagnosis of major depressive disorder were given either an evening infusion of 150 mg of clomipramine hydrochloride and placebo tablets or 150 mg of oral clomipramine hydrochloride and an isotonic saline infusion. Twenty-four hours later, this procedure was repeated using a dose of 200 mg of clomipramine hydrochloride. Patients received no further medication over the next five days. The mean Hamilton Depression Rating Scale score for all patients, five days after pulse loading, had dropped by 35% (range, 13.3% to -82.4%). This improvement was significant, as was the amelioration in the Raskin Severity for Depression Scale and the Beck Depression Inventory scores. Although the bioavailability of parenteral clomipramine was greater, there were no significant differences in either efficacy or side effects between the two groups. Pronounced early improvements in severe depressive symptoms may be achieved via loading dose regimens with clomipramine in the absence of continuous treatment.
The effect of an experimental subarachnoid hemorrhage (SAH) upon neurotransmitter content in sympathetic nerves supplying the major cerebral arteries of the rat has been examined by immunohistochemical analysis and high performance liquid chromatography with electrochemical detection (HPLC-ECD). In particular, changes that occur in sympathetic nerve content of the vasoconstrictor agents serotonin (5-HT) and neuropeptide Y (NPY), which are colocalized with noradrenaline, were assessed. Subarachnoid hemorrhage was induced by a single injection of autologous arterial blood into the cerebrospinal fluid (CSF) space of the cisterna magna. The density of 5-HT-containing and NPY-containing perivascular nerve fibers per unit area of vessels was measured at defined intervals from 15 min to 5 days post-SAH. In addition, an HPLC study was performed to quantify the actual amounts of 5-HT and noradrenaline present in circle of Willis vessels at 3 h post-SAH. Comparison was made with sham-operated animals and animals that received a cisternal injection of buffered saline in place of blood. Our results reveal a major increase in cerebrovascular sympathetic nerve content of serotonin, arising by uptake, presumably from subarachnoid blood clot, within the first 3 h post-SAH. Neuropeptide Y content, however, decreased from 3 up to 48 h posthemorrhage. By 3 days post-SAH, when the majority of subarachnoid clot had resorbed, the sympathetic nerve content of both NPY and 5-HT was restored to normal. This pattern of change was not observed in either sham-operated or saline-injected controls.
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Lung cancer is the most feared of all cancers because of its heterogeneity and resistance to available treatments. Cancer stem cells (CSCs) are the cell population responsible for lung cancer chemoresistance and are a very good model for testing new targeted therapies. Clomipramine is an FDA-approved antidepressant drug, able to inhibit in vitro the E3 ubiquitin ligase Itch and potentiate the pro-apoptotic effects of DNA damaging induced agents in several cancer cell lines. Here, we investigated the potential therapeutic effect of desmethylclomipramine (DCMI), the active metabolite of Clomipramine, on the CSCs homeostasis. We show that DCMI inhibits lung CSCs growth, decreases their stemness potential and increases the cytotoxic effect of conventional chemotherapeutic drugs. Being DCMI an inhibitor of the E3 ubiquitin ligase Itch, we also verified the effect of Itch deregulation on CSCs survival. We found that the siRNA-mediated depletion of Itch induces similar anti-proliferative effects on lung CSCs, suggesting that DCMI might exert its effect, at least in part, by inhibiting Itch. Notably, Itch expression is a negative prognostic factor in two primary lung tumors datasets, supporting the potential clinical relevance of Itch inhibition to circumvent drug resistance in the treatment of lung cancer.
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Electroencephalograms (EEGs) were recorded from 13 unmedicated and nondepressed patients with DSM-III-R obsessive-compulsive disorder (OCD) and from 10 age-matched controls. All subjects were also administered the Wechsler Memory Scale Delayed Logical Memory and Delayed Visual Reproduction tests. Quantitative analysis of the EEG revealed lower log absolute power in the delta, beta 1, and beta 2 bandwidths for OCD patients at frontal and right-hemisphere locations. OCD patients displayed greater hemispheric asymmetries in EEG activity based on difference measures of EEG power from homologous electrode pairs, indicative of severe right hemisphere EEG hypoactivity. Standardized measures of hemispheric asymmetry for the beta 2 bandwidth accurately predicted group membership and were correlated both with poorer patient performance on the visual-spatial memory task and better performance on the verbal memory task. OCD patients were significantly impaired on the visual-spatial task, but not on the verbal memory test, relative to controls.
We searched the Cochrane Neuromuscular Disease Group Register, MEDLINE, EMBASE, and LILACS (all to August 2005) and the Chinese Biomedical Retrieval System, the database of the Chinese Cochrane Center (The Cochrane Library, Issue 1 2005), conference paper databases and checked bibliographies. We handsearched ten Chinese journals.
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During the last decade, the number of patients who consult primary care physicians or psychiatrists for symptoms of depression has doubled. The majority of depressed patients are prescribed oral medication; however, in several European countries antidepressant therapy may be initiated with a daily intravenous infusion. The choice of intravenous antidepressants was previously limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been administered as an intravenous infusion to severely depressed patients. The results from both open and double-blind clinical studies with intravenous citalopram suggest that it is an effective and well-tolerated treatment for depression. Moreover, when treatment is initiated by infusion and continued orally, citalopram is at least as effective as clomipramine, doxepin and viloxazine. As with oral treatment, adverse events experienced by patients are mild to moderate in severity with 50 % of patients reporting no adverse events. The high bioavailability of citalopram indicates that the switch from intravenous to oral citalopram would prevent a deterioration of symptoms as plasma drug concentrations would be maintained. Thus citalopram, the only SSRI available as an intravenous formulation, may be a useful addition for the treatment of severely depressed patients who may benefit from more intensive therapy. The aim of this paper is to review available data detailing the clinical outcome of intravenously administered citalopram in depressed patients.
Monoamine oxidase (MAO) inhibitors are known to be effective in panic disorder, but a high incidence of adverse reactions have limited their use. The new, selective, and reversible MAO-A inhibitors exemplified by brofaromine and moclobemide do not require dietary restrictions, have fewer drug interactions, and are better tolerated. This paper reports a randomized, double-blind, 8-week trial in which the efficacy and safety of brofaromine was compared to clomipramine in patients with panic disorder with or without agoraphobia. Both treatments achieved a significant and comparable reduction in the number of panic attacks, and were equally effective in all the parameters measured. Side effects were typical of the drug class. Further trials are required to evaluate this promising new treatment.
The effects of clomipramine hydrochloride (CMI) versus placebo upon DSM-III-defined obsessive-compulsive disorder (OCD) were assessed in a 10-week double-blind multicenter trial and in a corresponding 1-year double-blind extension study. The NIMH global O-C scale, a 15-point ordinal severity scale, incorporating categorical features specific to OCD, was used to evaluate the severity of obsessive compulsive symptoms over the course of treatment, and a physician's rating of global therapeutic effect was used to assess overall change from baseline. In the core study, patients receiving placebo demonstrated minor and nonsystematic changes, whereas patients who received CMI had clinically and statistically significant reductions in the global severity of their disorder. Findings from the extension study were consistent with continuing efficacy for CMI, whereas corresponding data for patients receiving long-term placebo were difficult to interpret. Based upon shifts in categorical severity, symptoms for over half those patients who received CMI were rendered subclinical or within a range of normal functioning. In contast, less than 5% of patients receiving placebo had their symptoms reduced to a subclinical level. Generally, both treatments were well tolerated. Previous studies have indicated therapeutic potential for CMI in obsessive compulsive disorder. These findings confirm and extend previous observations.