Depression Nursing CE Course for APRNs

Complications: Suicide

Depression is linked to many complications, the most significant of which is suicide. Both depression and the medications used to treat depression increase an individual's risk of suicide. HCPs must screen all individuals with depression for suicide (NIMH, 2022d). Worldwide, over 700,000 people die by suicide each year, making it the fourth leading cause of death among individuals ages 15 to 29. Suicide is the tenth leading cause of death in the US and the second leading cause of death among those aged 10 to 24. More years of potential life are lost to suicide than to any other cause, except for heart disease, cancer, or unintentional injury. Suicide rates have increased by 30% from 2000 to 2020. In 2020, 45,979 people in the US died from suicide. On average, 132 people die by suicide daily; a person dies every 11.1 minutes (a male every 14.1 minutes and a female every 51.3 minutes). There are 3.6 male deaths by suicide for every female death (Centers for Disease Control and Prevention [CDC], 2022a, 2022b). Native American/Alaska Native males have the highest suicide rates (37.4 per 100,000), followed by White males (27.0 per 100,000), Black males (12.9 per 100,000), Hispanic males (12.3 per 100,000), and Asian/Pacific Islander males (10.3 per 100,000). Among females, Native American/Alaska Native females have the highest rate of suicide (10.8 per 100,000), followed by White females (6.9 per 100,000), Asian/Pacific Islander females (3.8 per 100,000), Black females (2.9 per 100,000), and Hispanic females (2.8 per 100,000). Suicide rates are highest among males older than 75 (40.5 per 100,000), followed by males aged 24 to 44 (28.3 per 100,000). Among females, those aged 45 to 64 have the highest rate of suicide (7.9 per 100,000), followed by those ages 25 to 44 (7.2 per 100,000; American Association of Suicidology [AAS], 2020; NIMH, 2022d).

Among adolescents aged 15 to 19, suicide rates have increased by 32% since 2016, rising from 8.4 to 11.1 per 100,000 deaths. Native Americans/Alaska Natives are the most prominently affected adolescent subgroup (31.6 per 100,000 deaths). Adolescent males are affected over 3 times more than females (16.7 per 100,000 male deaths compared to 5.2 per 100,000 female deaths; United Health Foundation, 2021). The Substance Abuse and Mental Health Services Administration's (SAMHSA's) 2020 National Survey on Drug Use and Health revealed an increasing prevalence of MDEs among adolescents, which corresponds to the rise in suicide deaths among adolescents. The percentage of MDEs increased from 5.5% (1.4 million people) in 2006 to 11.1% (2.7 million people) in 2020 (SAMHSA, 2021).    

During the lifetime of an individual suffering from major depressive disorder (MDD), over 46% express a desire to die, and over 39% contemplate suicide. Self-injurious behavior accompanied by an intent to die is classified as a suicide attempt. This means HCPs and society should err deliberately on the side of caution by classifying debatable behaviors as suicidal. While males are more likely to die by suicide, females are 3 times more likely to attempt suicide. Still, it is challenging to determine the exact number of attempted suicides in the US due to a lack of all-inclusive databases or tracking mechanisms. Data are primarily compiled through self-reported surveys and ICD-10-CM billing codes. Due to the high stigma associated with suicide attempts, they are vastly underreported (AAS, 2020; CDC, 2022b; SAMHSA, 2021). According to SAMHSA (2021), 12.2 million Americans aged 18 or older reported seriously thinking about suicide, 3.5 million made suicide plans, and 1.2 million attempted suicide. These numbers translate to a suicide attempt every 23 seconds and 25 attempts for every death by suicide across the nation (100-200:1 for young adults and 4:1 for older adults). People who survive a suicide attempt may experience serious injuries that can have long-term health consequences. Many individuals experience elevated levels of psychological distress for extended periods after surviving a suicide attempt (SAMHSA, 2021).

The Zero Suicide Institute and the National Strategy for Suicide Prevention put forth the Zero Suicide (ZS) Model, which provides a framework to coordinate a multilevel approach to implementing evidence-based practices. ZS encourages HCPs to screen all patients for suicide risk on their first contact with an organization and at each subsequent encounter. The core elements of the ZS model include ongoing risk assessment, collaborative safety planning, evidence-based interventions specific to the identified risk level, lethal-means reduction, and continuity of care. Structuring a suicide risk assessment is not straightforward and involves asking tough questions about suicidal ideation (i.e., thinking about, considering, or planning suicide) and prior attempts. Individuals may openly respond to queries and engage in discussion or be limited in their replies and offer minimal information. Sometimes, a patient may bring up the topic on their own, but research demonstrates that this is rare (Brodsky et al., 2018; SAMSHA, 2017; US Department of Health and Human Services [HHS], 2021).

The list below outlines the assessment of risk for suicide as compiled and adapted from the National Action Alliance for Suicide Prevention (Action Alliance, 2018) and HHS (2021) guidelines:

• A suicide risk assessment should consider risk and protective factors that may increase or decrease the patient's risk of suicide.
• The observation and reporting of warning signs and evaluation of suicidal thoughts, intent, behaviors, and other risk and protective factors should inform any decision about a referral to a higher level of care.
• A person's mental state and suicidal ideation can fluctuate considerably over time. People at risk for suicide should be reassessed regularly, especially if their circumstances have changed.
• The HCP should observe the patient's behavior during the clinical interview. Disconnectedness may indicate an increased risk for suicide.
• The HCP should remain both empathetic and objective. A direct, nonjudgmental approach allows the HCP to gather the most reliable information collaboratively and encourages the patient to accept help.

To assess a patient's suicidal thoughts, the HCP should inquire directly about thoughts of dying by suicide or feelings of engaging in suicide-related behavior. HCPs should be direct when inquiring about any current or past thoughts of suicide and ask individuals to describe such thoughts. According to the Action Alliance (2018) and HHS (2021), a comprehensive evaluation of suicidal thoughts should include the following:

• onset (when did it begin)
• duration (acute, chronic, recurrent)
• intensity (fleeting, nagging, intense)
• frequency (rare, intermittent, daily, unabating)
• passive or active nature of the ideation ("wish I were dead" vs. "thinking of killing myself")
• whether the individual wishes to kill themselves or is thinking about or engaging in potentially dangerous behavior such as cutting to relieve emotional distress
• lethality of the plan (no plan, overdose, hanging, firearm)
• triggering events or stressors (relationship, illness, loss)
• what intensifies the thoughts
• what distracts the thoughts
• association with states of intoxication (i.e., if thoughts are triggered only when the individual is intoxicated)
• understanding the consequences of future potential actions (Action Alliance, 2018; HHS, 2021; SAMSHA, 2017)

To assess suicidal intent, an HCP should appraise past or present evidence (implicit or explicit) that an individual wishes to die, means to kill themselves, and understands the probable consequences of their actions or potential actions (Action Alliance, 2018; HHS, 2021; SAMSHA, 2017). The evaluation of intent to die should be characterized by the following:

• strength of the desire to die,
• strength of the determination to act, and
• strength of the impulse to act or the ability to resist the impulse to act (Action Alliance, 2018; HHS, 2021)

These factors may be highlighted by inquiring about how much the individual has thought about a lethal plan, can engage in that plan, and is likely to carry out the plan. To assess for preparatory behavior, the HCP should evaluate whether the patient has begun to prepare for self-directed violence, such as assembling a method or preparing for death (Action Alliance, 2018; HHS, 2021; SAMSHA, 2017). In addition to obtaining collateral information from the patient's family members, medical records, and therapists, HCPs should assess preparatory behaviors by inquiring about the following:

• mentally walking through the potential attempt
• researching methods online
• thoughts about the location they would consider and the likelihood of being found or interrupted
• seeking access to lethal means or exploring the lethality of means, such as:
• walking to a bridge
• handling a weapon
• acquiring a firearm or ammunition
• hoarding medication
• purchasing a rope or blade
• taking action or other steps in preparing to end one's life, such as:
• writing a will or suicide note
• giving away possessions
• reviewing a life insurance policy (Action Alliance, 2018; HHS, 2021; SAMSHA, 2017)

A risk assessment for suicide should include information from the patient and other sources about previous suicide attempts and circumstances surrounding the event (e.g., triggers, the method used, consequences of behavior, and the role of substances of abuse) to determine the lethality of any previous attempt (Action Alliance, 2018; SAMSHA, 2017; Zero Suicide Institute, n.d.). HCPs should inquire about the following:

• whether the attempt was interrupted by the patient or another person
• whether there was evidence of an effort to isolate or prevent discovery
• whether there have been multiple attempts (Action Alliance, 2018; SAMSHA, 2017; Zero Suicide Institute, n.d.)

For patients with a history of self-interrupted suicide attempt(s), obtain additional details to determine factors that enabled the patient to resist the impulse. A comprehensive suicide risk assessment requires a validated, evidence-based screening tool consisting of a set of directed questions. Examples of screening tools include the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Assessment Five-Step Evaluation and Triage (SAFE-T), the Patient Safety Screener (PSS-3), and the Patient Health Questionnaire (PHQ). Evaluating the risk level and appropriate actions for each risk level is a critical aspect of suicide prevention. HCPs must understand how to perform a proper risk assessment, ascertain risk level, and respond according to evidence-based guidelines (Action Alliance, 2018; Zero Suicide Institute, n.d.). For more information, see the NursingCE course on suicide. 

