Beyond the Symptoms: A Primary Care Approach to Depression Management
In the vast mosaic of primary care, depression often remains in the shadows, embedded in patient care but easily overlooked. Left unrecognized, the prognosis worsens and complicates the management of other chronic conditions. However, with timely identification and effective treatment, the course of depression can be altered significantly.
Primary care providers (PCPs) often are at the forefront of this challenge, tasked with the critical role of recognizing, managing, and even preventing this multifaceted disorder.1 A comprehensive understanding of this condition, coupled with effective treatment strategies, empowers the PCP to mitigate the potentially debilitating effects of this condition.
Although this paper focuses primarily on major depressive disorder (MDD), it is important to recognize that there are other types of depressive disorders, each with unique but overlapping diagnostic criteria and treatment. These include:
- persistent depressive disorder, formerly known as dysthymia;
- disruptive mood dysregulation disorder;
- premenstrual dysphoric disorder;
- substance-/medication-induced depressive disorder;
- depressive disorder caused by another medical condition;
- unspecified depressive disorder.
These disorders all are defined in the latest edition of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR).2
This update goes beyond foundational knowledge, emphasizing clinical advancements in depression care. The case study presented reflects common, yet challenging, scenarios encountered in primary care. By focusing on a real-life example, this approach aims to provide the PCP with clinically relevant approaches, actionable insights, and nuanced medical information for the diagnosis and management of depression over time.
Treatment of MDD varies based on many factors, with the stage or phase of the disorder being particularly significant. The three phases of treatment can be understood as:
- Acute phase: Lasting up to approximately four months, this phase involves treating symptoms until resolution;3,4
- Continuation phase: Spanning up to nine months, the focus here is on prevention of relapse;3,4
- Maintenance phase: Following symptom remission, this phase aims to prevent a new episode of depression.3,4
The chosen case study illustrates the evolving understanding of depression management, offering strategies for recognizing depression, managing the acute phase of the disorder, providing care during the continuation phase, and monitoring for recurrence during the maintenance stage. Finally, the thorny issue of deprescribing is discussed.
Recognition of Depression: Meet A.W.
A.W., a 40-year-old mother of two who co-owns retail stores with her husband, is known to the provider for treatment of seasonal allergies and minor illnesses over the past five years. Today she presents for a check-up, stating, “I feel like I am not myself — I’m not sleeping well, I feel exhausted, and I make mistakes at work. I fear making decisions. My husband says I’m losing my patience with the kids — and I think he is right.” A physical examination reveals no overt issues.
Recognizing depression in a primary care setting is challenging since patients rarely present with a chief complaint of depressed mood. Instead, they often report vague symptoms such as decreased energy, insomnia, or somatic complaints, such as headache. Depression screening tools, such as the Patient Health Questionnaire (PHQ), are invaluable for identifying depression during routine visits. National guidelines recommend all adult patients be screened for depression annually.1,3-5
The PHQ-2, a two-item questionnaire, often is used for initial screening. If positive, the more comprehensive PHQ-9 is administered. Both questionnaires are straightforward, with responses ranging from “not at all” to “almost every day.” Scores help determine the likelihood of depression, with a PHQ-9 (a nine-item questionnaire) score between 5 and 27 suggesting a likelihood of mild to severe depression. Question number 9 on the PHQ-9 asks about suicidal thoughts; a patient who endorses any degree of a positive response to this question may need referral to mental health treatment. However, all screens are followed by a diagnostic interview before confirming a diagnosis.5,6
When A.W. completes the PHQ-2, she checks off “more than half the days” regarding question 1 (“Little interest or pleasure in doing things”) and “several days” in response to question 2 (“Feeling down, depressed, or helpless”), totaling to a score of 3 — the threshold for depression on this screen.5,6
The results of the screen serve as a natural transition to discuss depression and risk factors during the clinical interview.
Suspecting depression, the provider says, “I’m glad you mentioned this. The mistakes or concentration problems, sleep difficulty, and irritability you’re experiencing could be related to depression.”
“Depression!” A.W. responds, surprised. “I thought you were going to tell me I have a brain tumor.”
