6.3 Antidepressants

Antidepressants commonly take four to eight weeks for noticeable effects on mood symptoms.  Clients should also be counseled that if they do not feel better with the first antidepressant prescribed, the provider may need to try several different classes of medications to find one that works best for them. If a person’s symptoms do not improve after trying at least two antidepressants, esketamine may be prescribed for treatment-resistant depression. Esketamine is delivered as a nasal spray in a health care provider’s office, clinic, or hospital and acts rapidly within a few hours, to relieve depression symptoms. People usually continue to take an oral antidepressant(s) to manage their symptoms.^[12]

Clients should be instructed to never suddenly stop taking antidepressant medications or they may experience withdrawal symptoms.

Withdrawal Symptoms

To safely stop or change antidepressants, clients must have prescribed dosage reductions with  2-6 weeks between dose reductions. Withdrawal syndrome may occur if antidepressants are stopped abruptly due to the rapid changes in levels of neurotransmitters in the brain. Withdrawal symptoms can include the following^[13]:

• Flu-like symptoms, such as fatigue, headache, muscle aches, and sweating
• Fatigue
• Flushing
• Heart racing
• Trouble sleeping
• Vivid dreams or nightmares
• Nausea, diarrhea, and possibly vomiting
• Loss of appetite
• Dizziness, lightheadedness, or feeling unsteady on your feet
• Burning, tingling, or shock-like sensations
• Mood changes, such as anxiety, irritability, agitation, and aggression
• Brief shock-like feelings in the brain, short periods of blacking out, or a shock-like feeling with a buzzing sound

Side Effects

Nurses monitor clients receiving antidepressants for side effects and report concerns to the prescribing provider. Common side effects of SSRIs and SNRIs are as follows:

• Nausea
• Diarrhea
• Weight gain
• Insomnia
• Feeling agitated, shaky or anxious
• Sexual dysfunction (reduced sex drive, difficulties achieving orgasm, or difficulties obtaining or maintaining an erection)

Side effects generally improve within a few weeks, although some can occasionally persist and require tapering or switching to a different class of antidepressant.

Black Box Warning

A Black Box Warning is a significant warning from the Food and Drug Administration (FDA) that alerts the public and health care providers to serious side effects, such as injury or death. Black Box Warnings are in place for all classes of antidepressants used with children, adolescents, and young adults under age 25 due to a higher risk of suicide. All clients receiving antidepressants should be monitored for signs of worsening depression or changing behavior, especially when the medication is started or dosages changed. Clients should be instructed to immediately call their provider if they have any of the following symptoms:

• Thoughts about suicide or dying or attempts to commit suicide
• Worsening symptoms of depression
• Anxiety or feelings of mania
• Aggression, anger, or violence

Serotonin Syndrome

Serotonin Syndrome is a potentially life-threatening condition resulting from excessive serotonergic activity in the central nervous system, often triggered by the use or interaction of certain psychiatric medications. It most commonly occurs when two or more drugs that increase serotonin levels—such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), or certain over-the-counter supplements—are combined. Symptoms typically include altered mental status (e.g., agitation, confusion), autonomic instability (e.g., hyperthermia, tachycardia), and neuromuscular abnormalities (e.g., tremors, hyperreflexia, clonus). Nurses play an important role in early recognition and prompt intervention, including immediate discontinuation of serotonergic agents and supportive care.

A mnemonic commonly used to remember the symptoms of serotonin syndrome is SHIVERS:

• S: Shivering: A neuromuscular symptom similar to tremors specific to serotonin syndrome
• H: Hyperreflexia (and myoclonus): Hyperactive reflexes most prominent in the lower extremities.
• I: Increased Temperature
• V: Vital Sign Abnormalities: Tachycardia, tachypnea, and labile blood pressure
• E: Encephalopathy: Mental status changes such as agitation, delirium, and confusion
• R: Restlessness
• S: Sweating

People may get slowly worse and can become severely ill if not quickly treated. Untreated, serotonin syndrome can be deadly. With treatment, symptoms usually go away within 24 hours, but permanent kidney damage may result even with treatment. Uncontrolled muscle spasms can cause severe muscle breakdown called rhabdomyolysis. Myoglobin is released into the blood with muscle breakdown and clogs renal tubules, which can cause severe kidney damage if serotonin syndrome isn’t recognized promptly and treated.

Treatment of serotonin syndrome may include the following^[14],[15]:

• Stopping all serotonergic medications.
• Providing supportive care to normalize vital signs such as IV fluids, cooling measures, and medications to control heart rate and blood pressure.
• Sedating with benzodiazepines, such as diazepam or lorazepam, to decrease agitation, seizure-like movements, and muscle stiffness.
• If symptoms persist, administering cyproheptadine to block serotonin production.
• For clients with severe symptoms such as hyperthermia and muscle rigidity, more aggressive measures are required. These include sedation, intubation, neuromuscular paralysis, and active cooling techniques.^[16]

Clients with moderate to severe serotonin syndrome should be hospitalized for close monitoring and management. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome (NMS) caused by antipsychotic medications. However, NMS develops over a period of days to weeks.  Neuroleptic malignant syndrome (NMS) will be discussed further in Chapter 11.

Hypertensive Crisis

Hypertensive crisis can occur when clients taking monoamine oxidase inhibitors (MAOIs) also take medications containing pseudoephedrine or eat foods containing tyramine (aged foods; fermented foods; cured meats; alcoholic beverages such as beer or red wine; or overripe fruits such as raisins, prunes, or bananas). MAOIs inhibit the breakdown of tyramine, causing elevated tyramine levels in the body that can lead to hypertensive crisis.  Hypertensive crisis is a medical emergency defined as severe hypertension (blood pressure over 180/120 mm Hg) with acute end-organ damage such as stroke, myocardial infarction, or acute kidney damage. Symptoms may include a severe headache accompanied with confusion and blurred vision. Tachycardia or bradycardia may be present and associated with constricting chest pain. Other symptoms include neck stiffness or soreness, nausea or vomiting, sweating, dilated pupils, photophobia, shortness of breath, severe anxiety, and unresponsiveness. Seizures may occur, as well as intracranial bleeding in association with the increased blood pressure. Hypertensive crisis treatment involves discontinuation of the offending agent, administration of appropriate intravenous antihypertensive medications such as phentolamine or labetalol, and supportive care.. In severe cases, treatment in the intensive care unit may be required.^{[17][/footnote],[18]}

Client Education

Clients should be instructed it may take 4 to 8 weeks for antidepressants to achieve their full effectiveness. They should not suddenly stop taking antidepressants or they may experience withdrawal symptoms. When it is time to stop the medication, the provider will slowly and safely decrease the dose. If clients stop taking the medication before the provider advises, the depression may return. They may not feel better with the first antidepressant they try, and they may need to try several different classes of medications to find one that works best for them.  Education related to potential side effects and when to contact the provider, clinical worsening, avoiding alcohol, interference with cognitive or motor functioning, and potential drug interactions should also be provided.