Learning Outcomes
By the end of this section, you should be able to:
- 13.1.1 Identify the characteristics of drugs used to treat depression.
- 13.1.2 Explain the indications, actions, adverse reactions, and interactions of drugs used to treat depression.
- 13.1.3 Describe nursing implications of drugs used to treat depression.
- 13.1.4 Explain the client education related to drugs used to treat depression.
Depression is an affective disorder in which the person experiences feelings of sadness, anger, frustration, hopelessness, and helplessness. Although most individuals can feel this way at any point in their lives, genuine clinical depressive symptoms significantly interfere with daily life over a sustained period. This condition does not discriminate and can affect all ages, races, sexes, and genders. According to the American Psychiatric Association (2022), the diagnostic criteria for major depressive disorder (MDD) is having five or more symptoms present during the same 2-week period, and it represents a change from previous function. At least one of the symptoms is either depressed mood most of the day nearly every day or loss of interest or pleasure. Other depressive symptoms include significant changes in weight or appetite, insomnia or hypersomnia, observable psychomotor agitation or retardation, fatigue, feelings of worthlessness or excessive and/or inappropriate guilt, diminished ability to think or concentrate, difficulty with decision making, and recurrent thoughts of death. Additionally, the symptoms cause clinically significant distress or impairment and are not in response to a significant loss, a medical condition, or the effects of substance use.
The pathophysiology of depression is not well understood. Clients may need to try different medications before finding one that improves their symptoms with the fewest side effects. Research is ongoing to better understand the biochemical changes that occur with depression and, accordingly, which antidepressant medications are the most effective. Nurses who work with clients taking these medications should monitor current research and clinical guidelines for the most up-to-date findings and recommendations.
Special Considerations
Racial and Ethnic Considerations
Studies have shown there are differences in antidepressant responses in populations of color. These differences are mainly related to genetic or ethnic variations in the cytochrome P450 enzyme system responsible for the metabolism of most drugs.
- Black clients tend to have higher plasma drug levels for a given dose, respond more rapidly, experience a higher incidence of adverse drug reactions (ADRs), and metabolize tricyclic antidepressants more slowly than White clients.
- Asian clients metabolize antidepressants more slowly than White clients. Based on current studies, Asian clients are generally considered to not metabolize antidepressants as quickly as clients from other racial and ethnic backgrounds. Metabolism is important for preparing the drug for excretion. If metabolism is inadequate, the drug accumulates in the plasma, and elevated drug levels induce toxicity.
(Source: Marazziti et al., 2021)
Tricyclic Antidepressants (TCAs)
Tricyclic antidepressants (TCAs) were introduced in the late 1950s. For decades, these were the drugs of choice to treat depression. Although they have been very effective over the years, they have some serious adverse drug reactions (ADRs), including cardiotoxicity. Therefore, today they are considered second-line drugs. If a client was able to tolerate a TCA in the past and it was effective, this may be the basis for selecting a TCA over a different class.
Tricyclic antidepressants, in low doses, are frequently used for other indications, such as neuropathy and insomnia.
Adverse Effects and Contraindications
Tricyclic antidepressants block acetylcholine (muscarinic) receptors; therefore, blurred vision, dry mouth, constipation, and urine retention are common due to the anticholinergic properties. In addition, because they block histamine receptors, sedation and weight gain occur. Due to the blockade of alpha-1 adrenergic receptors, sedation and hypotension are common adverse effects. TCAs decrease vagal influence on the heart secondary to muscarinic blockade and act directly on the bundle of His to slow conduction. These drugs decrease the seizure threshold due to the blocking of ion channels, which can lead to the occurrence of seizures. Clients with a seizure disorder may need a dose increase for their antiseizure medication. Glaucoma is a contraindication because the anticholinergic properties can increase intraocular pressure (IOP).
Medications that lower the seizure threshold may increase the risk of seizures in clients taking TCAs. Concurrent use of TCAs with other anticholinergic and central nervous system (CNS) depressant drugs can worsen those effects. Certain antipsychotics can increase amitriptyline concentrations, and use of monoamine oxidase inhibitors (MAOIs) should be separated by 2 weeks due to the risk for serotonin syndrome (described in the following section). Because TCAs can prolong the heart’s QTc interval, use with caution in clients who have bradycardia, who are taking drugs that can induce bradycardia, or who have electrolyte abnormalities that could result in a life-threatening dysrhythmia.
