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Epidemiology and Psychiatric Sciences Apr 2022To provide a cross-country analysis of selection, availability, prices and affordability of essential medicines for mental health conditions, aiming to identify areas...
AIMS
To provide a cross-country analysis of selection, availability, prices and affordability of essential medicines for mental health conditions, aiming to identify areas for improvement.
METHODS
We used the World Health Organization (WHO) online repository of national essential medicines lists (EMLs) to extract information on the inclusion of essential psychotropic medicines within each country's EML. Data on psychotropic medicine availability, price and affordability were obtained from the Health Action International global database. Additional information on country availability, prices and affordability of essential medicines for mental disorders was identified by searching, up to January 2021, PubMed/Medline, CINAHIL, Scopus and the WHO Regional Databases. We summarised and compared the indicators across lowest-price generic and originator brand medicines in the public and private sectors, and by country income groups.
RESULTS
A total of 112 national EMLs were analysed, and data on psychotropic medicine availability, price and affordability were obtained from 87 surveys. While some WHO essential psychotropic medicines, such as chlorpromazine, haloperidol, amitriptyline, carbamazepine and diazepam, were selected by most national lists, irrespective of the country income level, other essential medicines, such as risperidone or clozapine, were included by most national lists in high-income countries, but only by a minority of lists in low-income countries. Up to 40% of low-income countries did not include medicines that have been in the WHO list for decades, such as long-acting fluphenazine, lithium carbonate and clomipramine. The availability of generic and originator psychotropic medicines in the public sector was below 50% for all medicines, with low-income countries showing rates lower than the overall average. Analysis of price data revealed that procurement prices were lower than patient prices in the public sector, and medicines in the private sector were associated with the highest prices. In low-income countries, the average patient price for amitriptyline and fluoxetine was three times the international unit reference price, while the average patient price for diazepam was ten times the international unit reference price. Affordability was higher in the public than the private sector, and in high-income than low-income countries.
CONCLUSION
Access to medicines for mental health conditions is an ongoing challenge for health systems worldwide, and no countries can claim to be fully aligned with the general principle of providing full access to essential psychotropic medicines. Low availability and high costs are major barriers to the use of and adherence to essential psychotropic medicines, particularly in low-and middle-income countries.
Topics: Amitriptyline; Costs and Cost Analysis; Diazepam; Drugs, Essential; Drugs, Generic; Health Services Accessibility; Humans; Mental Health
PubMed: 35438063
DOI: 10.1017/S2045796022000087 -
Revista Brasileira de Psiquiatria (Sao... 2013Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we...
OBJECTIVE
Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation.
METHODS
The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.]) 1 h before the injection of carrageenan (300 μg/0.1 mL/paw) or dextran (500 μg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10-6 M/mL/pouch) was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats.
RESULTS
All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01). Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001).
CONCLUSIONS
These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization.
Topics: Amitriptyline; Animals; Anti-Inflammatory Agents; Carrageenan; Cell Degranulation; Cell Movement; Clomipramine; Disease Models, Animal; Edema; Male; Maprotiline; Mast Cells; Neutrophil Infiltration; Rats; Rats, Wistar
PubMed: 24402214
DOI: 10.1590/1516-4446-2012-0977 -
Journal of Forensic Sciences Sep 2021For years, a number of professional groups have warned forensic and clinical toxicologists against calculating an administered dose of a drug based on postmortem blood...
For years, a number of professional groups have warned forensic and clinical toxicologists against calculating an administered dose of a drug based on postmortem blood drug concentrations. But to date, there has been limited information as to how unreliable these dose calculations may actually be. Using amitriptyline as a model drug, this study used empirically determined pharmacokinetic variables for amitriptyline from clinical studies coupled with clinical overdoses (where the individual survived), and death case studies (ascribed to amitriptyline toxicity) in which the dose of amitriptyline was known. Using these data, standard pharmacokinetic equations, and general error propagation, it was possible to estimate the accuracy of calculated doses of amitriptyline, compared with the doses that were consumed. As was expected in postmortem cases, depending on the pharmacokinetic equation used, the accuracy (mean +128% to +2347%) and precision (SD ± 383% to 3698%) were too large to allow reliable estimations of the dose of amitriptyline consumed prior to death based on postmortem blood drug concentrations. This work again reinforces that dose calculations from postmortem blood drug concentrations are unreliable.
Topics: Amitriptyline; Drug Dosage Calculations; Forensic Toxicology; Humans; Pharmacokinetics; Postmortem Changes
PubMed: 34302366
DOI: 10.1111/1556-4029.14801 -
Psychiatry and Clinical Neurosciences Oct 2008Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions.
METHODS
In this double-blinded study, 17 healthy male volunteers were given an acute, single, 25-mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high-performance liquid chromatography.