Signs and Symptoms of Depression

There are several types of depression, each with unique features and onset mechanisms, yet consistent signs and symptoms are recognized across all facets of depressive disorders. Depression substantially impairs day-to-day activities (e.g., work or school) and a person's ability to cope with daily life. It can be long-lasting or recurrent, and those affected may have multiple physical symptoms with no apparent physiological cause (APA, 2022a; NIMH, 2022a). The most common signs and symptoms of depression include the following:

• a loss of interest or pleasure in hobbies and activities
• a persistently sad, anxious, or "empty" mood
• feeling hopeless or having a pessimistic attitude
• changes in appetite or weight
• sleep disturbances
• irritability, agitation, or restlessness
• fatigue
• moving or talking slowly
• feelings of low self-worth, guilt, or shortcomings
• difficulty concentrating
• suicidal thoughts, intent, or attempts (APA, 2022a; NIMH, 2022a)

Depression differs from sadness or bereavement and is outside the normal grieving process. While grief can be a trigger for depression, grief does not cause depression. Children and adolescents suffering from depression have higher risks of being diagnosed with MDD as adults. Children with depression often present differently than adults. Behaviors may include avoidance of others, refusal to attend school, pretending to be sick, remaining at the parent's side in social situations, mood swings, getting into trouble at school, or irritability. Since some of these behaviors are common in adolescents, diagnosing depression in this age group can be challenging. It can be equally difficult to diagnose depression in older adults. Signs and symptoms of dementia (e.g., agitation, irritability, and fatigue) can mimic depression. Those with dementia are also less likely to have feelings of helplessness or hopelessness that a depressed individual often experiences (APA, 2022a; NIMH, 2022a).

Classification of Depression

The Diagnostic and Statistical Manual, 5^th edition Text Revision (DSM-5-TR) states that all forms of depressive disorders include a sad, empty, or irritable mood, alongside somatic and cognitive changes that significantly impact the patient's functional capacity. Their major distinctions are limited to symptom duration, timing, or presumed etiology. Table 1 briefly describes the clinical presentation of the main subtypes of depression. Although there are different forms of depression, MDD is the classic form diagnosed and referred to when using the general term depression. This form will be discussed later in this module (APA, 2022a; NIMH, 2022a). 

Table 1

Depression Subtypes*

 (APA, 2022a; NIMH, 2022a)

*This is a summary of the diagnostic criteria detailed in the DSM-5-TR; to make an actual diagnosis, the provider should reference the diagnostic guidelines listed in the DSM-5-TR for each depression subtype.

Depression Screening   

The US Preventive Services Task Force (USPSTF) suggests screening for depression in all adults and adolescents. Depression is associated with a lower quality of life, compromised interpersonal relationships, decreased work performance, and loss of life through suicide, increasing the urgency for proper recognition and diagnosis (USPSTF, 2022).

Best-practice guidelines recommend initially screening individuals for depression using the PHQ-2. The PHQ-2 asks the following priority questions (APA, 2022a; HHS, 2021; SAMHSA, 2017):

• Over the past 2 weeks, how often have you been bothered by any of the following problems?
• little interest or pleasure in doing things
• feeling down, depressed, or hopeless

Patients who respond "yes" to either question on the PHQ-2 should undergo additional screening with the PHQ-9, a multipurpose, 9-item symptom checklist used to screen for, diagnose, monitor, and measure the severity of depression. The PHQ-9 incorporates the DSM-5-TR diagnostic criteria for depression and a question that screens for the presence and duration of suicidal ideation (APA, 2022a). The tool is brief, easily used in clinical practice, and rapidly scored. It is also useful when monitoring for improving or worsening symptoms. Each question has four answers: "not at all," "several days," "more than half the days," and "nearly every day" (Kroenke et al., 2001; Na et al., 2018). The questions are as follows:

Over the last 2 weeks, how often have you been bothered by:

• little interest or pleasure in doing things
• feeling down, depressed, or hopeless
• trouble falling or staying asleep, or sleeping too much
• feeling tired or having little energy
• poor appetite or overeating
• feeling bad about yourself or that you are a failure or have let yourself or your family down
• trouble concentrating on things, such as reading the newspaper or watching television
• moving or speaking so slowly that others could have noticed, or being so fidgety/restless that you have been moving more than usual
• thoughts you would be better off dead or of hurting yourself (Kroenke et al., 2001; Na et al., 2018)

The response for each question is scored between 0 and 3 (0 for "not at all" to 3 for "nearly every day"), with a total possible score of 0-27 (Kroenke et al., 2001). A systematic review by O'Byrne and Jacob (2018) noted that depression is associated with a lower quality of life (QOL), compromised interpersonal relationships, decreased work performance, and loss of life through suicide. This systematic review identified 55 assessment tools for depression screening, including the PHQ-9. This tool has the most substantial literature and robust evidence validating its efficacy across studies and patients over the age of 11 (Spitzer et al., 1999). A recent meta-analysis of 58 studies (n=17,357) published by Levis and colleagues (2019) reaffirmed the accuracy and clinical utility of the PHQ-9. According to the researchers, the diagnostic accuracy of the PHQ-9 does not differ substantively across subgroups except for age, where it appears to be more specific among older patients (Levis et al., 2019). Table 2 demonstrates the scoring categories of the PHQ-9 and its correlation with the DSM-5-TR diagnostic criteria.

Table 2

Severity Level of Depression

(APA, 2022a; O'Byrne & Jacob, 2018)

False positives are possible with the PHQ-9 due to its high sensitivity. Therefore, a positive result on the screening tool does not equate to a formal diagnosis of depression. Advanced practice registered nurses (APRNs) are encouraged to use the tool in tandem with a thorough health assessment and evaluate the need for appropriate treatment of depression over time (O'Byrne & Jacob, 2018). In addition to the PHQ-9, APRNs should be mindful of any acute safety risks (e.g., harm to self or others, psychotic features) and assess each patient's functional status, medical history, past treatment, and family history. While the tool is practical and validated for the screening of patients for potential depression, most contend that the PHQ-9 is an insufficient assessment tool for suicide risk and suicidal ideation compared to other suicide-specific tools, such as the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Suicide Assessment Five-Step Evaluation and Triage (SAFE-T; Na et al., 2018). Additional depression screening tools frequently used in primary care are listed in Table 3.

Table 3

Screening Tools

(APA, 2019b)

Diagnosis

MDD is defined by the presence of at least one MDE in an individual with no history of mania or hypomania. Based on high-quality evidence, the APA (2022a) strongly recommends that clinicians use the DSM-5-TR criteria to determine a diagnosis of MDD, MDE, and other specified or unspecified depressive disorders. The DSM-5-TR outlines the required diagnostic criteria for a diagnosis of MDD, as summarized in Table 4. Of note, criteria A through C represent an MDE. These symptoms must be new for the individual or worsening of an existing symptom and must be present over 2 weeks. A diagnosis requires a thorough interview, as individuals often circumvent direct questioning when discussing their mood. For other patients, symptoms of MDD can present as a physical manifestation (e.g., pain). Other patients may report feelings of agitation or anger instead of sadness. This is true in adolescents and children who may present as irritable or cranky instead of sad or dejected. A diagnosis can be complicated if the individual has a concurrent disease that can produce similar symptoms (e.g., cancer, diabetes, or pregnancy; APA, 2022a).

Table 4

DSM-5-TR Diagnostic Criteria for Major Depressive Disorder*    

(APA, 2022a)

*This is an interpretive representation of the diagnostic criteria detailed in the DSM-5-TR; to make an actual diagnosis, the provider should reference the diagnostic guidelines listed in the DSM-5-TR.

While grief can trigger depression, grief does not cause depression. APRNs should consider that personal responses to a significant loss (e.g., loss of a loved one, bereavement, financial ruin, or a serious medical illness) may include intense feelings of sadness or loss, insomnia, poor appetite, and weight loss (as outlined in Criterion A). Although such symptoms may be understandable or considered an appropriate reaction to a loss, the presence of an MDE in the setting of a significant loss should be carefully considered. This decision should be premised on clinical judgment and balanced according to the individual's baseline functioning, history of expressing distress in the context of loss, and cultural norms (APA, 2019a, 2022a). A recent addition to the DSM, prolonged grief disorder cannot be diagnosed within 12 months of the death of the identified deceased individual (within 6 months in adolescents or children). The symptoms must cause substantial anguish or dysfunction, and the grief reaction extends beyond a period that would be considered typical.

At least one of the following must be present to a substantial degree most days (and almost every day during the last 30 days):

• a mental distraction related to constant ruminations of the identified individual (may be regarding the details surrounding the death, especially in children and adolescents)
• an extreme desire to be with/close to the identified individual

At least three of the following must be present to a substantial degree most days (and almost every day during the last 30 days):

• a lack of realization or belief that the death has occurred
• extreme emotional discomfort secondary to the death, which may be expressed as feeling sad, mad, or bitter
• a total lack of feelings regarding the death
• an expression of feeling extremely alone and isolated
• disruption of identity expressed as the sensation that a component of the patient left with the identified individual
• a desire to prevent being reminded that the identified individual is gone
• challenges restarting or re-engaging socially, professionally, or making future plans
• a sensation that life has lost its importance since losing the identified individual

The symptoms cannot be more appropriately attributed to another psychiatric or behavioral condition (APA, 2022a).

Differential Diagnosis

Once screening has been completed with a risk identified, the APRN will determine a diagnosis of depression through further assessment. No definitive diagnostic test exists for depression; it is commonly a diagnosis of exclusion. The first step in diagnosing any mental health condition is ruling out underlying medical conditions. Conditions such as hypothyroidism, malignancy (e.g., brain tumor), or vitamin deficiency can mimic depression and should be ruled out before initiating treatment. A complete blood count (CBC); vitamin B12 level; metabolic panel including glucose, renal, and hepatic functions; antinuclear antibody (ANA); erythrocyte sedimentation rate (ESR); and thyroid screening should be obtained. APRNs may consider ordering a urine or serum toxicology screening for patients with clinical suspicion of drug or substance use/abuse. Imaging studies (computed tomography [CT] scan or magnetic resonance imaging [MRI]) may be indicated to rule out intracranial pathology. The physical examination of a depressed patient may be unremarkable; however, outward changes may be apparent, such as poor hygiene, a flat affect, slowed speech, weight loss, or psychomotor excitement or delay. Mental status should be assessed to rule out cognitive decline, particularly in older patients. The exam should include an assessment for delusions, hallucinations, or mood swings (APA, 2019a, 2022a).

