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Tricyclic Antidepressant

Agents Tricyclic Antidepressive


Presentation

  • The only prognostic indicator of death in such patients is seizure after hospital presentation.[ncbi.nlm.nih.gov]
  • When presented with the limited history of an unknown ingestion in a patient with altered mental status, a clinician depends on the physical examination and a toxic screen to determine the ingested substance(s).[ncbi.nlm.nih.gov]
  • This guideline presents a summary of the best available evidence to guide the management of adult patients who present to the ED following an overdose of tricyclic antidepressant agents (TCA).[ncbi.nlm.nih.gov]
  • Level of consciousness at presentation is the most sensitive clinical predictor of serious complications.[ncbi.nlm.nih.gov]
  • In the present study, a number of pharmacological compounds that have been suggested to interact within the N-methyl-D-aspartate (NMDA) receptor complex, including tricyclic antidepressants (TCAs), were examined for their ability to inhibit the binding[ncbi.nlm.nih.gov]
Fever
  • Later you may experience tremors and muscle spasms or seizures, confusion, delirium, hallucinations, very high fever, rapid heart rate, high blood pressure, seizures and coma. Serotonin syndrome can result in death.[anti-depressants.com]
  • , sudden high fever with jaundice, priapism (condition marked by persistent erections), swollen lymph nodes and respiratory distress.[drugs.nmihi.com]
  • A tricyclic overdose may cause: Hallucinations Drowsiness Enlarged pupils Fever Irregular heartbeat Severe dizziness Severe muscle stiffness or weakness Restlessness or agitation Breathing problems, respiratory failure Vomiting Convulsions Coma A TCA[healthyplace.com]
  • High fever, convulsions, and even death can occur from such combinations. Epinephrine ( Primatene, Adrenalin, Ana-Kit, EpiPen, Marcaine ) should not be used with tricyclic antidepressants, since together they can cause severe high blood pressure.[rxlist.com]
  • Although rare, an interaction between these drugs may cause high fever, tremors, agitation, restlessness, or, in some cases, death.[healthcommunities.com]
Fatigue
  • Tricyclics can cause: Dry mouth Constipation Blurred vision Sleepiness Weight loss Weight gain Sweating Shaking Issues with your sex life If you take duloxetine, you might have: Nausea Dizziness Fatigue Headaches At first, SSRIs also can make you: Nauseated[webmd.com]
  • Possible side effects of tricyclic antidepressants include: dry mouth dry eyes blurred vision dizziness fatigue headache disorientation seizure (especially with maprotiline) drowsiness constipation urinary retention sexual dysfunction low blood pressure[healthline.com]
  • Common side effects with tricyclics may include: Headache Unpleasant taste Sensitivity to sunlight / heat; excessive sweating Dry mouth Constipation, diarrhea Nausea, indigestion Fatigue, sedation Insomnia Weakness Anxiety, nervousness Weight gain Some[healthyplace.com]
  • This delivery method helps decrease some side effects, such as dry mouth and fatigue. After a few weeks, side effects usually diminish considerably.[medicinenet.com]
  • Immune Deficiency Syndrome (CFIDS) Chronic Fatigue Syndrome Chronic Hepatitis Chronic Obstructive Pulmonary Disease Chronic Pancreatitis Chronic Pelvic Pain Syndrome (in men) Chronic Prostatitis Cigarette Addiction Cigarette Smokers, Nutrition Cirrhosis[therapy.epnet.com]
Congestive Heart Failure
  • Heart Failure Conjunctivitis Constipation Constipation (in Pregnancy) Contusions COPD Coronary Artery Disease (CAD) Coronary Heart Disease Cough Crohn's Disease Cuts CVA Cyclic Mastalgia Cyclic Mastitis Cystitis[therapy.epnet.com]
Hypothermia
  • Peter B Hedlund, Lisa Kelly, Curt Mazur, Timothy Lovenberg, J.Gregor Sutcliffe and Pascal Bonaventure, 8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents, European Journal of Pharmacology, 10.1016/j.ejphar.2004.01.031,[dx.doi.org]
Abdominal Obesity
  • RESULTS: Symptom severity was positively associated with prevalence of the MetSyn, [adjusted odds ratio (OR) 2.21 for very severe depression: 95% confidence interval (CI): 1.06-4.64, P 0.04], which could be attributed to abdominal obesity and dyslipidemia[ncbi.nlm.nih.gov]
Constipation
  • Far more adverse effects were reported in TCA-placebo groups compared with SSRI-placebo groups, e.g. dry mouth (odds ratio [OR] 3.5; 95% CI 2.9, 4.2); drowsiness (OR 2.7; 95%CI 2.2, 3.4); constipation (OR 2.7; 95%CI 2.1, 3.6); sexual problems (OR 2.3;[ncbi.nlm.nih.gov]
  • The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients.[ncbi.nlm.nih.gov]
  • Tricyclic antidepressants are more likely to cause constipation, weight gain, and sedation than other antidepressants. However, different drugs have different effects.[healthline.com]
  • The combination of tricyclics with antihistamines can lead to severe constipation, impacted stools, or difficulty urinating, particularly in older adults.[healthcommunities.com]
  • These products are not commonly used as first-line agents for multiple sclerosis-related depression because they can cause some annoying adverse effects such as dry mouth, constipation, bladder problems, sexual dysfunction, blurred vision, dizziness,[sharecare.com]
Nausea
  • The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs.[ncbi.nlm.nih.gov]
