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Depression

2 Contact Hours including 2 Advanced Pharmacology Hours
This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN), Athletic Trainer (AT/AL), Certified Nurse Midwife, Certified Nurse Practitioner, Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Occupational Therapist (OT), Occupational Therapist Assistant (OTA), Physical Therapist (PT), Physical Therapist Assistant (PTA), Registered Nurse (RN), Registered Nurse Practitioner
This course will be updated or discontinued on or before Thursday, June 27, 2024

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


CEUFast, Inc. is an AOTA Provider of professional development, Course approval ID#05005. This distant learning-independent format is offered at 0.2 CEUs Intermediate, Categories: OT Service Delivery and Foundational Knowledge. AOTA does not endorse specific course content, products, or clinical procedures. AOTA provider number 9575.


BOC

FPTA Approval: CE22-810726. Accreditation of this course does not necessarily imply the FPTA supports the views of the presenter or the sponsors.
Outcomes

≥92% of participants will report an increase in knowledge regarding assessing and managing depression.

Objectives

After this course, the learner will: 

  1. Describe the prevalence and comorbidities associated with depression.
  2. List four risk factors for depression.
  3. Distinguish diagnostic features of major depression.
  4. List four non-pharmacological interventions and state their role in the management of depression.
  5. Outline the safety and efficacy of different antidepressant medications.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Raymond Lengel (MSN, FNP-BC, RN)

Introduction

Depression is a common problem in healthcare. Despite its prevalence, it is underdiagnosed and undertreated, which is unfortunate because many treatments are available to relieve this disabling disease. Many reasons explain why it is underdiagnosed, but it is often not discussed enough in the medical office. Depression comes with a negative social stigma, and people are often ashamed to discuss it with their providers. In addition to doctors being reluctant to bring it up, they often lack time to dive into a discussion about depression with their patients.

Depression is more than feeling sad. Everyone has days when they are sad, but depression is a persistent feeling of sadness that disrupts life for the person afflicted and their loved ones.

Types of Depression

This article will focus on major depressive disorder (MDD), but depression can have other forms. Major depressive disorder is associated with a reduction in pleasure and feelings of sadness that affect the individual's ability to work, interact, eat, sleep and derive pleasure from life (American Psychiatric Association [APA], 2013).

Another common type of depressive disorder is persistent depressive disorder, previously known as dysthymic disorder. This depression is associated with more than two years of impaired function, but symptoms are not as severe as major depressive disorder (APA, 2013).

Bipolar depression is another type of depression where the individual cycles between depression and mania. Mania is characterized by an elevated mood, increased energy, and irritability and is associated with euphoria, reduced sleep times, excessive talking, and a lack of inhibitions (APA, 2013).

Postpartum depression is associated with depression within four weeks of delivering a child (APA, 2013).

The seasonal affective disorder is depression that starts in the fall, continues into the winter months, and is associated with less natural light. This type of depression improves in the spring and summer (APA, 2013).

Statistics

In 2015, among adults in the United States, an estimated 16.1 million had at least one major depressive episode in the past year. This number represented 6.7% of all adults (Halverson, 2020). Depression is more common in those between 40 to 59 years old. Females are seventy percent more likely to be depressed than males over their lifetime (Halverson, 2020). Eventually, depression can be successfully managed in most patients, but 40 percent do not respond to the first treatment (Blackburn, 2019).

Most patients with depression receive treatment. Approximately 66 percent of American adults with MDD received treatment over the last 12 months. About 71 percent of those with severe disease received treatment over the previous 12 months (National Institute of Mental Health, 2022).

Antidepressant use is increasing. Between 1999-2002 there was a 7.7 percent use rate, and between 2011-2014 the use rate was 12.7 percent (the female use rate was 16.5 percent) (Blackburn et al., 2019). Depression rates in children are high, with up to eight percent of teenagers meeting depression criteria in the last year; by age 21, almost 15 percent have had a mood disorder (Blackburn, 2019).

Suicide is a serious problem that often complicates depression. It is estimated that 45,979 people died by suicide in the United States in 2020 (Center for Disease Control and Prevention [CDC], 2022). It is the second leading cause of death for individuals aged 10 to 14 and 25 to 34 (CDC, 2022). Groups more commonly afflicted by suicide are veterans, rural residents, non-Hispanic Whites, non-Hispanic American Indian/Alaskan Natives, and younger people who identify as gay, lesbian or bisexual (CDC, 2022).

Complications

Depression is laced with many complications. The most severe complication is suicide. Along with substance abuse, depression is the most common mental disease that afflicts those who commit suicide (CDC, 2020).

While depression is more common in women, successful suicide is more common in men. Women more commonly attempt suicide (2-3 times more often) but are not as successful. Older white men have the highest rate of completed suicide (CDC, 2022; Halverston, 2020). Specific factors increase the risk of suicide, including chronic medical illness, access to firearms, depression, family history of suicide, social isolation, and delusions.

Depression is associated with many other problems in addition to suicide. Those with depression suffer more medical illness and have worse medical illness outcomes than those without depression (Thom et al., 2019). Depression significantly impacts work life. Those with depression are more likely to miss work and be inefficient at work. Depression can profoundly affect the quality of life (Malhi & Mann, 2018). It significantly disrupts family, friends, and work relationships. Some with depression are socially isolated, do not interact with other people, and may not leave home.

Depression is associated with higher rates of substance abuse. It is unclear if depression causes substance abuse or if substance abuse causes depression. There is likely a complex interaction between the two conditions (National Institute of Mental Health, n.d.).

Depression may lead to significant complications in a patient's physical health. Depression may lower compliance with medical treatment and occurs for many reasons, including depression leading to patients making poor lifestyle choices.