Table 13.1 is a drug prototype table for tricyclic antidepressants featuring amitriptyline. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Tricyclic antidepressant Mechanism of Action Blocks the reuptake of norepinephrine (NE) and serotonin at the presynaptic nerve endings |
Drug Dosage Adults: Initial dose: 25–50 mg/day orally at bedtime. Increase dose by 25 mg every 3–7 days. Maximum dose: 300 mg. Can be taken at one time or in divided doses. Adolescents (ages 12–17): 10 mg orally 3 times daily and 20 mg orally at bedtime. |
| Indications Major depressive disorder (MDD) Primary insomnia Anxiety Chronic pain syndromes Therapeutic Effects Increases the effects of both NE and serotonin Can increase dopamine neurotransmission in the frontal cortex |
Drug Interactions Tramadol Anticholinergic agents Fluvoxamine Phenothiazines or haloperidol Monoamine oxidase inhibitors (MAOIs) Calcium channel blockers/beta blockers/digoxin CNS depressants (opioids, antihistamines) Food Interactions No significant interactions |
| Adverse Effects Prolongation of QTc interval Tachycardia Dysrhythmias Sedation Dry mouth Blurred vision Urine retention/constipation Weight gain Hypotension Seizures Photosensitization |
Contraindications Children <12 years Recent myocardial infarction Uncompensated heart failure Cardiac dysrhythmia Caution: Seizures Urinary retention/benign prostatic hyperplasia (BPH) Angle-closure glaucoma |
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. All are indicated for major depression. Several of these medications are also prescribed “off-label” for other psychiatric disorders, meaning the prescriber is using them for purposes other than what they were approved for by the Food and Drug Administration (FDA) but still based upon scientific rationale (Van Norman, 2023). Normally, the actions of serotonin are terminated by active reuptake back into the nerve terminals from which it was released. By inhibiting the reuptake pump, the SSRIs cause serotonin to accumulate in the synaptic space. SSRIs have little effect on other neurotransmitters and accordingly cause fewer adverse effects (Chu & Wadhwa, 2023). The most common SSRIs include:
- Citalopram: This drug is FDA approved only for major depression; however, it is used off-label for other conditions.
- Paroxetine: In addition to major depression, this drug is used for obsessive-compulsive disorder (OCD), panic disorder, social phobia, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD).
- Fluoxetine: This drug is used for major depression, OCD, panic disorder, PMDD, and bulimia nervosa. Fluoxetine does not block receptors for histamine, NE, or acetylcholine; therefore, the drug does not cause sedation, orthostatic hypotension, anticholinergic effects, or cardiotoxicity.
- Sertraline hydrochloride: This is FDA approved for major depression, PMDD, OCD, PTSD, social anxiety disorder, and panic disorder.
- Escitalopram: This drug is FDA approved for GAD in addition to the indications listed for fluoxetine.
Table 13.2 lists common SSRIs and typical routes and dosing for adult and pediatric clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Citalopram (Celexa) |
Adults: Initial dose: 20 mg/day orally; maximum dose: 40 mg/day. Older adults (>60 years): 20 mg orally daily. |
| Escitalopram (Lexapro) |
Adults: 10 mg/day orally; may increase to maximum dose of 20 mg/day after a minimum of 1 week of therapy. Adolescents 12–17 years: 10 mg/day orally; may increase to maximum dose of 20 mg/day if symptoms do not lessen within 3 weeks of therapy. |
| Fluoxetine (Prozac) |
Adults: Immediate-release capsules: 20 mg orally once daily in the morning; may increase after several weeks if necessary; maximum dose: 80 mg/day. Delayed-release capsules: 90 mg orally weekly, starting 7 days after the last 20 mg immediate dose. Adolescents 12–17 years: Immediate-release capsules: 10 mg/day orally; may increase to 20 mg/day after 1 week if necessary. |
| Paroxetine (Paxil) |
Adults: Immediate-release tablets: 20 mg orally once daily in the morning; increase dose at 1-week intervals if necessary; usual range: 20–50 mg/day; maximum dose: 50 mg/day. Controlled-release tablets: 25 mg orally once daily in the morning; maximum dose: 62.5 mg/day. Older adults (>60 years): Immediate-release tablets: 10 mg orally once daily in the morning; maximum dose: 40 mg/day. |
| Sertraline (Zoloft) |
Adults: 50 mg orally once daily morning or evening; may increase dose at 1-week intervals if necessary; maximum dose: 200 mg/day. |
Adverse Effects and Contraindications
Sexual dysfunction is one main reason why clients may elect to stop taking SSRIs. Impotence, delayed or absent ejaculation or orgasm, and decreased libido can be side effects of these medications. This can be managed in several ways: reduction of the dose, taking drug holidays, or adding a drug that can overcome the problem. Weight gain can occur due to the decreased sensitivity of serotonin receptors that regulate appetite.