Treatment

An individualized treatment plan should be developed using shared decision-making and will vary based on the patient's severity level of depression (mild, moderate, moderate-severe, or severe). Treatment for depression may include counseling, therapy, and/or medication. Adequate treatment can prevent suicide related to depression. The most effective treatment for depression is a combination of psychotherapy with pharmacological treatment, such as antidepressant medication (NIMH, 2022a).

Psychotherapy  

Psychotherapy is a successful, beneficial, and cost-effective treatment for depression. The APA (2022b) defines psychotherapy as any psychological service moderated by a trained professional (i.e., psychotherapist) that employs communication and interaction principles to assess, diagnose, and treat mental health disorders. Also referred to as talk therapy, psychotherapy is premised on establishing a supportive environment and collaborative relationship between a patient and a psychotherapist to foster open discussion in an objective, neutral, and nonjudgmental manner. A psychotherapist includes any individual professionally trained and licensed according to their respective governing state-licensing boards to treat mental health conditions (e.g., psychologist, psychiatrist, psychiatric nurse, APRN, counselor, therapist, or social worker). Research demonstrates that depressed individuals who receive psychotherapy achieve more durable treatment responses (i.e., are less prone to relapse) and better symptom control than when medication is used alone. Although psychotherapy is effective, it is underutilized and can be difficult to access at times, depending on location, and may not be covered or only partially covered by medical insurance. Most forms of psychotherapy can be performed in private offices, community centers, inpatient or outpatient treatment programs, VA facilities, counseling centers, and educational settings. Traditional psychotherapy involves in-person sessions, but a growing number of therapists are providing online (remote) therapy sessions, as demand has dramatically risen during the COVID-19 pandemic with an increased reliance on technology. Research demonstrates that online psychotherapy has comparable efficacy to in-person approaches, and this continues to be a topic of investigation as more patients opt for online therapy (Luo et al., 2020). For more information on delivering patient care remotely, see the NursingCE course on telemedicine. 

While there are several types of psychotherapy, the most effective options for depression include cognitive-behavioral therapy (CBT), mindfulness-based cognitive therapy (MBCT), problem-solving therapy (PST), behavioral activation (BA), and interpersonal therapy (IPT). Each patient and psychotherapist are encouraged to set mutually agreed upon and realistic goals that are periodically reevaluated. Patient response varies based on the presenting issue, severity, complexity, interference with functioning, openness to receiving treatment, and specific interventions. If patient improvement does not occur within the planned duration of treatment, the intervention should be reassessed, and other therapeutic strategies should be considered. There is no universally effective approach to treating depression. Experienced psychotherapists typically blend modalities and tailor the treatment to meet each patient's needs, often altering the treatment course when underlying issues are revealed as the patient progresses through therapy (APA, 2019a; Luo et al., 2020; Wampold, 2019). 

Cognitive Behavioral Therapy 

CBT is among the most well-cited and established forms of psychotherapy, as it has the most rigorous evidence supporting its clinical utility. It is often referred to as the gold standard of psychotherapy, as other forms have not demonstrated superior efficacy.

Primary Uses. 

CBT was initially utilized for managing depression and was the first psychotherapy identified as evidence-based in most clinical guidelines (David et al., 2018). In addition to treating depression, CBT has demonstrated effectiveness for several other conditions, including anxiety, trauma (e.g., PTSD, childhood trauma, and sexual trauma), SUDs, eating disorders, and couples' discord. CBT may also help manage certain aspects of psychosis (e.g., psychotic episodes, schizophrenic delusions) and is validated across diverse demographics, including veterans and active service members (Stein & Norman, 2021). According to Craske (2017), the overarching features of CBT include short-term, problem-focused, cognitive, and behavioral interventions. It is not a one-size-fits-all model, as there are several variations. CBT teaches patients to restructure cognitive distortions and self-defeating behaviors and replace them with more accurate thoughts and functional behaviors. The focus is narrowed to each patient's current problem(s) to provide practical solutions and strategies to manage them successfully. The specific intervention(s) employed will depend on the underlying issue. Patients are encouraged to apply new behaviors to real-life settings, allowing them to practice skills during the therapeutic relationship to troubleshoot new behaviors and obtain feedback from the psychotherapist. Patients learn to track their thoughts and activities to identify the affective and behavioral consequences during debriefing sessions with their psychotherapist. CBT is time-limited and typically consists of 8 to 16 sessions. In addition to face-to-face and telephone sessions, CBT can also be administered via computer-based programs, which are known as computer-based CBT (CCBT; Craske, 2017; Stein & Norman, 2021).

CBT-Insomnia (CBT-I). Insomnia and depression commonly coexist, and CBT-I is recommended as a first-line treatment for affected patients. CBT-I is a multi-component approach targeting behaviors and thoughts that interfere with sleep. In a recent systematic review and meta-analysis, Feng and colleagues (2020) found CBT-I to be safe, effective, and superior to no treatment for insomnia. CBT-I may be delivered face-to-face in individual or group settings over an average of 4 to 8 sessions. This approach incorporates sleep hygiene principles, including:

• establishing a consistent bedtime routine
• abstaining from substances like caffeine after lunch or alcohol and nicotine before bed
• avoiding activities that interfere with sleep (e.g., vigorous exercise) within 2 to 3 hours of sleep
• eliminating daytime sleeping
• optimizing the sleep environment
• creating a consistent bedtime and waketime
• limiting the time spent in bed to established sleep times (i.e., sleep restriction; Reynolds & Cone, 2018; Winkelman, 2021)

Patients are advised to create a 2-week sleep log documenting their sleep habits, and the CBT-I approach is individualized based on the information recorded in the log. The time spent asleep should be added to half of the time spent awake in bed, yielding the prescribed sleep restriction. This time should never be under 5 hours. Once the patient sleeps for at least 80% of the specified time for 7 consecutive days, the prescribed sleep restriction should be increased by 20 minutes for the following week (Reynolds & Cone, 2018; Winkelman, 2021).

Mindfulness-Based Cognitive Therapy 

MBCT is a more recent form of CBT developed by the collaborative efforts of Zindel Segal, Mark Williams, and John Teasdale. The first clinical trial data was not published until the beginning of the 21st century. MBCT was initially developed as a relapse-prevention treatment for depression that encouraged patients to change their function rather than the content of negative thoughts. Patients with a history of depression experience a poor mood, negative memories, and unhelpful cognitive patterns, triggering the reoccurrence of depressive symptoms. Several randomized controlled trials (RCTs) have demonstrated the clinical utility and efficacy of MBCT for patients with depression who have endured multiple relapses. In a 2020 systematic review and meta-analysis by McCartney and colleagues (2020), including 14 RCTs (n=2,077), MBCT showed a statistically significant advantage over treatment as usual (TAU) and the placebo group in preventing depression relapse. Researchers determined that MBCT was more effective than TAU in the long-term prevention of depression relapse and had statistically significant advantages over TAU and placebo regarding the time to relapse (McCartney et al., 2020). It has also been successfully applied to patients with chronic pain conditions (e.g., fibromyalgia). Furthermore, studies have also demonstrated that it has yielded improvements in overall well-being when applied to patients with chronic illnesses such as cancer, heart disease, or diabetes (Craske, 2017; Stein & Norman, 2021).

MBCT integrates traditional CBT interventions with a mindfulness-based stress reduction (MBSR) modality into an 8-week program designed to help patients cope with health concerns and their physical and mental impact. MBCT helps patients focus on the present in a nonjudgmental and accepting manner. It does not seek to modify or eliminate dysfunctional thoughts. Instead, it focuses on assisting patients to become more detached and observe their thoughts objectively without necessarily attempting to change them. MBCT focuses on developing mindfulness through meditation, imagery, experiential exercises, and relaxation techniques (Craske, 2017; Stein & Norman, 2021).

MBCT teaches patients to view themselves as distinct from negative thoughts by employing cognitive methods and meditation to interrupt the automatic processes that re-trigger these feelings. This approach emphasizes changing one's reaction to unwanted thoughts, not the content of the thoughts themselves. A judgment of undesirable cognitions creates powerful secondary emotions (e.g., low mood, hopelessness, sadness). Through MBCT, patients learn to distance themselves from these thoughts by becoming more aware of how they practice judgment. Mindfulness teaches patients to break this cycle by continually refocusing on making deliberate choices to improve how they critique their thoughts. While the delivery of MBCT varies, it is primarily used in a group setting, with weekly sessions lasting 60 to 120 minutes for 8 weeks. Group sessions are accompanied by 30- to 45-minute homework assignments six times per week. Homework assignments help patients develop and practice mindfulness meditation techniques, usually through audio or video recordings. Since the definition of mindfulness can vary across clinical applications, it is difficult to conceptualize a model of mindfulness meditation that applies to all patients; therefore, most sources describe this concept as the practice of developing a deeper awareness of one's mind and body without judgment in the present moment. Specific strategies may include yoga, breathing meditations, and exercises (Parsons et al., 2017).

Problem-Solving Therapy 

PST is a structured cognitive-behavioral intervention that strives to improve a person's ability to prevent and cope with stressful life experiences by equipping them with various affective, cognitive, and behavioral tools. PST focuses on developing specific coping skills for problem areas and is particularly effective for stress management and depression. Most sources describe PST as a type of CBT-based psychotherapy, but some argue that problem-solving is the core of PST, and cognitive restructuring is often omitted. As cited in a 2018 meta-analysis by Cuijpers and colleagues (2018), PST is a highly examined psychotherapeutic intervention for managing depression in adults and is comparable to other psychological treatments for depression. PST has also demonstrated efficacy in managing anxiety disorders, including phobias (e.g., social phobia, agoraphobia), HIV risk behaviors, drug abuse, suicidal behaviors, childhood aggression, and conduct disorders. In a systematic review and meta-analysis including 11 studies and 2,072 participants, Zhang and colleagues (2018) demonstrated an overall significant treatment effect from PST with meaningful improvements in symptomology when applied to patients with depression and anxiety disorders treated in primary care settings (Zhang et al., 2018).

