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The New England Journal of Medicine May 1992Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective.
METHODS
We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients. Fifty-seven patients were randomly assigned to a study as well as to the order of treatment, permitting comparison among all three drugs and placebo as the first treatment. The patients rated the degree of pain present each day using verbal descriptors, and they also assessed the extent of pain relief globally at the end of each treatment period.
RESULTS
After individual dose titration, the mean daily doses of the drugs were as follows: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. There was moderate or greater relief of pain in 28 of the 38 patients (74 percent) who received amitriptyline, 23 of the 38 patients (61 percent) who received desipramine, 22 of the 46 patients (48 percent) who received fluoxetine, and 19 of the 46 patients (41 percent) who received placebo. The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant, but both amitriptyline and desipramine were superior to placebo. Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients, but fluoxetine was effective only in depressed patients.
CONCLUSIONS
Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the latter. Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy. Fluoxetine, which blocks serotonin uptake, is no more effective than placebo for the relief of pain.
Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Analgesics; Depression; Desipramine; Diabetic Neuropathies; Double-Blind Method; Female; Fluoxetine; Humans; Infant, Newborn; Male; Middle Aged; Pain
PubMed: 1560801
DOI: 10.1056/NEJM199205073261904 -
British Medical Journal Feb 1974The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966...
The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.
Topics: Amitriptyline; Arrhythmias, Cardiac; Child, Preschool; Depression; Enuresis; Female; Humans; Imipramine; Infant; Male
PubMed: 4818182
DOI: 10.1136/bmj.1.5902.261 -
Journal of Pharmacological Sciences May 2019The wide spread use of central nervous system (CNS) drugs has caused thousands of deaths in clinical practice while there are few antidotes or effective treatments to...
The wide spread use of central nervous system (CNS) drugs has caused thousands of deaths in clinical practice while there are few antidotes or effective treatments to decrease their accumulation in CNS. In this study, we used amitriptyline (AMI) and dexamethasone (DEX) as the corresponding poisoning and pre-protecting drugs, respectively, to study whether DEX has the potential to reduce AMI accumulation in brain. By measuring the pharmacokinetic data of AMI and its main metabolite nortriptyline (NOR), we found that DEX possibly accelerated the metabolism and elimination of AMI with minimal effects on the concentrations of NOR in blood. Nevertheless, the results indicated that DEX reduced the brain/plasma concentration ratio of AMI and NOR, even if the plasma concentration of NOR had an upward trend. Western blot results showed the overexpression of cyp3a2 and P-gp in rat liver and brain capillaries tissues. We propose that cyp3a2 and P-gp could be upregulated in the liver and blood-brain barrier (BBB) when using DEX. Further experiments suggest that DEX may serve as the ligand of PXR to induce P-gp expression.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Blood-Brain Barrier; Brain; Capillaries; Cytochrome P-450 CYP3A; Dexamethasone; Gene Expression; Liver; Male; Rats, Sprague-Dawley; Up-Regulation
PubMed: 31105024
DOI: 10.1016/j.jphs.2019.04.007 -
Cancer Control : Journal of the Moffitt... 2018A common feature of solid tumors, including glioblastoma multiforme (GBM), is mitochondrial dysfunction. However, it is reported that the current standard of anti-GBM...
UNLABELLED
A common feature of solid tumors, including glioblastoma multiforme (GBM), is mitochondrial dysfunction. However, it is reported that the current standard of anti-GBM therapies may potentiate mitochondrial damage and, in effect, support the aggressive character of cancer. As mitochondria are implicated in the modulation of cellular drug sensitivity and chemoresistance mechanisms, activation-stressed mitochondria in GBM cells may represent a new target for anti-GBM therapy that is nontoxic for normal cells.
METHODS
As mitochondria are possible targets for antidepressant drugs used as adjuvant therapy in patients with GBM, we examined their influence on mitochondrial volume and activity, reactive oxygen species level, extracellular lactate concentration, and p65 NF-κB gene expression in GBM cells.
RESULTS
Our investigation showed, for the first time, that tricyclic antidepressants, imipramine and amitriptyline, partially reverse GBM abnormalities.
CONCLUSION
In the light of reported studies, the mitochondrial disturbance observed in glioma cells is a dynamic process that can be reversed or silenced. Moreover, imipramine and amitriptyline are attractive cellular metabolic modulators and can potentially be used to restoring a proper function of mitochondria in GBM cells.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Brain Neoplasms; Cell Line, Tumor; Combined Modality Therapy; Drug Screening Assays, Antitumor; Extracellular Space; Glioblastoma; Humans; Imipramine; Lactic Acid; Mitochondria; Reactive Oxygen Species; Transcription Factor RelA
PubMed: 30213208
DOI: 10.1177/1073274818798594 -
Japanese Journal of Pharmacology Feb 2000The involvement of alpha2-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using...
