Course
SSRI Use in Major Depressive Disorder
Course Highlights
- In this SSRI Use in Major Depressive Disorder course, we will learn about common side effects, including severe possible side effects, of SSRIs.
- You’ll also learn alternatives to SSRI use for management of major depressive disorder .
- You’ll leave this course with a broader understanding of the clinical criteria for prescribing SSRIs.
About
Pharmacology Contact Hours Awarded: 1
Course By:
Sadia A.
MPH, MSN, WHNP-BC
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The following course content
Introduction
When hearing the phrase selective serotonin reuptake inhibitors, what comes to mind? If you're an advanced practice registered nurse (APRN) with prescriptive authority, you've heard of SSRIs before. Even as a nurse or maybe before nursing school, conversations about prescription drug use and mental health existed every so often.
Presently, patients seek guidance and information on various health topics from APRNs, including medication management, women's health, and mental health. The information in this course will serve as a valuable resource for APRNs with prescriptive authority of all specialties, education levels, and backgrounds to learn more about SSRIs and major depressive disorder (MDD).
Defining SSRIs
What Are SSRIs?
Selective serotonin reuptake inhibitors, known as SSRIs, are a type of pharmacological drug class. SSRIs have existed for the past several decades as a class of prescription medications that can manage major depressive disorder (MDD) and other mental health conditions (1).
While this course focuses explicitly on SSRI use in MDD management, SSRIs are also Food and Drug Administration (FDA) approved to manage obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD). In addition, several off-label uses for SSRI include management for binge eating disorder and menopausal vasomotor symptoms.
How and Where Are SSRIs Used?
SSRIs are commonly prescribed to manage MDD and other mood disorders in the U.S. and around the world in pediatric, adult, and geriatric populations (1, 2). SSRIs can be taken by mouth as a pill, capsule, or liquid oral solution. Presently, SSRIs cannot be offered via intravenous, rectal, buccal, or injection routes.
What Is the Clinical Criteria for Prescribing SSRIs?
Clinical criteria for prescribing SSRIs can vary depending on the intention for the SSRI. In the case of MDD, several factors can play a role in the clinical criteria for prescribing SSRIs. A patient's adherence to swallowing a pill daily, dosage given the patient's weight, medical history, and MDD concerns, and prior experience with other medications can influence prescribing SSRIs. When considering prescribing SSRIs for MDD management, consider assessing the patient for MDD first, taking a detailed health history, and discussing the risk versus benefits of starting SSRIs for this patient (1, 3).
What Is the Average Cost for SSRIs?
Cost for SSRIs can significantly vary depending on the type of SSRI, insurance, dosage, frequency, and other factors. Cost is among leading reasons why many patients cannot maintain their medication regime (4). If cost is a concern for your patient, consider reaching out to your local pharmacies or patient care teams to find cost-effective solutions for your patients.
What Is Major Depressive Disorder (MDD)?
Major depressive disorder (MDD) is a mental health condition in which a person has consistent appetite changes, sleep changes, psychomotor changes, decreased interest in activities, negative thoughts, suicidal thoughts, and depressed mood that interfere with a person's quality of life (5). According to the Diagnostic and Statistical Manual of Mental Health Disorders, a patient must have at least five persistent mood related symptoms, including depression or anhedonia (loss of interest in activities once enjoyed), that interferes with a person's quality of life to be formally diagnosed with MDD. Note that MDD does not include a history of manic episodes, and pediatric populations can present with more variable MDD symptoms (5). As an APRN, you can assess for MDD by doing a detailed patient health history or having a patient complete the Patient Health Questionnaire-9 (PHQ-9) - a depression assessment tool (5).
Self Quiz
Ask yourself...
- What are some medication administration options for SSRIs?
- What populations can be prescribed SSRIs?
SSRI Pharmacokinetics
Drug Class SSRIs
Selective serotonin reuptake inhibitors, known as SSRIs, are a type of pharmacological drug class part of the antidepressant drug class. They can be prescribed at various dosages depending on the patient history, severity of major depressive disorder (MDD), other medication use, and other factors based on patient-centered decision making. Currently, SSRIs that are FDA approved for MDD management include paroxetine, sertraline, citalopram, escitalopram, vilazodone, and fluoxetine. SSRIs can be prescribed for the oral route and are available via capsule, tablet, or liquid suspension/solution. SSRIs can be taken at any time of day. They can be taken with or without food, though vilazodone in particular is recommended with food. SSRIs are often prescribed to be taken once a day, sometimes twice a day, depending on the severity of MDD. Health care provider professional discretion and patient condition should guide therapy (1).
SSRIs are metabolized by and known to affect the cytochrome P450 system. CYP2D6 inhibitors include escitalopram, citalopram, sertraline, paroxetine, and fluoxetine. Fluoxetine and fluvoxamine are inhibitors of CYP2C19. Fluvoxamine is an inhibitor of CYP1A2. Consider reviewing a patient's medication history and health history prior to prescribing SSRIs (1).