PST offers a flexible therapeutic approach and is employed in a group setting or on an individual basis. It is often used as part of a larger treatment plan, helping patients overcome barriers associated with nonadherence to medical or psychological treatments (e.g., adhering to a weight-loss program or medication compliance). Patients engage in active problem-solving activities through a collaborative relationship with a psychotherapist. Specific PST interventions include psychoeducation, interactive critical thinking skills training exercises, homework assignments, and practice opportunities. Patients learn to identify and prioritize key problem areas and break them into manageable tasks to develop appropriate coping behaviors and solutions. PST focuses on empowering patients to learn how to solve problems on their own. Depending on patient needs, therapy may range from 4 to 12 individual sessions, with an average of 45 to 60 minutes per session. While there are different styles of PST, they are all premised on the same principle of resolving depression by engaging patients in active problem-solving activities (Craske, 2017; Suicide Prevention Resource Center, 2017). PST typically involves the following seven stages: 

• selecting and defining the problem
• establishing realistic and achievable goals for problem resolution
• generating alternative solutions
• implementing decision-making guidelines
• evaluating and choosing solutions
• implementing the preferred solutions
• evaluating the outcome (Craske, 2017; Suicide Prevention Resource Center, 2017)

Behavioral Activation 

BA is chiefly indicated for those suffering from depression, presupposing that cognitions are sources of avoidance that sustain depressive symptoms. Research demonstrates that when people feel depressed, they tend to disengage from (or avoid) everyday routines and withdraw from social environments. Over time, avoidant behaviors worsen depression as people isolate themselves and lose opportunities for positive reinforcement. A Cochrane review of 53 RCTs involving 5,495 participants evaluated the effects of BA compared to other psychological therapies, medications, and treatments for depression in adults. Findings revealed no difference in short-term treatment efficacy between BA and CBT based on moderate-certainty evidence, but BA was more efficacious than medication therapy. Not enough data were available to compare BA directly with other forms of psychotherapy, specifically psychodynamic, interpersonal, and integrative therapies (Hofmann & Asmundson, 2017; Uphoff et al., 2020).

BA targets the connection between behavior, feelings, and depression. BA is considered a critical and powerful CBT skill for treating depression. It helps patients understand how their behaviors influence their emotions and envision how they can control this process. BA seeks to increase behaviors that bring a patient into contact with positive reinforcements and decrease behaviors that impede this contact based on the assumption that action precedes emotions. Activation changes an individual's brain state—a concept referred to as reinforcing positive context contingencies. The simplest example of this concept is engaging in cardiovascular exercise (e.g., running) to induce an endorphin release (i.e., endogenous chemicals produced by the body to relieve pain) into the bloodstream, which improves mood. The more an individual activates a specific behavior that derives a perceived benefit, the more situations they will expose themselves to that result in positive emotions. BA focuses on positive reinforcement by increasing a patient's contact with rewarding and pleasant experiences and social activities. This approach also teaches patients how to identify processes that inhibit activation and encourage avoidant behaviors, thereby boosting critical thinking skills (Hofmann & Asmundson, 2017; Uphoff et al., 2020).

BA effectively treats depression by generating a balance of goals centered on values, pleasure, and proficiency. Patients track their activities and identify the affective and behavioral consequences of such actions. Activity monitoring creates awareness of and insight into underlying behaviors that negatively impact mood. It explores three fundamental elements of behavior change: the patient's values (i.e., things they find meaningful), pleasures (i.e., enjoyable activities or hobbies), and mastery (i.e., actions such as work or sports that involve the development of new skills, a sense of accomplishment, and a feeling of mastery over the environment; Craske, 2017; Stein & Norman, 2021). Brief Behavioral Activation Treatment for Depression (BATD) is a type of BA specifically designed to treat depression. The core components of BATD include the following:

• understanding the cyclic nature of depression
• identifying goals and values
• activity and mood monitoring (e.g., tracking moods across activities throughout the day, week, or month)
• building motivation and energy in a stepwise approach by incorporating pleasure and proficiency in skills
• activity scheduling (i.e., purposefully scheduling enjoyable and meaningful activities)
• reducing avoidant behaviors
• completing between-session assignments or tasks (e.g., meeting small-scale goals by practicing a target behavior; Craske, 2017; Society of Clinical Psychology, 2016; Uphoff et al., 2020)

BA typically occurs over 20 to 24 sessions, but BATD is shorter, lasting for 8 to 15 sessions (Society of Clinical Psychology, 2016). 

Interpersonal Psychotherapy (IPT)

IPT is a structured, evidence-based treatment that draws upon the principles of psychodynamic therapy to focus on interpersonal difficulties that lead to psychological problems. IPT was designed as a brief, time-limited intervention for patients with depression, with the primary objective of improving relationships to alleviate symptoms. Although a specific event or relationship may not cause depression, depression commonly affects relationships and creates interpersonal problems (Swartz, 2021).

IPT is an adaptive and versatile treatment easily modified for disorders, demonstrating efficacy for SUD, bipolar disorder, and peripartum depression. Treatment is present-focused (e.g., on psychological difficulties sparked by recent conflicts or transitions), but aspects of attachment theory are used to analyze how past relationships affect current relationships. Attachment theory maintains that the relationship between a caregiver and an infant is crucial to survival and remains essential throughout life. A secure attachment early in life provides a solid foundation for psychological security and healthy intimacy in adult relationships. In contrast, early disturbances in attachment increase a person's vulnerability to depression and other psychological difficulties, particularly in interpersonal relationships. IPT teaches patients to evaluate their interactions to build an awareness of how they relate to others. The short-term goals of IPT are to reduce symptoms and improve social adjustment, whereas the long-term goal is to help patients learn how to make necessary adjustments independently in the future (Lebow, 2019; Swartz, 2021).

 This approach targets the social and interpersonal context of a patient's problems. IPT focuses on the present and highlights the patient's interpersonal life in four problem areas:

• role disputes (conflicts with significant others, non-reciprocal expectations between individuals)
• interpersonal skill deficits (communication shortfalls, impaired social skills, social isolation, series of unfulfilling relationships)
• grief over the loss (death of a close contact, loss of an intimate relationship)
• role transitions (changing roles, such as going from working to retiring or from married to divorced; Lebow, 2019; Swartz, 2021)

IPT is typically limited to 3 or 4 months (up to 20 sessions) and is organized into three session groups (opening, middle, and final). IPT can be administered as a sole form of therapy or in conjunction with medications. Most studies indicate that the combination of medication and IPT may be more beneficial than either method alone. Psychotherapists may employ techniques such as role-playing to help patients understand and adjust how they relate to their world (Craske, 2017; Stein & Norman, 2021). For more information, see the NursingCE course on psychotherapy. 

Complementary and Alternative Treatment

Complementary and alternative treatments can be used as an adjunct to other evidence-based treatments for depression. When combined with evidence-based treatment options, such as prescription medications and psychotherapy, these interventions can contribute positively to the overall treatment plan for depression. There are pharmacological agents available over the counter (OTC) for the management of depression, such as hypericum perforatum (St. John's wort), omega-3 fatty acid (fish oil), and s-adenosyl methionine (SAM-e). However, these agents are not US Food and Drug Administration (FDA)-approved for depression, nor are they regulated by the FDA to ensure their safety and efficacy. The lack of FDA oversight and regulation of these agents poses concerns regarding the consistency of formulations, the purity of their ingredients, and safety profiles. Although patients do not require a prescription to obtain these drugs, they still pose a risk of significant adverse effects and dangerous drug interactions. Some complementary and alternative treatments with evidence of positive contributions to the treatment of depression are described below (National Center for Complementary and Integrative Health [NCCIH], 2021).  

Exercise and Yoga 

Exercise increases endorphins and stimulates the secretion of norepinephrine, which can improve a person's mood. According to a recent report by Harvard Health Publishing, the hippocampus in the brain (the region responsible for regulating mood) is smaller in depressed individuals. Low-intensity exercise over time stimulates the release of proteins that cause the nerve cells to grow and generate new connections. These processes improve brain function, support nerve cell growth in the hippocampus, and improve nerve cell connections, all of which alleviate depressive symptoms (Harvard Health Publishing, 2021). Yoga is a mind and body practice founded in ancient Indian philosophy. It centers on achieving a relaxation response through spirituality and meditation, an integral component of yoga. Meditation is especially beneficial for reducing stress and depressive symptoms. Studies have shown that yoga and meditation positively benefit people with depression and other mental health conditions (NCCIH, 2021). Sharma and colleagues (2017) evaluated the feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention for patients with MDD. SKY is a breathing-based meditative technique that focuses on slow, medium, or fast rhythmic breathing cycles. It has been reported to decrease cortisol, increase prolactin, and improve antioxidant status. Their findings demonstrated that SKY helped alleviate severe depression in people who did not fully respond to treatment with antidepressants (Sharma et al., 2017).

Light Therapy

Light therapy was initially introduced in the early 1980s and is currently recognized as an effective and safe treatment for SAD. Light therapy utilizes a lightbox with fluorescent tubes, a reflector, and a diffusing screen to filter out ultraviolet light. Patients are instructed to sit in front of the light daily, typically in the morning, for 30 to 60 minutes, with their eyes open but not looking directly at the light source. This may activate the suprachiasmatic nucleus, the brain's circadian pacemaker (Lampner, 2018). Recently the use of light therapy for non-season depression has been studied. A 2016 systematic review and meta-analysis of patients with non-seasonal depression found a beneficial effect despite the poor quality of evidence (Perera et al., 2016). Similar findings were replicated in a 2018 systematic review and meta-analysis analyzing the efficacy of light therapy in older patients (those over 60) diagnosed with non-seasonal depression. Researchers found a statistically significant improvement in depressive symptoms among older patients receiving light therapy than in the control groups (Zhao et al., 2018).