MAOIs and fluoxetine should be separated at least 5 weeks apart to prevent serotonin syndrome. The remaining SSRIs and MAOIs should be separated by 2 weeks. This is due to the long half-life of fluoxetine. Serotonin syndrome is characterized by altered mental status, anxiety, hallucinations, hyperpyrexia, muscle rigidity, hyperreflexia, diaphoresis, and tremor. Tramadol also can increase the risk of serotonin syndrome when combined with SSRIs. The syndrome will resolve spontaneously after the drug(s) have been stopped.
Fluoxetine and other SSRIs can increase the risk of gastrointestinal (GI) bleeding either by impeding platelet aggregation or by increasing gastric acidity (Edinoff et al., 2022). These drugs can increase the risk for bleeding, so caution needs to be exercised for clients taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants because these can further the risk of bleeding. Fluoxetine also has CNS stimulant effects, which can cause insomnia and anxiety.
Table 13.3 is a drug prototype table for SSRIs featuring fluoxetine. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Selective serotonin reuptake inhibitor Mechanism of Action Selectively blocks neuronal reuptake of serotonin; over time, adaptive cellular changes take place in response to prolonged reuptake blockade |
Drug Dosage Adults: Immediate-release capsules: 20 mg orally once daily in the morning; may increase after several weeks if necessary; maximum dose: 80 mg/day. Delayed-release capsules: 90 mg orally weekly, starting 7 days after the last 20 mg immediate dose. Adolescents 12–17 years: Immediate-release capsules: 10 mg/day orally; may increase to 20 mg/day after 1 week if necessary. |
| Indications Major depression (≥8 years of age) OCD (≥7 years of age) Panic disorder PMDD Bulimia nervosa Bipolar depression (in combination with olanzapine) Treatment-resistant depression (in combination with olanzapine) Therapeutic Effects Concentration of serotonin in the synapse increases, resulting in enhanced activation of postsynaptic serotonin receptors |
Drug Interactions Tramadol MAOIs Warfarin Aspirin NSAIDs Food Interactions No significant interactions |
| Adverse Effects Nausea Headache Insomnia Nervousness Sexual dysfunction Weight gain Suicidal ideations (especially in children/adolescents) |
Contraindications Hypersensitivity Caution: GI ulcers History of GI bleeding Adults >60 years of age |
Safety Alert
Similarly Named Drugs Associated with SSRIs
Do not confuse:
- Celexa (SSRI) with Celebrex (proton pump inhibitor) or Zyprexa (antipsychotic)
- Fluoxetine (SSRI) with loxitane (antipsychotic)
- Prozac (SSRI) with Prograf (immunosuppressant), Provera (progesterone hormone), or Prilosec (proton pump inhibitor)
- Paxil (SSRI) with Plavix (antiplatelet) or Taxol (chemotherapy)
- Sertraline (SSRI) with cetirizine (histamine-1 receptor antagonist)
(Source: Institute for Safe Medication Practices [ISMP], 2023)
Serotonin Norepinephrine Reuptake Inhibitors
Besides blocking norepinephrine (NE) and serotonin, serotonin norepinephrine reuptake inhibitors (SNRIs) have minimal effects on other transmitters or receptors. SNRIs increase the levels of serotonin and NE in the brain, which play an important role in mood. These drugs can also weakly inhibit dopamine reuptake. Pharmacological effects are similar to the SSRIs. The most common SNRIs are:
- Venlafaxine: Used in major depression, panic disorder, social phobia, and GAD
- Duloxetine: Used for MDD, diabetic peripheral neuropathic pain, fibromyalgia, GAD, social anxiety, panic disorder, and chronic musculoskeletal pain in adults; used for depression, GAD, and fibromyalgia in children
- Levomilnacipran: FDA approved only for major depression but used off-label for GAD and chronic pain disorder
Table 13.4 lists common SNRIs and typical routes and dosing for adult and pediatric clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Venlafaxine (Effexor) |
Adults: Initial dose: 37.5 mg/day (extended release) or 25–50 mg divided into 2–3 doses (immediate release) for 1 week; increase daily dose no faster than 75 mg every 4 days until desired response is optimal; maximum dose: 225 mg/day. |
| Duloxetine (Cymbalta) |
MDD in adults: Initial dose: 40 mg/day orally in 2 doses; can increase to 60 mg/day in 1–2 doses if necessary; maximum dose: 120 mg/day. GAD in adults: 30–60 mg/day orally in capsules; maximum dose: 120 mg/day orally. MDD and GAD in children (7–17 years): 30 mg orally once daily; maximum dose: 120 mg/day. |
| Levomilnacipran (Fetzima) |
Adults: Initial dose: 20 mg/day orally for 2 days, then increase to 40 mg/day; can increase by 40 mg/day every 2 or more days; maximum dose: 120 mg/day. |
Adverse Effects and Contraindications
Similar to most SSRIs, SNRIs should not be taken until the client has stopped taking MAOIs for at least 14 days. This is to decrease the risk of serotonin syndrome.
