Cardiovascular system antidepressant effects

Side Effects and Toxicity. Adverse effects to the tricycHc antidepressants, primarily the result of the actions of these compounds on either the autonomic, cardiovascular, or central nervous systems, are summarized in Table 3. The most serious side effects of the tricycHcs concern the cardiovascular system. Arrhythmias, which are dose-dependent and rarely occur at therapeutic plasma levels, can be life-threatening. In order to prevent adverse effects, as weU as to be certain that the patient has taken enough dmg to be effective, the steady-state semm levels of tricycHc antidepressant dmgs are monitored as a matter of good practice. A comprehensive review of stmcture—activity relationships among the tricycHc antidepressants is available (42). 

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. 

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). 

Tricyclic antidepressants inhibit the uptake of catecholamines, such as adrenaline, into sympathetic neurons and can enhance the cardiovascular effects, so that even the small amounts of adrenaline present as additives in some local anesthetics can have a marked effect on the cardiovascular system. 

Patients may deteriorate rapidly and progress from no symptoms to life-threatening cardiotoxicity or seizures within 1 hour. Major symptoms of tricyclic antidepressant overdose typically are manifest within 6 hours of ingestion. The principal effects of tricyclic antidepressant poisoning involve the cardiovascular system and the central nervous system and can result in arrhythmias, hypotension, coma, and seizures (see below). 

While amphetamine had important antifatigue and moderate antidepressant properties, its therapeutic usefulness was severely limited because its stimulant action was followed by a depressive phase, tolerance to the drug developed, it depressed appetite, it tended to cause anxiety and jitteriness, and it had fairly potent effects on the cardiovascular system. 

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. 

Bupropion is a well-tolerated antidepressant. It is non-sedating and lacks the cardiovascular and anticholinergic side effects of tricyclic antidepressants. Bupropion s most commonly observed adverse effects are insomnia and dry mouth. The drug is also known to be associated with a low rate of seizures however, no seizure incidents were reported in the smoking cessation clinical trials. Other less frequently occurring side effects include nervous system disturbances (mainlytremor) and skin rashes (170,182). 

Patients with coexisting cardiovascular and pulmonary conditions (e.g., ARDS, pulmonary infection, pulmonary aspiration) may be more susceptible to the toxic effects or complications of tricyclic antidepressant poisoning. The influence of chronic exposure to tricyclic antidepressants on the risks of an acute overdose is unclear. Tricyclic antidepressants interact with other central nervous system depressant drugs, which together may lead to increased central nervous system and respiratory depression. 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

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