“It’s understandable to be worried when you notice changes in how you are functioning,” the provider notes. “Let’s do some tests to rule out medical causes, such as anemia and thyroid issues, check your pregnancy status, and I’d also like for you to complete a slightly longer depression screen today to help us get a clearer picture.”
“Don’t you have a lab test for depression?” asks A.W.
Current research is looking closely at serum biomarkers indicating depression, as well as neuroimaging studies. Although promising, the clinical application of these is not yet established.7
A diagnosis of major depressive disorder (see Table 1) still relies on subjective criteria established by the DSM-5-TR.2-4
Table 1. Criteria for MDD from the DSM-5-TR1-4 |
|
Diagnostic Criteria |
Caveats |
Depressed mood most of every day (in youth, this may present as irritability) |
Five or more of these symptoms for more than two weeks |
Marked decrease in interest in pleasure nearly every day |
Symptoms include (one or more) depressed mood, loss of interest, or loss of energy |
Significant weight loss, weight gain, or appetite loss |
Symptoms cause functional impairment |
Insomnia or hypersomnia nearly every day |
Symptoms cannot be attributed to the physiologic effect of a substance or another medical condition |
Fatigue or loss of energy nearly every day |
|
Feelings of worthlessness or excessive guilt nearly every day |
|
Decreased ability to think or concentrate or indecisiveness nearly every day |
May be self-described or noticed by others |
Recurrent thoughts of death or suicide |
Increased risk of suicide: evaluate carefully and consider referral |
MDD: major depressive disorder; DSM-5-TR: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision |
|
The diagnosis is characterized by the presence of five or more depressive symptoms, including either a depressed mood, loss of interest, or loss of energy, persisting for at least two weeks. These symptoms must lead to significant functional impairment and cannot be attributed to another mental disorder, substance use, or medical condition. A history of a hypomanic or manic episode would suggest a bipolar spectrum disorder.2
A.W.’s PHQ-9 score is 13, suggesting moderate major depressive disorder. Significantly, the provider notes A.W. checks off “very difficult” in response to item 10 (“How difficult have these problems made it for you … ?”) Rather than focusing on the score, the provider uses the instrument to guide the clinical interview.1,4-6,8,9
“I see you have been feeling down about yourself,” notes the provider. “Are you comfortable saying more about that feeling?”
A.W. hesitates, “I think it comes from the mistakes at work — I feel like a failure. That screen asked about suicide. I would never do that … but sometimes I think my family would be better off if I disappeared.”
The provider rechecks item 9 (the question on the PHQ-9 asking about suicide), remembering that a positive answer on this item is associated with a significant risk of suicide over the next several months and says, “I was glad to see you didn’t indicate suicidal thoughts on the screen, but thinking your family would be better off without you is a tough load to carry. When do you think you started feeling badly?”4,9
A.W. looks away. “Probably after I came back to full-time work about six months ago. When COVID hit, my mother-in-law got sick and moved in with us. I stayed home while my husband manned the stores, until his mother died. Now the kids are older, and I have more time to work, but I feel like I do everything wrong. My husband and I, we don’t seem to remember how to work together. We argue more than anything.”
The provider reflects, “I guess it’s hard to know if the depression started first and made working together harder, or if the depression symptoms came later.”
A.W. sighs, looking relieved, “I feel better just talking about it. I feel so guilty wishing I didn’t have to work with my husband. I love him — I just don’t know if I can keep working with him.”
The provider states, “Voicing a problem is a good first step in figuring out how to solve it.”
“Yes,” replies A.W. “I should talk with my husband, but I don’t think that is the whole problem. My mom told me she had depression after I was born, and she takes medicine even now, but I don’t know much about that. Could this be genetic?”
“Certainly,” replies the provider. “What do you know about others in your family with depression or mental health issues?”
“I don’t think the older people in my family would discuss that,” replies A.W. “I guess we are more bent toward keeping a stiff upper lip.”
“I appreciate your openness today,” says the provider. “Let’s talk about next steps.”