Those with depression have reduced survival rates when compared to those without depression. Depression is a risk factor for heart disease and subsequent myocardial infarction. In addition, those who have depression are more likely to have more severe cardiac symptoms, reduced quality of life, and a worse prognosis for heart disease (Zhang, 2018). Depression has also been noted to increase the risk of dementia. In addition, depression is a risk factor for cognitive decline in those diagnosed with dementia (Sáiz-Vázquez et al., 2021).

Those who are depressed are more likely to make poor lifestyle choices. Obesity rates are higher in those with depression than in those without depression. A study confirmed that those who are obese are more likely to become depressed, and those who are depressed are more likely to become obese. In addition, management of depression helps obesity, and management of obesity helps depression (Jantaratnotai et al., 2017).

Case Studies

The following case studies are descriptions of the patient's presentation. The conclusion of the case study is presented later in this course after the discussion of treatment options.

Case Study 1

Jenny, a 36-year-old married, white female with three children, presents to her primary nurse practitioner at her husband's request because she has been increasingly irritable, tired, and complaining of dizziness and frequent low back pain. The physical exam was unremarkable. Routine blood work was unremarkable, including a complete blood count, complete metabolic panel, and thyroid panel.

The nurse practitioner reviewed her labs on the follow-up exam and performed a Physician Depression Questionnaire (PDQ-9). The PDQ-9 score was 14, which equated to moderate depression. The patient denied any suicidal thoughts, and no grief was noted. The exam did not reveal any manic or psychotic symptoms. The patient revealed that she had felt like this before, but the feelings did not persist and never impacted the lives of her family or friends.

Case Study 2

John, a 78-year-old man, presents with low back pain to his primary care physician. John lives with his son and daughter-in-law, and his son accompanies him to the appointment. The low back pain has been present for three weeks, and there has been no trauma or injury that would indicate a cause of the back pain. John reports that the pain is mild, but he is apprehensive about cancer. He is convinced that he is going to die.

John's son is not as concerned about the low back pain; he reports that he has complained of on and off back pain his whole life. He is most concerned about his increased irritability and social withdrawal. John's past medical history is positive for hypertension, arthritis, and mild dementia. He has never had surgery.

He lives with his son because his son had noticed an increase in confusion after the death of his wife one year ago. He could not cook, clean, or handle finances but could still drive and shop. Over the past couple of months, he has become more isolated in his room and has had increased irritability. His daughter-in-law is threatening to put him in a nursing home. After moving in with his son, he has limited contact with his friends and has no friends in his new neighborhood. His son discourages him from driving the 20 miles to visit his old friends.

The physical exam was unremarkable, and his Mini-Cog score was 2.

Pathophysiology

The exact pathophysiology of depression is unknown, but there are many theories. It is likely caused by biochemical, genetic, psychological, and environmental factors. Major theories revolve around disturbances in neurotransmitters and chemicals in the central nervous system, particularly serotonin, norepinephrine, and dopamine.

It is clear that depression runs in families, but it is unknown exactly how it is transmitted. Likely multiple genes interact together to increase the risk of depression. Individuals with a family history of depression or alcohol dependence have a higher risk of depression (McHugh & Weiss, 2019).

Life can contribute to depression. Stressors and interpersonal loss are often associated with depression. While some depressive episodes occur without an apparent cause, a direct reason is usually responsible. Trauma, loss of a loved one, a complicated relationship, or any stressful situation may trigger a depressive episode. Stress increases cortisol levels and may affect mood. An early life loss increases the risk of depression over a lifetime (Halverson, 2020; McCarron, 2021).

Signs and Symptoms of Depression

Depression presents differently in different individuals. A common pneumonic to help nurses remember the classical signs and symptoms of major depressive disorder is SIG-E-CAPS.

Depressed Mood
SSleep disturbances - not sleeping enough (usually early morning wakening) or excessive sleep
ILoss of interest in activities that the individual used to find enjoyable - anhedonia
GGuilt or feeling worthless or hopeless
ELow energy or fatigue
CConcentration problems
AAppetite disturbances - eating too much or too little
PPsychomotor retardation or agitation
SSuicidal thoughts or attempts

Other symptoms that can present with depression include irritability, restlessness, pessimism, a variety of pain complaints, headaches, or gastrointestinal problems.

According to the DSM-V criteria (APA, 2013), to meet the diagnostic criteria for major depression, an individual must have five signs/symptoms that change from the previous function over two weeks. Depressed mood or reduced interest/pleasure must be present, and at least four other criteria described above.

In addition, the individual must not have manic episodes. The symptoms must cause impairment in function or significant distress. Other medical problems (such as hyperthyroidism, drug abuse, or alcohol abuse) must be ruled out, and the symptoms must not be related to bereavement/grief.

Depression in the Older Adult and Dementia

It is often more challenging to diagnose depression in those who have dementia. Those with dementia may demonstrate increased agitation, irritability, fatigue, hallucinations, or delusions. Those with dementia may be less likely to have feelings of hopelessness/helplessness or guilt.

Children and Depression

Children who are depressed have a higher risk of developing severe depression when they become adults. Children may present differently with depression when compared to adults. Children with depression may practice avoidance behaviors, including refusing to go to school, pretending to be sick, or not wanting to leave the parent's side. They may also demonstrate behavioral problems, get into trouble, be irritable or have mood swings. Many of these behaviors are common among teenagers without depression, and it is often difficult to determine if depression is present in children.

Physical examination

A physical exam is typically unremarkable in the depressed patient. Certain features may be noticed on the exam, including flat affect, poor personal hygiene, psychomotor agitation or retardation, or slow speech. Many patients with depression will have none of these features. Mental status should be checked, particularly in the older patient, to assess for cognitive declines. The exam should reveal any key features of depression noted above and any mood swings, delusions, and hallucinations.