Neonatal syndrome can occur when duloxetine is taken late in pregnancy. This syndrome is characterized by irritability, high-pitched cry, tremor, respiratory distress, and possible seizures in the neonate.
Use with caution for clients who have bipolar disorder, unless they are treated with a concomitant mood-stabilizing agent.
SNRIs have the potential to increase blood pressure; therefore, anyone with uncontrolled hypertension should avoid this class of drugs. Unwanted effects of insomnia, decreased appetite, increased blood pressure, and urinary retention can occur when the levels of serotonin and NE become elevated in certain parts of the brain and periphery that play no role in inducing the therapeutic effects.
Table 13.5 is a drug prototype table for SNRIs featuring duloxetine. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Serotonin norepinephrine reuptake inhibitor Mechanism of Action Powerful blockade of NE and serotonin reuptake Weak blockade of dopamine reuptake |
Drug Dosage MDD in adults: Initial dose: 40 mg/day orally in 2 doses; can increase to 60 mg/day in 1–2 doses if necessary; maximum dose: 120 mg/day. GAD in adults: 30–60 mg/day orally in capsules; maximum dose: 120 mg/day orally. MDD and GAD in children (7–17 years): 30 mg orally once daily; maximum dose: 120 mg/day. |
| Indications MDD Diabetic peripheral neuropathic pain Fibromyalgia GAD Social anxiety Panic disorder Chronic musculoskeletal pain Therapeutic Effects Increases concentration of NE and dopamine in the brain |
Drug Interactions MAOIs Antiplatelet agents Anticoagulants Food Interactions No significant interactions |
| Adverse Effects Nausea Headache Anxiety/nervousness Hyperhidrosis (excessive sweating) Insomnia Hepatotoxicity Weight loss (dose-dependent) Sexual dysfunction Elevated blood pressure Urinary retention Neonatal withdrawal syndrome Suicidal ideations (especially in children) Seizures |
Contraindications None Caution: Significant hepatic dysfunction Orthostatic hypotension Angle-closure glaucoma Substantial alcohol user Uncontrolled hypertension Seizure disorders Bipolar disorder Hyponatremia Depression/suicidal ideations in children, adolescents, and young adults |
Norepinephrine Dopamine Reuptake Inhibitors
Norepinephrine dopamine reuptake inhibitors (NDRIs) inhibit the reuptake of dopamine, NE, and serotonin. Several metabolites are active, giving this class a prolonged duration of action. The most common drug in this class is bupropion hydrochloride (Aplenzin, Wellbutrin, Zyban). It is used for depression, seasonal affective disorder (SAD), and smoking cessation and as an adjunct to other antidepressants if the client did not obtain a full therapeutic response with them.
Adverse Effects and Contraindications
NDRIs have several CNS stimulant effects including agitation, anxiety, excitement, increased motor activity, and restlessness. These effects usually occur during the first few days of treatment. (The client may require a sedative for the first few days.) These effects occur because this drug is similar in structure to amphetamines. These effects also could potentially increase the risk of misuse.