RESULTS
A significant positive correlation was observed between the plasma amitriptyline concentration and road-tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence.
CONCLUSIONS
Amitriptyline produces a concentration-related impairment on road-tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving.
Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Arousal; Attention; Automobile Driving; Computer Simulation; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Male; Neuropsychological Tests; Psychomotor Performance
PubMed: 18950383
DOI: 10.1111/j.1440-1819.2008.01838.x -
Molecules and Cells Aug 2015Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson's disease (PD). However, it remains unclear whether...
Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson's disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.
Topics: Adenosine Triphosphate; Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Antioxidants; Apoptosis; Cell Line, Tumor; Desipramine; Dopaminergic Neurons; Humans; Male; Mice, Inbred C57BL; Mitochondria; Parkinson Disease; Reactive Oxygen Species
PubMed: 26242194
DOI: 10.14348/molcells.2015.0131 -
Cellular Physiology and Biochemistry :... 2013Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF). Normalization of ceramide concentrations in lungs of CF mice employing the functional acid sphingomyelinase inhibitor amitriptyline also normalized mucociliary clearance, chronic inflammation and infection susceptibility to pulmonary P. aeruginosa in these mice.
METHODS
To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study. Twenty-one CF patients were treated with 25 mg/d amitriptyline twice daily for 28 days. The placebo consisted of 19 patients and was also treated twice per day. The primary endpoint was the change in lung function in the intention-to-treat (ITT) population. Secondary endpoints were ceramide levels in epithelial cells and safety.
RESULTS
After treatment, forced expiratory volume in 1 sec predicted (FEV1) increased 6.3 ± 11.5% (p=0.08) in the ITT population (36 of 40 CF patients) and 8.5 ± 10% (p=0.013) in the per protocol (PP) population (29 of 40 patients). Ceramide levels decreased in nasal epithelial cells after amitriptyline treatment. Amitriptyline had no severe and only mild and mostly transient adverse effects, i.e. xerostomia and tiredness.
CONCLUSION
Amitriptyline is safe in CF-patients, increases FEV1 and reduces ceramide in lung cells of CF patients.
Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Amitriptyline; Ceramides; Cohort Studies; Cystic Fibrosis; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Placebo Effect; Treatment Outcome; Young Adult
PubMed: 23572075
DOI: 10.1159/000350071 -
The Cochrane Database of Systematic... Jul 2009Myofascial pain (MP) is a painful condition characterized by pain transmitted from trigger points (TP) within myofascial structures (in the muscles), local or distant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myofascial pain (MP) is a painful condition characterized by pain transmitted from trigger points (TP) within myofascial structures (in the muscles), local or distant from the pain. TPs can produce a characteristic pattern of irradiated pain or autonomic symptoms when stimulated. Cyclobenzaprine, a muscle relaxant that suppresses muscle spasm without interfering with muscle function, is used in clinical management of MP to improve quality of sleep and reduce pain.
OBJECTIVES
To assess efficacy and safety of cyclobenzaprine in treating MP.
SEARCH STRATEGY
The Pain Palliative and Supportive Care Review Group's Specialised Register, CENTRAL, PubMed, EMBASE, LILACS and Scielo were searched in February 2009.
SELECTION CRITERIA
All RCTs and quasi-RCTs reporting use of cyclobenzaprine for treating MP with pain assessment as a primary or secondary outcome.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies identified, extracted data, assessed trial quality and analyzed results.
MAIN RESULTS
We identified two studies with a total of 79 participants. One study, with 41 participants, compared cyclobenzaprine with clonazepam and with placebo. Participants taking cyclobenzaprine had some improvement of pain intensity compared to those on clonazepam, mean difference (MD) -0.25 (95% CI, -0.41 to -0.09; P value 0.002) and placebo, MD -0.25 (95% CI, 0.41 to -0.09; P value 0.002). The other study, with 38 participants, compared cyclobenzaprine with lidocaine infiltration. Thirty days after treatment there were statistically non-significant differences between comparison groups, favoring lidocaine infiltration, for the mean for global pain, MD 0.90 (95% CI -0.35 to 2.15, P value 0.16), and for the mean for pain at digital compression, MD 0.60 (95% CI -0.55 to 1.75, P value 0.30). There were no life-threatening adverse events associated with the medications.
AUTHORS' CONCLUSIONS
There was insufficient evidence to support the use of cyclobenzaprine in the treatment of MP. We identified only two small studies in which a total of 35 participants were given cyclobenzaprine, and it was not possible to estimate risks for benefits or harms. Further high quality RCTs of cyclobenzaprine for treating MP need to be conducted before firm conclusions on its effectiveness and safety can be made. Experts in this area should elect cut-off points for participants to identify whether a patient has achieved a clinically relevant reduction of pain (primary outcome), so that their results can be combined easily into future versions of this review.