Diagnostics

Diagnostic testing

No test definitively diagnoses depression, but diagnostic testing is used to rule out other contributing or causative factors of a depressed mood. Standard blood tests run on the depressed patient include:

  • Complete blood count
  • Thyroid panel
  • Kidney function tests
  • Liver function tests
  • Electrolytes
  • Vitamin B-12 level
  • Urine drug screen toxicology
  • Alcohol level
  • Antinuclear antibody (ANA)
  • Erythrocyte sedimentation rate (ESR)
  • Rapid plasma reagin (RPR)
  • Human immunodeficiency virus blood test

Imaging studies are rarely performed in the evaluation of depression. Some patients may be candidates for computed tomography or magnetic resonance imaging for the brain to rule out intracranial pathology. Rarely electroencephalography (EEG) or lumbar puncture is performed.

Screening tests

Screening for depression

Few patients discuss depression with their primary care provider (PCP). Many patients with depression present with somatic symptoms (commonly pain issues such as headache, myalgia, or back pain), making diagnosis much more challenging.

Because few patients readily bring it up to their PCP, screening for depression is very important. Without screening, only about 50 percent of patients with major depression are diagnosed (McCarron et al., 2021). Detecting depression is important because untreated depression increases the risk of suicide, reduces the quality of life, contributes to poorly controlled chronic diseases, and increases death rates. The US Preventive Services Task Force (USPSTF) advocates regular screening for depression in adults if staff is available for diagnosis, treatment, and follow-up (Williams & Nieuwsma, 2018).

Screening is essential as depression is a common condition that often goes undetected. Multiple tools are available to screen in primary care. Screening has been found to detect the condition but has not been proven to enhance clinical outcomes (Williams & Nieuwsma, 2018). There are downsides to screening, including overdiagnosis of patients, unnecessary treatments, overtreatment with resultant unnecessary side effects, and extra costs of treating a disease that is not present.

Screenings may be done by performing a screening test on all patients during routine visits, which the US Preventive Services Task Force recommends. Screening may also occur in patients with specific findings suggestive of depression, such as chronic pain, insomnia, unexplained symptoms, fatigue, life stressors, recent life changes, or fair/poor self-health ratings.

A few of the standard screening tests to evaluate for depression include:

  • Patient Health Questionnaire 9 (PHQ-9) is a commonly used quick screening tool that asks nine questions to evaluate for the presence of depression. It is scored from 0-27, with scores greater than or equal to 10 suggestive of depression. It has a sensitivity of 88 percent and specificity of 85 percent. It screens for depression and monitors response to treatment. Those with a score greater than 10 have a positive predictive value of 45 percent, and those with a score less than 10 have a negative predictive value of 99 percent (Williams & Nieuwsma, 2018).
  • Beck Depression Inventory is a 21-question multiple-choice test that helps identify and measure the severity of depression. Therefore, this screening test requires a license and a fee and is not frequently used.
  • Hamilton Depression Inventory asks 17 questions to evaluate mood. A score above 11 is likely associated with depression. A higher score is associated with more severe depression.
  • Mood Disorder Questionnaire (MDQ) is a five-minute questionnaire that helps screen for the presence of bipolar disease.
  • Geriatric Depression Scale is used on geriatric patients. This test does not work well on those with dementia advanced beyond mild.
  • Cornell Depression Scale was developed for older adults with dementia and interviews the patient and someone who knows the patient to help determine the patient's mental state. A score above 18 is highly suggestive of depression, a score between 10 and 17 indicates probable depression, and a score below ten likely suggests the absence of depression.

A quick screen, the Patient Health Questionnaire-2 (PHQ-2), for depression can be run by asking the patient two questions. This test has a sensitivity of 76 percent and a specificity of 87 percent (Williams & Nieuwsma, 2018). A single yes response is a positive test.

  1. In the last two weeks, have you felt down or depressed?
  2. Have you had little interest or pleasure in doing things in the last two weeks?

Diagnosis and Differential Diagnosis

Depression is a diagnosis of exclusion. No diagnostic test is available to diagnose the disease. When it is suspected, other conditions must be ruled out with a history, physical exam, selected blood tests, and occasionally radiographic tests to rule out conditions that mimic depression.

For the condition to be managed appropriately, it needs to be diagnosed. Adults should be screened for depression when there is a place to ensure a correct diagnosis, appropriate treatment, and follow-up (AHRQ, 2016). A similar statement has been made for adolescents with depression. Those between the ages of 12-18 years old should be screened for major depression if a system is in place to diagnose, provide psychotherapy and follow up accurately. For those between 7-11 years old, there is not enough evidence to evaluate if screening is appropriate (Forman-Hoffman et al., 2016).

Depression often co-exists with other mental health conditions. Healthcare professionals need to be on the lookout for different conditions. Identifying other disorders is important because it can significantly impact treatment options. For example, certain antidepressant medications are indicated for both anxiety and depression. Other antidepressant medications, while treating the depression, will worsen anxiety.

One of the most common co-existent conditions is anxiety disorders. Anxiety disorders may include generalized anxiety disorder, social phobia, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder.

Other mental health conditions co-existing with depression include substance and alcohol abuse, personality disorders, bipolar disease, eating disorders, adjustment disorder, and schizophrenia.

In addition to mental illness, depression often co-exists with many medical diseases. Depression may result from the medical disease, or depression may exacerbate the medical disease. Common medical conditions that are seen in combination with depression include heart disease, cancer, stroke, Parkinson's disease, dementia, and diabetes.

When evaluating someone with depression, identifying these medical conditions is critical concerning the medication selection. For example, individuals with high blood pressure and heart disease may want to avoid certain antidepressants that increase blood pressure, such as venlafaxine.

