Tricyclic antidepressants cardiovascular effects

Agents from this class of antidepressants are selective blockers of the re-uptake of serotonin at presynaptic neurones and have little if any effects on muscarinic, histaminergic, adrenergic or serotonergic receptors. They are as effective as the tricyclic antidepressants in the management of depressive disorders, but have less cardiovascular effects. They have less anticholinergic activity and because of their lower risk of cardiotoxicity in overdose they... 

Expensive, non-narcotic, "narcotic -tricyclic antidepressant combination analgesic potential use in chronic pain demonstrated efficacy in a variety of pain syndromes minimal cardiovascular and respiratory side effects... 

Gardner DM, Lynd LD Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother 32 33-38, 1998 Gardner DM, Shulman KI, Walker SE, et al The making of a user friendly MAOI diet. J Clin Psychiatry 57 99-104, 1996 Glassman AH, Bigger JT Cardiovascular effects of therapeutic doses of tricyclic antidepressants a review. Arch Gen Psychiatry 38 815-820,1981... 

Glassman AH, Roose SP. Cardiovascular effects of tricyclic antidepressants. PsychiatrAnn 1987 17 340-347. 

Sedation is uncommon and instead many patients will find that these drugs may impair sleep, which is why the dose is best taken in the morning. There is also little effect on psychomotor function. Occasional patients have a small reduction in heart rate but otherwise effects on the cardiovascular system are rare. Epileptic convulsions can occur but are rare and much less common than with tricyclic antidepressants. There is some evidence for potentiation of electroconvulsive therapy (ECT)-induced seizures. Sexual dysfunction is reported, principally delayed ejaculation and anorgasmia. 

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures the body s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, 13 blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and any other drugs that may be given. 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

The tricyclic antidepressants are effective in treating severe major depression. Some panic disorders also respond to TCAs. Imipr-amine has been used to control bed-wetting in children (older than 6 years) by causing contraction of the internal sphincter of the bladder. At present it is used cautiously, because of the inducement of cardiac arrhythmias and other serious cardiovascular problems. 

The older tricyclic antidepressants and monoamine oxidase inhibitors also cause withdrawal mania and a variety of other adverse withdrawal effects, including cognitive and emotional disturbances and psychosis. Many of them have strong anticholinergic effects and therefore produce severe anticholinergic rebound on withdrawal, including cardiovascular and gastrointestinal symptoms. I have seen patients who have taken tricyclics for many years and then been unable to withdraw from them. 

The cardiac toxicity of tricyclic antidepressants in overdose has been a source of continued concern. Undesirable cardiovascular effects, besides representing a major therapeutic limitation for this category of drugs, delineate an area in which tricyclic compounds with novel structures, as well as second-generation antidepressants, may have significant advantages. The cardiovascular effects of tricyclic antidepressants and the new generation of antidepressants have been reviewed (SEDA-18,16) (16). 

In 190 patients taking tricyclic antidepressants that could not be discontinued before surgery, who underwent general and 61 local or regional anesthesia, there were no changes in the cardiovascular effect of halothane, induction time with pentobarbital, propanidid, or ketamine, or the duration of depolarization or recovery time (160). The general conclusion was that it is safer to continue treatment with tricyclic antidepressants than to risk potential disruption from withdrawal before surgery. 

Azar I, Lear E. Cardiovascular effects of electroconvulsive therapy in patients taking tricyclic antidepressants. Anesth Analg 1984 63(12) 1140. 

Bigger JT, Kantor SJ, Glassman AH, et al. Cardiovascular effects of tricyclic antidepressant dmgs. In Lipton MA,... 

Veith RC, Raskind MA, Caldwell JH, Barnes RF, Gumbrecht G, Ritchie JL. Cardiovascular effects of tricyclic antidepressants in depressed patients with chronic heart disease. N Engl J Med 1982 306(16) 954-9. 

Thorstrand C. Cardiovascular effects of poisoning with tricyclic antidepressants. Acta Med Scand 1974 195(6) 505-14. 

Mianserin is a tetracyclic compound, related to cyproheptadine (SEDA-5,18). It is an effective antidepressant with antiserotonergic properties and a sedative profile, but minimal anticholinergic effect and less action on the cardiovascular system than tricyclic antidepressants (1). 

Based on animal research and restricted experience in overdosage (SEDA-7, 19-21), early attempts to differentiate trazodone from tricyclic antidepressants suggested that it might be relatively free of cardiotoxic effects. However, a preliminary report of a study of the effects of trazodone on the cardiovascular system in 20 subjects mentioned two patients who had ventricular dysrhythmias (7). Others have reported ventricular tachycardia (8-10), atrial fibrillation (11), and complete heart block (12). 

Wilens TE, Biederman J, Baldessarini RJ, Seller B, Schleifer D, Spencer TJ, Birmajer B, Goldblatt A. Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents. J Am Acad Child Adolesc Psychiatry 1996 35(11) 1491-501. 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

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