These drugs counteract neurotransmitter deficiencies three ways: they inhibit monoamine oxidase (MAO), raising norepinephrine and serotonin or 5-hydroxytryptamine (5-HT) in the synaptic cleft; they block reuptake at the synaptic cleft, raising neurotransmitter levels; or they regulate receptor sites and neurotransmitter breakdown so the neurotransmitter accumulates. They fall into three groups: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs).
Antidepressants: Generic and Brand Names
Here is a table of commonly encountered antidepressant agents, their generic names, and brand names:
- Tricyclic Antidepressants
- Amines
- amitriptyline
- amoxapine (Asendin)
- clomipramine (Anafranil)
- doxepin (Sinequan)
- imipramine (Tofranil)
- Secondary Amines
- despiramine (Norpramin)
- nortriptyline (Aventyl)
- protriptyline (Vivactil)
- tetracyclic (Maprotiline)
- Monoamine Oxidase Inhibitors (MAOI)
- isocarboxazid (Marplan)
- phenelzine (Nardil)
- tranylcypromine (Parnate)
- Selective Serotonin Reuptake Inhibitors (SSRI)
- citalopram (Celexa)
- escitalopram (Lexapro)
- fluoxetine (Prozac)
- fluvoxamine (Luvox)
- paroxetine (Paxil)
- sertraline (Zoloft)
Manifestation Spotlight: Depression
Depression is an affective disorder marked by persistent, intense sadness far more severe and lasting than any precipitating event, sometimes with no external cause. Patients have little energy, disturbed sleep, loss of appetite, and no motivation for daily activities, and describe overwhelming sadness, despair, and hopelessness. It disrupts family, work, and relationships, drives physical problems that deepen the depression, and raises suicide risk. The biogenic amine theory holds that depression results from a deficiency of biogenic amines (NE, dopamine, 5-HT) in brain areas regulating arousal, alertness, attention, mood, appetite, and sensory processing.
Antidepressants across age groups
These cautions apply across the classes, with class-specific exceptions noted below. Treating depression in children is difficult because they respond unpredictably, studies have not shown antidepressants effective in children, and the drugs are linked to increased suicidal ideation and behavior in depressed children. Adults must be told that drug effects may not appear for 4 weeks, and the cause of depression must be ruled out before therapy. Use cautiously in pregnant and lactating women because of potential harm to the fetus and baby. Older adults are more susceptible to adverse and CNS effects (sedation, dizziness), need reduced doses, and require careful monitoring for toxicity, especially with hepatic or renal impairment.
Tricyclic Antidepressants (TCAs)
TCAs have three subclasses (amines, secondary amines, tetracyclics) and primarily reduce uptake of 5-HT and NE into nerves; the choice depends on individual response and tolerance. By inhibiting presynaptic reuptake of NE and 5-HT, they let these neurotransmitters accumulate in the synaptic cleft and increase postsynaptic stimulation.
They relieve depression, particularly anxiety and sleep disturbance, and also act as anticholinergics. Some TCAs treat enuresis in children older than 6 years; only clomipramine, imipramine, nortriptyline, and trimipramine have established pediatric doses for children older than 6 years. Clomipramine is approved for obsessive-compulsive disorder (OCD). Research into chronic and intractable pain is ongoing.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Varies | 2-4 h | – |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 8-16 h | liver | urine |
Contraindications and Cautions
Avoid with TCA allergy. Recent myocardial infarction can recur because of the drug's cardiac effects, and preexisting cardiovascular disorders worsen with its cardiac stimulation. Avoid with myelography within the previous 24 hours or the next 48 hours to prevent interaction with dyes. Do not combine with MAOIs (serious or toxic reactions). Avoid in pregnancy and lactation. Anticholinergic effects exacerbate angle-closure glaucoma, urinary retention, prostate hypertrophy, and GI or GU surgery. A history of seizures is a caution because the seizure threshold drops. Hepatorenal disease raises toxicity risk by impairing metabolism and excretion.
Adverse Effects
CV: orthostatic hypotension, hypertension, arrhythmias, palpitations, myocardial infarction, angina, stroke. GI: dry mouth, constipation, nausea, vomiting, anorexia, increased salivation, cramps, diarrhea. GU: urinary retention and hesitancy, loss of libido, changes in sexual function. Miscellaneous: alopecia, weight gain or loss, flushing, chills, nasal congestion. Abrupt cessation causes a withdrawal syndrome of nausea, headache, vertigo, malaise, and nightmares.
Interactions
Cimetidine, fluoxetine, and ranitidine increase TCA therapeutic and adverse effects. Oral anticoagulants reach higher serum levels with increased bleeding risk. Sympathomimetics or clonidine increase hypertension and arrhythmia risk. MAOIs increase the risk for severe hyperpyretic crisis with convulsions, hypertensive episodes, and death.
Monoamine Oxidase Inhibitors (MAOIs)
MAO is an enzyme in nerves and other tissues that breaks down the biogenic amines NE, dopamine, and 5-HT. MAOIs inhibit it, letting those amines accumulate in neuronal storage vesicles and increase postsynaptic stimulation, which is thought to relieve depression. They are used rarely now because of the strict dietary regimen needed to prevent toxicity, but some patients respond only to MAOIs, so they remain available for patients who do not respond to safer antidepressants. Avoid in children when possible because of drug-food interactions and serious adverse effects.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Slow | – | 48-96 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| unknown | liver | urine |
Contraindications and Cautions
Avoid with MAOI allergy. Pheochromocytoma is dangerous because a sudden NE increase can cause severe hypertension and CV emergencies. CV disease (hypertension, coronary artery disease, angina, congestive heart failure) worsens with increased NE. A history of headaches is a caution. Abnormal CNS vessels or defects can precipitate a stroke from increased blood pressure and vasoconstriction at higher NE levels. Avoid with myelography within the previous 24 hours or the next 48 hours. Avoid in pregnancy and lactation. Hepatorenal disease raises toxicity risk.