SSRIs Method of Action
SSRI method of action has been subject to several studies, especially in the last few years. Serotonin is a neurotransmitter that plays a role in mood and other bodily functions. It can be measured in plasma, blood, urine, and CSF (6). It is important to note that serotonin is rapidly metabolized to 5-hydroxyindoleacetic acid (5-HIAA) (6). SSRIs work by inhibiting the reuptake of serotonin at certain chemical receptors, thereby increasing serotonin activity and concentration (1). SSRIs inhibit the serotonin transporter (SERT) at the presynaptic axon terminal.
By obstructing the SERT, a higher amount of serotonin (5-hydroxytryptamine or 5HT) remains in synaptic clefts. This higher amount of serotonin can then stimulate postsynaptic receptors for a more extended period (1). While SSRIs can increase serotonin activity, there is some evidence that suggests the possibility of long-term SSRI use reducing serotonin concentration (6). In addition, the clinical response to SSRIs in patients with MDD can take anywhere from a few to several weeks to emerge (7). While some research suggests that there are initial improvements in mood, evidence remains inconclusive as to the exact time SSRIs can take to provide a therapeutic response for patients (7). Also, while research suggests that SSRIs can increase serotonin levels, there is still mixed evidence on the exact method of action for SSRIs (7).
As a result, it is important to counsel patients that SSRIs can take a few weeks to provide a therapeutic response and to monitor mood and symptoms while taking SSRIs.
SSRI Side Effects
Every medication has the possibility of side effects, and SSRIs are no exception. Fortunately, SSRIs are known to have less side effects than other drug classes of antidepressants, such as monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs). The most commonly known side effects of SSRIs include weight gain, sleep changes, headache, gastrointestinal issues, drowsiness, orthostatic hypotension, and sexual function changes (1).
Sleep changes can include an increased desire to sleep, increase in the amount of time sleeping, or insomnia. Gastrointestinal issues can include an upset stomach, nausea, or dry mouth. Mood changes, such as anxiety, are possible side effects as well. Sexual function changes can include erectile dysfunction, libido changes, impaired orgasmic response, and vaginal dryness (1, 8).
There are more serious possible side effects of SSRIs as well. For instance, SSRIs have the possible side effect of QT prolongation, which if left untreated or undiagnosed, can lead to fatal cardiac arrythmias (1, 8). In particular, the SSRI citalopram has been shown to have more of a risk for QT prolongation compared to other SSRIs. Also, like any other medication that can possibly increase levels of serotonin in the body, there is a possibility of serotonin syndrome as a complication of SSRI use. Possible serotonin syndrome clinical manifestations include increased blood pressure, increased sweating, increased reflex ability, and increased dry eyes (8). Due to the wide varied range of side effects, patient counseling, monitoring, and education is essential when prescribing SSRIs.
SSRI Black Box Warning
In 2004, the FDA issued a black box warning for SSRIs and other antidepressant medications due to the possible increased risk of suicidality in pediatric and young adult populations (up to age 25). When considering SSRI use in patients under 25 and knowing MDD is a risk factor for suicidality, having a conversation with the patient about risks versus benefits must be considered. However, in the past several years since the FDA's warning, there is no clear evidence showing a correlation between SSRIs and the increased risk of suicidality (1, 8). Health care provider professional discretion and patient condition should guide therapy.
SSRI Alternatives
MDD can be a complex, chronic condition to manage with varying clinical presentation and influence on a patient's quality of life. There are several alternatives to SSRI use, such as: (1, 9)
- Other prescription drugs
- Serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly known SNRIs include milnacipran, venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran.
- Atypical antidepressants. Commonly known atypical antidepressants include bupropion and mirtazapine.
- Tricyclic antidepressants (TCAs). Commonly known TCAs include amitriptyline, desipramine, imipramine, clomipramine, doxepin, and nortriptyline.
- Monoamine oxidase inhibitors (MAOIs). Commonly known MAOIs include phenelzine, tranylcypromine, isocarboxazid, and selegiline.
- Psychotherapy, such as cognitive behavioral therapy (CBT) or interpersonal therapy
- Electroconvulsive therapy (ECT)
- Vagus Nerve Stimulation (VNS)
- Transcranial Magnetic Stimulation (TMS)
Self Quiz
Ask yourself...
- What are some possible side effects of SSRIs?
- What are some pharmacological alternatives to SSRIs?
Nursing Considerations
Nurse’s Role
What Is the Nurses' Role in SSRI Patient Education and Management?
Nurses remain the most trusted profession for a reason, and APRNs are often pillars of patient care in several health care settings. Patients turn to nurses for guidance, education, and support. While there is no specific guideline for the nurses' role in SSRI education and management, here are some suggestions to provide quality care for patients interested in or currently taking SSRIs to manage current or suspected major depressive disorder (MDD).