Patients with MDD carry an eight-fold higher risk of suicide compared to those without the disorder. A positive response on question 9 on the PHQ-9 signals an increased likelihood of suicide within the following 90 days. Additionally, specific suicide screening tools (such as the Columbia Suicide Severity Rating Scale) can be used to better understand the risk of suicide.1,4,6,9,10
As with all screens, a diagnostic interview following the screen is essential to place responses into context. While patients may be hesitant to directly bring up thoughts about suicide, open-ended, nonjudgmental questions about suicidal thoughts, plans, or intentions may open the discussion.1,4,6,10
When a patient is at high risk for suicide and specialty consultation is not immediately available, the PCP can work with the patient and caregiver/family to develop a safety plan. This plan should include removing access to the most lethal means of suicide, such as firearms, and securing medications.1,4,10
Clinical Pearls
- Be aware of the heterogenous presentation of depression, including vague and nonspecific symptoms.1,3,4
- The DSM diagnostic criteria for depression must include depressed mood, loss of interest, or loss of energy persisting for at least two weeks and leading to functional impairment.1-4
- Pay particular attention to item 9 (regarding suicidal thoughts) on the PHQ-9 and item 10, indicating the level of impairment. When there are positives on item 9 and/or a high level of impairment, consider referral or mental health collaboration, with urgency determined by diagnostic interview.1,4-6,9
- Do not depend on a screen for a diagnosis — use screen responses to conduct an empathic interview with open-ended questions to fully understand patient strengths, degree of impairment, and extent of distress.1,4-6
Current guidelines from the American College of Physicians for patients in the acute or actively symptomatic phase of MDD recommend monotherapy with either a second-generation antidepressant or cognitive behavioral therapy or a combination of the two.9 There is little evidence of superiority of one of these options, but there is a difference in side effects, leading to a suggestion that patients with a mild form of MDD start with cognitive behavioral therapy or a similar, structured talk therapy (see Table 2). There is some evidence that a combination of these two approaches is most effective at relieving symptoms of depression.4,10,11
Table 2. Psychotherapies Recommended for Treatment of MDD3,4,10 |
||
Type of Therapy |
Brief Description |
Caveats |
Cognitive behavioral therapy (CBT) |
Individual or group; focus on challenging negative thoughts |
Often effective for anxiety symptoms as well |
Behavioral activation |
Individual or group; focus on activity |
Often effective for anxiety symptoms as well |
Problem-solving therapy |
Individual or group; focus on identifying and managing problems and stressors |
May be tailored to specific ages |
Interpersonal therapy |
Individual; focus on improving relationships related to current depressive episode |
Often used during life transitions (divorce, grief) |
Psychodynamic therapy |
Individual; focus on unconscious motivations driving behaviors |
Often effective for anxiety as well |
Mindfulness-based therapy |
Typically group-based; focus on introspection and self-awareness to address unwanted responses |
Often used when other modalities are not successful at eliciting change |
MDD: major depressive disorder |
||
“There are several ways to treat depression,” says the provider. “Cognitive behavioral therapy (CBT) is a talk therapy that — ”
“No,” A.W. says abruptly. “I don’t want to go to a therapist — I don’t have time, and I think it would make me feel even worse — like I’m weak.”
“OK,” replies the provider, “just keep in mind it is a medical treatment that can be very effective for depression. We may want to revisit this idea down the road. But there also are medicines to try, and current research shows using either one of these approaches is the best bet. Using an antidepressant medicine, we can try to target your treatment by deciding which symptom to address first.”
Enlisting a patient to select a target symptom helps focus treatment, individualizes the plan, and engages the patient in the overall treatment.3,4,10,11
“I just want to feel more like myself,” replies A.W. “I want to stop second-guessing and get my confidence back. But I guess I should mention that I don’t want a medicine that can be addictive. In my younger days, I drank too much. And I think that could be a problem for me, so I stay away from alcohol and drugs now.”
“Thanks for sharing that,” replies the provider. “None of the antidepressant medications are addictive, like drugs. They do need to be taken regularly to avoid discontinuation — a feeling of significant discomfort if the medicine is stopped abruptly instead of tapered.”
“So, you think a pill can help me feel more confident?” asks A.W.