  • BACKGROUND: Cyclic vomiting syndrome in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods.[ncbi.nlm.nih.gov]
  • Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping.[ncbi.nlm.nih.gov]
  • Symptoms of abdominal fullness, nausea, abdominal discomfort, and bloating will be graded by the study subject from 0 (none) to 5 (severe).[clinicaltrials.gov]
  • Abruptly stopping tricyclic antidepressant treatment can cause: nausea headache dizziness lethargy flu-like symptoms Your doctor will taper your dosage over time to avoid these effects.[healthline.com]
Abdominal Pain
  • pain Palpitations, irregular heartbeat Fever, chills Rash Hiccups Nasal congestion Difficult and/or frequent urination You'll find helpful information about antidepressant side effects and how to manage them here.[healthyplace.com]
  • Intuniv Side Effects include: Headache Fatigue Abdominal pain Sleepiness and sedation Since Intuniv can cause drowsiness, make sure you know how it affects you before you try driving or operating heavy machinery.[medicinenet.com]
  • Adverse effects commonly reported for tricyclics include dizziness, gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhoea, dry mouth), headache, lethargy, sleep disturbance.[doi.org]
  • Side effects included: dizziness, headache, sweating, drowsiness/lethargy, sleep disturbance/restlessness, apathy/depression, sullenness, tremor, flu, upset stomach/abdominal pain, vomiting/diarrhoea, constipation, dry mouth, rash, nausea, neutropenia[dx.doi.org]
Xerostomia
  • The blockade of these receptors gives as a result: Anticholinergic (atropine-like) effects: blurred vision, xerostomia, urinary retention, constipation and narrow angle glaucoma.[pharmacologycorner.com]
Hypotension
  • A 29-year-old woman ingested 8 g of nortriptyline and presented to the emergency department with coma, hypotension, and widened QRS interval.[ncbi.nlm.nih.gov]
  • Class II agents (beta-blockers) may also precipitate hypotension and cardiac arrest.[ncbi.nlm.nih.gov]
  • Successful management of cardiovascular failure with terlipressin after TCA intoxication refractory to catecholamines suggests a potential role for terlipressin as an adjunct vasopressor in severely hypotensive patients.[ncbi.nlm.nih.gov]
  • Cardiovascular toxicity is classically manifested as ventricular dysrhythmias, hypotension, heart block, bradyarrhythmias, or asystole. Activated charcoal binds tricyclic antidepressants.[ncbi.nlm.nih.gov]
  • Hypotension was reported in 1.4% (3/209) of cases, and a vasopressor was used in one case (0.5%).[ncbi.nlm.nih.gov]
Tachycardia
  • A 46-year-old woman presented to the emergency department with coma, hypotension, tachycardia, and a prolonged QRS interval after the ingestion of a large quantity of Elavil.[ncbi.nlm.nih.gov]
  • Side effects include altered mental status, tachycardia, mydriasis, seizures, coma, and death.[ncbi.nlm.nih.gov]
  • Aside from the sinus tachycardia due principally to anticholinergic effects, TCA-toxic changes seen on the ECG are attributable primarily to the sodium channel blockade caused by these agents.[ncbi.nlm.nih.gov]
  • Patients with an amitriptyline overdose were more likely to have seizure, coma, tachycardia, a wide QRS or ventricular dysrhythmia, and have received sodium bicarbonate or be intubated.[ncbi.nlm.nih.gov]
  • Sinus tachycardia is the most common arrhythmia due to anticholinergic activity and inhibition of norepinephrine uptake by tricyclic antidepressants but bradyarrhythmias (due to atrioventricular block) and tachyarrhythmias (supraventricular and ventricular[ncbi.nlm.nih.gov]
Hypertension
  • A 36-year-old active duty male with migraine headaches presented for evaluation of poorly controlled hypertension.[ncbi.nlm.nih.gov]
  • After adjusting for age, baseline APRI score, diabetes, hypertension, alcohol use, drug abuse and HCV RNA levels, TCAs use was associated with decreased risk of cirrhosis (hazard ratio [HR] 0.77, 95% CI 0.60, 0.99) and delayed time to development of cirrhosis[ncbi.nlm.nih.gov]
  • K Channel Blockade QTC Prolongation NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension Na Channel Blockade QRS Prolongation Hypotension — depresses myocardial contractility Ventricular dysrhythmias Brugada-like findings[em3.org.uk]
  • Recent emerging concerns regarding use of SSRIs in pregnancy with Neonatal Adaptation Syndrome and a possible association with Persistent Pulmonary Hypertension of the Newborn (PPHN) are likely to lead to increased prescription by clinicians (See SSRI[mothersmatter.co.nz]
  • (J Emerg Med 1995;13(6):781-5) This one is from Bryan Hayes) Pharmacologic Effects of TCAs K Channel Blockade QTC Prolongation NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension Na Channel Blockade QRS Prolongation[emcrit.org]
Increased Sweating
  • sweating Urinary retention Constipation Tremor Increased appetite Weight gain Low sex drive Difficulty achieving an erection, and other sexual difficulties Low blood pressure when rising to a stand Confusion in the elderly Drug Interactions TCAs interact[everydayhealth.com]
  • Side effects of tricyclic medications The side effects of amitriptyline and nortriptyline include: sedation drowsiness dry mouth (which could contribute to dental decay) blurred vision constipation increased sweating ( hyperhidrosis ) difficultly urinating[dermnetnz.org]