Depression adversely affects chronic disease. Those with depression typically have more severe underlying medical illnesses and more costs associated with their medical condition. When faced with a person with probable depression, it is essential to consider other diagnoses. Some of them include:

  • Anxiety disorders and other mental health conditions as discussed above
  • Dementia
  • Cancer of the central nervous system; mood changes are often noted before other neurological signs and symptoms
  • Substance abuse: alcoholism, cocaine use, marijuana use, or opioid abuse
  • Inflammatory conditions such as systemic lupus erythematosus
  • Sleep problems such as obstructive sleep apnea or insomnia
  • Infectious diseases such as Lyme Disease, syphilis, or HIV
  • Chronic fatigue syndrome
  • Endocrine diseases such as hypothyroidism/hyperthyroidism, Cushing disease, prolactinoma, and hyperparathyroidism
  • Anemia
  • Female hormonal disorders such as menopause or premenstrual dysphoric disorder

Some medications can cause depression. Common medications to consider as causes of depression include beta-blockers, calcium channel blockers, corticosteroids, H2 blockers, sedatives, chemotherapy agents, or hormones.

Treatments

A variety of treatments are available to manage depression. Common treatments include lifestyle changes, psychotherapy, medications, electroconvulsive therapy, and light therapy.

The goal of treatment is to alleviate symptoms and restore the patient's function. Treatment with both pharmacotherapy and psychotherapy for mild to moderate unipolar depression is preferred (Halverson, 2020). Studies have shown that those treated with psychotherapy will have benefits that will persist, and those treated with antidepressants are more likely to relapse (Halverson, 2020).

Lifestyle changes

Exercise is helpful as a treatment and an add-on method in treating depression. It has been shown that modest levels of exercise may improve depression. It is unclear how much, and the exact type of exercise helps manage depression, but getting patients to adhere to an exercise regime is critically important in managing depression.

No scientific proof exists to suggest that nutrition will cure depression, but eating a healthy diet may improve some of the symptoms of depression. Depressed patients should be encouraged to eat a balanced diet that provides adequate vitamins and minerals. Research suggests the following links between nutrition and depression:

  • Dietary omega-3 fatty acids may play a role in preventing and treating depression (Wani et al., 2015).
  • Depression is linked with deficiencies in vitamins B1, B3, B6, B9, and B12 ( Mikkelsen et al., 2016).
  • Low vitamin D levels are linked to depression (Geng et al., 2019).
  • Zinc levels are lower in those with depression (Wang et al., 2019).

Psychotherapy

Talk therapy can treat depression either alone or in combination with medications. Psychotherapy is more effective than placebo, and the total number of sessions is not associated with the degree of clinical benefit. Psychotherapy and medications are generally comparable for mild to moderate major depression (Rush, 2020).

Cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) are popular. Cognitive-behavioral therapy helps change thought patterns and behaviors to improve mood. It is believed that how one thinks and behaves contributes to their depression. Interpersonal therapy helps people with relationships that may be contributing to their depression.

Talk therapy is more effective in certain groups of people. Talk therapy is recommended for those with mild to moderate depression. In severe depression, it is recommended to use a combination of pharmacotherapy and talk therapy (Rush, 2020). In children, talk therapies are often carried out over internet platforms (Hazell, 2021).

Psychotherapy helps to address the causative factors and the maintaining factors in depression. It is most effective in moderate-to-severe depression after a medication has stabilized the disease.

For those individuals with mild depression, self-guided self-help therapy may be considered, which involves using a structured workbook or guidance by a clinician. Talk therapy is more commonly implemented on internet-based platforms. If this option is attempted, the patient should let the staff know if there is no response, worsening, or suicidal ideation. Research suggests a significant benefit to this type of treatment which is more pronounced in those with moderate to severe depression (Karyotaki et al., 2021).

Using relaxation techniques such as relaxation imagery, progressive muscle relaxation, and autogenic training effectively manages depression. It has similar effectiveness to psychotherapy (Jia et al., 2021).

Medications

Many medications are available for the treatment of depression. Medications used to manage depression work mainly by altering the chemicals in the brain, particularly serotonin, norepinephrine, and dopamine. Medications take a period before they work. The effect may be noticed as early as one to two weeks, but it typically requires four to six weeks.

Medications for depression are not as effective as medications for many other conditions. Antidepressant medications effectively manage symptoms of depression in 40-60 percent of people at 6-8 weeks (National Institute of Health, 2020).

Those with depression must be diligent and follow up with their healthcare provider to optimize medication management. The first drug at the initial dose is often not enough to provide an adequate response for depression. The dose often needs to be increased, or the medication needs to be changed or augmented. Follow-up is also critical because the FDA suggests that all agents with antidepressant properties may increase the risk of suicide – especially in patients under the age of 25.

Many different medication choices are available for the management of depression. The medication choice depends on physician preference, patient preference, adverse side effects, and comorbid conditions.

For years the treatment of choice for depression was tricyclic antidepressants (TCAs). Common TCAs include desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Pamelor), doxepin (Sinequan), and imipramine (Tofranil).

The TCAs have fallen out of favor with the advent of newer antidepressants. TCAs have more side effects when compared to the newer agents. Selective serotonin reuptake inhibitors (SSRIs) have many advantages over TCAs. TCAs' common side effects include urinary retention, drowsiness, blurred vision, dry mouth, constipation, orthostatic hypotension, lower seizure threshold, and sexual side effects. One primary concern with TCAs is that they are more lethal in overdose when compared to newer antidepressants. TCAs in high doses increase the risk of cardiac arrhythmia, and they should be avoided after a heart attack or in those with ventricular arrhythmias or ischemic heart disease. TCAs are also associated with several drug-to-drug interactions. TCAs should not be used in those with narrow-angle glaucoma.

