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Duloxetine and venlafaxine are selective serotonin-norepinephrine-reuptake-inhibitors used as antidepressants and co-analgesics. While venlafaxine rather than duloxetine induce cardiovascular side-effects, neither of the substances are regarded cardiotoxic. Inhibition of cardiac Na(+)-channels can be associated with cardiotoxicity, and duloxetine was demonstrated to block neuronal Na(+)-channels. The aim of this study was to investigate if the non-life threatening cardiotoxicities of duloxetine and venlafaxine correlate with a weak inhibition of cardiac Na(+)-channels. Effects of duloxetine, venlafaxine and amitriptyline were examined on endogenous Na(+)-channels in neuroblastoma ND7/23 cells and on the α-subunits Nav1.5, Nav1.7 and Nav1.8 with whole-cell patch clamp recordings. Tonic block of the cardiac Na(+)-channel Nav1.5 and rat-cardiomyocytes (CM) revealed a higher potency for duloxetine (Nav 1.5 IC50 14±1µM, CM IC50 27±3µM) as compared to venlafaxine (Nav 1.5 IC50 671±26µM, CM IC50 452±34µM). Duloxetine was as potent as the cardiotoxic antidepressant amitriptyline (IC50 13±1µM). While venlafaxine almost failed to induce use-dependent block on Nav1.5 and cardiomyocytes, low concentrations of duloxetine (1, 10µM) induced prominent use-dependent block similar to amitriptyline. Duloxetine, but not venlafaxine stabilized fast and slow inactivation and delayed recovery from inactivation. Duloxetine induced an unselective inhibition of neuronal Na(+)-channels (IC50 ND7/23 23±1µM, Nav1.7 19±2µM, Nav1.8 29±2). Duloxetine, but not venlafaxine inhibits cardiac Na(+)-channels with a potency similar to amitriptyline. These data indicate that an inhibition of Na(+)-channels does not predict a clinically relevant cardiotoxicity.
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Records of patients with OCD were analyzed for clinical features, medication used, extent of behavior modification, and outcome.
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Overall, the principles of rational prescribing were followed. The hospital drug schedule should include more SSRIs. The practice of using 1(st) generation/ typical anti-psychotics as the first line was as per current recommendations. Anti-cholinergics should be used only in selected cases of patients on anti-psychotics. The use of diazepam should be curtailed and it should be used for short term only.
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In a 21-day investigation in 15 patients with depression the authors investigated the incidence of undesirable side-effects in relation to plasma amitriptyline levels. The authors found the upper range of plasma concentrations when the patient's risk is minimal as regards serious undesirable complications. This upper limit is 350 micrograms/l; as compared with previous work, they consider amitriptyline levels from 150 to 350 350 micrograms/l safe and therapeutically effective. The authors consider investigation of plasma levels indicated in risk patients and in patients with an inadequate response to treatment.
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Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.
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This study used a retrospective design with analyses of archival clinical data.
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Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4 g/day), pregabalin (1200 mg/day), prosaptide (16 mg/day), peptide-T (6 mg/day), acetyl-L-carnitine (1g/day), mexilitine (600 mg/day), lamotrigine (600 mg/day) and topical capsaicin (0.075% q.d.s.).
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The syndrome of cardiovascular involvement is one of the most frequently occurring syndromes in the toxicogenic phase of acute poisonings in children. Analysis of the results of comprehensive examination of cardiac function in 168 infants poisoned with clopheline, caustic poisons, barbiturates, and amitriptyline showed changes in the ECG and central and peripheral hemodynamics which are characteristic of each type of poisonings.
Baseline data, collected upon admission to the rehabilitation intervention was compared to follow-up data collected by telephone interview. Data was evaluated for differences and relationships using the appropriate parametric or non-parametric tests.
Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients.
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A paradoxical increase in suicide threats, paranoid ideation, and demanding and assaultive behavior occurred among 15 borderline inpatients receiving amitriptyline in a double-blind study. This pattern differed significantly from that of 14 nonresponding patients receiving placebo.
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Amitriptyline (10 microM), either applied acutely or by pre-incubation for 2-6 h, had no effect on inward currents evoked by ATP (0.3-100 microM) at human P2X4 receptors. At rat and mouse receptors, amitriptyline (10 microM) caused a modest reduction in the maximum responses to ATP, without changes in EC(50) values, but it had no effect at 1 microM. Amitriptyline also had no effects on currents evoked by ATP at rat P2X2 receptors, or at rat or human P2X7 receptors.