- Take a detailed health history. Often times, mental health symptoms, such as depressive thoughts or anxiety, are often dismissed in health care settings, even in mental health settings. If a patient is complaining of symptoms that could be related to major depressive disorder, inquire more about that complaint. Ask about how long the symptoms have lasted, what treatments have been tried, if these symptoms interfere with their quality of life, and if anything alleviates any of these symptoms. If you feel like a patient's complaint is not being taken seriously by other health care professionals, advocate for that patient to the best of your abilities.
- Review medication history at every encounter. Often times, in busy clinical settings, reviewing health records can be overwhelming. While a vast number of people take SSRIs, many are no longer benefiting from the medication. Ask patients how they are feeling on the medication, if their symptoms are improving, and if there are any changes to medication history.
- Ask about family history. If someone is complaining of symptoms that could be related to MDD, ask if anyone in their immediate family, such as their parent or sibling, experienced similar conditions.
- Be willing to answer questions about mental health and SSRIs. Society can often stigmatize open discussions of prescription medication and mental health. SSRIs are no exception. There are many people who do not know about the benefits and risks of SSRIs, the long-term effects of unmanaged MDD, or possible treatment options. Be willing to be honest with yourself about your comfort level discussing topics and providing education on SSRIs and MDD.
- Communicate the care plan to other staff involved for continuity of care. For several patients, MDD management often involves a team of mental health professionals, nurses, primary care specialists, pharmacies, and more. Ensure that patients' records are up to date for ease in record sharing and continuity of care.
- Stay up to date on continuing education related to SSRIs and mental health conditions, as evidence-based information is always evolving and changing. You can then present your new findings to other health care professionals and educate your patients with the latest information. You can learn more about the latest research on SSRIs and mental health by following updates from evidence-based organizations.
Identifying Major Depressive Disorder
How can nurses identify if someone has major depressive disorder?
Unfortunately, it is not possible to look at someone with the naked eye and determine if they have MDD. APRNs can identify and diagnose if someone has MDD by taking a complete health history, listening to patient's concerns, having patients complete the PHQ-9 questionnaire and communicating any concerns to other health care professionals (9).
Patient Education
What should patients know about SSRIs?
Patients should know that anyone has the possibility of experiencing side effects of SSRIs, just like any other medication. Patients should be aware that if they notice any changes in their mood, experience any sharp headaches, or feel like something is a concern, they should seek medical care. Due to social stigma associated with mental health and SSRI use, people may be hesitant to seek medical care for fear of being dismissed by health care professionals (1, 6). In addition, side effects (that interfere with the quality of life) are often normalized (1, 6). However, as more research and social movements discuss mental health and SSRI use more openly, there is more space and awareness for SSRI use and mental health.
Nurses should also teach patients to advocate for their own health in order to avoid progression of MDD and possible unwanted side effects of SSRIs. Here are important tips for patient education in the inpatient or outpatient setting.
- Tell the health care provider of any existing medical conditions or concerns (need to identify risk factors)
- Tell the health care provider of any existing lifestyle concerns, such as alcohol use, other drug use, sleeping habits, diet, menstrual cycle changes (need to identify lifestyle factors that can influence SSRI use and MDD)
- Tell the health care provider if you notice any changes in your mood, behavior, sleep, sexual health (including vaginal dryness or erectile dysfunction), or weight (possible changes that could hint at more chronic side effects of SSRIs)
- Tell the health care provider if you have any changes in urinary or bowel habits, such as increased or decreased urination or defecation (potential risk for SSRI malabsorption or possible unwanted side effects)
- Tell the nurse of health care provider if you experience any pain that increasingly becomes more severe or interferes with your quality of life
- Keep track of your mental health, medication use, and health concerns via an app, diary, or journal (self-monitoring for any changes)
- Tell the health care provider right away if you are having thoughts of hurting yourself or others (possible increased risk of suicidality is a possible side effect for SSRI use)
- Take all prescribed medications as indicated and ask questions about medications and possible other treatment options, such as non-pharmacological options or surgeries
- Tell the health care provider if you notice any changes while taking medications or on other treatments to manage your MDD (potential worsening or improving mental health situation)
Self Quiz
Ask yourself...
- What are some possible ways you can obtain a detailed, patient centric health history?
- What are some possible ways APRNs can educate patients on SSRIs and major depressive disorder?
Research Findings
What Research on SSRIs exists presently?
There is extensive publicly available literature on SSRIs via the National Institutes of Health and other evidence-based journals.
What are some ways for people who take SSRIs to become a part of research?
If a patient is interested in participating in clinical trial research, they can seek more information on clinical trials from local universities and health care organizations.
Self Quiz
Ask yourself...