Monoamine oxidase inhibitors (MAOIs) are another older class of antidepressants. They are not used often today because of better-tolerated agents. MAOIs have the potential for severe interactions with both food and other medications, including over-the-counter medications. MAOIs are typically only prescribed by a well-versed prescriber in monitoring these medications.

Individuals taking MAOIs and consuming foods containing tyramine have a significant risk of a hypertensive crisis. High tyramine foods include yogurt, fava beans, aged cheese, soy sauce, avocados, meat tenderizer, raisins, pickled/cured fish or meat, sauerkraut, and caviar. Alcohol should not be used in those on MAOI. All individuals who take these drugs need to be well versed in which foods they need to avoid and which medications need to be avoided. Common side effects include sexual dysfunction, insomnia, orthostatic hypotension, anxiety, and weight gain. Two common MAOIs are phenelzine (Nardil) and tranylcypromine (Parnate).

Serotonin Reuptake Inhibitors

In more recent years, serotonin reuptake inhibitors (SSRIs) have come on the market and have become a drug of choice for first-line treatment of depression. Medications in this class include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), fluvoxamine (Luvox®), citalopram (Celexa®), and escitalopram (Lexapro®). Compared to older antidepressants, SSRIs are easy to titrate, have fewer side effects, have fewer drug interactions, and are less toxic.

Different medications in the SSRI class have other side effects and interactions, but a few common adverse effects include nausea, agitation, weight changes, delayed ejaculation, fatigue, impotence, and restlessness. One major concern with SSRIs is that there are reports of increased suicidal thoughts and attempts in children on SSRIs with depression.

Fluoxetine (Prozac®) is dosed at 20 mg in the morning and may increase to 80 mg daily. Each titration must occur after a few weeks on the medication. It is not indicated for those less than eight years old. Fluoxetine has a long half-life and is less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week.

Fluoxetine can increase levels of warfarin, phenytoin, carbamazepine, TCAs, and benzodiazepines, and it may lower the therapeutic effect of codeine. It may cause serotonin syndrome when combined with other SSRIs and other antidepressants. Fluoxetine crosses the placenta, and its impact on pregnancy is not fully known. As a class, SSRIs in the third trimester can lead to multiple adverse effects, including apnea, hypoglycemia, feeding difficulty, seizures, and respiratory distress.

Sertraline (Zoloft®) is started at 25-50 mg orally daily, and the dose can be increased gradually to a maximum of 200 mg per day. It is not indicated for those less than six years old. Common side effects include dizziness, fatigue, headache, insomnia, drowsiness, nausea, tremor, and diaphoresis. It may interact with warfarin, cimetidine, digoxin, and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder.

Paroxetine (Paxil®) has a short half-life and may lead to discontinuation syndrome when the medication is stopped or missed doses. It has the strongest anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 20 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 25 mg once a day to a maximum of 62.5 mg orally every day. Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include drowsiness, insomnia, dizziness, headache, nausea, dry mouth, constipation, diarrhea, weakness, tremor, and diaphoresis.

Fluvoxamine (Luvox®) is approved for obsessive-compulsive disorders but is used off-label to treat depression and anxiety. The starting dose for adults is usually 50 mg once a day and has multiple drug interactions, including benzodiazepines.

Citalopram (Celexa®) is indicated for depression and is dosed at 20 mg once a day, and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungals, omeprazole, and carbamazepine. Side effects include sleep disturbance, dry mouth, nausea, and diaphoresis.

Escitalopram (Lexapro®) is dosed at 10 mg once a day and increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine, and alcohol. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) can prolong the QT interval and may be fatal. They should be used cautiously in those with underlying heart disease and those prone to becoming hypokalemic.

SNRIs

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are related to SSRIs to treat depression. Drugs in this class include venlafaxine (Effexor®), duloxetine (Cymbalta®), desvenlafaxine (Pristiq®), milnacipran (Savella®), and levomilnacipran (Fetzima®). The SNRIs have similar safety to SSRIs, but occasionally they may be associated with increased blood pressure. They can be used as a first-line agent to treat depression or those who do not respond to SSRIs. The SNRIs work on multiple neurotransmitters and do a better job reducing pain and other somatic complaints in depression when compared to other antidepressants.

Venlafaxine (Effexor®) comes in an immediate-release form and an extended-release form. The extended-release form is dosed 37.5 to 75 mg a day and maybe titrated up to 225 mg a day. The immediate-release form, which is not frequently used, is started at 75 mg, divided two to three times a day, and titrated to a maximum of 375 mg a day. It may interact with other antidepressants, cimetidine, diuretics, and alcohol and should not be used in those with severe uncontrolled hypertension. It mainly affects serotonin levels at doses less than 150 mg a day, but it affects dopamine and norepinephrine levels at higher doses. Discontinuation syndrome is high with this medication.

Desvenlafaxine (Pristiq®) is dosed at 50 mg once a day for adults and may be titrated up to 100 mg once a day. Common side effects include nausea, headache, dizziness, dry mouth, insomnia, fatigue, and bowel disturbance. It may interact with other SSRIs or blood thinners.

Milnacipran (Savella®) is not FDA-approved for depression. When used, it is dosed with 12.5 mg once a day on the first day and titrated upwards to a maximum of 200 mg daily divided every 12 hours. It should be used cautiously in those with moderate to severe renal and hepatic impairment. Those who take it may suffer from nausea, headache, dizziness, sleep disturbance, and constipation.

Levomilnacipran (Fetzima®) is started at 20 mg once a day and increased to 40 mg once a day. The maximum dose is 120 mg a day. Doses should be reduced in those with moderate and severe renal insufficiency. Common side effects include nausea but may also be associated with sexual dysfunction, constipation, urinary hesitancy, and elevated heart rate.