  • Other side effects include orthostatic hypotension, weight gain, seizures, bone fractures, sexual dysfunction, increased sweating, and increased or irregular heartbeats. Contraindication TCAs should not be used within 14 days of taking an MAOI.[rxlist.com]
Seizure
  • Data of patients with seizures due to poisoning were evaluated with respect to the causes, frequencies and complications of seizures.[ncbi.nlm.nih.gov]
  • The only prognostic indicator of death in such patients is seizure after hospital presentation.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: Cyclobenzaprine overdoses were not reported to cause widened QRS, ventricular dysrhythmias, or seizures, and hypotension was rarely reported.[ncbi.nlm.nih.gov]
  • The overall fatality rate was 6%, arrhythmia occurred in 21% and 31% of the patients developed seizures.[ncbi.nlm.nih.gov]
  • A significant increase in adverse outcomes was again found with the BEP group: seizures (RR 3; 95% CI 1.1 to 8.6), widened QRS (RR 4.8; 95% CI 1.5 to 15.1), and hypotension (RR 3.4; 95% CI 1.9 to 22.3).[ncbi.nlm.nih.gov]
Confusion
  • The withdrawal symptoms can be very uncomfortable, and they include sweating, tremors, twitching, muscle spasms, seizures, anxiety, nervousness, confusion, agitation, restlessness, nightmares and sleep problems.[anti-depressants.com]
  • Symptoms include agitation , confusion, sweating, tremors, and a rapid heart rate The precipitation of a manic episode in people with undiagnosed bipolar disorder An increased risk of seizures in people with a history of seizures An increased risk of[drugs.com]
  • The patient started with a confused mental state and decreased to a GCS of eight, potentially indicating the need for an advanced airway.[ems1.com]
  • Drowsiness Restlessness Racing heartbeat Increased sweating Urinary retention Constipation Tremor Increased appetite Weight gain Low sex drive Difficulty achieving an erection, and other sexual difficulties Low blood pressure when rising to a stand Confusion[everydayhealth.com]
  • […] disturbance Tremor and sweating Postural Hypotension – due to α blockade Epileptic fits – even in those with no history of the condition Weight gain – due to appetite stimulation Hyponatraemia – due to inappropriate ADH secretion – this can cause drowsiness, confusion[almostadoctor.co.uk]
Agitation
  • Previous case reports describe cognitive-enhancing effects, such as improved arousal, attention, memory, and initiation, of dopaminergic agents, and in the case of tricyclic antidepressants, effects on agitation.[ncbi.nlm.nih.gov]
  • The withdrawal symptoms can be very uncomfortable, and they include sweating, tremors, twitching, muscle spasms, seizures, anxiety, nervousness, confusion, agitation, restlessness, nightmares and sleep problems.[anti-depressants.com]
  • Symptoms of withdrawal include; agitation, sweating, headache, malaise, GI upset Interactions Alcohol – together these have an exaggerated depressive effect MAOIs – so never give these drugs together![almostadoctor.co.uk]
  • The patient remained agitated for 48 hours after presentation and required frequent sedation.[doi.org]
Tremor
  • RESULTS: Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing.[ncbi.nlm.nih.gov]
  • The withdrawal symptoms can be very uncomfortable, and they include sweating, tremors, twitching, muscle spasms, seizures, anxiety, nervousness, confusion, agitation, restlessness, nightmares and sleep problems.[anti-depressants.com]
  • Symptoms include agitation , confusion, sweating, tremors, and a rapid heart rate The precipitation of a manic episode in people with undiagnosed bipolar disorder An increased risk of seizures in people with a history of seizures An increased risk of[drugs.com]
  • […] mood Common Side Effects Tricyclic antidepressants may cause a number of side effects, including: Dry mouth Blurred vision Sweating Dizziness or lightheadedness Drowsiness Restlessness Racing heartbeat Increased sweating Urinary retention Constipation Tremor[everydayhealth.com]
  • […] to H1 and α-adrenoceptor blockade, this effect may be useful in some patients to help their sleep pattern, but can be troublesome during the day Antomuscarinic effects – e.g. dry mouth, constipation, urinary retention, impotence, visual disturbance Tremor[almostadoctor.co.uk]
Hyperactivity
  • Multiple agents may be necessary in the successful treatment of some complex attention deficit hyperactivity disorder patients. Lippincott-Raven Publishers. Related Articles[journals.lww.com]
  • They have been used in the treatment of various forms of depression, anxiety disorders, attention deficit hyperactivity disorder and enuresis in children.[randoxtoxicology.com]
  • In this study, parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech, but clinician ratings found no significant impact on these symptoms.[cochrane.org]
  • Keywords: attention deficit hyperactivity disorder (ADHD), genes, reward dependence, reward deficiency syndrome, treatment, neuropsychological deficits This work is published and licensed by Dove Medical Press Limited.[doi.org]
  • Notably, the TCAs are more effective in treating the behavioral aspects of ADHD than the cognitive deficits, as they help limit hyperactivity and impulsivity, but have little to no benefits on attention.[en.wikipedia.org]

