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- A Randomized Controlled Trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in the treatment of chronic tension-type facial pain. [Journal Article]
- Rhinology 2013 Jun; 51(2):143-53.
Patients often present to otolaryngologists with chronic facial pain, presumed to be of sinus origin despite normal nasal endoscopy and sinus CT. This pain has increasingly been recognized as being of neurological origin with one of the commonest underlying causes being mid-facial segmental tension-type pain (MFP) which is a version of tension-type headache affecting the midface.Primary outcome measures: 1. To determine whether low-dose amitriptyline reduces pain scores compared to surrogate placebo in patients with chronic MFP. 2. To determine whether the addition of pindolol, a beta blocker with serotonin receptor blocking properties hastens onset of action or improves efficacy of amitriptyline. Secondary outcome measure: to determine whether amitriptyline or amitriptyline with pindolol significantly reduces analgesic consumption.Sixty two patients were randomized to three treatment groups (a) amitriptyline 10mg daily (b) amitriptyline 10mg daily with pindolol 5mg twice daily and (c) loratadine 10mg daily. Daily pain scores using a facial pain diary were recorded over eight weeks.At 8 weeks, pain frequency and intensity were significantly reduced in patients treated with amitriptyline and in those receiving amitriptyline with pindolol compared to surrogate placebo. Patients on the combination therapy showed significantly improved clinical outcome and significantly reduced analgesic intake compared to those on amitriptyline alone.Low dose amitriptyline is effective in the management of MFP and is enhanced by the addition of pindolol.
- Lipid Rescue 911: Are Poison Centers Recommending Intravenous Fat Emulsion Therapy for Severe Poisoning? [JOURNAL ARTICLE]
- J Med Toxicol 2013 May 10.
Intravenous fat emulsion (IFE) therapy is a novel treatment that has been used to reverse the acute toxicity of some xenobiotics with varied success. We sought to determine how US Poison Control Centers (PCCs) have incorporated IFE as a treatment strategy for poisoning. A closed-format multiple-choice survey instrument was developed, piloted, revised, and then sent electronically to every medical director of an accredited US PCC in March 2011. Addresses were obtained from the American Association of Poison Control Centers listserv, and participation was voluntary and remained anonymous. Data were analyzed using descriptive statistics. The majority of PCC medical directors completed the survey (45 out of 57; 79 %). Of the 45 respondents, all felt that IFE therapy played a role in the acute overdose setting. Most PCCs (30 out of 45; 67 %) have a protocol for IFE therapy. In a scenario with "cardiac arrest" due to a single xenobiotic, directors stated that their center would "always" or "often" recommend IFE after overdose of bupivacaine (43 out of 45; 96 %), verapamil (36 out of 45; 80 %), amitriptyline (31 out of 45; 69 %), or an unknown xenobiotic (12 out of 45; 27 %). In a scenario with "shock" due to a single xenobiotic, directors stated that their PCC would "always" or "often" recommend IFE after overdose of bupivacaine (40 out of 45; 89 %), verapamil (28 out of 45; 62 %), amitriptyline (25 out of 45; 56 %), or an unknown xenobiotic (8 out of 45; 18 %). IFE therapy is being recommended by US PCCs; protocols and dosing regimens are nearly uniform. Most directors feel that IFE is safe but are more likely to recommend IFE in patients with cardiac arrest than in patients with severe hemodynamic compromise.
- Management of sialorrhoea in motor neuron disease: A survey of current UK practice. [JOURNAL ARTICLE]
- Amyotroph Lateral Scler Frontotemporal Degener 2013 May 7.
Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres. Sixteen centres were specialist MND Care Centres. Clinicians estimated seeing a total of 1391 newly diagnosed patients with MND in 2011. One hundred and ninety-three patients were described. Forty-two percent of patients reviewed in clinicians' last clinic had sialorrhoea and 46% of those with sialorrhoea had uncontrolled symptoms. Clinicians' preferred drugs were hyoscine patches, amitriptyline, carbocisteine and botulinum toxin. Botulinum toxin was used in 14 centres. Risk of dysphagia and staff skills were identified as the main barriers to botulinum toxin use. This survey suggests that there may be as many as 1700 patients with MND in the UK who have symptoms of sialorrhoea and that symptoms may be poorly controlled in nearly half. Treatment strategies varied, reflecting the lack of evidence based guidelines. The use of specialist treatments was influenced by local infrastructure. This study highlights the need for further work to develop evidence based guidance.
- Clinical Management of Trichotillomania With Bimatoprost. [JOURNAL ARTICLE]
- Optom Vis Sci 2013 May 2.
