Tricyclic Anti-Depressant

Tricyclic Antidepressants
Tricyclic antidepressants are a class of drugs used in the treatment of depression, as well as in the treatment of migraine headache and neuropathic pain (pain originating from compression of nerves or from direct nerve involvement, e.g., diabetic neuropathy). Common tricyclics include amitriptyline, imipramine, nortriptyline, desipramine, doxepin, and the related agents amoxapine, bupropion, and trazodone. Overdosing on tricyclic antidepressants can lead to involvement of many organ systems but primarily affects the heart and the brain. In 1995, over 20,000 cases of tricyclic antidepressant overdoses were reported in the United States, and of those reported, nearly 2% of patients died from the overdose. According to one source, approximately 500,000 cases of tricyclic toxicity per year are reported in the United States. (Source DN Ionescu, MD, JK Janssen, MS, BI Omalu, MD, MPH , University of Pittsburgh School of Medicine, Pathology Department). Most of the cases are reported to be intentional and not accidental.
Mild to moderate poisoning usually occurs when more than 10 mg/kg of tricyclics is ingested. Severe poisoning can occur at dosages of more than 15 - 20 mg/kg. Death can occur after coma and sudden cardiac arrhythmia in patients who overdose. Patients using tricyclics will usually see effects within 30 to 60 minutes of ingestion. Tricyclics reach their peak level in the blood within 4 to 12 hours.
Patients with tricyclic toxicity may have dilated pupils, dry mouth, drowsiness, lethargy, sinus tachycardia, agitation, seizures, muscle twitching, and jerking muscle movements urinary retention, increased tendon reflexes, and extensor plantar responses are some of the signs seen with tricyclic overdose.  Patients have fallen into coma with an extremely low blood pressure and rapid heart rate. Life-threatening heart rhythm disturbances called ventricular tachycardia, heart blocks, and electromechanical dissociation can all occur. Tricyclics can significantly decrease the heart's pumping ability, leading to shock and death. Tricyclic toxicity has been associated with Brugada syndrome, a pro-arrhythmogenic repolarization abnormality of the heart, a cause of collapse and sudden cardiac death.
Sudden Death in Children
Imipramine (Tofranil and others) has been approved for children for nighttime bedwetting.   Sudden death has occurred in at least three children who were receiving the tricyclic antidepressant desipramine, a metabolite of imipramine. Desipramine is available as Norpramin, Pertofrane, and generically.   While the FDA has not approved the use of tricyclics in children because of the lack of extensive study in children, these drugs have been used to treat childhood depression, and attention deficit disorder (ADD).   Tricyclic antidepressants are cardiotoxic. They may cause conduction changes in the heart; they may prolong the PR interval, widen the QRS complex, invert or flatten the T-waves, or cause tachycardia or ventricular fibrillation. These cardiac effects are dose-related and have been seen in adults who have overdosed on tricyclics. Children may be more susceptible to adverse effects from tricyclics. The blood plasma levels of desipramine obtained from the three children who died were at or below therapeutic range.

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