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Antidepressants - Tricyclic antidepressants (TCAs) & monoamine oxidase inhibitors (MAOIs): Nursing Pharmacology




Tertiary TCAs: amitriptyline (Elavil), imipramine, clomipramine (Anafranil)

Secondary TCAs: desipramine (Norpramin), nortriptyline (Pamelor)

isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)
selegiline (Emsam, Zelapar)

Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitors (MAOIs)
Inhibition of serotonin and norepinephrine reuptake into nerve endings
Monoamine oxidase inhibition to prevent the  breakdown of serotonin, norepinephrine, and dopamine
  • Major depressive disorder
  • Phobic, panic, anxiety disorders
  • Obsessive-compulsive disorder
  • Neuropathic pain
  • Migraine prevention
  • Major depressive disorder
  • Parkinson disease
  • PO
  • PO
  • Transdermal (selegiline)
  • Sedation
  • Orthostatic hypotension
  • Atropine-like side effects
  • Lower seizure threshold
  • Serotonin syndrome
  • Black box warning: suicidal thinking in children, adolescents, and young adults
  • Hypertensive crisis
  • Serotonin syndrome
  • Black box warning: suicidal thinking in children, adolescents, and young adults
  • Administration within 14 days of MAOIs
  • Pheochromocytoma
  • Cerebrovascular diseases
  • Severe hepatic / renal impairment
  • Dietary: avoid
    • tyramine-rich food or drinks
    • foods containing phenylalanine
    • caffeine
All antidepressants
  • Baseline assessment of depressive symptoms; continue during antidepressant therapy
  • Monitor for suicidal thoughts, especially during the first few weeks
  • Mental status
  • Baseline and periodic ECG
  • Mental status
  • Baseline renal and hepatic
  • Signs of hypertensive crisis
All antidepressants
  • Therapeutic effects can take 1–3 weeks
  • Take medication exactly as prescribed
  • Report any changes in symptoms or suicidal thoughts to health care provider
  • Make position changes slowly to manage orthostatic hypotension
  • Manage anticholinergic side effects with sugar free gum, or candies; sips of water; fiber, fluids, physical activity;  before taking the medication
  • Take medication in evening; avoid hazardous activities to manage sedative effects
  • Make position changes slowly to manage orthostatic hypotension
  • Avoid tyramine-rich foods; also foods containing tryptophan, phenylalanine
  • Seek medical attention for symptoms of hypertensive crisis

Antidepressants are medications primarily used to treat major depressive disorder, which is a condition associated with a persistent feeling of sadness and loss of interest in everyday activities.

Even though the exact cause of major depressive disorder is still unknown, there's some evidence that suggests that it’s related to low levels of neurotransmitters called monoamines, which include serotonin, norepinephrine, and dopamine.

In this video, we’re going to cover two of the main classes of antidepressants: tricyclic antidepressants and monoamine oxidase inhibitors.

First, let’s focus on tricyclic antidepressants or TCAs for short, which can be further subdivided into tertiary or non-selective TCAs, like amitriptyline, imipramine, and clomipramine; and secondary or selective TCAs, such as desipramine and nortriptyline.

Now, tricyclic antidepressants are taken orally, and once absorbed into the bloodstream, they travel to the brain. Here, TCAs inhibit the reuptake of serotonin and norepinephrine.

As a result, their free levels within the synaptic cleft are increased right away, although the effect of TCAs alleviating symptoms of depression is not evident for a few weeks.

Other indications for TCAs include phobic, panic, obsessive-compulsive, and anxiety disorders; neuropathic pain; as well as migraine prevention.

Now, even though TCAs are very effective in the treatment of depression, they can also act on other receptors, so they’re not considered as the first line therapy due to their side effects.

Blockade of muscarinic receptors results in anticholinergic side effects, such as dry mouth, blurred vision, tachycardia, urinary retention, and constipation.

On the other hand, blockade of alpha-1 adrenergic receptors may cause orthostatic hypotension; whereas blockade of histamine receptors may result in sedation.

Moreover, TCAs may also block GABAA receptors, which normally send inhibitory neuronal signals, so by blocking these inhibitory signals, TCAs can result in a lower seizure threshold.

Additionally, tricyclic antidepressants can also cause serotonin syndrome, which usually occurs in clients who are treated with a combination of TCAs and other antidepressants that increase the level of serotonin in the brain.

Clients that develop serotonin syndrome typically present with skin flushing, hyperthermia, agitation, muscle rigidity, seizures, and altered mental status or even coma.

TCAs can also inhibit cytochrome P450 enzymes in the liver. So when combined with other medications that are broken down and metabolized by these enzymes, TCAs will prevent their breakdown, and cause them to build up in the body.

The most common causes of death in clients treated with TCAs include convulsions, coma, and cardiotoxicity, which involves arrhythmias and prolongation of QT interval.

Finally, an important boxed warning for all antidepressants is that they may increase the risk of suicidal thinking in children, adolescents, and young adults.

As far as contraindications go, TCAs should be avoided in clients with heart disease, and recent myocardial infarction. Also, TCAs should not be administered within 14 days of monoamine oxidase inhibitors.

Speaking of monoamine oxidase inhibitors, or MAOIs for short, these include medications like isocarboxazid, phenelzine, and tranylcypromine, which are taken orally, as well as selegiline, which can also be administered transdermally.

As their name implies, MAOIs work by inhibiting enzymes called monoamine oxidases, which are responsible for the breakdown of serotonin, norepinephrine, and dopamine.

As a result, these neurotransmitters start to accumulate in the brain, eventually alleviating symptoms of depression.

Besides major depressive disorder, some monoamine oxidase inhibitors can also be used to treat Parkinson’s disease.

Now, just like TCAs, one of the most dangerous side effects of MAOIs includes serotonin syndrome, which typically occurs when combined with other antidepressants that increase the level of serotonin in the brain.

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