“I think an antidepressant will slowly help your sleep and that helpless feeling you noted. That can help with confidence. A little more than one-third of people taking antidepressants for the first time notice symptoms beginning to lift after several weeks.”1,3,4
“One-third. Not the best odds,” muses A.W.
“True,” replies the provider. “But that includes people with much more severe symptoms who may need much more extensive treatment. But that’s one reason why I want to see you back in the office soon — if you don’t feel improvement as we raise the dose slowly or within the first month, then we can look at other options.”
Up to 70% of patients will not achieve remission or symptom resolution with a first trial of an antidepressant or with the initial course of a structured talk therapy such as CBT. The more severe the initial symptoms, the less likely remission is to be achieved.4,10,12
General guidelines are to start at about one-half of a usual dose and advance to the desired lowest dose within therapeutic range over the first two weeks. Connect with the patient at least every four to six weeks until symptoms are resolved.1,3,4,10
Expect to start seeing some improvement in symptoms after week 2 or week 3. If there is no improvement by week 3 or week 4, consider optimizing the dose and/or augmenting it with psychotherapy or another antidepressant. If the agent is at the optimal dose, consider a switch to another antidepressant.4,10,12
Be aware that the differential diagnosis of MDD includes other types of depression and mood disorders, and that comorbid disorders of mental health may affect treatment direction and plan. These include:
- Bipolar disorder: About 7% of patients presenting with depression to their PCP may have an underlying bipolar disorder and require treatment with mood stabilizers. Screens for this condition are not clinically useful. Factors that raise the likelihood of this disorder include family history of bipolar and/or completed suicide, early onset of depression, highly recurrent depressive episodes, and adverse response to antidepressants.4,13
- Anxiety is a common comorbid disorder that may complicate treatment of depression. Screening for symptoms of anxiety with a scale such as the Generalized Anxiety Disorder-7 (GAD-7) and/or conducting a sensitive clinical interview is recommended. If anxiety is present, be cautious with the use of more activating antidepressants and slow down the tapering schedule.4,10,14
- Substance use disorder is highly prevalent with MDD. Patients with these two disorders tend to have more depressive symptoms and a poorer prognosis than those with only MDD. Interventions for the substance use are essential to achieve symptom remission for MDD.3,4,10,15
Commonly used second-generation antidepressants are listed in Tables 3-5. The choice of an agent often comes down to patient preference, side effect profile, target symptoms, and affordability. Generic formulations, available for most of these agents, should be used when possible.4,10,12
Table 3. Common Second-Generation Antidepressants: SSRIs, Dose Range, and Some Side Effects4,10,12 |
|||||
Citalopram |
Escitalopram |
Fluoxetine |
Paroxetine |
Sertraline |
|
Dose Range |
20 mg to 40 mg |
10 mg to 20 mg |
20 mg to 80 mg |
20 mg to 50 mg |
50 mg to 200 mg |
Side Effect |
|||||
Agitation |
X |
||||
Anxiety |
X |
X |
|||
Cardiac (QT prolongation) |
Dose-dependent |
Dose-dependent |
Not clinically significant |
Not clinically significant |
Not clinically significant |
Dizziness |
X |
X |
X |
X |
X |
GI discomfort |
X |
X |
X |
X |
X |
Headache |
X |
X |
X |
X |
|
Insomnia |
X |
X |
X |
X |
X |
Sedation |
X |
X |
X |
X |
X |
Weight gain |
X |
X |
X |
X |
X |
Sexual dysfunction |
X |
X |
X |
X |
X |
Generic? |
Yes |
Yes |
Yes |
Yes |
Yes |
SSRI: selective serotonin reuptake inhibitor; GI: gastrointestinal |
|||||
Table 4. Common Second-Generation Antidepressants: SNRIs, Dose Range, and Some Side Effects4,10,12 |
||||
Desvenlafaxine |
Duloxetine |
Levomilnacipran |
Venlafaxine |
|
Dose Range |
50 mg |
20 mg to 60 mg |
40 mg to 120 mg |
75 mg to 225 mg |
Side Effect |
||||