Workup

  • An extensive workup was pursued to evaluate the cause of her mental status, which only revealed a positive urine toxicology screen for TCA.[ncbi.nlm.nih.gov]
  • The workup included an endocrinological examination, which revealed a moderately elevated urine normetanephrine level, suggesting the possibility of a pheochromocytoma.[ncbi.nlm.nih.gov]
Wide QRS Complex
  • After preclinical resuscitation with prolonged external cardiac massage, he was admitted to the intensive care unit with persistently severe hypotension and wide QRS complexes (230-260 ms).[ncbi.nlm.nih.gov]
Torsades De Pointes
  • Torsade de pointes occurs uncommonly. Hypotension results from a combination of reduced myocardial contractility and reduced systemic vascular resistance due to alpha-adrenergic blockade.[ncbi.nlm.nih.gov]
  • RESULTS: Ten cases and none of the controls had advanced ECG changes (ventricular fibrillation, torsades des pointes, or asystole).[ncbi.nlm.nih.gov]
  • There may also be a ventricular arrythmia, particularly polymorphic ventricular tachycardia, specifically Torsades de Pointes. This should be treated typically with a magnesium sulfate infusion of 2 g over two minutes.[ems1.com]
Ischemic Changes
  • Though with the amitriptyline poisoning no significant anatomic changes were noted, the desipramine-caused death was further supported by the multisystem vascular congestion and ischemic changes consistent with cardiopulmonary failure.[ncbi.nlm.nih.gov]

