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Ideggyogyaszati Szemle Jan 2019Tension type headache, the most common type of primary headaches, affects approximately 80% of the population. Mainly because of its high prevalence, the socio-economic... (Review)
Review
Tension type headache, the most common type of primary headaches, affects approximately 80% of the population. Mainly because of its high prevalence, the socio-economic consequences of tension type headache are significant. The pain in tension type headache is usually bilateral, mild to moderate, is of a pressing or tightening quality, and is not accompanied by other symptoms. Patients with frequent or daily occurrence of tension type headache may experience significant distress because of the condition. The two main therapeutic avenues of tension type headache are acute and prophylactic treatment. Simple or combined analgesics are the mainstay of acute treatment. Prophylactic treatment is needed in case of attacks that are frequent and/or difficult to treat. The first drugs of choice as preventatives of tension type headache are tricyclic antidepressants, with a special focus on amitriptyline, the efficacy of which having been documented in multiple double-blind, placebo-controlled studies. Among other antidepressants, the efficacy of mirtazapine and venlafaxine has been documented. There is weaker evidence about the efficacy of gabapentine, topiramate, and tizanidin. Non-pharmacological prophylactic methods of tension type headache with a documented efficacy include certain types of psychotherapy and acupuncture.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Humans; Tension-Type Headache
PubMed: 30785242
DOI: 10.18071/isz.72.0013 -
Lancet (London, England) Nov 2023Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health... (Randomized Controlled Trial)
Randomized Controlled Trial
Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.
BACKGROUND
Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting.
METHODS
This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants.
FINDINGS
Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication.
INTERPRETATION
To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial.
FUNDING
National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).
Topics: Humans; Male; Female; Middle Aged; Irritable Bowel Syndrome; Amitriptyline; England; Double-Blind Method; Primary Health Care; Treatment Outcome
PubMed: 37858323
DOI: 10.1016/S0140-6736(23)01523-4 -
Toxicology Letters Jan 2022Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by...
Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by inhibiting the thyroperoxidase (TPO) enzyme, which is key to thyroid hormone synthesis. For the potent TPO-inhibiting drug propylthiouracil (PTU) this has been shown to result in thyroid hormone system disruption and altered brain development in animal studies. However, an outstanding question is which chemicals beside PTU can cause similar effects on brain development and to what degree thyroid hormone insufficiency must be induced to be able to measure adverse effects in rats and their offspring. To start answering these questions, we performed a perinatal exposure study in pregnant rats with two TPO-inhibitors: the drug methimazole (MMI) and the triazole herbicide amitrole. The study involved maternal exposure from gestational day 7 through to postnatal day 22, to MMI (8 and 16 mg/kg body weight/day) or amitrole (25 and 50 mg/kg body weight/day). Both MMI and amitrole reduced serum T4 concentrations in a dose-dependent manner in dams and offspring, with a strong activation of the hypothalamic-pituitary-thyroid axis. This reduction in serum T4 led to decreased thyroid hormone-mediated gene expression in the offspring's brains and caused adverse effects on brain function, seen as hyperactivity and decreased habituation in preweaning pups. These dose-dependent effects induced by MMI and amitrole are largely the same as those observed with PTU. This demonstrates that potent TPO-inhibitors can induce effects on brain development in rats and that these effects are driven by T4 deficiency. This knowledge will aid the identification of TPO-inhibiting thyroid hormone system disruptors in a regulatory context and can serve as a starting point in search of more sensitive markers of developmental thyroid hormone system disruption.
Topics: Amitrole; Animals; Animals, Newborn; Antithyroid Agents; Disease Models, Animal; Enzyme Inhibitors; Female; Maternal Exposure; Methimazole; Motor Activity; Neurotoxicity Syndromes; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Signal Transduction; Thyroid Function Tests; Thyroid Gland
PubMed: 34757178
DOI: 10.1016/j.toxlet.2021.10.010 -
BMJ Clinical Evidence Jul 2009Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to... (Review)
Review
INTRODUCTION
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for chronic tension-type headache? What are the effects of non-drug treatments for chronic tension-type headache? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 50 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture; amitriptyline; analgesics; anticonvulsant drugs; benzodiazepines; botulinum toxin; chiropractic and osteopathic manipulations; cognitive behavioural therapy (CBT); Indian head massage; mirtazapine; relaxation and electromyographic biofeedback; selective serotonin reuptake inhibitor antidepressants (SSRIs); and tricyclic antidepressants (other than amitriptyline).