Agitation |
X |
X |
||
Anxiety |
X |
X |
X |
|
Dizziness |
X |
X |
X |
|
GI discomfort |
X |
X |
X |
|
Headache |
X |
|||
Orthostatic hypotension |
X |
X |
||
Insomnia |
X |
X |
||
Sedation |
X |
X |
||
Weight gain |
X |
X |
X |
|
Sexual dysfunction |
X |
X |
X |
|
Generic? |
Yes |
Yes |
No |
Yes |
SNRI: selective norepinephrine reuptake inhibitor; GI: gastrointestinal |
||||
Table 5. Common Second-Generation Antidepressants: Others, Dose Range, and Some Side Effects4,10,12 |
|||||
Bupropion |
Mirtazapine |
Trazodone |
Vilazodone |
Vortioxetine |
|
Dose Range |
150 mg to 450 mg |
15 mg to 45 mg |
50 mg to 400 mg |
20 mg to 40 mg |
5 mg to 20 mg |
Side Effect |
|||||
Agitation |
X |
||||
Anxiety |
X |
||||
Chest pain |
X |
X |
|||
Dizziness |
X |
X |
X |
||
GI discomfort |
X |
X |
X |
X |
X |
Headache |
X |
X |
|||
Orthostatic hypotension |
X |
||||
Insomnia |
X |
X |
|||
Sedation |
X |
X |
X |
||
Weight change |
X (weight loss) |
X |
X |
X |
X |
Sexual dysfunction |
X |
X |
X |
||
Generic? |
Yes |
Yes |
Yes |
No |
No |
GI: gastrointestinal |
|||||
After a discussion of side effects and cost factors, A.W. decides to try sertraline.
“The only side effect I really worry about is the sexual one,” she notes. “If that hits me, I probably will go off it.”
“Let’s make sure to work together,” replies the provider. “Start just on 25 mg once a day. If you tolerate it well, without stomach upset or headache, for example, go to 50 mg in one week and let me see you back in two weeks. Each time you come in, we can look at a new screen and discuss any changes. Make sure to tell me if you are noticing decreased sex drive, and especially if you notice any suicidal or worrisome thoughts about death. Most people will stay on the antidepressant for nine to 12 months after they start feeling better, so we want to make sure you are comfortable on the medication.”
Boxed Warnings
The U.S. Food and Drug Administration (FDA) issued a boxed warning in 2005 regarding the potential of increased suicidal thoughts, especially in children, adolescents, and young adults taking any antidepressant. Although there is controversy regarding the validity of the findings and the usefulness of the warning, clinicians should discuss the warning with patients, weigh the risks of medication treatment, and monitor carefully, especially when changing doses.1,4,10
“OK,” replies A.W. “Maybe if we keep the dose down, there will be fewer side effects. What else can I do to make this depression go away?”
“One thing that comes to mind is to talk with your husband, like you mentioned earlier,” replies the provider. “Healthy, open communication may relieve some of the guilt and help you manage the stress you mentioned. Also, consider if there is a way for you to increase exercise, eat as healthy as possible, and try to have a regular sleep routine and schedule. I know it’s a lot, but each of these can help antidepressants work better.”16,17
Clinical Pearls
- Think about the phase of the disorder before initiating treatment.4,10
- Begin monotherapy for the acute phase of MDD, using shared decision-making with the patient regarding choice of therapy or second-generation antidepressant.3,4,9,10
- Enlist the patient in the treatment plan, including the expectations for timing for symptom resolution, the need for close follow-up, and monitoring for side effects and/or emerging suicidal thoughts.3,4,9,10
- Recommend lifestyle interventions, introducing the concept of a holistic approach.3,4,9,10
Acute Phase: Week 2
A.W. returns for a video visit and reports good tolerance of the sertraline (50 mg) with mild nausea initially that resolved and no thoughts of self-harm. The PHQ-9, completed during the check-in for the visit, has dropped by one point to 12. All laboratory tests have come back without any noticeable abnormalities.
“Can we increase the dose a little?” asks A.W. “I think I feel better, but I know I am not yet back to how I used to be. I still wake up early and dread facing the day.”
“That sounds tough. Could you tell me a little more about your sleep pattern? Maybe we can figure something out,” replies the provider.
