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In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While long term studies showed bias towards a higher mean apparent oral clearance, studies in normal subjects nevertheless indicated a higher apparent oral clearance than that calculated from steady-state concentrations in depressed patients. Methodological issues could account for some of the discrepancies in mean values of the pharmacokinetic parameters of amitriptyline. Broad individual variability in the elimination rate of amitriptyline has been confirmed but could not be attributed to the clinical characteristics of the subjects.
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The development of a field-amplified sample stacking technique is presented. Sensitivity enhancement in this technique was obtained by repetitive injections of a sample followed by steps of sample matrix removal through the application of counter-pressure. Under optimized conditions the background electrolyte (BGE) was composed of 80 mM H3PO4 while the sample matrix contained 0.5mM H3PO4 and 30% (v/v) methanol. The elaborated method enabled a 4-fold effective injection of the sample (53 s, 0.5 psi). Each injection was followed by a focusing step during which the application of a voltage (2 kV) and counter-pressure (-1 psi) was performed for 0.65 min. The method was developed for the determination of six psychiatric drugs (opipramol, hydroxyzine, promazine, amitriptyline, fluoxetine, and thioridazine). The elaborated method was applied for analysis of human urine samples after a simple liquid-liquid extraction procedure. The detection limits obtained were in the range of 2.23-6.21 ng/mL.
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The effect of acute (single dose) or repeated (twice daily, for 14 days) administration of 10 mg kg-1 p.o. of imipramine, amitriptyline, citalopram or mianserin has been examined on the hyperthermia induced by thyrotropin-releasing hormone (TRH) (40 mg kg-1 i.p., 2, or 2 and 72 h after single or last dose of antidepressants, respectively) in mice. Both imipramine and amitriptyline, given repeatedly, potentiated the TRH response, though the effect was observed 2 but not 72 h after the last dose of those drugs. Potentiation was also found after the single dose of imipramine or amitriptyline. On the other hand, citalopram and mianserin, administered either acutely or repeatedly, did not affect the TRH-induced hyperthermia.
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Since 1911, when E. Bleuler thought of the so-called latent schizophrenia as the most frequent type of schizophrenia, but most seldom diagnosed as such, the question, whether there exist abortive forms of schizophrenia, was discussed again and again; so in 1932 by Mayer-Gross, who devoted to the uncharacteristic onset of schizophrenia a special chapter, in 1938 by Stern (so-called borderline neuroses) und in 1949 by Hoch and Polatin (pseudoneurotic schizophrenias). Since the 50s Huber had described by means of follow-up studies the uncharacteristic basic stages occurring long before the onset and after remission of the florid symptomatology, in 1957 the cenesthetic schizophrenia and in 1961 and 1966 the asthenic or pure defect of schizophrenia, which he also counts to the subclinical syndromes or formes frustes of endogenous psychoses just as the endogenous juvenile-asthenic failure syndromes, the larvate schizophrenia, the endogenous obsessive-compulsive disorder and the circumscribed cenesthopathy. The recognition of these subthreshold stages and types of the schizophrenia spectrum, which cannot be diagnosed by valid diagnostic criteria for schizophrenia, is the presupposition for an adequate therapy. The patients complain about subjectively experienced mainly dynamic, affective, cognitive (thought, perception and action disturbances), cenesthetic and vegetative basic symptoms, can be registered and documented by the Bonn Scale BSABS. We will deal with symptomatology, course and therapy of the mentioned sublinical syndromes. The psychopharmacological treatment is chosen according to the psychopathological cross-section picture and will be continued until improvement or remission of the symptomatology and after stepwise reduction stopped. If dynamic and affective basic symptoms predominate, we prefer antidepressants (e. g. amitriptyline-type or the newer SSRIs), in case of prevailing cognitive and cenethetic basic symptoms neuroleptics, today mainly atypical ones. In the past also classical neuroleptics, e. g. haloperidol, fluphenazine or pimozide in low dosage of or low potent drugs as thioridazine or perazine have proved to be worthwhile.
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Fibrositis (fibromyalgia) is best treated by attaining patient acceptance of and compliance with a comprehensive treatment program. This includes education, physical therapy, muscle and mental relaxation, examination and adjustment of goals and priorities, and pacing of activities, as well as pharmacotherapeutics. Of the medications in use, anti-inflammatory agents with a high degree of analgesia are more effective than "pure" anti-inflammatory agents. Tricyclic derivatives are beneficial muscle relaxants. The use of long-acting agents improves compliance and is therefore favored. Local agents are of adjunctive value in some cases. Double-blind, placebo-controlled studies show cyclobenzaprine to be an effective medication in the treatment of fibrositis (fibromyalgia).