The involvement of alpha2-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using the hot-plate and abdominal constriction tests. The antinociception produced by amitriptyline (15 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.) was prevented by reserpine (2 mg/kg, i.p.) and yohimbine (3-10 mg/kg, i.p.) but not by naloxone (1 mg/kg, i.p.), atropine (5 mg/kg, i.p.), CGP 35348 (100 mg/kg, i.p.) and prazosin (1 mg/kg, i.p.). On the basis of the above data, it can be postulated that amitriptyline and imipramine exerted their antinociceptive effect by activation of alpha2-adrenoceptors. Administration of the alpha2A-adrenoceptor antagonist BRL 44408 (1 mg/kg, i.p.) prevented amitriptyline and imipramine antinociception, whereas the alpha2B/C-adrenoceptor antagonist ARC 239 (10 mg/kg, i.p.) was ineffective. These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of alpha2A-adrenoceptors. Neither tricyclic antidepressants nor the antagonists used impaired mouse performance evaluated by the rota-rod and hole-board tests.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Antidepressive Agents, Tricyclic; Dose-Response Relationship, Drug; Imidazoles; Imipramine; Indoles; Isoindoles; Male; Mice; Naloxone; Organophosphorus Compounds; Receptors, Adrenergic, alpha-2; Yohimbine
PubMed: 10877531
DOI: 10.1254/jjp.82.130 -
The Science of the Total Environment Dec 2022The continual discharge of pharmaceuticals from wastewater treatment plants (WWTPs) into the marine environment, even at concentrations as low as ng/L, can exceed levels...
The continual discharge of pharmaceuticals from wastewater treatment plants (WWTPs) into the marine environment, even at concentrations as low as ng/L, can exceed levels that induce sublethal effects to aquatic organisms. Amitriptyline, a tricyclic antidepressant, is the most prescribed antidepressant in Norway, though the presence, potential for transport, and uptake by aquatic biota have not been assessed. To better understand the release and bioaccumulative capacity of amitriptyline, laboratory exposure studies were carried out with field-collected sediments. Influent and effluent composite samples from the WWTP of Stavanger (the 4th largest city in Norway) were taken, and sediment samples were collected in three sites in the proximity of this WWTP discharge at sea (WWTP discharge (IVAR), Boknafjord, and Kvitsøy (reference)). Polychaetes (Nereis virens) were exposed to field-collected sediments, as well as to Kvitsøy sediment spiked with 3 and 30 μg/g amitriptyline for 28 days. The WWTP influent and effluent samples had concentrations of amitriptyline of 4.93 ± 1.40 and 6.24 ± 1.39 ng/L, respectively. Sediment samples collected from IVAR, Boknafjord, and Kvitsøy had concentrations of 6.5 ± 3.9, 15.6 ± 12.7, and 12.7 ± 8.0 ng/g, respectively. Concentrations of amitriptyline were below the limit of detection in polychaetes exposed to sediment collected from Kvitsøy and IVAR, and 5.2 ± 2.8 ng/g in those exposed to Boknafjord sediment. Sediment spiked with 3 and 30 μg/g amitriptyline had measured values of 423.83 ± 33.1 and 763.2 ± 180.5 ng/g, respectively. Concentrations in worms exposed to the amended sediments were 9.5 ± 0.2 and 56.6 ± 2.2 ng/g, respectively. This is the first known study to detect measurable concentrations of amitriptyline in WWTP discharge in Norway and accumulation in polychaetes treated with field-collected sediments, suggesting that amitriptyline has the potential for trophic transfer in marine systems.
Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Bioaccumulation; Environmental Monitoring; Geologic Sediments; Pharmaceutical Preparations; Polychaeta; Water Pollutants, Chemical
PubMed: 35995163
DOI: 10.1016/j.scitotenv.2022.158193 -
Anesthesiology Sep 2005Pain after amputation is common but difficult to treat, and few controlled treatment studies exist. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.
METHODS
In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.
RESULTS
After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.
CONCLUSIONS
In treatment-naive patients, both amitriptyline and tramadol provided excellent and stable phantom limb and stump pain control with no major adverse events. Both drugs demonstrated consistent and large antinociceptive effects on both the stump and the intact limbs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amitriptyline; Amputation Stumps; Cytochrome P-450 CYP2D6; Female; Humans; Male; Middle Aged; Pain Measurement; Pain Threshold; Phantom Limb; Phenotype; Tramadol
PubMed: 16129989
DOI: 10.1097/00000542-200509000-00027 -
Pain Physician Sep 2021The patients with chronic migraine (CM) respond poorly to pharmacological agents including tricyclic antidepressants, beta-blockers, anticonvulsants, calcium channel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The patients with chronic migraine (CM) respond poorly to pharmacological agents including tricyclic antidepressants, beta-blockers, anticonvulsants, calcium channel blockers, flunarizine, and melatonin. The combination of 2 or more pharmacological agents has not shown better efficacy but increased side effects. High rate repetitive transcranial magnetic stimulation (rTMS) has been reported effective in episodic migraine and converts CM to episodic migraine. A combination of high rate rTMS with a pharmacological agent may be more effective compared to rTMS alone.