“I fall asleep around 11 p.m. after the kids are in bed,” says A.W. “But by 4 or 4:30 a.m., I am up — no matter what. I usually start my day then with a pot of coffee, sometimes even more. I used to wake up excited for the day — now I just hope to make it through.”
“That little sleep would make anyone’s day difficult. I’m concerned about increasing the sertraline this early, and it will not necessarily help your sleep right away,” explains the provider. “I remember we spoke a little about exercise last time you were here. Let’s talk about how you are doing with that — it can help with both depression and with sleep.”
Lifestyle medicine refers to an emerging branch of medicine that focuses on comprehensive and intensive changes in lifestyle factors, such as nutrition, exercise, management of stress, and sleep to prevent and manage many non-communicable chronic diseases, including depression.16,17
International guidelines for treatment of depression now point to the importance of such interventions first-line, either as monotherapy or combined with medication, psychotherapy, or both. Studies have pointed to the dual benefits of lifestyle modifications in the treatment of depression — both in symptom reduction and mitigating comorbidities, such as obesity and heart disease.16,17
Key lifestyle interventions in depression include:16-18
- Physical activity: Aerobic and anaerobic exercise have strong evidence supporting their benefits in depression.
- Sleep modification: Techniques to regulate and restore healthy sleep patterns are critical for the prevention and treatment of depression.
- Nutrition/diet: A balanced diet, rich in protein, vitamins, and nutrients, supports overall well-being. The anti-inflammatory diet (similar to the Mediterranean diet) is one of the diets recommended to help with depression.
- Stress management: Mindfulness and other general stress-reduction techniques show potential benefit in alleviating depression.
- Psychosocial: Modifying work hours or environment to alleviate stress and promote regular sleep may have benefits in depression. Social connectedness appears to benefit antidepressive therapies as well.
- Bright light therapy: 10,000 lux for 30 minutes in the morning is first-line treatment for seasonal depression; newer studies show mixed evidence on the usefulness of this intervention in MDD (without a seasonal component).
A.W. looks down. “I really haven’t started anything with exercise. I just don’t have the energy — I used to love to run, but … ”
“I understand. It’s hard to find energy, especially with early wake-ups. But I also hear that exercise has been important to you — you must miss that in your life,” says the provider.
“I really do,” replies A.W., looking up.
“How did you used to motivate yourself to get going? Maybe you could use some of those same techniques now,” the provider says.
A.W. pauses, then says, “I think running with my friend, and sometimes a group, was a factor. I felt like others were depending on me and I didn’t want to let them down.”
“It sounds like relationships were a big part of running for you,” says the provider. “Do you see any advantage to recreating a situation like that?”
“We moved away from my running buddies and then, with COVID, I never found another group. But my husband runs every morning,” A.W. says slowly, “and he always asks me to join him.”
Nodding, the provider notes, “Speaking of your husband, I remember at your last visit you mentioned you wanted to talk with him.”
“Yes,” notes A.W. “I haven’t figured out the right time to talk. You know, maybe if I run with him — or even if I join him at the end of his run, and we walk — that could work. And that would probably get me away from that second pot of coffee. I know that’s not a great habit!”
“I agree,” says the provider. “I gather you are saying that walking with your husband could help you both physically and emotionally.”
“I think so,” says A.W. “I will ask my husband about starting tomorrow morning. I know he is eager to help me. I guess it doesn’t have to be every day — starting with three days a week is doable.”