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We describe a 12-year-old patient with severe, protracted complex regional pain syndrome type I. His pain did not respond to gabapentin, amitriptyline, physical therapy, opioids, or nonsteroidal drugs. Sympathetic or regional block was not attempted because of persistent bacteremia and severe local sepsis. His pain responded dramatically to the addition of oxcarbazepine, with rapid improvement in his symptoms and functional status. We suggest that oxcarbazepine might be a useful adjunct in the treatment of gabapentin-resistant complex regional pain syndrome type I in children and should be considered.
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Medication overuse headache is a common condition with a population-based prevalence of more than 1-2%. Treatment is based on education, withdrawal treatment (detoxification), and prophylactic treatment. It also includes management of withdrawal headache.
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Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations.
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We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased.
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Use of potentially inappropriate pain-related medications among older adults with PNDs is common. Further research is needed to ascertain whether the benefits of these agents outweigh their risks in this population.
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Despite the large number of elderly patients in nursing homes and the intensity of medication use there, few current data are available on patterns of medication use in this setting. We studied all medication use among 850 residents of 12 representative intermediate-care facilities in Massachusetts. Data on all prescriptions and patterns of actual use were recorded for all patients during one month. On average, residents were prescribed 8.1 medications during the month (interquartile range, 7.4 to 8.8) and actually received 4.7 (range, 4.2 to 5.4) medications during this period. More than half of all residents were receiving a psychoactive medication, with 26% receiving antipsychotic medication. Twenty-eight percent of patients were receiving sedative/hypnotics during the study month, primarily on a scheduled rather than an as-needed basis. Of patients receiving a sedative/hypnotic, 26% (range, 14% to 41%) were taking diphenhydramine hydrochloride, a strongly anticholinergic hypnotic. Of those receiving one of the benzodiazepines, 30% were receiving long-acting drugs, generally not recommended for elderly patients. The typical benzodiazepine dose was equivalent to 7.3 mg per patient per day of diazepam. The most commonly used antidepressant was amitriptyline hydrochloride, the most sedating and anticholinergic antidepressant in common use. These data indicate that despite growing evidence of the risks of psychoactive drug use in elderly patients, the nursing home population studied was exposed to high levels of sedative/hypnotic and antipsychotic drug use. Suboptimal choice of medication within a given class was common, and use of standing vs as-needed orders was often not in keeping with current concepts in geriatric psychopharmacology. Additional research is needed to assess the impact of such drug therapy on cognitive and physical functioning, as well as to determine how best to improve patterns of medication use in this vulnerable population.
Gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female chronic pelvic pain.
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BAY 59-3074 [3-[2-cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butane-sulfonate] is a structurally novel cannabinoid CB1/CB2 receptor partial agonist with analgesic properties. The present study was performed to confirm its receptor binding profile in a highly sensitive in vivo assay. Rats (n=10) learned to discriminate BAY 59-3074 (0.5 mg/kg, p.o., t-1 h) from vehicle in a fixed-ratio: 10, food-reinforced two-lever procedure after a median number of 28 training sessions. BAY 59-3074 generalized dose-dependently (ED(50): 0.081 mg/kg, p.o.) and the cue was detectable between 0.25 and 4 h after administration. The selective cannabinoid CB1 receptor antagonist SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] blocked the discriminative effects of BAY 59-3074 (ID50: 1.79 mg/kg, i.p.). Complete generalization was also obtained after i.p. administration of BAY 59-3074 (ED50 value: 0.41 mg/kg), and the reference cannabinoids BAY 38-7271 [(-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-butanesulfonate, 0.011 mg/kg], CP 55,940 [(-)-cis-3-[2-hydroxy-4(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol, 0.013 mg/kg], HU-210 [(-)-11-OH-Delta8-tetrahydrocannabinol dimethylheptyl, 0.022 mg/kg], WIN 55,212-2 [(R)-4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo [3,2,1-ij] quinolin-6-one, 0.41 mg/kg] and (-)-Delta9-tetrahydrocannabinol (0.41 mg/kg). Non-cannabinoids with analgesic properties, such as morphine, amitriptyline, carbamazepine, gabapentin and baclofen, did not generalize to the cue. It is concluded that the discriminative stimulus effects of BAY 59-3074 are specifically mediated by cannabinoid CB1 receptor activation.