Folate

Folate, also known as folic acid or vitamin B9, is an essential nutrient in green leafy vegetables and fortified grain products. Low folate levels have been associated with depression, as well as dementia. When folate levels are deficient, patients may not receive the full therapeutic effect of their prescribed antidepressant medication. Studies have shown that adding a folate supplement such as L-methyl folate (Folic acid) can enhance the effectiveness of antidepressant medications without causing dangerous drug interactions. Furthermore, some studies have demonstrated that L-methyl folate (Folic acid) supplementation may be an effective adjunctive therapy or a stand-alone treatment for reducing depressive symptoms and improving cognitive function (MHA, 2016; NCCIH, 2021; NIMH, 2022c).

Hypericum Perforatum (St. John's Wort)

Hypericum perforatum (St. John's wort) is a supplement with chemical properties similar to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), the two most prescribed classes of antidepressants. APRNs should warn patients not to take hypericum perforatum (St. John's wort) with a prescribed antidepressant, as the combination causes increased levels of serotonin in the body, which can have mild to severe effects. Hypericum perforatum (St. John's wort) is notorious for interacting with several other prescription medications (e.g., benzodiazepines, warfarin [Coumadin], digoxin [Lanoxin], hormonal contraceptives, and antiepileptics), either expediting or diminishing the metabolism of the prescribed agent, leading to reduced efficacy or higher toxicity (MHA, 2016; NCCIH, 2017b).

Omega-3 Fatty Acids (Fish or Algae Oil) 

Omega-3 fatty acids (Fish or algae oil) have been widely studied for their benefits to cardiovascular health but have also been subject to significant research regarding their potential role in depression. Individuals who do not consume enough omega-3 fatty acids via dietary sources are more prone to depression. Some studies have revealed that omega-3 fatty acids (Fish or algae oil) supplementation may help stabilize mood when taken long-term, but the evidence is conflicting. Unlike other dietary supplements, omega-3 fatty acids (Fish or algae oil) can be used as adjunctive therapy with prescribed antidepressants such as SSRIs and SNRIs without heightening the risk for dangerous drug interactions or serotonin syndrome. However, it has been known to interact with anticoagulants such as aspirin (ASA) and coumadin (Warfarin) by increasing the risk of bleeding. Furthermore, not all omega-3 fatty acids (Fish or algae oil) supplementations are created equal. Without FDA regulation, there is an ongoing concern regarding the purity of ingredients. Toxins and contaminants have been found in some omega-3 fatty acids (Fish or algae oil) preparations, such as mercury and dioxins (industrial toxins) found in predatory fish (e.g., salmon, swordfish, perch, pike, and tuna; MHA, 2016; NCCIH, 2021; NIMH, 2022c). Additionally, potential adverse effects include the following:

• allergic reactions in patients who have underlying fish allergies
• hyperglycemia
• increased vitamin D and A levels
• may cause increased low-density lipoprotein (LDL) cholesterol levels (NCCIH, 2021; NIMH, 2022c)

S-Adenosyl-L-Methionine (SAM-e)

S-adenosyl-L-methionine (SAM-e) is a naturally occurring chemical component present in all cells of the body, as it serves necessary functions in numerous metabolic pathways. It participates in the synthesis of many essential molecules, including the neurotransmitters norepinephrine, dopamine, and serotonin. SAM-e has been approved for nearly three decades as a prescription drug for depression in several European countries. It may be used alone or as adjunctive therapy with prescription antidepressants, including SSRIs, SNRIs, monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs). Studies demonstrate that SAM-e poses fewer side effects than prescription antidepressants, with mild nausea reported as the most common side effect. It can worsen underlying agitation, panic, or anxiety in some patients. SAM-e works more rapidly than prescription antidepressants, does not cause weight gain or sexual dysfunction, and has no known drug interactions (MHA, 2016; NCCIH, 2017a; NIMH, 2022c).

Antidepressants

Antidepressant medications are the pharmacological treatment of choice for depression. Medication therapy aims to help reduce or control the symptoms of depression. The bulk of medications currently FDA-approved for treating depression target the three neurotransmitters historically associated with depression: serotonin, norepinephrine, and dopamine. Due to their side effect profiles, most antidepressants need to be initiated at low doses, tapered up slowly, and tapered down before discontinuing. If they are stopped abruptly, withdrawal-like symptoms may ensue, such as dizziness, headaches, flu-like syndrome (tiredness, chills, muscle aches), agitation, irritability, insomnia, nightmares, diarrhea, and nausea. Discontinuation can also lead to the return of depressive symptoms. Regardless of the medication prescribed, patients must be counseled that antidepressants may take at least 2 to 4 weeks to have an effect and 12 weeks to achieve full benefits. Disturbances in sleep, appetite, and concentration often improve before a notable change in mood. While mild-to-moderate depression can often be treated with therapy alone, moderate-to-severe cases of depression often require the addition of medication. Women of childbearing age should be advised that most antidepressants were previously categorized by the FDA as pregnancy category C (risk cannot be ruled out) except for paroxetine (category D) and bupropion (category B), with slight variations between the medications' safety for lactating mothers (National Alliance on Mental Illness [NAMI], 2017; NIMH, 2022c).

In 2004, the FDA required a warning to be printed on the labels of all antidepressant medications regarding the risk of increased suicidality among children and adolescents taking these medications. The warning was expanded in 2007 to include all young adults, especially those under 25, stating that these individuals may experience increased suicidal thoughts or behaviors during the first few weeks of taking an antidepressant. Before starting medication therapy, the individual may have been too paralyzed by depression to make a suicide plan. Therefore, the risk of suicide rises as symptoms begin to improve on antidepressant therapy. An increase in suicidal thoughts has also been documented in patients taking antidepressants for other conditions or indications. As antidepressants became more commonly prescribed for anxiety and other mental health conditions, reports of patients' suicidal thoughts and actions became more worrisome to clinicians and family members. If a depressed person on antidepressants becomes suicidal, it is always a cause for concern. However, if someone who was not previously depressed and taking antidepressants for another indication becomes suicidal, it raises additional questions about these medications' safety. Researchers found evidence that individuals taking antidepressant medication may have an even higher risk of suicide than individuals whose depression is improving for other reasons (Fornaro et al., 2019). The FDA also requires manufacturers of antidepressants to provide a Patient Medication Guide (MedGuide), which is distributed to patients prescribed these medications, advising them on precautions that can reduce the risk of suicide. APRNs should ask patients, especially young persons, about suicidal thoughts before prescribing antidepressants (FDA, 2018). Table 5 lists the points that must be included in the boxed warning.

Table 5

FDA Antidepressants Boxed Warning Points

 (FDA, 2018)

The current evidence base does not recommend one prescribed agent over another, although SSRIs are typically cited as the safest initial choice that causes the fewest side effects. A systematic review and meta-analysis published by Cipriani and colleagues in 2018 reviewed 522 double-blind, randomized controlled trials involving 116,477 patients diagnosed with MDD and 21 different antidepressants. Unfortunately, this analysis only recorded outcomes at or around 8 weeks, which is a brief period, especially for long-acting medications. The authors noted that 426 of the 522 (81%) reviewed trials were of moderate- or high-risk bias. Despite these limitations, the results demonstrated that all antidepressants were more effective than placebo. Agomelatine (Valdoxan), amitriptyline (Elavil), escitalopram (Lexapro), mirtazapine (Remeron), paroxetine (Paxil), venlafaxine (Effexor), and vortioxetine (Trintellix) were among the most effective, while fluoxetine (Prozac), fluvoxamine (Luvox), reboxetine (Edronax), and trazodone (Desyrel) were among the least effective. Agomelatine (Valdoxan) is a novel antidepressant that acts as a melatonin agonist and serotonin antagonist. It has been marketed in Europe since 2009 and in Australia since 2010 but is not currently approved by the FDA for use in the US. Reboxetine (Edronax) is a norepinephrine reuptake inhibitor that is not approved for use in the US. Regarding tolerability, agomelatine (Valdoxan), citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), sertraline (Zoloft), and vortioxetine (Trintellix) had the lowest dropout rates. In contrast, amitriptyline (Elavil), duloxetine (Cymbalta), fluvoxamine (Luvox), reboxetine (Edronax), trazodone (Desyrel), and venlafaxine (Effexor) had the highest dropout rates. Overall, when evaluating effectiveness as well as tolerability, the authors determined that the best options for the treatment of depression are agomelatine (Valdoxan) and escitalopram (Lexapro), and the worst choices are fluvoxamine (Luvox), reboxetine (Edronax), and trazodone (Desyrel; Cipriani et al., 2018).

The American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (i.e., the Beers Criteria, or BC) was last updated in 2019. The 2019 BC recommends avoiding TCAs for older adults due to their anticholinergic effects. In addition, SSRIs and SNRIs were recently added to the BC for patients with a history of falls or fractures, citing an increased risk of falls for older adults taking antidepressants. The 2019 criteria recommendation is to "avoid [antidepressants] unless safer alternatives are not available." The guidance also mentions that "data for antidepressants are mixed, but [there is] no compelling evidence that certain antidepressants confer less fall risk than others" (AGS Beers Criteria Update Expert Panel, 2019, p. 46).

While antidepressants typically do not require routine laboratory or drug-level monitoring, APRNs should remain alert to the potential side effects and adverse effects outlined in each category below. APRNs should counsel patients that side effects typically improve after the first 2 weeks of treatment. As a drug class, the most common adverse effects of antidepressants include nausea, weight gain, diarrhea, sleepiness, and sexual dysfunction (i.e., loss of libido or impotence; Dodd et al., 2017; NIMH, 2022c). The major antidepressant drug classes are outlined in the next section and Table 6 below.

