The newer selective serotonin re-uptake inhibiting (SSRI) agents continue to gain popularity in the treatment of depression because of their vastly improved safety profile when compared to the older tricyclic antidepressant (TCA) agents. Despite this clear pharmacologic advantage, many patients continue to take TCAs because of their proven individual success or for selective indications. As a result, TCA overdose continues to be a major cause of morbidity and mortality in depressed patients and their families.
Tran and colleagues retrospectively analyzed the therapy and response of all patients with TCA-induced hypotension requiring a pressor agent who presented to two teaching hospitals over a two-year period. Of the 26 patients who met enrollment criteria, 15 received dopamine, and 11 received norepinephrine as initial pressor therapy. While only nine of 15 patients had a favorable response to dopamine, all 11 patients responded to norepinephrine (P = 0.02). In addition, all six patients who failed dopamine therapy responded to norepinephrine. Although this study suffers somewhat from its non-randomized retrospective design, Tran et al have taken significant steps to convince the reader that the two groups are essentially well-matched. (Tran TP, et al. Response to dopamine vs. norepinephrine in tricyclic antidepressant-induced hypotension. Acad Emerg Med 1997;4:864-868.)
COMMENT BY ROBERT HOFFMAN, MD
The clinical course of overdose with a TCA is somewhat unique because of a propensity for rapid progression from mild sedation to seizures and severe cardiotoxicity that includes wide-complex dysrhythmias and hypotension. Over the last 10-15 years, significant achievements have been accomplished in the diagnosis and management of patients with TCA overdose. The abandonment of the use of physostigmine, the definition of the diagnostic and prognostic role of the ECG, and the reliance on the use of hypertonic sodium bicarbonate for the treatment of dysrhythmias highlight some of these advances. Despite these advances, mortality continues to occur.
One of the most challenging problems in the management of patients with TCA overdose is the treatment of hypotension. Unless rapidly treated, TCA-induced hypotension can be catastrophic. Hypotension creates a vicious cycle by producing metabolic acidosis that exacerbates cardiotoxicity, further exacerbating the hypotension. The difficulty arises from the multifactorial nature of TCA-induced hypotension; direct myocardial depression, catecholamine depletion, and alpha-adrenergic antagonism all play a role. Each of these mechanisms would necessitate different pharmacotherapythe wrong choice being potentially detrimental. When the mechanism of hypotension is unclear and patients have failed fluid bolus and hypertonic sodium bicarbonate therapy, many clinicians elect to choose a balanced pressor agent. As a result of its familiarity, dopamine is often selected. Yet, if catecholamine depletion is a potential cause of hypotension, dopamine would be expected to fail, and patient safety would be jeopardized by time lost while attempting resuscitation with this agent.
This study confirms toxicologic intuition. Those patients with TCA-induced hypotension who are catecholamine-depleted are unlikely to have a favorable response to dopamine, an agent with pressor effects that are largely indirect. In addition, the clinical observations reported here are supported by both animal and human experience.1-3 As a result, the choice of agents should be clear. Even if dopamine is effective in some cases, norepinephrine is effective in all cases. Since hypotension needs to be reversed rapidly, it is not logical to use dopamine as the first agent. Instead, patients with TCA-induced hypotension who fail fluids and hypertonic sodium bicarbonate therapy should be given norepinephrine to restore their hemodynamics.
References
1. Teba L, et al. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose. Am J Emerg Med 1988;6:566-568.
2. Jackson JE, Banner W. Tricyclic antidepressant overdose: Cardiovascular responses to catecholamines. Vet Hum Toxicol 1981;23:367.
3. Buchanan AL, et al. The use of vasoactive agents in the treatment of refractory hypotension seen in tricyclic antidepressant overdose. J Clin Psychopharmacol 1990;10:409-413.
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