Duloxetine (Cymbalta®) is dosed at 30 to 60 mg once a day. The maximum dose is 120 mg a day. It may interact with ciprofloxacin, SSRIs, TCAs, antiarrhythmic agents, and anticoagulants. Common adverse effects include nausea, headache, dry mouth, dizziness, sleep disturbance, and fatigue.

Duloxetine has multiple indications. It is approved to treat depression, diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia, and generalized anxiety disorder. This drug is often used by those with depression in addition to one of these comorbid conditions.

Other Antidepressants

Other antidepressants include bupropion (Wellbutrin®), mirtazapine (Remeron®), vortioxetine (Brintellix®), vilazodone (Viibryd®), and trazodone (Desyrel®). Generally, this group has low toxicity in overdose and may have an advantage over the SSRIs by causing less sexual dysfunction and gastrointestinal distress.

Bupropion is indicated for major depression, seasonal affective disorder, and smoking cessation. It increases the risk of seizures at higher doses, particularly in those with a history of seizures. Common side effects include headache, nausea, dry mouth, weight loss, dizziness, and insomnia.

Mirtazapine (Remeron®) is dosed at 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg a day in adults. It is given at bedtime because sedation is one of its major side effects. Another common side effect is weight gain. Other side effects include dry mouth, constipation, and dizziness.

Vortioxetine (Brintellix®) was approved on September 30, 2013. The starting dose is 10 mg once a day and may be increased to 20 mg a day. The dose may be lowered to 5 mg a day for those who do not tolerate the higher dose. It works on multiple receptors and increases noradrenaline, dopamine, and glutamatergic transmission. The medication's half-life is long at approximately 57 hours, leading to a low rate of withdrawal effects. Major interactions include linezolid, other antidepressants, fentanyl, ritonavir, tramadol and clopidogrel. Nausea is the most common side effect, but other side effects include diarrhea, constipation, dry mouth, headache, and dizziness.

A recent review showed that vortioxetine effectively managed acute depression but no more than SNRIs in general and less effective than duloxetine. The side effect profile is better with vortioxetine when compared to duloxetine. More research is needed to compare this agent to SSRIs (Long, 2019).

Vilazodone (Viibryd®) selectively inhibits serotonin reuptake and does not work on dopamine or norepinephrine reuptake. It is dosed at 10 mg once a day for seven days, then maybe titrated up to 20 mg, then 40 mg once a day. This medication should be taken with food. It is commonly associated with diarrhea and nausea, and other side effects may include dizziness, dry mouth, insomnia, and fatigue. Vilazodone (Viibryd) showed favorable effects on weight gain and possibly less sexual dysfunction than SSRIs (Schwasinger-Schmidt & Macaluso, 2019).

Trazodone is indicated for those 18 years of age and older. It is not commonly used as an antidepressant because it is very sedating.

Strategy

Initial medication treatment for depression is typically done with SSRIs. Still, consideration may be given to a serotonin-norepinephrine reuptake inhibitor, an atypical antidepressant (e.g., bupropion®, mirtazapine®), or a serotonin modulator (e.g., vilazodone®). Tricyclic antidepressants and monoamine oxidase inhibitors are not typically used as initial treatment.

A recent systematic review and meta-analysis looked at the most effective antidepressant medications. The review showed that all medications were more effective than placebo in managing depression (Cipriani et al., 2018). The most effective medications noted were escitalopram, paroxetine, venlafaxine, amitriptyline, mirtazapine, and vortioxetine. The most tolerable medications include fluoxetine, sertraline, citalopram, escitalopram, and vortioxetine. The least effective medications were fluvoxamine, trazodone, and fluoxetine, and the highest dropout rates were noted with duloxetine, amitriptyline, fluvoxamine, venlafaxine, and trazodone (Cipriani et al., 2018).

Research has not clearly defined a superior antidepressant, so the agent selected is dependent on multiple factors, including drug-to-drug interactions, comorbid conditions, safety, side effects, cost, personal response, or response of family members to medications in the past. Sometimes specific medications are helpful based on other symptoms or comorbidities the patient suffers. For example, those with insomnia may be prescribed trazodone or mirtazapine because of their sedating properties. Those who wish to stop smoking may consider the use of bupropion. Escitalopram and citalopram are least likely to lead to drug-to-drug interactions.

Treatment is typically started at a low dose and slowly titrated upwards to the therapeutic range. Some response is generally seen within one to two weeks. Individuals who respond early to treatment with antidepressants are more likely to go into remission (Kang et al., 2020). Up to three months of treatment is generally recommended to determine if the treatment was effective. The treatment regime should be reevaluated in those with minimal effect after 4-6 weeks (Gautman et al., 2017).

Medications must be continued for at least 4-9 months (Halverson, 2020; informedhealth.org, 2020). If treatment is discontinued early, there is a high risk of relapse. Most antidepressants need to be weaned gradually. Abrupt discontinuation of antidepressants can result in serious side effects known as the discontinuation syndrome. Medications should be discontinued over two months for those on treatment for 6-12 months and up to 6 months for long-term treatment. Gradually tapering the medication is more critical if the patient is on a high dose.

Some individuals benefit from long-term treatment. Individuals who would benefit from long-term treatment have had multiple relapses, suffer from chronic depression, and want to avoid relapse (National Institute of Health [NIH], 2020). Long-term treatment with an antidepressant over an extended period reduces the risk of relapse in about 27 out of 100 people (NIH, 2020).

Many medications are available for the treatment of depression. Not all medications are equally effective in all individuals. When one medication is ineffective, switching to another medication may be more effective. Those with more severe depression are more likely to benefit from treatment. Research suggests that antidepressants improve symptoms in up to 60 percent of patients, but symptoms improve in only about 20 out of 100 patients above expected with a placebo (NIH, 2020).