SSRIs and SNRIs

SSRIs work by selectively blocking serotonin reuptake, thereby increasing the amount of serotonin available within the brain. SSRIs include medications such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and vortioxetine (Trintellix). Prozac (fluoxetine) is the only antidepressant that is FDA-approved for use in children with depression. Common side effects of SSRIs include nausea, vomiting, diarrhea, headaches, dry mouth, drowsiness, insomnia, nervousness, agitation, restlessness, sexual dysfunction, and appetite changes leading to weight loss or weight gain. Rarer side effects include hyponatremia, abnormal bleeding or bruising, and a decline in bone mineral density. APRNs should perform a routine evaluation of patients on SSRIs, including a baseline sodium level (Woods, 2023).

SNRIs include duloxetine (Cymbalta), venlafaxine (Effexor), desvenlafaxine (Pristiq), and levomilnacipran (Fetzima). Side effects include nausea, headaches, dizziness, excessive sweating, dry mouth, tiredness, constipation, insomnia, sexual dysfunction, and anorexia. Patients prescribed venlafaxine (Effexor) should have their blood pressure checked at baseline and periodically after starting and following any dose increase to monitor for hypertension. The risk for hypertension with this medication is dose-dependent and typically heightens with doses of 225 mg or higher. Patients taking duloxetine (Cymbalta) should have liver function tests performed at least annually due to the low risk of elevated alanine transaminase levels (ALT; Dodd et al., 2017; Woods, 2023).

SSRIs and SNRIs can increase serotonin levels in the body, posing a risk for serotonin syndrome. Serotonin syndrome is characterized by agitation, anxiety, confusion, a high fever, sweating, tremors, a lack of coordination, dangerous fluctuations in blood pressure, and rapid heart rate. Patients must seek immediate medical attention because this is a potentially life-threatening condition. Furthermore, SSRIs and SNRIs are associated with increased suicide risk and withdrawal symptoms if stopped abruptly. These medications should not be used within 14 days of an MAOI (Dodd et al., 2017; Woods, 2023).

Tricyclic Antidepressants and Tetracyclic Antidepressants

TCAs and tetracyclic antidepressants are an older class of medications that include nortriptyline (Pamelor), imipramine (Tofranil), amitriptyline (Elavil), and desipramine (Norpramin). TCAs inhibit norepinephrine and serotonin reuptake but with significantly more adverse effects, such as sedation, increased appetite, weight gain, dry mouth, constipation, hypotension, lightheadedness, drowsiness, blurred vision, tremors, excessive sweating, and sexual dysfunction. Less common but serious side effects include life-threatening irregular heart rate, urinary retention, and seizures. Before being prescribed TCAs, patients should be evaluated for the presence of any cardiac history, and a baseline electrocardiogram (ECG) should be performed. An ECG should be performed again once the therapeutic dose is achieved. These medications should be used cautiously in patients receiving electroconvulsive therapy (ECT). If signs of psychosis occur, the daily dose should be reduced until symptoms subside. TCAs also carry a risk for serotonin syndrome, suicide risk, and withdrawal symptoms if discontinued abruptly. These medications should also be avoided within 14 days of MAOI use (NIMH, 2022c; Woods, 2023).

Mirtazapine (Remeron) is an atypical tetracyclic antidepressant that antagonizes alpha-2 adrenergic and serotonin receptors. It can cause increased cholesterol and triglyceride levels and should be used cautiously by patients with a personal or family history of heart disease or irregular heart rhythm. Mirtazapine (Remeron) should not be taken within 14 days of an MAOI due to the heightened risk for serotonin syndrome. Other common side effects include sedation, increased appetite, weight gain, and dizziness. Rare and serious side effects consist of agranulocytosis (low white blood cells) and angle-closure glaucoma (eye pain, changes in vision, swelling, or redness in or around the eye). APRNs should advise patients to take the medication before bedtime to avoid daytime drowsiness, especially if performing tasks that involve alertness, such as operating heavy machinery (Dodd et al., 2017; NAMI, 2020; Woods, 2023).  

Monoamine Oxidase Inhibitors 

MAOIs were the first type of antidepressant developed. They impair the metabolism of serotonin and block monoamine oxidase, an enzyme that breaks down excess tyramine in the body. Tyramine is an amino acid that helps regulate blood pressure and is found naturally in the body and in certain foods. MAOIs include tranylcypromine (Parnate), phenelzine (Nardil), isocarboxazid (Marplan), and a transdermal skin patch selegiline (Emsam). Due to the risk of serious adverse effects, the use of MAOIs for the treatment of depression is reserved for patients who have failed all other treatment options. MAOIs have dangerous drug and food interactions; APRNs must warn patients to avoid foods containing high levels of tyramine, such as aged cheese (aged cheddar, swiss, parmesan, and blue cheeses); cured, smoked, or processed meats (pepperoni, salami, hotdogs, bologna, bacon, corned beef, smoked fish); pickled or fermented foods (sauerkraut, kimchi, tofu); sauces (soy sauce, miso and teriyaki sauce); soybean products; and alcoholic beverages (beer, red wine, liquors). Other side effects of MAOIs include dry mouth, nausea, diarrhea or constipation, headaches, drowsiness, insomnia, dizziness, lightheadedness, hypotension, loss of libido, weight gain, urinary retention, involuntary muscle jerks, muscle cramps, and paresthesia. MAOIs are associated with increased suicidality and withdrawal symptoms if stopped abruptly. Before prescribing MAOIs, APRNs must ensure all other antidepressants have been discontinued for at least 14 days due to the heightened risk for serotonin syndrome. Patients should also be counseled to avoid OTC decongestants and other cold medications due to the heightened risk for dangerous hypertensive crises (Dodd et al., 2017; Sub Laban & Saadabadi, 2022; Woods, 2023).

Table 6

Antidepressants by Medication Class

(Woods, 2023)

Uncategorized and Atypical Antidepressants 

There are a few uncategorized and atypical antidepressants that have varying mechanisms of action. Bupropion (Wellbutrin) is an atypical antidepressant that works by inhibiting the reuptake of dopamine, serotonin, and norepinephrine. It is prescribed for depression, as well as SAD and smoking cessation. Initial IR dosing is 100 mg orally twice daily, which is increased to 3 times daily if there is no improvement after several weeks. Initial sustained-release dosing is 150 mg once daily in the morning, increasing to a target dose of 150 mg twice daily after 4 days. Bupropion (Wellbutrin) is one of the few antidepressants not frequently associated with sexual dysfunction. However, it poses a seizure risk, so it should be avoided in patients with preexisting seizure disorders. It primarily affects dopamine in the brain and therefore does not carry a risk for serotonin syndrome. The most common side effects include headaches, weight loss, dry mouth, insomnia, nausea, dizziness, constipation, fast heartbeat, and sore throat (FDA, 2017; Woods, 2023).

Trazodone (Desyrel) is an antidepressant that inhibits both serotonin transporters and serotonin type 2 receptors. It inhibits the reuptake of serotonin and blocks histamine and alpha-1-adrenergic receptors. It is usually prescribed for depression when other medications have failed. When used for MDD, the initial dosing is 150 mg daily in divided doses, increasing the dose by 50 mg every 3 to 4 days as needed to a maximum daily dose of 600 mg in an inpatient setting and 400 mg in outpatient settings. Trazodone (Desyrel) should not be used by patients being treated with MAOIs, linezolid (Zyvox), methylene blue (ProvayBlue), fentanyl (Duragesic), or any other serotonergic drugs due to its heightened risk for serotonin syndrome. APRNs must ensure that MAOIs are discontinued at least 14 days before initiating trazodone (Desyrel). Patients should be advised to take the medication before bedtime due to drowsiness and sedation. Rare adverse effects include priapism (a persistent and painful erection not associated with sexual arousal) and cardiac arrhythmias (Dodd et al., 2017; Shin & Saadabadi, 2022). 

Brexanolone (Zulresso) is a neuroactive steroid gamma-aminobutyric acid (GABA)-a receptor-positive modulator approved by the FDA in 2019 to treat postpartum depression for individuals older than 15. While the mechanism of action is not fully understood, it is thought to be related to its positive allosteric modulation of GABA-a receptors. Brexanolone (Zulresso) is administered by continuous intravenous (IV) infusion over 60 hours. Patients may experience excessive fatigue, tiredness, sedation, or a sudden loss of consciousness during the infusion. Due to the risk of alterations in consciousness, brexanolone (Zulresso) can only be administered in a facility with a provider on-site. The drug is only available through a restricted risk evaluation and mitigation strategy (REMS) drug-safety program. Patients must be monitored for sedative effects every 2 hours during non-sleep periods and should be advised to report any signs of excessive tiredness. Continuous pulse oximetry should be maintained to monitor for hypoxia. The infusion should be immediately discontinued for any signs or symptoms of excessive sedation. Other common side effects include dry mouth and facial flushing. Patients should avoid alcohol, opioids, benzodiazepines, and other central nervous system (CNS) depressants due to the heightened risk of sedation and loss of consciousness. It is also associated with an increased risk for suicidality. Brexanolone (Zulresso) carries a risk for abuse, can lead to dependence, and is classified as a schedule IV controlled substance under the Controlled Substances Act (Sage Therapeutics, 2022; Woods, 2023).