Counseling patients to change behavior is different from motivating patients to change behavior. In this example, rather than counselling the patient or directly advising her about what she should do, the provider provides some education and then, using techniques borrowed from motivational interviewing (MI), encourages the patient to give voice to her own reasons to adopt healthier behavior and set goals.19,20
MI is a technique developed and pioneered by psychologists William Miller and Stephan Rollnick in the 1980s. The foundation of MI rests on understanding that, when discussing behavioral change, our role as a provider is not directive — we are not able to “order” change. In fact, the responsibility for change and to summon the motivation for change lies within the patient.19,20
This concept does not relegate the provider to the sidelines. Rather, the provider takes the role of a trusted partner or guide, developing empathy and assuring patient autonomy in decision-making while encouraging that the patient voices internal motivations and a desire for change. The OARS model (see Table 6), developed by the founders of MI, gives some practical suggestions to assist with this process. Many of these are incorporated into the patient interview with A.W.19,20
Table 6. The OARS Model |
O: Open-ended questions. These are questions that are not able to be answered with a single yes/no response. Remember the goal is not to find a solution for the patient, but to develop empathy and understanding so the patient feels comfortable discussing the health dilemma and contemplating potential solutions. A: Affirmations. Find and acknowledge true internal strengths of the patient. R: Reflective listening. Listen and voice back to the patient the concept, idea, or theme the patient is attempting to convey. S: Summarizing. Summarizing statements can be used midway and toward the conclusion of the interview. |
The provider and A.W. agree to keep the sertraline at 50 mg daily while A.W. adopts more physical activity and addresses her concerns about working with her husband. The two decide to meet in another two to three weeks to continue to monitor for side effects and watch for improvement in symptoms.
Be aware that higher doses of an antidepressant are not always correlated with a better response.1,4,10
Acute Phase: Weeks 4-6
A.W. returns for her second follow-up visit. She continues taking 50 mg sertraline daily. Her PHQ-9 score dropped to 11. She remains without suicidal thoughts and indicates that sleep, concentration problems, and poor energy still are her most impairing symptoms.
A.W. asks, “OK, now should we increase the sertraline? I am very careful to take it every day, but I read that I am on a low dose.”
The provider nods. “Sure, you have been taking it long enough to justify an increase to 100 mg since your symptoms have improved only marginally. Your PHQ indicates sleep, concentration, and energy still are major problems. Can you update me about these?”
A.W. sighs. “I did try to start walking with my husband. And that helped me sleep for a few days — I felt more rested and slept longer. Maybe my concentration was better. Then my husband went on a business trip, and it all fell apart. I just haven’t started back. I really don’t have the energy.”
“It is hard to start new routines,” notes the provider.
“I also read a little about therapy,” begins A.W., “and that sometimes therapy and medicine together can help depression even more than using just one of these. And I read that therapy can help with sleep. And you had mentioned therapy at first, also.”
“Good idea,” says the provider. “One option is to increase the sertraline and make an appointment to start some cognitive behavioral therapy targeting sleep. We can give you a referral to an in-person or an online group. It may take a while to get an appointment.”
“Online,” remarks A.W. “That sounds OK. I guess while I wait, we can see if the higher dose of sertraline helps with sleep, concentration, and energy.”
“That sounds like a good plan,” remarks the provider. “I also recall you saying at your first appointment there were times when you just ‘wanted to disappear.’ I am wondering if those thoughts remain.”
“Actually,” notes A.W. slowly, “I haven’t thought that way in a while. I see how much my family needs me, even though it didn’t seem that way before.”
At each follow-up visit, it remains important to continue to monitor for any signs of suicidal or self-harming behaviors or thoughts.1,4,10,12
When first-line intervention does not appear to have effectively addressed symptoms of depression, second-line strategies include:1,4,10,11
- optimizing the dose of antidepressant and assuring compliance;
- augmenting with CBT;
- switching to a different second-generation antidepressant of the same or different class if the dose of the first agent is optimized;
- augmenting the initial antidepressant with a second pharmacologic treatment, such as mirtazapine for sleep, bupropion for concentration, or a non-antidepressant (such as buspirone for anxiety or a low dose of an atypical antipsychotic);
- considering referral to a mental health specialist if second-line treatment fails to improve symptoms;
- looking for comorbidities and considering other diagnoses.
A note about third-line treatments (typically after referral to a mental health specialist):
- Electroconvulsive therapy (ECT): Widely considered one of the most effective and safest interventions for certain forms of depression, stigma and lack of widespread availability limit use of this intervention.3,4,10
- Noninvasive brain stimulation (includes transcranial magnetic stimulation and transcranial direct stimulation): Potential for intervention in a number of psychiatric disorders, including depression.3,4,21
- Ketamine: This N-methyl D-aspartate receptor antagonist, developed in the 1960s and used medically as an anesthetic agent, is being investigated for use as an antidepressant. Although potential for this agent is clear, safety and long-term efficacy are not well established. In 2019, the FDA approved esketamine nasal spray, with rigid guidelines for supervised use only.22,23
Acute Phase: Weeks 8-12
A.W. returns for her third follow-up visit. Her PHQ score has dropped to 7, suggesting a still clinically significant, but significantly improved, level of depression.