Adverse Effects
CNS: dizziness, excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation, blurred vision. CV: orthostatic hypotension, arrhythmias, palpitations, angina, and a potentially fatal hypertensive crisis (occipital headache, palpitations, neck stiffness, nausea, vomiting, sweating, dilated pupils, photophobia, tachycardia, chest pain). GI: liver toxicity, nausea, vomiting, diarrhea or constipation, anorexia, weight gain, dry mouth, abdominal pain. GU: urinary retention, dysuria, incontinence, changes in sexual function.
Interactions
TCAs cause hypertensive crisis, coma, and severe convulsions. SSRIs cause potentially life-threatening serotonin syndrome, so 6 weeks should elapse after stopping an SSRI before starting an MAOI. Sympathomimetics increase sympathomimetic effects. Insulin and oral antidiabetic agents add hypoglycemic effects. Phentolamine is the treatment for hypertensive crisis.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the newest group, blocking only the reuptake of 5-HT with little to no effect on NE, which raises 5-HT in the synaptic cleft. Full therapeutic effect takes up to 4 weeks. They have fewer adverse effects than TCAs and MAOIs, making them a better choice for many patients. They treat depression, OCD, panic attacks, bulimia, premenstrual dysphoric disorder (PMDD), social phobias, and social anxiety disorders.
In children they can cause serious adverse effects; only fluvoxamine and sertraline have established pediatric dosage for OCD, and fluoxetine is widely used to treat depression in adolescents.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Slow | 6-8 h | – |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 2-4 weeks | liver | urine, feces |
Contraindications and Cautions
Avoid with SSRI allergy. Hepatorenal disease raises toxicity risk. Severely depressed, suicidal patients carry a risk of increased suicidality. Avoid in pregnancy and lactation.
Adverse Effects
CNS: headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation, seizures. Respiratory: cough, dyspnea, upper respiratory infections, pharyngitis. GI: nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, changes in taste. GU: painful menstruation, cystitis, sexual dysfunction, urgency, impotence. Miscellaneous: sweating, rash, fever, pruritus.
Interactions
MAOIs increase serotonin syndrome risk. TCAs increase SSRI therapeutic and adverse effects.
Nursing Considerations
The assessment and evaluation framework is the same across all three classes. Assess for the cautions and contraindications above (drug allergies, hepatorenal disease, cardiac dysfunction, glaucoma, severe depression and suicidality). With TCAs and MAOIs, also screen for seizure disorders, psychiatric problems, suicidal thoughts, and myelography within the past 24 hours or the next 48 hours. Do a thorough physical exam for baseline data, and monitor ECG and labs (renal and liver function) to track effectiveness and catch complications early. Likely diagnoses include acute pain from anticholinergic, sympathomimetic, headache, GI, GU, and CNS effects; decreased cardiac output from CV effects; disturbed thought processes and sensory perception from CNS effects; and risk for injury from CNS effects.
For TCAs, limit drug access in suicidal patients to reduce overdose risk, give a major portion of the dose at bedtime when drowsiness and anticholinergic effects are severe, and add comfort and safety measures (voiding before dosing, taking food with the drug, adequate lighting, raised side rails).
For MAOIs, limit drug access in suicidal patients, monitor 2 to 4 weeks for full therapeutic onset, check blood pressure carefully for dose adjustments, and keep phentolamine at the bedside to treat a hypertensive crisis. Teach a low tyramine-containing diet and provide a list of drug-food interactions that can cause severe toxicity.
For SSRIs, lower the dose in elderly patients and those with renal or hepatic impairment, limit drug access in suicidal patients, monitor 4 weeks for full effect, set suicide precautions for severely depressed patients, and give the dose once daily in the morning for optimal effect. Advise barrier contraceptives, since serious fetal abnormalities can occur.
To evaluate across classes, track relief of depression signs and symptoms, watch for adverse effects (hypotension, suicidal thoughts, cardiac arrhythmias, hypertensive crisis, sedation, respiratory and GU problems), confirm understanding by having the patient name the drug, its indication, and adverse effects to watch for, and monitor compliance.
Frequently Asked Questions
How long do antidepressants take to work?
Full therapeutic effect usually takes about 4 weeks across all three classes. Tell patients to expect this lag, keep taking the drug, and not stop early just because they feel no immediate change.
Why is the early treatment period the highest-risk window for suicide?
Energy and motivation often return before mood lifts, which can give a still-depressed patient the drive to act on suicidal thoughts. This is the basis for the FDA boxed warning on increased suicidality in patients up to age 24, so monitor closely during the first weeks and after any dose change.
Why must MAOIs and SSRIs not be combined?
Combining them can cause life-threatening serotonin syndrome. Allow about 6 weeks after stopping an SSRI before starting an MAOI, and do not overlap the two classes.
What dietary teaching is essential for a patient on an MAOI?
Teach a low tyramine diet. Tyramine-rich foods can trigger a hypertensive crisis. Keep phentolamine available to treat a crisis, and teach the patient to report severe occipital headache, palpitations, neck stiffness, and sweating.
Why are SSRIs usually preferred over TCAs and MAOIs?
SSRIs block serotonin reuptake selectively and have fewer adverse effects than TCAs and MAOIs, which makes them safer for many patients and a common first choice. TCAs add anticholinergic and cardiac effects, and MAOIs require a strict diet to avoid toxicity.