Resistant Depression

Depression may be resistant to standard treatments, with up to 67% of patients failing to respond to first-line therapy. Resistant depression is the failure of at least two other antidepressants (administered for at least 6 weeks each) without achieving remission or at least a 50% improvement in mood. Often, the resistance is not related to the medication or treatment but to compliance with administration by the patient. Failure can also be due to an incorrect dose or inadequate time to develop a therapeutic response. When treating resistant depression, HCPs should reevaluate the diagnosis to ensure accuracy and consider comorbidities such as anxiety, SUD, or psychosis. APRNs should ensure consistency in medication administration and consider an upward titration in dosage, if appropriate. For some patients, a change in medication therapy may be warranted, such as switching from an SSRI to an SNRI or adding a second medication to the regimen. Psychotherapy should be added if not already a component of the treatment plan, and brain-stimulation therapies can be considered (APA, 2022a; Hasin et al., 2018). Although depression is typically managed in primary care, consultation with a psychiatrist should be considered in the following circumstances:

• suicidal ideations
• mania
• severe or resistant depression
• psychosis
• consideration of brain-stimulation therapies (Hasin et al., 2018)

Esketamine (Spravato) 

Esketamine (Spravato) is an n-methyl D-aspartate (NMDA) antagonist made from ketamine, an anesthetic introduced in the 1960s to treat battle wounds during the Vietnam War. Since then, ketamine has gained attention regarding its role in treating severe depression. In 2019, esketamine (Spravato) nasal spray, a more potent version of ketamine, earned FDA approval when used in conjunction with an oral antidepressant for adults with treatment-resistant depression. Esketamine (Spravato) works by increasing levels of the neurotransmitter glutamate in the brain. It has a rapid onset, immediately impacting brain cells and offering relief from depressive symptoms within hours. Common side effects include dissociation (e.g., difficulty with attention, judgment, and thinking), nausea, dizziness, drowsiness, vertigo, and anxiety. It has a boxed warning related to its risk for sedation, dissociation, misuse, dependence, and suicidal thoughts and behaviors. Therefore, it is a federally controlled substance only available through a REMS program. Esketamine (Spravato) must be administered under the supervision of an HCP in a healthcare setting that is certified in the REMS program. Patients cannot take the spray home and must be monitored for signs of sedation and dissociation for at least 2 hours following each dose. During the first 1 to 4 weeks of treatment, administration is twice weekly. It is then administered once weekly during weeks 5 to 8. The recommended maintenance dose is either once weekly or every other week, depending on the patient's response (FDA, 2019; Woods, 2023.).

Brain Stimulation Therapy 

Brain stimulation therapies are typically reserved for treating resistant depression when other treatments have proven ineffective. The three major types consist of electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (TMS), and vagus nerve stimulation (VNS; NAMI, 2022; NIMH, 2016).

Electroconvulsive Therapy 

ECT involves transmitting short electrical impulses into the brain. These controlled electrical currents provoke a brief period of seizure-like activity. ECT is typically performed in a series of 4 to 6 treatments before an improvement can be expected, with a total of 6 to 12 treatments administered over 2 to 6 weeks; monthly maintenance treatments are sometimes required. The patient is placed under general anesthesia for the treatments and can resume regular activity about an hour following the procedure. ECT can have significant adverse effects, such as headaches, muscle pain, nausea, confusion, and memory loss. It is only utilized for patients with severe depression, depression with psychosis, or bipolar disorder that has not responded to medication and psychotherapy with more conventional methods. In uncomplicated severe depression, ECT has been shown to improve mood in 80% of patients. Patients need to understand the potential risks and benefits of ECT before beginning treatment (Holtzheimer, 2022; NAMI, 2022; NIMH, 2016).

Transcranial Magnetic Stimulation 

TMS is a relatively new type of brain stimulation that uses a magnet instead of an electrical current to activate the brain. It has not yet been proven effective as a maintenance therapy but has been approved by the FDA to treat MDD and OCD. TMS creates rapidly alternating magnetic fields using a large magnetic coil placed on the patient's forehead. Patients may need to complete 4 to 5 sessions lasting 40 minutes each per week over 4 to 6 weeks to see improvement. TMS is not recommended for patients with psychotic symptoms, bipolar disorder, or a high risk of suicide. TMS is contraindicated in patients with pacemakers or metal objects in their heads. The patient remains alert throughout the treatment, and general anesthesia is not required. TMS must be used with caution in patients with a history of seizures, as it can induce seizure activity. Mild adverse effects include muscle contractions, facial and jaw tingling, headaches, and lightheadedness (Holtzheimer, 2022; NAMI, 2022; NIMH, 2016).

Vagus Nerve Stimulation

VNS is FDA-approved for resistant depression only after attempts with four different medications and ECT have failed. Originally developed to treat seizure disorders, its use in depression treatment is controversial and rare. VNS requires the placement of a pulse stimulator on the upper left chest to stimulate the vagus nerve. The VNS sends an electrical pulse up the vagus nerve to the brainstem to change the function of brain cells. How it functions can be compared to a pacemaker's effect on cardiac cells. Adverse effects include voice changes, hoarseness, a sore throat, coughing, difficulty swallowing, neck pain, and breathing difficulty while exercising (Holtzheimer, 2022; NAMI, 2022; NIMH, 2016).

References

American Association of Suicidology. (2020). USA suicide: 2019 official final data. https://suicidology.org/wp-content/uploads/2021/01/2019datapgsv2b.pdf

American Geriatrics Society Beers Criteria Update Expert Panel. (2019). American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 67(4), 674–694. https://doi.org/10.1111/jgs.15767

American Psychiatric Association. (2019a). Clinical practice guideline for the treatment of depression across three age cohorts. https://www.apa.org/depression-guideline/guideline.pdf

American Psychiatric Association. (2019b). Depression assessment instruments. https://www.apa.org/depression-guideline/assessment/index

American Psychiatric Association. (2022a). Diagnostic and statistical manual of mental disorders (DSM-5-TR). American Psychiatric Association Publishing.

American Psychiatric Association. (2022b). Understanding psychotherapy and how it works. https://www.apa.org/topics/psychotherapy/understanding

Brodsky, B. S., Spruch-Feiner, A., & Stanley, B. (2018). The zero suicide model: Applying evidence-based suicide prevention practices to clinical care. Frontiers in Psychiatry, 9(33). https://doi.org/10.3389/fpsyt.2018.00033

Brody, D. J., Pratt, L. A., & Hughes, J. P. (2018). Prevalence of depression among adults aged 20 and over: United States, 2013–2016. NCHS Data Brief, no 303. National Center for Health Statistics. https://www.cdc.gov/nchs/data/databriefs/db303.pdf

Centers for Disease Control and Prevention. (2022a). Fatal injury and violence data. https://www.cdc.gov/injury/wisqars/fatal.html

Centers for Disease Control and Prevention. (2022b). Suicide prevention. https://www.cdc.gov/suicide/index.html

Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M. Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357-1366. https://doi.org/10.1016/s0140-6736(17)32802-7

Craske, M. G. (2017). Cognitive-behavioral therapy (2nd ed.). American Psychiatric Association.

Cuijpers, P., de Wit, L., Kleiboer, A., Karyotaki, E., & Ebert, D. D. (2018). Problem-solving therapy for adult depression: An updated meta-analysis. European Psychiatry, 48(1), 27-37. https://doi.org/10.1016/j.eurpsy.2017.11.006

David, D., Cristea, I., & Hofmann, S. G. (2018). Why cognitive behavioral therapy is the current gold standard of psychotherapy. Frontiers in Psychiatry, 9(4). https://doi.org/10.3389/fpsyt.2018.00004

Dodd, S., Mitchell, P. B., Bauer, M., Yatham, L., Young, A. H., Kennedy, S. H., Williams, L., Suppes, T., Jaramillo, C. L., Trivedi, M. H., Fava, M., Rush, A. J., McIntyre, R. S., Thase, M. E., Lam, R. W., Severus, E., Kasper, S., & Berk, M. (2017). Monitoring for antidepressant-associated adverse effects in the treatment of patients with major depressive disorder: An international consensus statement. The World Journal of Biological Psychiatry, 19(5), 333-348. https://doi.org/10.1080/15622975.2017.1379609

Feng, G., Han, M., Li, X., Geng, L., & Miao, Y. (2020). The clinical effectiveness of cognitive-behavioral therapy for patients with insomnia and depression: A systematic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine, 8071821, 1-14. https://doi.org/10.1155/2020/8071821

Fornaro, M., Anastasia, A., Valchera, A., Carano, A., Orsolini, L., Vellante, F., Rapini, G., Olivieri, L., Di Natale, S., Perna, G., Martinotti, G., Di Giannantonio, M., & De Berardis, D. (2019). The FDA "black box" warning on antidepressant suicide risk in young adults: More Harm than Benefits? Frontiers in Psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00294

Goldberg, J. F. (2018). The psychopharmacology of depression: Strategies, formulations, and future implications. Psychiatric Times, 35(7), 9-14. http://www.psychiatrictimes.com/depression/psychopharmacology-depression-strategies-formulations-and-future-implications

Harvard Health Publishing. (2021). Exercise is an all-natural treatment to fight depression. https://www.health.harvard.edu/mind-and-mood/exercise-is-an-all-natural-treatment-to-fight-depression

Hasin, D. S., Sarvet, A. L., Meyers, J. L., Saha, T. D., Ruan, W. J., Stohl, M., & Grant, B. F. (2018). Epidemiology of adult DSM-5 major depressive disorder and its specifiers In the United States. JAMA Psychiatry, 75(4), 336-346. https://doi.org/10.1001/jamapsychiatry.2017.4602

Hofmann, S. G., & Asmundson, G. J. G. (2017). The science of cognitive-behavioral therapy. Academic Press.