- What are some problems that can occur if SSRIs are not managing major depressive disorder symptoms adequately?
- What are some reasons someone might want to enroll in SSRI clinical trials?
Case Study
Case Study Part 1
Susan is a 22-year-old Black woman working as a teacher. She arrives for her annual exam at the local health department next to her place of work. She reports nothing new in her health, but she says she's been feeling more tired over the past few months. Susan reports having some trouble sleeping and trouble eating but doesn't feel too stressed overall. She heard one of her friends talking about SSRIs and wants to try them, but she's never taken prescription medications long-term before. She also thinks she might have some depression because she looked at some forums online and resonated with a lot of people's comments.
Self Quiz
Ask yourself...
- What are some specific questions you'd want to ask about her mental health?
- What are some health history questions you'd want to highlight?
- What lab work would you suggest performing?
Case Study Part 2
Susan agrees to complete bloodwork later this week and thinks she might have a family history of depression. She said that no one in her family talks about mental health, but she heard about depression from her friends recently and family a long time ago. She's back in the office a few weeks later, and her labs are within normal limits. Susan states she's still feeling fatigued and feeling a bit more hopeless these days. She denies thinking about hurting herself or others.
Self Quiz
Ask yourself...
- How would you discuss Susan's mental health concerns?
- How would you explain to Susan the influence of lifestyle, such as sleep, diet, and environment, on mood?
Case Study Part 3
Susan completed the PHQ-9 questionnaire and had a high score. After discussing her responses with her, you diagnose her with MDD. Susan admits that she is open to trying SSRIs. She is also open to seeing a therapist, as she states that she's never been to therapy. She would like resources on any therapy services, medication options, and non-pharmacological options to help her manage her condition.
Self Quiz
Ask yourself...
- Knowing Susan's concerns, what are some possible non-pharmacological management options for her MDD?
- What are some major SSRI side effects to educate Susan on?
Conclusion
Major depressive disorder is a complex chronic health condition that affects many people nationwide. SSRIs are often a first-line pharmacological option for MDD management. However, clinical presentation and symptom management with SSRIs can vary widely. While some patients would prefer a low-dose SSRI, others will need a higher dose and possible extra medication management. Education and awareness of SSRIs can influence the lives of many people.
References + Disclaimer
- Chu A. and Wadhwa R. Selective Serotonin Reuptake Inhibitors. (2023). In: StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK55440
- Woodall, A. and Walker, L. (2022). A guide to prescribing antidepressants in primary care. Prescriber, 33: 11-18. https://doi.org/10.1002/psb.2006
- Bains N. and Abdijadid S. Major Depressive Disorder. (2023). In: StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK559078/
- Rohatgi, K. W., Humble, S., McQueen, A., Hunleth, J. M., Chang, S. H., Herrick, C. J., & James, A. S. (2021). Medication Adherence and Characteristics of Patients Who Spend Less on Basic Needs to Afford Medications. Journal of the American Board of Family Medicine: JABFM, 34(3), 561–570. https://doi.org/10.3122/jabfm.2021.03.200361
- Lam, M. K., Lam, L. T., Butler-Henderson, K., King, J., Clark, T., Slocombe, P., Dimarco, K., & Cockshaw, W. (2022). Prescribing behavior of antidepressants for depressive disorders: A systematic review. Frontiers in Psychiatry, 13, 918040. https://doi.org/10.3389/fpsyt.2022.918040
- Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: a systemic umbrella review of the evidence. Molecular Psychiatry, 28, 3243-3256. https://doi.org/10.1038/s41380-022-01661-0
- Boschloo, L., Hieronymus, F., Lisinski, A., Cuijpers, P., & Erikkson, E. (2023). The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective. Translational Psychiatry, 13, 2-25. https://doi.org/10.1038/s41398-022-02285-2
- Hirsch, M., Birnbaum, R. J. (2023). Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. UptoDate. Retrieved 12 Jan 2024 from https://www.uptodate.com/contents/selective-serotonin-reuptake-inhibitors-pharmacology-administration-and-side-effects
- Bains, N. & Abdijadid, S. (2023). Major Depressive Disorder. In: StatPearls: Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK559078/
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Use of Course Content. The courses provided by NCC are based on industry knowledge and input from professional nurses, experts, practitioners, and other individuals and institutions. The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NCC. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare. The information provided in this course is general in nature and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals. Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication. Knowledge, procedures or insight gained from the Student in the course of taking classes provided by NCC may be used at the Student’s discretion during their course of work or otherwise in a professional capacity. The Student understands and agrees that NCC shall not be held liable for any acts, errors, advice or omissions provided by the Student based on knowledge or advice acquired by NCC. The Student is solely responsible for his/her own actions, even if information and/or education was acquired from a NCC course pertaining to that action or actions. By clicking “complete” you are agreeing to these terms of use.
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