PURPOSE:This case report presents the use of bimatoprost 0.03% to help regrow eyelashes on a patient suffering from trichotillomania. Trichotillomania is characterized by repetitive compulsive hair pulling that leads to noticeable hair loss. Trichotillomania sufferers are affected by this condition in many ways including shame, embarrassment, guilt, and lower self-esteem. Although a formal therapy regimen does not exist, current treatment approaches include behavioral therapy and pharmacotherapy. In cases where a patient pulls the eyelashes, topical bimatoprost (Latisse) may be used to treat madarosis of the eyelashes by increasing growth, including length, thickness, and darkness.
CASE REPORT:A 55-year-old white female presented to the clinic with an interest in using bimatoprost ophthalmic solution (Latisse; Allergan). The patient reported a history of eyelash pulling since age 12 and began treatment to control the impulses with amitriptyline 1 week before her appointment. Follow-up appointments showed increased lash growth bilaterally over a 4-month period as a result of Latisse usage.
CONCLUSIONS:Those who pull their eyelashes may benefit from using bimatoprost 0.03%. The management of trichotillomania involving the eyelashes presents an opportunity for eye care professionals to collaborate with mental health providers for the betterment of shared patients. By expediting the patient's lash growth, Latisse can improve patients' self-image, reinforce compliance, and play an important adjunctive role in any therapy regimen.
- Therapeutic doses of antidepressants are projected not to inhibit human α4β2 nicotinic acetylcholine receptors. [JOURNAL ARTICLE]
- Neuropharmacology 2013 Apr 30.:88-95.
Inhibition of central α4β2 nAChRs by antidepressants, proposed to contribute to their clinical efficacy, was assessed for monoamine reuptake inhibitors (amitriptyline, nortriptyline, fluoxetine, sertraline, paroxetine, citalopram) by comparing projected human unbound brain drug concentrations (Cu,b) at therapeutic doses with concentrations that inhibit human α4β2 nAChRs in vitro. Inhibitory concentrations (IC50) were determined by patch clamp and ranged from 0.8-3.2 μM, except for nortriptyline (IC50 = 100 nM). Cu,b values were calculated from human unbound plasma drug concentrations (Cu,p) and rat-derived brain-to-plasma and extracellular fluid-to-plasma ratios for the unbound drug, which are near unity, due to much higher brain tissue binding than plasma protein binding of these drugs. Accordingly in humans, antidepressant Cu,b are projected to essentially equal Cu,p, with average values from 3-87 nM, which are 30-to-250-fold below their IC50 concentrations. Based on our model, monoaminergic antidepressants minimally inhibit central nAChRs and it is unlikely that α4β2 nAChR antagonism contributes to their antidepressant activity. Nortriptyline is an exception with a Cu,b that is 2-fold below its IC50, which is comparable to the nAChR antagonist (±)-mecamylamine, for which Cu,b is 4-fold below its IC50; both drugs will inhibit a substantial fraction of α4β2 nAChRs. The Cu,b of the α4β2 nAChR partial agonist varenicline, which has antidepressant-like activity in a murine model, is higher than its IC50 and varenicline is projected to cause ∼70% inhibition of α4β2 nAChRs. Taken together these data may help explain the negative outcome of recent antidepressant augmentation trials with mecamylamine and the partial agonist CP-601927.
- Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration - an Experimental Intoxication Study in Pigs. [JOURNAL ARTICLE]
- Basic Clin Pharmacol Toxicol 2013 May 3.
Intravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline distribution into well-perfused organs. Twenty anaesthetized pigs received amitriptyline intravenously 10 mg/kg for 15 min. Thirty minutes later, in random fashion, 20% Intralipid(®) (Lipid group) or Ringer's acetate (Control group) was infused 1.5 ml/kg for 1 min. followed by 0.25 ml/kg/min. for 29 min. Arterial and venous plasma amitriptyline concentrations and haemodynamics were followed till 75 min. after amitriptyline infusion. Then, frontal brain and heart apex samples were taken for amitriptyline measurements. Arterial plasma total amitriptyline concentrations were higher in the Lipid than in the Control group (p<0.03) from 20 min. on after the start of the treatment infusions. Lipid emulsion reduced brain amitriptyline concentration by 25% (p=0.038) and amitriptyline concentration ratios brain/arterial plasma (p=0.016) and heart/arterial plasma (p=0.011). There were no differences in ECG parameters and no severe cardiac arrhythmias occurred. Two pigs developed severe hypotension during the lipid infusion and were given adrenaline. In conclusion, lipid infusion, given not earlier than after an initial amitriptyline tissue distribution, was able to entrap amitriptyline back into plasma from brain and possibly from other highly perfused, lipid-rich tissues. In spite of the entrapment, there was no difference in haemodynamics between the groups. This article is protected by copyright. All rights reserved.
- Association Between Sedating Medications and Delirium in Older Inpatients. [JOURNAL ARTICLE]
- J Am Geriatr Soc 2013 Apr 30.
OBJECTIVES:To examine the association between Beers criteria sedative medications and delirium in a large cohort of hospitalized elderly adults with common medical conditions.
DESIGN:Retrospective cohort and nested case-control studies.