Resistant Depression

Resistant depression is when treatment does not fully improve the condition. In resistant depression, standard treatments usually do not help. Thirty-three to sixty-seven percent of people fail to respond to first-line therapy (Halverson, 2020). It is often not a failure of the medication but a failure in the use of the medication. Failure can stem from the patient not taking the medication appropriately, the dose being incorrect, the patient not tolerating the medication, or not using the medication for the correct amount of time.

A few steps must be taken when faced with treatment-resistant depression (Halverson, 2020). First, the clinician must reevaluate the diagnosis to ensure it is correct. Determine if there is a comorbid factor that is contributing to the depression. Is there any anxiety, substance abuse, or psychosis? Review the differential diagnosis list and determine if depression is still the diagnosis. Next, determine if the medication is being used correctly. Has an adequate trial been used, has the duration been long enough, and has the patient taken the medication as prescribed?

A few strategies can be implemented if all of this checks out.

  • The clinician can increase the dose of the medication if the drug allows.
  • Different medications can be tried. For example, going from an SSRI to an SNRI.
  • Augmentation - adds a different medication to the current treatment.
  • The addition of talk therapy.
  • Electroconvulsive therapy.

Augmenting therapy

For those with resistant depression, many medications are available to add to typical antidepressants to see if a response can be elicited. Augmentation is beneficial if a comorbid condition is responsive to a specific medication. For example, those with psychotic depression may respond to an antipsychotic added to their antidepressant.

A meta-analysis found that adding an atypical antipsychotic is more effective than a placebo (Zhou et al., 2015). Side effects are significantly more pronounced with antipsychotics. Typical antipsychotics used in augmentation for depression include aripiprazole and quetiapine. Other augmentation strategies include combining an SSRI and TCA; adding triiodothyronine, buspirone, lithium, methylphenidate (Ritalin®), esketamine nasal spray, or dextroamphetamine (Dexedrine®) to an antidepressant (Halverson, 2020).

St. John's Wort

St. John's wort (Hypericum perforatum) is an herbal remedy for the treatment of depression and has been around for many years. St. John's wort is used as a primary agent for depression in Europe, but in the United States, it is an over-the-counter product. Its dosing is inconvenient as it is dosed 300 mg three times a day. It is associated with nausea and should be taken with food.

Providers infrequently recommend St. John's wort for many reasons, including lack of standardization of active ingredients and lack of mention in the guidelines. (Forsdike & Pirotta, 2019). Evidence suggests it is helpful in mild to moderate depression (Ng et al., 2017).

Concern exists with some drug-to-drug interactions associated with St. John's wort. Case reports have suggested that it may lower cyclosporine levels and lead to organ rejection (in organ transplant patients). It may also interact with other SSRIs and may lead to serotonin syndrome. Serotonin syndrome most often occurs when two drugs that affect the body's level of serotonin are taken together. Other drugs that may lead to serotonin syndrome include antidepressants, tramadol, and migraine treatments such as triptans, dextromethorphan, or lithium. Symptoms occur within minutes to hours and may include:

  • Agitation or restlessness
  • Diarrhea
  • Tachycardia
  • Hallucinations
  • Increased body temperature
  • Loss of coordination
  • Nausea
  • Overactive reflexes
  • Rapid changes in blood pressure
  • Vomiting

Other drugs that may interact with St. John's wort include birth control pills, digoxin, warfarin, and indinavir. Side effects include fatigue, dry mouth, headache, anxiety, dizziness, nausea, and sexual dysfunction.

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) can be used in specific resistant or severe depression cases, which involves sending an electrical impulse to an unconscious patient, triggering a small seizure. It is done a few times a week for 2-4 weeks. Benefits may be noticed after a few treatments, but a full course is needed for maximal effectiveness. The patient is at high risk for relapse if there is no follow-up (Hermida et al., 2018).

ECT is believed to alter the chemistry of the brain. The benefits of this treatment are that it provides rapid onset of effect instead of other treatments. It can be used in those with severe depression at high risk of suicide, those with catatonia, severe weight loss, or not eating. It is helpful for those with depression, delusions, and bipolar disease (Hermida et al., 2018; Halverson, 2020).

ECT is associated with side effects. Confusion may occur, but this typically subsides within a few hours. No major long-term side effects are noted. Memory loss may occur. Most commonly, it is retrograde amnesia, meaning the patient may not recall things before the treatment. Retrograde amnesia typically improves after 1-2 months. Other side effects include headaches and muscle aches. ECT is done under anesthesia which is associated with risk. The patient must be evaluated before the treatment to ensure safe anesthesia (Kellner, 2021).

ECT increases heart rate, blood pressure, and intracranial pressure, so it is essential to identify those with unstable cardiovascular disease, increased intracranial pressure, or aneurysms as they are more likely to have complications.

Light therapy

Light therapy is primarily used in those with seasonal affective disorder. It involves being exposed to bright light and changing the circadian rhythm. Bright light gives off an intensity that is more than the typical lighting found in the home and may affect brain chemistry to help reduce depression related to seasonal affective disorder. It can also be used in those with typical depression as an augmentation method to an antidepressant (Bias, 2021). Side effects are typically mild and usually only transient. Side effects include nausea, vomiting, fatigue, headache, agitation, and sleep problems.

Light therapy should be used cautiously in bipolar depression as it may precipitate a manic episode. In addition, those with sensitive skin or taking medication (retinoids or some antibiotics) that increase sun sensitivity may want to avoid this type of therapy. Light therapy may not be effective as solo therapy. It is often combined with other treatments for maximal effectiveness. Light therapy may take a few weeks to work, but some notice benefits in a few days.

Special Issues in Depression

Pregnancy

Depression is a prevalent problem in pregnancy, but medication has some potential drawbacks. It is particularly problematic because many people are on antidepressants when they get pregnant and abrupt withdrawal of these agents is problematic.