OBJECTIVES
We evaluate the efficacy and safety of 10 Hz rTMS compared to rTMS and amitriptyline in CM.
STUDY DESIGN
Randomized controlled trial.
SETTING
Tertiary care teaching institute in India.
METHODS
Patients with CM as per International Classification of Headache Disorder third edition (ICHD-3) beta criteria were included whose age was between 18 years and 55 years. CM was defined if there were 15 headache days per month and at least 8 of these attacks having migraine characteristics for a period of more than 3 months. Patients with major psychiatric, other neurological or systemic disease, and those on migraine prophylaxis were excluded. The demographic details, frequency of headache attacks and headache days per month, migraine triggers, and associated symptoms were noted. The severity of headache was noted using a 0-10 Visual Analog Scale and the number of abortive drugs per month was noted. CM patients were randomly assigned to rTMS (group I) or rTMS and amitriptyline (group II). 10 Hz rTMS was applied using a figure of eight magnetic stimulation coil. The coil was placed over the left frontal cortex corresponding to the hot spot of the right abductor digiti minimi, which is approximately 7 cm lateral from the midline and 2 cm anterior to interaural line. The motor threshold was measured, and 70% of it was used for rTMS. Ten trains of 10 Hz rTMS, each train comprising of 60 pulses with an inter-train interval of 45 seconds were delivered in one session. Three such sessions were delivered on an alternate day and were repeated every month for 3 months. Amitriptyline was prescribed in a dose of 10mg, increased to 25mg after 2 weeks; thereafter increase in dose to 50 mg was optional. The primary outcome was > 50% reduction in headache days, and secondary outcomes were the reduction in severity of headache, abortive drug, and side effects.
RESULTS
Forty-one patients were included in group I and 42 in group II, and their baseline characteristics were comparable. A higher proportion of group II patients had more than 50% reduction in headache days at 3 months (76.2 vs 31.7%; P < 0.001) compared to group I. More than 50% reduction in headache severity was also greater in group II compared to group I at 3 months (47.6% vs 19.5%; P = 0.01). Side effects were comparable, and none had to be withdrawn.
LIMITATIONS
A higher proportion of patients was shifted from group I to group II.
CONCLUSION
Combination of rTMS and amitriptyline is safe and more effective in CM compared to rTMS alone.
Topics: Adolescent; Amitriptyline; Headache; Humans; Migraine Disorders; Transcranial Magnetic Stimulation; Treatment Outcome; Visual Analog Scale
PubMed: 34554691
DOI: No ID Found -
Diabetes Care Apr 2011To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).
RESEARCH DESIGN AND METHODS
In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient's global assessment of efficacy, using a visual analog scale (0-100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25-50%, and <25% were considered good, moderate, and mild responses, respectively.
RESULTS
There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18).
CONCLUSIONS
Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.
Topics: Adolescent; Adult; Aged; Amitriptyline; Cross-Over Studies; Diabetic Neuropathies; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Thiophenes; Young Adult
PubMed: 21355098
DOI: 10.2337/dc10-1793 -
British Journal of Clinical Pharmacology 19781. Twenty volunteers were treated with amitriptyline 25 mg, mianserin 10 mg, and placebo, three times daily for 2 weeks each, in a double-blind cross-over study. Tests... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1. Twenty volunteers were treated with amitriptyline 25 mg, mianserin 10 mg, and placebo, three times daily for 2 weeks each, in a double-blind cross-over study. Tests of psychomotor function and of learning and memory, were carried out after consumption of alcohol or a placebo drink at intervals during each treatment period. 2. Coordinative and reactive skills were affected by mianserin on the first day only, but by amitriptyline up to day 7 in most of the tests. Both drugs seemed to interact additively with alcohol. 3. Amitriptyline impaired short-term memory span and acquisition, and alcohol enhanced these effects. Mianserin did not affect learning and memory, and did not interact with alcohol in this respect. 4. The differing effects of amitripyline and mianserin are considered in relation to anticholinergic properties.
Topics: Adult; Amitriptyline; Clinical Trials as Topic; Dibenzazepines; Double-Blind Method; Ethanol; Female; Humans; Male; Memory, Short-Term; Mianserin; Motor Skills; Placebos
PubMed: 341944
DOI: No ID Found