6.3 Antidepressants

Antidepressants are commonly used to treat depression but are also used to treat other conditions, such as anxiety, obsessive compulsive disorder, chronic pain, and insomnia. According to a research review by the Agency for Healthcare Research and Quality, antidepressant medications work to treat symptoms of depression as well as for maintenance of improved mood.^[1] For reasons not yet well understood, some people respond better to certain antidepressant medications than to others, so an individual may have to try different types of antidepressants before finding one that effectively treats their symptoms.^[2] Additionally, it may take antidepressants two or more weeks to achieve peak effect.

There are several classes and types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and dopamine reuptake inhibitors (NDRIs) , serotonin antagonist and reuptake inhibitors (SARIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). TCAs and MAOIs are often referred to as first-generation antidepressants because they were first marketed in the 1950s. They have many side effects and are not prescribed as frequently to treat depression as are SSRIs, SNRIs, and bupropion that have fewer side effects. Boxed Warnings are in place for all classes of antidepressants used with children, adolescents, and young adults for a higher risk of suicide. Patients receiving antidepressants should be monitored for signs of worsening depression or changing behavior, especially when the medication is started, or dosages are changed.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants. Serotonin is heavily involved in many processes in the brain and body, including sleep regulation, hunger and satiety, nausea and vomiting, sexual behaviors, anxiety, and mood states. SSRI medications prevent the uptake of serotonin at the synapse, causing the serotonin neurotransmitter to stay in the synapse longer and overall raise the level of serotonin in the brain. SSRIs are primarily used to treat depression but are also used to treat bipolar disorder, obsessive-compulsive disorder, bulimia, panic disorder, post-traumatic stress disorder, anxiety, premenstrual syndrome, and migraines. Examples of common SSRIs include fluoxetine, citalopram, sertraline, paroxetine, and escitalopram.^[3],[4]

SSRIS are generally given once daily. Nurses need to monitor for expected effects of improved depressive symptoms, lessening of anxiety, improved sleep, and reduction of suicidal thoughts. Adverse effects include alterations in gastrointestinal functioning such as change in appetite, nausea, or diarrhea. Changes in sleep pattern may occur. The most important assessment parameter for nurses is suicidality. For some patients, suicidal thoughts can become more frequent. The provider should be notified and suicide precautions increased if a patient’s suicidal ideation worsens.

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, particularly with concomitant use of serotonergic drugs, drugs that impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Symptoms should be reported immediately to the provider and the SSRI discontinued.^[5]

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin norepinephrine reuptake inhibitors (SNRI) prevent the reuptake of serotonin and norepinephrine, with weak inhibition of dopamine reuptake. Common SNRIs include venlafaxine, desvenlafaxine, and duloxetine. SNRIs are more frequently prescribed for patients who are not responding completely to SSRIs. Another strong advantage of SNRIs is their potential for reduction in pain, particularly neuropathic pain. These medications have become mainstays in the treatment of diabetic neuropathy and fibromyalgia^[6]

Similar to the SSRI class, nurses need to assess for improvement in mood and anxiety. Adverse effects include those for SSRIs but in addition, due to the influence of norepinephrine, patients need to be monitored for increased blood pressure and heart rate. They may also report excessive sweating, especially at night. Discontinuing an SNRI must be done slowly due to the potential for discontinuation syndrome. Discontinuation syndrome consists of flu-like symptoms, nausea, dizziness, paresthesias, “zapping” sensations in the brain, and trouble sleeping. The symptoms start two to four days after stopping the antidepressant and usually resolve over four to six weeks. Nurses should instruct patients to avoid abruptly stopping the medication.