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Of 22 drugs with either a N,N-dimethylamino, N,N-diethylamino or N-morpholino group in the molecule, eight were converted to volatile N-nitrosamines by nitrosative cleavage in reactions of nitrite and drug in a molar ratio of 4:1 at pH 3. Under standardized conditions yields were greatest with aminopyrine and minocycline which contains two N,N-dimethylamino groups in the molecule. Oxytetracycline, chlortetracycline, tetracycline, promethazine, chlorpromazine, imipramine and disulfiram gave much lower yields and amitriptyline, clomiphene, clomipramine, dextropropoxyphene, diphenhydramine, disopyramide, erythromycin, mepyramine, methapyrilene, penicillin G procaine salt, procaine, tamoxifen, trimeprazine and tripelennamine yielded no detectable levels of volatile N-nitrosamines. Nitrosation products of 57 drugs were also examined by a group selective procedure estimating both volatile and non-volatile N-nitroso compounds. Virtually all of the yield obtained from aminopyrine or minocycline could be accounted for by N-nitrosodimethylamine (NDMA). However, compounds yielding excess N-nitrosamines compared to NDMA were obtained from the other three tetracyclines, presumably as a result of the cleavage of a methyl group from the N,N-dimethylamino substituent to form desmethyl-N-nitroso compounds. In general, the drugs giving the highest yields of N-nitroso compounds were those containing secondary rather than tertiary amino groups. A considerable range of susceptibilities towards nitrous acid was observed overall; ten drugs containing a secondary or tertiary amino- or amido- or hydrazido - group did not react with nitrous acid to form N-nitroso compounds.
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Do antidepressants cause, promote, or inhibit cancers?
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Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.
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We reviewed the use of physostigmine in the diagnosis and management of acute toxic psychosis due to drugs with anticholinergic properties. The syndrome of agitation and toxic confusional psychosis associated with peripheral signs of cholinergic blockade is produced by several plant toxins, antispasmodics, ophthalmic preparations, and certain proprietary sedatives, as well as antiparkinson medications, antidepressants, and some antipsychotic drugs. Physostigmine, uniquely among the available reversible anticholinesterase agents, can pass the blood-brain barrier to exert central as well as peripheral cholinomimetic actions to reverse this syndrome. Psychiatrists should make more use of this safe, specific, rapid, and effective treatment for anticholinergic drug toxicity, and should particularly be alert to reversible anticholinergic brain syndromes associated with antidepressants and antiparkinson medications, and even with antipsychotic medications.
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A systematic review of published studies was performed. Articles describing the development of criteria for PIM Use in Older Adults published in the last decade and which provided a list of medications that should be considered inappropriate were included. The searches were conducted on Pubmed/Medline for articles published from 1st of January 2006 to 31st of December 2015. We analyzed the medications/classes reported in all criteria, most common classes and how many indications each medication made.
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To report a case of successful treatment of neuropathic pain with venlafaxine.
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Electroencephalographic (EEG) effects of lopramine, a new antidepressant, were investigated in rabbits with chronic electrode implants, and compared with those of imipramine and amitriptyline. All drugs were administered i.v. Lopramine (10, 20 mg/kg) induced a drowsy pattern of spontaneous EEG consisted of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal thetha waves. Imipramine and amitriptyline (1-5 mg/kg) also elicited similar EEG changes but were much more potent than lopramine in this effect. Lopramine (10, 20 mg/kg) failed to suppress the EEG arousal responses induced by not only auditory stimulation but also electrical stimulation of the mesencephalic reticular formation, centromedian thalamus and posterior hypothalamus, whereas imipramine and amitriptyline (1 approximately 5 mg/kg) markedly inhibited these responses. The EEG arousal response induced by i.v. injection of physostigmine 0.1 mg/kg showed no change after lopramine (20 mg/kg), while the response was significantly suppressed by imipramine (2, 5 mg/kg) and amitriptyline (1, 2 mg/kg). Lopramine showed no effect on the recruiting response induced by electrical stimulation (8 Hz) of the centromedian thalamus and slightly enhanced the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while imipramine (2, 5 mg/kg) and amitriptyline (1--5 mg/kg) caused an initial depression followed by sustained enhancement of these afterdischarges. These results demonstrate lopramine to be an antidepressant of a new type which has no effect on the ascending reticular activating system and no central anticholinergic action.
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These findings provide new insight into the pathogenesis of MDD and the effects of amitriptyline treatment on NLRP3 inflammasome activation and IL-1β and IL-18 serum levels.
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Functional gastrointestinal disorders are common, accounting for up to 50% of gastroenterology referrals, and several randomized controlled trials have evaluated antidepressant therapy for their treatment.
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Comparisons of the behavioural side-effect profiles of antidepressants that inhibit either serotonin or both serotonin and noradrenaline reuptake, may reveal differences in cognitive and psychomotor functions, which may be attributed to their relative pharmacological selectivity for potentiating monoamine neurotransmission in the central nervous system. The aim of the present study was to determine the acute pharmacodynamic effects of citalopram and venlafaxine, on cognitive and psychomotor performance. Nine healthy male volunteers received a single clinical dose of citalopram, venlafaxine or amitriptyline (positive control) in a double-blind placebo-controlled design. Cognitive and psychomotor tests and a subjective measure of sedation were examined before and 1, 2 and 4 hours after drug administration. Citalopram improved psychomotor responses to sensory stimuli and sustained attention, with significant decreases in movement times of the choice reaction time test and an increase in critical flicker fusion threshold. Venlafaxine did not affect performances on any of the cognitive or psychomotor tests examined. Differences may be related to relative potencies of the compounds for monoamine reuptake inhibition.