The American Psychiatric Association and the American College of Obstetricians and Gynecologists developed a statement to discuss how depression during pregnancy should be managed (Yonkers et al., 2009). The group determined that depression increases the risk of preterm birth, miscarriage, fetal growth problems, and developmental delay.

Antidepressant medications are problematic. Antidepressants increase the risk of low birth weight, miscarriage, and pulmonary hypertension (Fischer Fumeaux, 2019). Each case must be evaluated individually. Ideally, depression should be identified and treated before the female becomes pregnant. Individuals who become mildly to moderately depressed during pregnancy should participate in psychotherapy. Those with severe depression are the most problematic. A few options are available.

  • Treat the patient with medications after a complete discussion of the risks and benefits with the patient.
  • Referral to a psychiatrist can be considered especially for those who have severe depression, suicidal ideation, psychosis, bipolar disease, or those who are considering ECT.

One glaring omission from the statement was that there was no recommendation about which medication to use during pregnancy if needed. There was a warning against paroxetine as this drug was associated with a higher risk of cardiac malformations. Although, this may be a class effect of the SSRIs. Infants born to mothers who took SSRIs after the 20th week of pregnancy had a six times higher risk of persistent pulmonary hypertension (PPHN) compared to infants born to pregnant women who did not take antidepressants (Yonkers et al., 2009; Fischer Fumeaux, 2019).

Recent evidence suggests the risk of PPHN is more common in those who use SSRIs while pregnant, but the risk is small, and in most individuals, the benefits of treatment outweigh the risk (Ng et al., 2019).

Postpartum depression is also a significant issue. It is common, with rates seen around 8-10 percent (Viguera, 2021). Most cases are mild, but they can be severe and lead to significant morbidity for the mother. Most antidepressants are safe for breastfeeding mothers, but research does not definitively prove their safety (Halverson, 2020). Like in pregnancy, psychotherapy is a safe option.

Infants born to mothers on SSRIs may exhibit a withdrawal syndrome evidenced by feeding problems, crying, increased muscle tone, and shivering.

Bipolar disease

Bipolar depression is a mental health condition with both depression and manic episodes. Undiagnosed bipolar depression can be a common cause of resistant depression. Providers must consider this when faced with resistant depression. Bipolar depression can be picked up if the clinician performs the Mood Disorders Questionnaire. Treatment of bipolar depression often requires the addition or the sole use of a mood-stabilizing agent such as lithium, divalproex sodium, olanzapine, or quetiapine.

Antidepressants and Children

A black box warning has been posted on the use of some antidepressants, indicating that antidepressant medications increase the risk of suicidal thoughts and attempts. This warning includes everyone taking antidepressants under the age of 25.

Clinicians must closely monitor young patients on antidepressants, especially in the early phase of treatment. Healthcare providers need to watch out for suicidal thoughts, depression that is becoming worse or behavioral changes such as withdrawal and agitation.

Consultations

The majority of cases of depression are managed in primary care. Some situations require the help of a psychiatrist. Primary care doctors and psychiatrists should ensure adequate patient treatment, especially medically complex ones. The psychiatrist should be consulted when there are:

  • Suicidal ideation
  • Mania
  • Severe depression
  • Resistant depression
  • Psychosis
  • ECT is being considered

A psychologist is a valuable part of the team to help maximize depression therapy. Consultation with a psychologist is helpful when:

  • Psychotherapy is being considered
  • Specialized testing is desired

Case study resolutions

Case study 1

Jenny was diagnosed with depression and was started on Sertraline (Zoloft) at 25 mg, and then the dose was titrated up after two weeks to 50 mg. She had a follow-up appointment in six weeks after the initial appointment. She reported that she had more energy but still felt a little sad. Her dose was increased to 100 mg once a day. She was encouraged to see a psychotherapist but did not have time. Her PDQ-9 score improved to 10, which, while improved, still equated to moderate depression.

She had another appointment in 6 weeks. At this time, she noticed an improvement in her mood but did not feel 100%. Her PDQ-9 score was 9, classified as the upper range of minimal symptoms. She reported having no side effects from the drug, so at this point, the nurse practitioner increased the dose to 150 mg. Even though her symptoms were classified as mild, she still had depression, and given the improvement in response to the progressively increased dose and the lack of side effects, the decision to increase the dose was carried out. At the follow-up appointment in 6 weeks, she reported that she had started seeing the psychotherapist that the nurse practitioner recommended and felt as well as she had in years.

The point of this case study is that sometimes the dose needs to be pushed to achieve an adequate response. When medications improve mood, patients will consider getting involved in therapy to enhance treatment.

Case study 2

John did not report depression on the exam, but his irritability, social withdrawal, and preoccupation with death were suggestive of depression. Depression is common after the loss of many social contacts. Dementia can cloud the depression picture. John reported that he is frustrated with his memory loss which was likely a contributing factor to his depression.

The patient was placed on escitalopram 10 mg and had a follow-up appointment in four weeks. This drug is an excellent choice for older adults because it lacks many drug interactions and has a rapid onset. The son reported that he was much less irritable at the follow-up appointment but continued social isolation. The Mini-Cog score improved to 3. At this point, the escitalopram was increased to 20 mg. The son was given the local Alzheimer's Association number to help with support. The patient was also given the number of a psychologist to discuss some of his issues.

After another four weeks, the patient was feeling much better. He was involved with a therapist and a social group of older adults. At his follow-up appointment, depression was not clinically evident.

Conclusion: the Healthcare Professionals' Role

Depression is a prevalent, disabling disease. Healthcare professionals need to evaluate for depression using some of the many screening tools. In addition, treatment options should be understood and discussed with patients. A significant role is to encourage patients to discuss depression with their primary healthcare provider.

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