Topics: Amitriptyline; Headache; Humans; Manipulation, Osteopathic; Selective Serotonin Reuptake Inhibitors; Tension-Type Headache
PubMed: 21696647
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Amitrole; Animals; Carcinogens; Enzyme Inhibitors; Herbicides; Humans; Neoplasms
PubMed: 21829250
DOI: No ID Found -
BMJ Case Reports Aug 2012A 48-year-old immunosuppressed woman presented to a rheumatology follow-up clinic after suffering from herpes zoster infection. She had manifestations of foot drop 3...
A 48-year-old immunosuppressed woman presented to a rheumatology follow-up clinic after suffering from herpes zoster infection. She had manifestations of foot drop 3 months after the initial infection. She was diagnosed with motor radiculopathy following herpes zoster infection that was effectively managed by physiotherapy and amitriptyline.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Female; Gait Disorders, Neurologic; Herpes Zoster; Humans; Middle Aged; Physical Therapy Modalities; Radiculopathy
PubMed: 22891019
DOI: 10.1136/bcr-2012-006246 -
British Medical Journal Jun 1973
Topics: Amitriptyline; Dibenzazepines; Diphenhydramine; Electroconvulsive Therapy; Humans; Methaqualone; Sleep; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 4733259
DOI: 10.1136/bmj.2.5868.716-b -
Annals of the Academy of Medicine,... Apr 2020Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of... (Review)
Review
INTRODUCTION
Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of AMT-associated movement disorders.
MATERIALS AND METHODS
A search for relevant reports in 6 databases was performed. Studies that reported patients developed only ataxia or tremor after AMT use were excluded.
RESULTS
A total of 48 reports on 200 cases were found. AMT-associated movement disorders included myoclonus (n = 26), dyskinesia (n = 11), dystonia (n = 8), stutter (n = 5), akathisia (n = 3) and restless legs syndrome (n = 1). For less well-defined cases, 99 patients had dyskinesia, 19 had psychomotor disturbances, 3 had myoclonus, 11 had dystonia, 12 had Parkinsonism and 1 each had akathisia and extrapyramidal symptoms. Mean and standard deviation (SD) and median ages were 45.40 years (SD 16.78) and 40 years (range 3.7-82 years), respectively. Over half were women (58.13%) and the most common indication was depression. Mean and median AMT doses were 126 mg (SD 128.76) and 75 mg (range 15-800 mg), respectively. In 68% of patients, onset of movement disorders was <1 month; time from AMT withdrawal to complete recovery was <1 month in 70% of cases. A weak negative linear correlation (r = -0.0904) was found between onset of movement disorders and AMT dose. AMT withdrawal was the most common treatment.
CONCLUSION
Amitriptyline is associated with various movement disorders, particularly myoclonus, dystonia and dyskinesias. Stutters and restless legs syndrome are some of the less common associations.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Humans; Movement Disorders
PubMed: 32419008
DOI: No ID Found -
Revista de Neurologia Apr 2022Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not... (Review)
Review
INTRODUCTION
Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not covered, and has a high number of therapeutic failures in recent randomized clinical trials.
DEVELOPMENT
This narrative review presents an update on the pharmacological treatment of NP with emphasis on the new published clinical guidelines, new drugs in development, and the new challenges that arise in the therapeutic management of this entity.
CONCLUSIONS
First-line drugs proposed include tricyclic antidepressants (particularly amitriptyline), serotonin and norepinephrine reuptake inhibitors (particularly duloxetine), pregabalin, and gabapentin. However, the latest recommendations are still relevant and the most recent clinical studies even question the role of pregabalin as a first-line treatment. Therefore, we consider that periodic updates of the clinical guidelines in NP are necessary to better guide our daily clinical practice and rationalize the use of all available therapeutic options. Furthermore, the expansion of knowledge in NP has generated a series of challenges, such as the development of new drugs based on pathophysiological mechanisms investigated in animals, and the development of optimal therapeutic approaches in clinical trials, based more on personalized than etiological approaches.
Topics: Amitriptyline; Analgesics; Animals; Antidepressive Agents, Tricyclic; Gabapentin; Humans; Neuralgia; Pregabalin
PubMed: 35383875
DOI: 10.33588/rn.7408.2021381 -
American Journal of Men's Health Mar 2018Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with... (Meta-Analysis)
Meta-Analysis Review
Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Depression; Humans; Male; Sexual Dysfunctions, Psychological
PubMed: 29019272
DOI: 10.1177/1557988317734519