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Amitriptyline is in the tricyclic antidepressant (TCA) drug classification and acts by blocking the reuptake of both serotonin and norepinephrine neurotransmitters. Amitriptyline is an FDA-approved medication to treat depression in adults. The non-FDA approved indications are anxiety, post-traumatic stress disorder, insomnia, chronic pain (diabetic neuropathy, fibromyalgia), irritable bowel syndrome, interstitial cystitis (bladder pain syndrome), migraine prophylaxis, postherpetic neuralgia, and sialorrhea. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of amitryptiline in the clinical setting related to the essential points needed by members of an interprofessional team managing the care of patients with indications that can benefit from amitriptyline therapy. Objectives: Identify FDA-approved and off-label indications of amitriptyline. Select the appropriate patient who could benefit from therapy with amitriptyline. Assess patients for potential adverse drug reactions of amitriptyline. Coordinate the patient's amitriptyline therapy with the rest of the medication regimen in light of the drug-drug interaction profile of this medication. Access free multiple choice questions on this topic.

Amitriptyline toxicity is measurable by a dose of over 5 mg/kg. The clinical symptoms of amitriptyline toxicity include neurological, cardiac, and anticholinergic adverse reactions. Neurological symptoms include sedation, seizure, and coma. Cardiac symptoms include tachycardia, hypotension, conduction abnormalities, and QTc prolongation. Anticholinergic symptoms include dilated pupils, dry mouth, decreased (or absent) bowel sounds, and urinary retention. Amitriptyline toxicity can be serious and even fatal. In treating the toxicity, the top priority is stabilizing the patient, which may require admission to the ICU for monitoring. The most important steps include - protecting the airways, breathing, and stabilizing circulation. Some patients may need tracheal intubation; if required, administer supplemental oxygen. All patients suspected of tricyclic antidepressant overdose should receive gastrointestinal decontamination. This should include large-volume gastric lavage followed by activated charcoal.[41] Seizures secondary to overdose are treatable with diazepam or lorazepam.[42] If the patient is hypotensive, an IV bolus of isotonic crystalloid is a therapeutic option. Vasopressors are the next choice if the patient remains hypotensive despite fluid resuscitation. If QRS exceeds 100 msec, intravenous sodium bicarbonate is the appropriate intervention. Sodium bicarbonate is cardioprotective (it increases extracellular sodium concentration) and diminishes the effect of amitriptyline on the cardiac membrane, resulting in less sodium channel blockage. Alkalization favors the neutral form of amitriptyline and decreases the amount of active cyclic antidepressants.[43][44] Intravenous lipid emulsion (ILE) has been used in severe overdose.[45] A recent case report describes the successful use of esmolol for intractable ventricular arrhythmias and ventricular tachycardia associated with amitriptyline overdose.[46]

Amitriptyline is a tricyclic antidepressant that is FDA-approved to treat depression in adults. The drug is also used off-label to treat chronic pain syndrome, anxiety, and insomnia. It has a considerable side effect profile and is no longer commonly used as a first-line agent to treat depression. It may be useful for patients who have insomnia, severe depression, treatment-resistant depression, and patients with co-morbid chronic pain syndromes. Patients on amitriptyline can have anticholinergic, antihistaminic, and alpha-adrenergic blocking adverse effects. It may not be appropriate for patients with cardiac problems. Amitriptyline has many potential drug interactions, increasing the risk of arrhythmias and serotonin syndrome. Toxicity can be life-threatening, and patients must be stabilized and monitored closely. Healthcare providers must also know the increased risk of suicidality in children, adolescents, and young adults, requiring discussion with families.[40] When a prescribing clinician (MD, DO, NP, PA) starts a patient on amitriptyline, they should counsel the patient about the risks associated with their therapy; it is always prudent to obtain a psychiatry consultation when prescribing amitriptyline for major depressive disorder. There are significant drug-drug interactions with other medications and amitriptyline; therefore, pharmacists should report to the prescriber if there is any concern. Pharmacists should also perform medication reconciliation, ensure appropriate dosage, and provide further patient counseling regarding administration and possible adverse effects. Specially trained nurses can provide medication counseling, evaluate patient adherence, and monitor for side effects on follow-up visits. Nurses should report to clinicians with their recommendations in case of concern regarding therapy. In an acute amitriptyline overdose, emergency medicine clinicians and triage nurses should rapidly stabilize the patient. Critical care clinician supervision is necessary if the patient remains in the ICU. In severe overdose, clinicians should obtain a medical toxicologist consultation and contact the poison control center. In an intentional overdose, the clinician should obtain a psychiatrist consultation.

Specially trained nurses can provide medication counseling, evaluate patient adherence, and monitor for side effects on follow-up visits. Nurses should report to clinicians with their recommendations in case of concern regarding therapy. In an acute amitriptyline overdose, emergency medicine clinicians and triage nurses should rapidly stabilize the patient. Critical care clinician supervision is necessary if the patient remains in the ICU. In severe overdose, clinicians should obtain a medical toxicologist consultation and contact the poison control center. In an intentional overdose, the clinician should obtain a psychiatrist consultation. As described above, there needs to be excellent communication between interprofessional healthcare providers involved in caring for the patient receiving amitriptyline. Each provider should understand their responsibility and work collaboratively. When the interprofessional team collaborates in therapeutic decisions, amitriptyline can effectively treat depression, and patients can achieve optimal outcomes with minimal adverse events. [Level 5]