The dose must be reduced with any impaired hepatic or renal function. Clients should be screened for bipolar disorder before starting therapy to prevent mania or hypomania. When the drug is being used for smoking cessation, it can cause neuropsychiatric adverse effects. Postmarketing reports include serious or clinically significant changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic as well as suicidal ideation, suicide attempt, and death by suicide (DailyMed, Bupropion, 2023). This drug should be used cautiously in clients with a history of psychosis.
Unlike other antidepressants, this class does not cause sexual dysfunction or orthostatic hypotension.
A higher incidence of seizures was observed in clients being treated with the immediate-release formulation who have a current or past diagnosis of anorexia or bulimia nervosa. In addition, clients with a history of seizure disorders may need their drug dosages modified because bupropion decreases the seizure threshold and could trigger seizure activity.
The SSRIs listed in Table 13.2 inhibit the metabolism of bupropion; therefore, bupropion levels are increased, which increases the risk of seizures. MAOIs can increase the risk for bupropion toxicity as well as increase the risk of hypertensive crisis. Clients should discontinue MAOIs at least 2 weeks before starting bupropion.
Table 13.6 is a drug prototype table for NDRIs featuring bupropion hydrochloride. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Norepinephrine dopamine reuptake inhibitor Mechanism of Action Inhibits the reuptake of dopamine, norepinephrine, and serotonin |
Drug Dosage Immediate release: Initial dose: 75 mg orally twice daily, increasing to 100 mg twice daily, and then 100 mg 3 times daily. Maximum dose: 450 mg/day. Extended release: Initial dose: 150 mg/day; can increase to 300 mg/day after 4 days; maximum dose: 400 mg/day. Sustained release: 100 mg orally twice daily; increase to 150 mg after 3 days; maximum dose: 400 mg/day. |
| Indications Depression SAD Smoking cessation Therapeutic Effects Increases the levels of dopamine, NE, and serotonin |
Drug Interactions Sertraline Fluoxetine Paroxetine MAOIs used within 14 days Food Interactions No significant interactions |
| Adverse Effects Seizures Activation of mania/hypomania Neuropsychiatric effects Insomnia/tremors Tachycardia Increase in blood pressure Dry mouth Headache Constipation/nausea/vomiting Anorexia/weight loss Photosensitivity |
Contraindications Hypersensitivity Seizures Conditions that may lower seizure threshold (anorexia/bulimia nervosa, alcohol/substance withdrawal) Caution: History of psychosis Impaired hepatic function Impaired renal function Hyperthyroidism Hypertension |
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOIs) are third-line agents for treating depression. MAOIs are not often used in practice today, mainly because of the numerous food and drug interactions that produce severe hypertension. Blood pressure could be elevated enough to cause a stroke or myocardial infarction. MAOIs are used when other antidepressants have been unsuccessful. The most common MAOIs are:
- Phenelzine sulfate: Used to treat major depression.
- Selegiline hydrochloride: This is the first and only transdermal treatment for major depression. It is a potent irreversible MAOI with a great affinity for MAO-B in the brain at therapeutic doses. At higher doses, the drug becomes nonselective and can inhibit both MAO-A and MAO-B. It increases dopaminergic activity by interfering with dopamine reuptake at the synapse.
Table 13.7 lists common MAOIs and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Phenelzine sulfate (Nardil) |
15 mg orally 3 times daily; maximum dose: 90 mg/day. |
| Selegiline (Emsam) |
6 mg/24 hours transdermally; may titrate based on clinical response in increments of 3 mg/day every 2 weeks; maximum dose: 12 mg/24 hours. |
Adverse Effects and Contraindications
MAOIs are contraindicated in older adults due to their high risk of diminished hepatic, renal, and cardiac function.
Tyramine is a monoamine precursor of NE. Normally, tyramine is deactivated in the GI tract and liver by the monoamine oxidase enzyme to avoid large amounts reaching the systemic circulation. Because these drugs block the monoamine oxidase enzyme, tyramine is absorbed systemically. It is transported to the adrenergic nerve terminals, where it causes a sudden release of significant amounts of NE. This NE activates the sympathetic nervous system.
The antidepressants listed here can increase the risk of serotonin syndrome. Vasoconstrictors and sympathomimetics can intensify the hypertensive effect. The use of opioids and MAOIs can result in hyperpyrexia (high fever). Caffeine can also exacerbate the CNS stimulatory effect. Blood glucose levels may decrease with MAOIs, resulting in hypoglycemic effects. In addition, MAOIs can enhance insulin receptor sensitivity, compounding the hypoglycemic state. A decrease in dosage may be necessary.