Topics: Adult; Amitriptyline; Anesthetics, Local; Clonazepam; Fascia; Humans; Lidocaine; Muscle Relaxants, Central; Muscular Diseases; Pain; Randomized Controlled Trials as Topic
PubMed: 19588406
DOI: 10.1002/14651858.CD006830.pub3 -
International Journal of Molecular... Aug 2019Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis... (Review)
Review
Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.
Topics: Amitriptyline; Animals; Antioxidants; Apoptosis; Ceramides; Dermatitis, Atopic; Humans; Linoleic Acid; Sphingolipids
PubMed: 31443157
DOI: 10.3390/ijms20163967 -
American Journal of Physiology. Cell... Jun 2023Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome....
Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome. However, the mechanism by which these atypical effects manifest is unclear. Among the proposed mechanisms is the well-known pain-related inhibitory G-protein coupled receptor, namely the opioid receptor (OR). Here, we confirmed that TCA indeed stimulates OR and regulates the gating of TRPC4, a downstream signaling of the G-pathway. In an ELISA to quantify the amount of intracellular cAMP, a downstream product of OR/G-pathway, treatment with amitriptyline (AMI) showed a decrease in [cAMP] similar to that of the μOR agonist. Next, we explored the binding site of TCA by modeling the previously revealed ligand-bound structure of μOR. A conserved aspartate residue of ORs was predicted to participate in salt bridge interaction with the amine group of TCAs, and in aspartate-to-arginine mutation, AMI did not decrease the FRET-based binding efficiency between the ORs and Gα. As an alternative way to monitor the downstream signaling of G-pathway, we evaluated the functional activity of TRPC4 channel, as it is well known to be activated by Gα. TCAs increased the TRPC4 current through ORs, and TCA-evoked TRPC4 activation was abolished by an inhibitor of Gα or its dominant-negative mutant. As expected, TCA-evoked activation of TRPC4 was not observed in the aspartate mutants of OR. Taken together, OR could be proclaimed as a promising target among numerous binding partners of TCA, and TCA-evoked TRPC4 activation may help to explain the nonopioid analgesic effect of TCA. Endogenous opioid systems modulate pain perception, but concerns about opioid-related substance misuse limit their use. This study has raised TRPC4 channel as a candidate target for alternative analgesics, tricyclic antidepressants (TCAs). TCAs have been shown to bind to and activate opioid receptors (ORs), leading to downstream signaling pathways involving TRPC4. The functional selectivity and biased agonism of TCA towards TRPC4 in dependence on OR may provide a better understanding of its efficacy or side effects.
Topics: Antidepressive Agents, Tricyclic; Analgesics, Opioid; Aspartic Acid; Ligands; Carrier Proteins; Amitriptyline; Receptors, Opioid
PubMed: 37154492
DOI: 10.1152/ajpcell.00535.2022 -
Journal of Environmental Management Oct 2023Three-dimensional heteroatom-doped graphene presents a state-of-the-art approach for effective remediation of pharmaceutical wastewater on account of its distinguished...
Three-dimensional heteroatom-doped graphene presents a state-of-the-art approach for effective remediation of pharmaceutical wastewater on account of its distinguished adsorption and physicochemical attributes. Amitriptyline is an emerging tricyclic antidepressant pollutant posing severe risks to living habitats through water supply and food chain. With ultra-large surface area and plentiful chemical functional groups, graphene oxide is a favorable adsorbent for decontaminating polluted water. Herein, a new boron-doped graphene oxide composite reinforced with carboxymethyl cellulose was successfully developed via solution-based synthesis. Characterization study revealed that the adsorbent was formed by graphene sheets intertwined into a porous network and engrafted with 13.37 at% of boron. The adsorbent has a zero charge at pH 6 and contained various chemical functional groups favoring the attachment of amitriptyline. It was also found that a mere 10 mg of adsorbent was able to achieve relatively high amitriptyline removal (89.31%) at 50 ppm solution concentration and 30 °C. The amitriptyline adsorption attained equilibrium within 60 min across solution concentrations ranging from 10 to 300 ppm. The kinetic and equilibrium of amitriptyline adsorption were well correlated to the pseudo-second-order and Langmuir models, respectively, portraying the highest Langmuir adsorption capacity of 737.4 mg/g. Notably, the predominant mechanism was chemisorption assisted by physisorption that contributed to the outstanding removal of amitriptyline. The saturated adsorbent was sufficiently regenerated using ethanol eluent. The results highlighted the impressive performance of the as-synthesized boron-doped adsorbent in treating amitriptyline-containing waste effluent.
Topics: Graphite; Amitriptyline; Boron; Adsorption; Pharmaceutical Preparations; Kinetics; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37413724
DOI: 10.1016/j.jenvman.2023.118363