SETTING:374 U.S. hospitals.
PARTICIPANTS:All individuals aged 65 and older admitted to the hospital between September 2003 and June 2005 with one of six principal diagnoses (acute myocardial infarction, chronic obstructive pulmonary disease, community-acquired pneumonia, congestive heart failure, ischemic stroke, urinary tract infection).
MEASUREMENTS:Primary outcome was presumed hospital-acquired delirium, defined as initiation of an antipsychotic medication or restraints on hospital Day 3 or later. Logistic and proportional hazards regression were used to model the associations between sedative exposure and delirium.
RESULTS:The dataset contained 225,028 participants (median age 82; 58% female). Four percent fit the definition of hospital-acquired delirium (median onset Day 5). In all, 38,883 (17%) participants received one or more sedative medications. In the cohort study, diphenhydramine (adjusted odds ratio (AOR) = 1.22, 95% confidence interval (CI) = 1.09-1.36) and short-acting benzodiazepines (AOR = 1.18, 95% CI = 1.03-1.34) were associated with greater risk of subsequent delirium. In the nested case-control study, diphenhydramine, short- and long-acting benzodiazepines and promethazine were associated with delirium. Amitriptyline and muscle relaxants were not associated with delirium in either study. Confounding by indication could not be excluded for drugs that are sometimes used improperly to treat delirium.
CONCLUSION:An association was found between several Beers criteria sedative medications and delirium in hospitalized medical patients. Given the prevalence of these medications and the morbidity associated with delirium, further investigation into the appropriateness of such prescribing is warranted.
- Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential. [JOURNAL ARTICLE]
- Psychopharmacology (Berl) 2013 Apr 27.
RATIONALE:Sesamol, a natural compound with anti-inflammatory, antioxidant and neuroprotective properties, has shown promising antidepressant-like effects. However, its molecular target(s) have not been well defined, which merits further investigation.
OBJECTIVES:Based on the interaction between the neurotrophin and endocannabinoid (eCB) systems and their contribution to emotional reactivity and antidepressant action, we aimed to investigate the involvement of nerve growth factor (NGF) and eCB signalling in the mechanism of action of sesamol.
METHODS:Following acute and 4-week intraperitoneal (i.p.) administration of sesamol (40, 80 and 100 mg/kg), the classical antidepressant amitriptyline (2.5, 5 and 10 mg/kg) or the benzodiazepine flurazepam (5, 10 and 20 mg/kg), brain regional levels of NGF and eCB contents were quantified in rats by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry, respectively. In the case of any significant change, the cannabinoid CB1 and CB2 receptor antagonists (AM251 and SR144528) were administered i.p. 30 min prior to the injection of sesamol, amitriptyline or flurazepam.
RESULTS:Following the chronic treatment, sesamol, similar to amitriptyline, resulted in the sustained elevation of NGF and eCB contents in dose-dependent and brain region-specific fashion. Neither acute nor chronic treatment with flurazepam altered brain NGF or eCB contents. Pretreatment with 3 mg/kg AM251, but not SR144528, prevented the elevation of NGF protein levels. AM251 exerted no effect by itself.
CONCLUSIONS:Sesamol, similar to amitriptyline, is able to affect brain NGF and eCB signalling under the regulatory drive of the CB1 receptors.
- Determination of zolpidem in human hair by micropulverized extraction based on the evaluation of relative extraction efficiency of seven psychoactive drugs from an incurred human hair specimen. [Journal Article]
- J Chromatogr A 2013 Jun 7.:28-35.
A micropulverization method for rapid extraction of psychoactive drugs from hair was developed. A hair sample (10mg) was micropulverized for 10min at 42Hz with 0.2mL of 45% (w/v) aqueous ammonium phosphate (pH 8.4). Liquid-liquid extraction was carried out in the same tube using acetonitrile, and the organic layer was removed and filtered. Conventional methods, including solid-liquid extraction with an ammonium phosphate solution or methanol, were also employed, and the relative extraction efficiencies of amitriptyline, nortriptyline, norfludiazepam, flunitrazepam, 7-aminoflunitrazepam, mianserin and zolpidem with these methods from an incurred human hair specimen were compared using liquid chromatography/tandem mass spectrometry. The highest extraction efficiencies for all the analytes were achieved using the method developed here, even though the extraction time (10min) was short. Overnight methanol extraction has frequently been used for hair analysis; however, the extraction efficiency was not sufficient for amines. The method was successfully applied to the quantification of zolpidem in human hair. The range of quantification was 1-25,000pg/mg, and interday accuracy and precision (n=5) at three concentrations were 1.8-8.8% and 3.3-8.1%, respectively. The developed method was applied to three actual (incurred) samples, for which the concentrations of zolpidem were determined to be 78.9-18,300 (pg/mg).
- Effective treatment of notalgia paresthetica with amitriptyline. [LETTER]
- J Dermatol 2013 Apr 27.