Table 13.8 is a drug prototype table for MAOIs featuring phenelzine sulfate. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Monoamine oxidase inhibitor Mechanism of Action Irreversibly binds to the MAO-A enzyme |
Drug Dosage 15 mg orally 3 times daily; maximum dose: 90 mg/day. |
| Indications Major depression Therapeutic Effects Increases and enhances the effect of norepinephrine, dopamine, and serotonin |
Drug Interactions Antidepressants (TCAs, SSRIs, SNRIs, bupropion, carbamazepine) Vasoconstrictors Sympathomimetics (amphetamines, dextromethorphan, and diet pills) Opioids Insulin Food Interactions Caffeine Foods high in tyramine (milk, turkey, chicken, oats, seeds, soy products, seafood, canned tuna, aged cheeses, brewer’s yeast, whole-wheat bread) |
| Adverse Effects Hypertensive crisis (headache, tachycardia, nausea and vomiting) Dysrhythmias CNS stimulation (insomnia, anxiety, agitation) Hepatotoxicity Orthostatic hypotension Sexual dysfunction Dizziness |
Contraindications Severe hepatic disease Pheochromocytoma (adrenal tumor) Congestive heart failure Hypersensitivity to the drug or its ingredients Caution: Renal impairment Hepatic insufficiency Older adults |
Miscellaneous Antidepressants
Some drugs work just as well for depressive symptoms but do not fit into the criteria of other drug classes. They include:
- Mirtazapine: Used to treat major depressive disorder.
- Trazodone hydrochloride: This drug is a serotonin 2 antagonist/reuptake inhibitor. It increases the amount of serotonin available. It is more frequently used for sedation and sleep than for depression. High doses are needed for antidepressant effects; however, these doses cause significant sedation. The drug is often concurrently administered with a stimulating antidepressant such as bupropion.
- Vortioxetine: Increases the release of several neurotransmitters (serotonin, NE, dopamine, glutamate, acetylcholine, and histamine). In addition, it reduces the release of GABA, a neurotransmitter that inhibits mood-related neurotransmitters, through three different modes of action.
Table 13.9 lists common miscellaneous antidepressants and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Mirtazapine (Remeron) |
Initial dose: 15 mg/day orally in the evening; increase every 1–2 weeks until desired effect is achieved; maximum dose: 45 mg/day. |
| Trazodone hydrochloride (Desyrel) |
Initial dose: 150 mg/day orally in divided doses; can increase by 50 mg/day every 3–4 days; maximum dose: 400 mg/day divided into 2 doses. |
| Vortioxetine (Trintellix) |
Initial dose: 10 mg/day orally; can increase to 20 mg/day or decrease to 5 mg/day. |
Adverse Effects and Contraindications
The antihistamine effects of mirtazapine and trazodone hydrochloride cause sedation and weight gain. Agranulocytosis is an identified adverse effect. If a client experiences generalized malaise, chills, fever, or myalgia, similar to the flu, this may indicate a low white blood cell (WBC) count. The provider should be notified. Because mirtazapine is associated with significant weight gain, clients should be weighed prior to starting the drug to determine their body mass index (BMI). If they are deemed to have overweight or obesity, it is important to identify whether the client is prediabetic or diabetic and/or dyslipidemic. If so, clients should be treated or referred for therapy.
Any of the miscellaneous antidepressants can cause a fatal serotonin syndrome when combined with MAOIs. Do not use with MAOIs or within 14 days after they have been discontinued. Drugs such as benzodiazepines, opioids, and antihistamines can increase the sedative properties.
