Antidepressants (cont.)

TCAs may inhibit the antihypertensive effect of clonidine (Catapres). Therefore, combining TCAs with clonidine may lead to dangerous elevations in blood pressure.

TCAs may affect the heart's electrical conduction system. Combining TCAs with drugs that also affect the heart's conduction system [for example, disopyramide (Norpace), pimozide (Orap), procainamide (Pronestyl, Procan SR, Procanbid)] may increase the frequency and severity of an abnormal heart rate and rhythm.

Combining TCAs with carbamazepine (Tegretol) may result in lower TCA blood levels because carbamazepine increases the break down of TCAs, potentially reducing the effect of TCAs.

TCAs may increase the blood pressure elevating effect of epinephrine, norepinephrine, dopamine, phenylephrine, and dobutamine.

 Cimetidine (Tagamet) may reduce the breakdown of some TCAs, for example, amitriptyline (Elavil, Endep), increasing the level of the TCA in the body and potentially leading to increased side effects. As mentioned previously, TCAs should not be combined with MAOIs.

TCAs are associated with a number of cardiovascular (heart and blood vessels) effects such as orthostatic hypotension and abnormal heart rates and rhythms. Orthostatic hypotension may lead to dizziness, falls, and fractures. Orthostatic hypotension may be managed by reducing or discontinuing the TCA dose, increasing salt intake, or treatment with steroids. If abnormal heart rhythms develop, TCAs should be discontinued. TCAs are not a good choice for patients with cardiovascular conditions.

 TCAs have anticholinergic effects which manifests as dry mouth, constipation, urinary hesitation, sexual dysfunction, increased heart rate, and visual disturbance.

Desipramine (Norpramin) and nortriptyline (Pamelor)  cause less anticholinergic effects than other TCAs.

  • Sugarless gum or candy, or pilocarpine (Salagen) oral rinse may alleviate dry mouth;
  • constipation may be reduced by bulk laxatives and increased hydration;
  • urinary hesitation may be treated with bethanechol; and
  • visual disturbance may be treated with pilocarpine eye drops.

Sexual dysfunction may be managed with sidenafil (Viagra), reducing the TCA dose or discontinuing the TCA. Yohimbine, ginkgo, bethanechol, and neostigmine have also been used for managing TCA induced sexual dysfunction.

TCAs should be avoided by individuals with prostatic hypertrophy, cognitive impairment, or narrow-angle glaucoma because drugs with anticholinergic side effects can worsen symptoms of these conditions.

TCAs also cause sedation. Amitriptyline (Elavil, Endep), doxepin (Sinequan), and trimipramine (Surmontil) are more sedating than amoxapine and desipramine (Norpramin). Sedation may improve after a few weeks of treatment. Sedating TCAs may be beneficial for depressed patients who have insomnia.

Dose dependant and reversible weight gain may occur during TCA treatment. Amitriptyline (Elavil, Endep) causes weight gain more often than desipramine (Norpramin).

What are examples of TCAs?

What are selective serotonin reuptake inhibitors (SSRIs)?

SSRIs were developed after TCAs and are the most widely used class of antidepressants. They work by increasing the level of serotonin in the brain. Unlike MAOIs and TCAs, they do not significantly affect norepinephrine levels in the brain. SSRIs also have fewer and milder side effects, fewer drug interactions, and are much less likely to be effective for committing suicide than TCAs.

Confusion, high blood pressure, tremor, hyperactivity, coma, and death may occur when SSRIs are combined with drugs that increase brain serotonin levels, for example, MAOIs, TCAs, sumatriptan (Imitrex), linezolid (Zyvox), St John's Wort, tramadol (Ultram), and meperidine (Demerol).



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