Treatment

  • Eighty-six patients were treated twice weekly with ECT until recovery or no progress during at least 10 bilateral treatments. Patients were maintained drug free during the ECT treatment.[ncbi.nlm.nih.gov]
  • Moreover, the antiallodynic property of antidepressant treatment is absent in mice deficient for the delta-opioid receptor gene.[ncbi.nlm.nih.gov]
  • For treatment, alkalinization and hypertonic saline are recommended. The role of extracorporeal, treatment procedures is not clear.[ncbi.nlm.nih.gov]
  • We present a case of a dilated cardiomyopathy, which seemed idiopathic, but occurred during treatment with imipramine and recovered after its withdrawal.[ncbi.nlm.nih.gov]
  • We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms.[ncbi.nlm.nih.gov]

Prognosis

  • Altered mental status in an adolescent presents a diagnostic challenge, and the clinician depends on clinical evaluation and laboratory studies to determine therapy and prognosis.[ncbi.nlm.nih.gov]
  • The patient's presentation at the emergency department (ED) exemplified tricyclic antidepressant toxidrome with a poor prognosis, based on measurable criteria and physical findings. Respiratory and cardiovascular collapse was managed emergently.[ncbi.nlm.nih.gov]

Etiology

  • Fitzgerald, Is elevated norepinephrine an etiological factor in some cases of Parkinson’s disease?, Medical Hypotheses, 10.1016/j.mehy.2014.01.026, 82, 4, (462-469), (2014). H.P.[doi.org]
  • The etiology of female breast cancer. Med Principles Pract. 2000; 9 :1–24. [ Google Scholar ] Sharpe CR, Collet JP, McNutt M, Belzile E, Boivin JF, Hanley JA.[ncbi.nlm.nih.gov]
  • Cancer Res 49 : 5736–5747 Sharpe CR, Boivin JF (2000) The etiology of female breast cancer.[doi.org]

Epidemiology

  • Author information Affiliations Centre for Clinical Epidemiology and Community Studies, Sir Mortimer B.[doi.org]
  • Epidemiology, Principles and Methods 1996Boston: Little, Brown; 2502nd ed [ Google Scholar ] Marx J. Do antidepressants promote tumors? Science. 1992; 257 :22–23. [ PubMed ] [ Google Scholar ] Miettinen OS. Theoretical Epidemiology.[ncbi.nlm.nih.gov]
  • Epidemiology. 1999; 10 :211–213. [ PubMed ] [ Google Scholar ][pubmedcentral.nih.gov]
  • Next, we included the Center for Epidemiologic Studies Depression Scale score category at each visit in the model rather than a history of depressive symptoms.[doi.org]
  • Epidemiology of migraine and other types of headache in Asia. Curr Neurol Neurosci Rep 2003 ; 3 : 104 -8. Rasmussen BK. Epidemiology of headache. Cephalalgia 2001 ; 21 : 774 -7. Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML.[bmj.com]
Sex distribution
Age distribution

Pathophysiology

  • L Bendtsen, Central sensitization in tension‐type headache—possible pathophysiological mechanisms, Cephalalgia, 20, 5, (486-508), (2001).[doi.org]
  • Pharmacotherapy: A Pathophysiologic Approach. From Reviewed by: Marina Katz, MD American Board of Psychiatry & Neurology[rxlist.com]
  • This last point is important because the pathophysiological changes in the brains of patients with AD require several years to occur. 16 Finally, these studies did not take into account that certain anticholinergics are used to manage insomnia and depression[doi.org]
  • With improved understanding about the pathophysiology of nocturnal enuresis and the promotion by the International Children's Continence Society (ICCS) for using standardised nomenclature in paediatric continence research ( Austin 2014 ), enuresis is[doi.org]

Prevention

  • A low-dose infusion of ILE was well tolerated and may have successfully prevented recurrent toxicity in a case of severe tricyclic antidepressant overdose.[ncbi.nlm.nih.gov]
  • The patient was noted to be taking amitriptyline for migraine headache prevention. With approval from Neurology, the medication was discontinued and a repeat urine normetanephrine level revealed normalization.[ncbi.nlm.nih.gov]
  • TCAs are thought to increase neurotransmitter levels by preventing nerve endings — called synapses — from drawing these chemicals back into their tissues, which is normally how the body reduces their concentrations.[everydayhealth.com]
  • These unwanted effects tend to disappear over time in children who take tricyclic antidepressants to prevent bedwetting. Antidepressants must be used with great caution in children, as the U.S.[drugs.nmihi.com]
  • […] headaches in 1964 4 and have become a standard modality in headache prevention. 5 Based on current standards for preventive treatment in the United States, 43% of males and 34% of females who are candidates for such treatment are not receiving it. 6[bmj.com]

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