Table 13.10 is a drug prototype table for miscellaneous antidepressants featuring mirtazapine. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Miscellaneous antidepressant Mechanism of Action Blocks alpha-2 adrenergic presynaptic receptors, increasing NE neurotransmission Blocks alpha-2 adrenergic presynaptic receptor on serotonin neurons, leading to an increase in serotonin levels Blocks histamine-1 receptors |
Drug Dosage Initial dose: 15 mg/day orally in the evening; increase every 1–2 weeks until desired effect is achieved; maximum dose: 45 mg/day. |
| Indications Major depressive disorder Therapeutic Effects Increased levels of NE and serotonin |
Drug Interactions MAOIs Benzodiazepines/opioids/antihistamines Food Interactions No significant interactions |
| Adverse Effects Sedation Weight gain Increased appetite Elevates cholesterol and triglyceride levels Hypotension Malaise, fever, sore throat, myalgia, chills Leukopenia (low WBC count) |
Contraindications Hypersensitivity to the drug or any of its ingredients Severe neutropenia Caution: Dyslipidemia Angle-closure glaucoma Risk factors for QT prolongation Seizures Hyponatremia Impaired hepatic function Bipolar disorder Depression/suicidal ideations in adolescents and young adults |
Nursing Implications
The nurse should do the following for clients who are taking antidepressants:
- Obtain orders for baseline testing prior to the client starting the medication and continue during treatment to monitor for side effects: an electrocardiogram for clients over age 50 and lab work (complete blood count [CBC], electrolytes, lipid panel, liver function tests, and HgbA1C). If client is on anticoagulants, such as warfarin, monitor PT/INR frequently.
- Obtain baseline weight and body mass index (BMI) and monitor throughout treatment.
- Monitor blood pressure and heart rate twice weekly during treatment.
- Monitor for signs and symptoms of mania or hypomania.
- Check mood and anxiety periodically during treatment.
- Monitor for seizure activity.
- Ensure safety precautions are in place due to sedation.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antidepressant should:
- Be aware that these drugs can take 2 weeks to start seeing effects and 4–6 weeks for full therapeutic effects.
- Be informed about the high probability of sexual dysfunction and told to report any problems so they can be appropriately addressed.
- Immediately notify their provider about any clinical manifestations of increased depression or suicidal ideations.
- Contact their provider with signs of diabetes, such as increased thirst (polydipsia), extreme hunger (polyphagia), or increased urination (polyuria).
- Report signs of sore throat and/or fever.
- Assess for any signs of bleeding such as blood in urine (hematuria); dark, tarry stools; easy bruising; nosebleed (epistaxis); or bleeding gums.
- Notify their provider if there are any signs of liver disease, such as right upper quadrant pain, light-colored stools, and dark urine.
The client taking an antidepressant should not:
- Drive or engage in activities that require alertness until the effects of the medication are known.
- Eat foods high in tyramine (milk, turkey, chicken, oats, seeds, soy products, seafood, canned tuna, aged cheeses, brewer’s yeast, whole-wheat bread) if using an MAOI.
- Be in direct sunlight without appropriate clothing and sunscreen.
- Take aspirin or NSAIDs.
FDA Black Box Warning
Antidepressants
In short-term trials, antidepressant use for major depressive disorder increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults under age 24 when compared to placebos. These trials did not show an increase in the risk of suicidal thoughts and behavior in individuals over age 24. There was a reduction in risk with antidepressant use in individuals ages 65 and older.
Case Study
Read the following clinical scenario to answer the questions that follow.
Jadalyn Sanchez is a 21-year-old female student who arrives at the university’s student health center with complaints of frequent crying throughout the day and lack of motivation or interest in being with friends or engaging in activities she used to enjoy. She describes a sense of helplessness and inadequacy at school. Jadalyn states it takes everything for her to get out of bed to attend classes. She has had no appetite and lost 12 pounds over the past month. She reports that her symptoms have been present for approximately 6 weeks. She denies any recent or past traumatic events or losses. She reports occasional dating but currently is not in any committed relationship. She is sexually active and states that she is compliant with her prescribed oral contraceptives. She denies tobacco or illicit drug use and says she drinks two or three 6 oz glasses of wine on the weekends. She does not recall being this sad in the past. She states normally she is very active, meets all due dates, and takes her academics very seriously. Her roommate talked her into coming to the center because of the drastic change.
Family History
Mother (age 50): History of depression
Father (age 54): History of hypertension and bipolar disorder
Sister (age 24): Panic disorder and ADHD
Brother (age 16): ADHD and GAD
Current Medications
Loestrin Fe 1/20, once daily
| Vital Signs | Physical Examination | |
|---|---|---|
| Temperature: | 97.6°F |
|
| Blood pressure: | 106/68 mm Hg | |
| Heart rate: | 74 beats/min | |
| Respiratory rate: | 16 breaths/min | |
| Oxygen saturation: | 98% on room air | |
| Height: | 5'5" | |
| Weight: | 124 lb | |