Adverse Effects

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (H1) often results in sedation and weight gain. Antagonism of ^-adrenoceptors in the vas-culature can cause orthostatic hypotension.

TCA drugs have potent membrane-stabilizing properties similar to those of quinidine. Conduction is slowed throughout the heart, and serious ventricular arrhythmias may develop in patients with preexisting conduction abnormalities at therapeutic doses and in all patients at toxic doses. At therapeutic doses, the TCA drugs lower the seizure threshold and at toxic doses can cause life-threatening seizures. Maprotiline has a greater potential for reducing the seizure threshold and should not be used in patients with a seizure disorder. Amoxapine has dopamine receptor antagonist properties (see Chapter 31) and can induce extrapyramidal side effects, gynecomastia, lactation, and neuroleptic malignant syndrome. To increase tolerance to the anti-cholinergic and orthostatic effects of the TCA drugs, the dose is usually titrated with increasing increments over the first few weeks of therapy.

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Constipation Prescription

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