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New mode-of-action insecticides are sought to provide continued control of pesticide resistant arthropod vectors of neglected tropical diseases (NTDs). We previously identified antagonists of the AaDOP2 D1-like dopamine receptor (DAR) from the yellow fever mosquito, Aedes aegypti, with toxicity to Ae. aegypti larvae as leads for novel insecticides. To extend DAR-based insecticide discovery, we evaluated the molecular and pharmacological characteristics of an orthologous DAR target, CqDOP2, from Culex quinquefasciatus, the vector of lymphatic filariasis and West Nile virus.
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Delusional disorders are one of the psychiatric disorders with unknown etiology. Various factors have been considered as risk factors (predisposing factors) for delusional disorders. Positive family history of psychiatric disorders particularly delusional disorders, is the most important risk factor. In this report, we present a 40-year old man with somatic delusions following intoxication with Phenobarbital and left brachial plexus injury (C6, C7, C8) in stupor state. Two weeks after discharge from the hospital, he developed a significant somatic delusion about his left upper extremity. To our knowledge, somatic delusions secondary to peripheral neuropathy has not been reported up to now therefore this case illustrates a very rare organic delusional disorder.
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Our findings prove that the changes in the phospholipid-protein balance in the hippocampus and prefrontal cortex may be related to depressive disorders, thus leading to the development of adverse changes in the molecules necessary for the correct functioning of the brain. Furthermore, these results suggest a stability of the structure changes/damage of phospholipids in depression, which are present in brain tissues even after effective pharmacotherapy. This study also shows that an infrared spectroscopy can be applied for monitoring changes in mood disorders.
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To observe the clinical efficacy on fibromyalgia syndrome treated with acupuncture at the acupoints selected from the affected meridians based on the location differentiation and the heavy moxibustion at painful points by the randomized controlled trial with medication.
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Pain scores and sensory abnormalities decreased significantly (p < 0.05) with respect to baseline data from week 4. No adverse events were reported.
A multimodal stepped care approach has been successfully applied to a patient with complex regional pain syndrome type 1 and severe intractable pain, not responding to regular neuropathic pain medication. The choice to administer drugs in creams was made because of the intolerable adverse effects to oral medication. With this method, peak-dose adverse effects did not occur. The multimodal stepped care approach resulted in considerable and clinically relevant decrease in pain after every step, using topical amitriptyline, ketamine, and dimethylsulphoxide.
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In a chronic pain model, the arthritic rat, tricyclic antidepressants (TCAs) have been shown to clearly reduce behavioural signs of nociception. In the present work, using a test of acute nociception (vocalization threshold to graded foot pressure) in the same model, we evaluated the possible potentiation of morphine analgesia by 2 TCAs: amitriptyline (AMIT) and imipramine (IMIP). Using this test of acute nociception, we failed to demonstrate any analgesic effect of AMIT or IMIP given either acutely or chronically. We also failed to demonstrate any potentiation of morphine by these compounds. On the contrary, we found a significant decrease of morphine antinociception after acute AMIT administration and a tendency towards diminution with both TCAs given chronically. These results appear to temper enthusiasm for human application of this combination. They also indicate that careful further studies in a chronic pain model using behaviour evaluations are necessary before definite conclusions can be drawn concerning TCAs/opiate interaction.
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A boy aged 11 years 11 months, with normal premorbid personality, presented with a severe depressive episode with somatic and psychotic features. A clinical response to amitriptyline was complicated by ECG changes leading to the abrupt withdrawal of amitriptyline, with the development of a withdrawal syndrome. Further trials of antidepressant medication were unsuccessful, including paroxetine (clinical deterioration), lofepramine (ECG changes and clinical deterioration), and trazodone (priapism). Finally, a good clinical response to dothiepin augmented with lithium was achieved. ECG changes were assessed as being idiosyncratic responses to medication, rather than ischaemic in nature. A dose/response relationship with dothiepin was observed. All medication was successfully stopped after 26 months of treatment. Clinical phenomena relevant to the development of guidelines for use of tricyclic antidepressants in childhood and adolescence are discussed.
The cases of two borderline patients are presented, dexamethasone suppression test (DST) positive and refractory to many therapeutic interventions and treated successfully with high doses of amitriptyline (225 and 200 mg/day, respectively). During the therapeutic intervention, the psychopathological condition of the patients was evaluated using Hamilton's rating scale for depression and a constructed scale based on items 11, 12 and 13 (dysphoria, anger, sense of emptiness, boredom, anhedonia) of the diagnostic interview for borderline patients.