Norepinephrine and Dopamine Reuptake Inhibitors (NDRI)

Bupropion is an example of a norepinephrine and dopamine reuptake inhibitor. It is used to treat depressive disorders, seasonal affective disorder, attention deficit disorder and to help people stop smoking. It is unique in that it does not impact sexual functioning, due to lack of serotonin impact, and it may result in weight loss. It is available in extended-release formulations and is generally taken in the morning due to its potential to cause insomnia. An important nursing implication is an increased risk for seizures. This medication is contraindicated for patients with pre-existing seizure risks, such as seizure disorders, head injuries, or alcohol withdrawal.^[7]

Serotonin Antagonist and Reuptake Inhibitors (SARIs)

Trazodone is an example of a serotonin antagonist and reuptake inhibitor (SARI). It is an antidepressant but most commonly prescribed off-label for anxiety or as a hypnotic. Trazodone reduces levels of the neurotransmitters associated with arousal effects, such as serotonin, norepinephrine, dopamine, acetylcholine, and histamine. Low-dose trazodone use exerts a sedative effect for sleep, so is typically administered in the evening. Its use has been increasing because it is one of few hypnotics that are not controlled substances with potential for misuse. In addition to adverse effects discussed above, nurses need to monitor for morning sleepiness and orthostatic hypotension.^[8]

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are older first-generation antidepressants that block the reuptake of serotonin and norepinephrine in the synapse, which leads to increased concentration of these neurotransmitters in the brain. They are now more commonly used to treat neuropathic pain and insomnia. An example of a TCA is amitriptyline.^[9]

TCAs are often administered at bedtime due to sedating effects. Older adults are particularly sensitive to the anticholinergic side effects of tricyclic antidepressants (e.g., tachycardia, urinary retention, constipation, dry mouth, blurred vision, confusion, psychomotor slowing, sedation, and delirium). Elderly clients should be started on low doses of amitriptyline and observed closely because they are at increased risk for falls. Blockage of adrenergic receptors can cause cardiac conduction disturbances and hypotension.^[10]

Death may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. If overdose occurs, call 911 in an outpatient setting or rapid response in an inpatient setting. Responders can consult with a Certified Poison Control Center (1-800-222-1222) or go to America’s Poison Center’s Poison Help webpage for the latest treatment recommendations.^[11]

Monoamine Oxidase Inhibitors (MAOI)

Monoamine oxidase inhibitors (MAOIs) are older first-generation antidepressants and infrequently prescribed. They are considered last-line agents in the treatment of depression. MAOIs are contraindicated with all other classes of antidepressants. Monoamine oxidase is an enzyme that prevents the destruction of the neurotransmitters norepinephrine, serotonin, and dopamine from the brain. By inhibiting this enzyme, MAOIs cause the levels of these transmitters to increase. Tranylcypromine is an example of an MAOI.^[12]

A significant disadvantage to MAOIs is their potential to cause a hypertensive crisis when taken with stimulant medications or foods or beverages containing tyramine. Examples of foods containing tyramine are aged cheese, cured or smoked meats, alcoholic beverages, and soy sauce. Older adults are at increased risk for postural hypotension and serious adverse effects.^[13]

Newer Antidepressants

Research and drug development continues, resulting in new medications at a rapid pace. While some are newer members of the previously discussed classes, two novel agents are mentioned here.

Esketamine is chemically related to ketamine and is used as a nasal spray. It’s proposed mechanism of action is the blocking the effects of the neurotransmitter glutamate. It is only available for use in restricted settings under direct supervision of a healthcare provider. Dissociation is a common side effect, necessitating the need for the patient to be monitored and supervised for two to three hours after administration.

Brexanolone is a medication that modulates gamma amino butyric acid A (GABA-A) and has been approved specifically for post-partum depression. It is a neuroactive steroid that is given by infusion over a period of 60 hours within a hospital setting. Patients need to be monitored for level of consciousness and possible hypoxia.^[14]

Another newer agent, Auvelity, is a combination of dextromethorphan and bupropion. This is the first NMDA receptor antagonist for use in depression and produces antidepressant effects by binding to serotonin and norepinephrine and affects pathways to glutamate. The bupropion is used to increase and prolong the plasma concentration of the dextromethorphan. It typically works within a week and is not a controlled substance.^[15]