Holtzheimer, P. E. (2022). Unipolar depression in adults: Overview of neuromodulation procedures. UpToDate. Retrieved August 29, 2022, from https://www.uptodate.com/contents/unipolar-depression-in-adults-overview-of-neuromodulation-procedures#H2496009

Kroenke, K., Spitzer, R. L., & Williams, J. B. (2001). The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine, 16(9), 606-613. https://doi.org/10.1046/j.1525-1497.2001.016009606.x

Lampner, C. (2018). Light therapy effective for older adults with nonseasonal depression. https://www.psychiatryadvisor.com/home/depression-advisor/light-therapy-effective-for-older-adults-with-nonseasonal-depression

Lebow, J. (2019). Overview of psychotherapies. UpToDate. Retrieved August 27,

2022, from https://www.uptodate.com/contents/overview-of-psychotherapies

Levis, B., Benedetti, A., Thombs, B. D., & the DEPRESsion Screening Data (DEPRESSD) Collaboration. (2019). Accuracy of patient health questionnaire-9 (PHQ-9) for screening to detect major depression: Individual participant data meta-analysis. BMJ, 365, 11476. https://doi.org/10.1136/bmj.l1476

Luo, C., Sanger, N., Singhal, N., Pattrick, K., Shams, I., Shahid, H., Hoang, P., Schmidt, J., Lee, J., Haber, S., Puckering, M., Buchanan, N., Lee, P., Ng, K., Sun, S., Kheyson, S., Chung, D. C., Sanger, S., Thabane, L., & Samaan, Z. (2020). A comparison of electronically-delivered and face-to-face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis. The Lancet, 24(100442). https://doi.org/10.1016/j.eclinm.2020.100442

McCartney, M., Nevitt, S., Lloyd, A., Hill, R., White, R., & Duarte, R. (2020). Mindfulness-based cognitive therapy for prevention and time to depressive relapse: Systematic review and network meta-analysis. Acta Psychiatrica Scandinavica, 143(1), 6-21. https://doi.org/10.1111/acps.13242

Mental Health America. (2016). Complementary and alternative medicine for mental health. https://www.mhanational.org/sites/default/files/MHA_CAM.pdf

Mental Health America. (2021). The state of mental health in America report 2022. https://mhanational.org/issues/state-mental-health-america

Na, P. J., Yaramala, S. R., Kim, J. A., Kim, H., Goes, F. S., Zandi, P. P., Vande Voort, J. L., Sutor, B., Croarkin, P., & Bobo, W. V. (2018). The PHQ-9 Item 9 based screening risk: A validation study of the patient health questionnaire (PHQ)-9 Item 9 with the Columbia Suicide Severity Rating Scale (C-SSRS). Journal of Affective Disorders, 232, 34-40. https://doi.org/10.1016/j.jad.2018.02.045

National Action Alliance for Suicide Prevention. (2018). Recommended standard care for people with suicide risk: Making health care suicide safe. https://theactionalliance.org/resource/recommended-standard-care

National Alliance on Mental Illness. (2017). Types of medication. https://nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication

National Alliance on Mental Illness. (2020). Mirtazapine (Remeron). https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)

National Alliance on Mental Illness. (2022). ECT, TMS, and other brain stimulation therapies. https://www.nami.org/Learn-More/Treatment/ECT,-TMS-and-Other-Brain-Stimulation-Therapies

National Center for Complementary and Integrative Health. (2017a). S-Adenosyl-L-Methionine (SAMe): In depth. https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth

National Center for Complementary and Integrative Health. (2017b). St. John's wort and depression: In depth. https://nccih.nih.gov/health/stjohnswort/sjw-and-depression.htm

National Center for Complementary and Integrative Health. (2021). Depression and complementary health approaches. https://www.nccih.nih.gov/health/providers/digest/depression-and-complementary-health-approaches

National Center for PTSD. (2022). Depression, trauma, and PTSD. US Department of Veteran Affairs. https://www.ptsd.va.gov/understand/related/depression_trauma.asp

National Institute of Mental Health. (2016). Brain stimulation therapies. https://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml

National Institute of Mental Health. (2021). Chronic illness and mental health: Recognizing and treating depression. https://www.nimh.nih.gov/health/publications/chronic-illness-mental-health

National Institute of Mental Health. (2022a). Depression. https://www.nimh.nih.gov/health/topics/depression/index.shtml

National Institute of Mental Health. (2022b). Major depression. https://www.nimh.nih.gov/health/statistics/major-depression

National Institute of Mental Health. (2022c). Mental health medications. https://www.nimh.nih.gov/health/topics/mental-health-medications/index.shtml

National Institute of Mental Health. (2022d). Suicide. https://www.nimh.nih.gov/health/statistics/suicide.shtml

O'Byrne, P., & Jacob, J. D. (2018). Screening for depression: Review of the patient health questionnaire-9 for nurse practitioners. Journal of the American Association of Nurse Practitioners, 30(7), 406-411. https://doi.org/10.1097/JXX.0000000000000052

Parsons, C. E., Crane, C., Parsons, L. J., Fjorback, L. O., & Kuyken, W. (2017). Home practice in mindfulness-based cognitive therapy and mindfulness-based stress reduction: A systematic review and meta-analysis of participants' mindfulness practice and its association with outcomes. Behaviour Research and Therapy, 95, 29-41. https://doi.org/10.1016/j.brat.2017.05.004

Perera, S., Eisen, R. Bhatt, M., Bhatnagar, N., de Souza, R., Thabane, L, & Samaan, Z. (2016). Light therapy for non-seasonal depression: Systematic review and meta-analysis. BJ Psych Open, 2(2), 116-126. https://doi.org/10.1192/bjpo.bp.115.001610

Reynolds, M. E., & Cone, P. H. (2018). Managing adult insomnia confidently. The Journal for Nurse Practitioners, 14(10), 718-724.E1. https://doi.org/10.1016/j.nurpra.2018.08.019

Sage Therapeutics. (2022). Highlights of prescribing information: ZULRESSO (brexanolone) injection for intravenous use. https://assets.sagerx.com/zulresso/prescribing-information.pdf

Sharma, A., Barrett, M. S., Cucchiara, A. J., Gooneratne, N. S., & Thase, M. E. (2017). A breathing-based meditation intervention for patients with major depressive disorder following inadequate response to antidepressants: A randomized pilot study. Journal of Clinical Psychiatry, 78(1), e59-e63. https://doi.org/10.4088/JCP.16m10819

Shin, J. J., & Saadabadi, A. (2022). Trazodone. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK470560

Society of Clinical Psychology. (2016). Treatment: Behavioral activation for depression. American Psychological Association. https://div12.org/treatment/behavioral-activation-for-depression

Spitzer, R. L., Kroenke, K., Williams, J. B., & PHQ Primary Care Study Group. (1999). Validation and utility of a self-report version of the PRIME-MD. JAMA, 282, 1737-1744. https://doi.org/10.1001/jama.282.18.1737

Stein, M. B., & Norman, S. (2021). Psychotherapy and psychosocial interventions for posttraumatic stress disorder in adults. UpToDate. Retrieved August 27, 2022, from https://www.uptodate.com/contents/psychotherapy-and-psychosocial-interventions-for-posttraumatic-stress-disorder-in-adults#H1772362614

Sub Laban, T., & Saadabadi, A. (2022). Monoamine oxidase inhibitors (MAOIs). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK539848

Substance Abuse and Mental Health Services Administration. (2017). National strategy for suicide prevention implementation assessment report. https://store.samhsa.gov/sites/default/files/d7/priv/sma17-5051.pdf

Substance Abuse and Mental Health Services Administration. (2021). Key substance use and mental health indicators in the United States: Results from the 2020 national survey on drug use and health (HHS Publication No. PEP21-07-01-003, NSDUH Series H-56). https://www.samhsa.gov/data/sites/default/files/reports/rpt35325/NSDUHFFRPDFWHTMLFiles2020/2020NSDUHFFR1PDFW102121.pdf

Suicide Prevention Resource Center. (2017). Problem-solving therapy (PST). https://www.sprc.org/resources-programs/problem-solving-therapy-pst

Swartz, H. A. (2021). Interpersonal psychotherapy (IPT) for depressed adults: Indications, theoretical foundation, general concepts, and efficacy. UpToDate. Retrieved August 27, 2022, from https://www.uptodate.com/contents/interpersonal-psychotherapy-ipt-for-depressed-adults-indications-theoretical-foundation-general-concepts-and-efficacy

United Health Foundation. (2021). Teen suicide in the United States. https://www.americashealthrankings.org/explore/health-of-women-and-children/measure/teen_suicide/state/ALL

Uphoff, E., Ekers, D., Robertson, L., Dawson, S., Sanger, E., South, E., Samaan, Z., Richards, D., Meader, N., & Churchill, R. (2020). Behavioural activation therapy for depression in adults. Cochrane Database of Systematic Reviews, 7, CD013305. https://doi.org/10.1002/14651858.CD013305.pub2

US Department of Health & Human Services. (2021). The surgeon general's call to action to implement the national strategy for suicide prevention. https://www.hhs.gov/sites/default/files/sprc-call-to-action.pdf

US Food & Drug Administration. (2017). Wellbutrin (bupropion hydrochloride) tablets – FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018644s052lbl.pdf

US Food & Drug Administration. (2018). Suicidality in children and adolescents being treated with antidepressant medications. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications

US Food & Drug Administration. (2019). FDA approves new nasal spray medication for treatment-resistant depression; Available only at a certified doctor's office or clinic. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified

US Preventive Services Task Force. (2022). Draft recommendation statement: Depression and suicide risk in children and adolescents - Screening. https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/screening-depression-suicide-risk-children-adolescents

Wampold, B. E. (2019). The basics of psychotherapy: An introduction to theory and practice (2^nd ed.). American Psychological Association.

Winkelman, J. W. (2021). Overview of the treatment of insomnia in adults. UpToDate. Retrieved August 27, 2021, from https://www.uptodate.com/contents/overview-of-the-treatment-of-insomnia-in-adults

Woods, A. D. (2023). Nursing 2023 drug handbook. Wolters Kluwer.

World Health Organization. (2021). Depression: Key facts. https://www.who.int/news-room/fact-sheets/detail/depression

Zero Suicide Institute. (n.d.). Screening for and assessing suicide risk. National Action Alliance for Suicide Prevention. Retrieved August 26, 2022, from https://zerosuicide.edc.org/toolkit/identify/screening-options

Zhang, A., Park, S., Sullivan, J. E., & Jing, S. (2018). The effectiveness of problem-solving therapy for primary care patient's depressive and/or anxiety disorders: A systematic review and meta-analysis. Journal of the American Board of Family Medicine, 31(1), 139-150. https://doi.org/10.3122/jabfm.2018.01.170270

Zhao, X., Ma, J., Wu, S., Chi, I., & Bai, Z. (2018). Light therapy for older patients with non-seasonal depression: A systematic review and meta-analysis. Journal of Affective Disorders, 232, 291-299. https://doi.org/10.1016/j.jad.2018.02.041