Notably, her response to item 10 (regarding functional impairment) is decreased from “very difficult” to “somewhat difficult.”
“I just started the CBT group,” begins A.W. “Did you know they give homework? Actually, it has been helpful. Or maybe the higher dose of sertraline helped too — but either way I am sleeping later most days.”
She has not had suicidal thoughts and reports that she has not had thoughts about “just disappearing.”
“How long do I need to stay on the medication?” asks A.W. “I know people who have been taking antidepressants for years and I don’t want that for me.”
“We would be looking at nine to 12 months of medication at least after you are back to your baseline functioning,” notes the provider. “After that time, we can discuss backing off the medicine and make sure the symptoms don’t come back as you taper. It can be tricky to stop this medicine, so it’s best if we work together during that stage.”1,3,4,10
“I don’t think I’m quite back to baseline,” replies A.W. “Do you think we should increase the sertraline again? The increase really seemed to help last time.”
“Possibly,” replies the provider. “It is probably hard to know what has been the most effective for you — raising the dose, staying on the medication longer, the group, or a combination of any of these.”
“True,” says A.W. “Also, I am getting some exercise. I’m walking with my husband occasionally, but, even better, I joined a walking group at work — that has made me feel better about fitting in at work.”
“OK,” replies the provider. “That is good to hear. Did you ever talk with your husband about working together?”
“Oh yes,” replies A.W. “I don’t know why I was so hesitant. Probably I was afraid to hear what he was thinking. Maybe I am doing better … let’s wait for a couple more weeks of CBT to decide about increasing the medicine.”
Clinical Pearls
- Connect every four to six weeks during the acute phase of treatment for depression to monitor for side effects, track the degree of suicidal ideation, and assess the efficacy of intervention.1,3,4,10
- Consider second-line strategies if there is no clear response to the initial intervention despite optimal dose and duration of treatment.1,3,4,10
- Individualize treatment according to patient preferences, attitudes, and needs.1,3,4,10
- Use MI techniques when discussing recommended lifestyle interventions.19, 20
Acute Phase: Weeks 16-28
A.W. calls the office for a refill. She states she is doing well, with stable symptoms and no recurrence of sleep or concentration problems or any new symptoms.
Continuation Phase: Weeks 34-40
A.W. comes in for a follow-up. Her PHQ-9 score has dropped to 5. Her response to item 10 is that the symptoms she notices are “not difficult at all.”
“I finished the CBT group and would recommend it to anyone with sleep problems,” says A.W. “It was once per week for six weeks, but the time was well worth it. I learned techniques that work to get myself back to sleep, I started journaling, and I figured out how to stop some self-defeating thoughts.”
“Good for you,” says the provider. “I know you had some healthy skepticism at first.”
A.W. smiles. “Yes, and I should mention that I was feeling so well that I decided to stop the sertraline. But that didn’t last long. I felt dizzy and thought I was going to throw up. The worst part was I had these electric shock-like feelings — it was awful. I suppose I really need the medicine.”
“I am glad you restarted it,” says the provider. “Remember, you should continue the medication for about nine months after your symptoms are gone. But it is hard to know if what you experienced was a return of your depression or a discontinuation of symptoms because of suddenly stopping the medication.”24,25
Discontinuation symptoms when stopping antidepressants often are non-specific, uncomfortable, and distressing. The most frequent symptoms include dizziness, nausea, insomnia, and irritability, but up to 40 different symptoms have been documented.
A large meta-analysis in 2021 found that approximately 15% of all patients treated with antidepressants will experience discontinuation symptoms and that the likelihood of this happening is higher with the following antidepressants: venlafaxine, desvenlafaxine, and paroxetine.
Conversely, fluoxetine and sertraline carry the lowest risk of discontinuation symptoms.26
About one in 35 patients are expected to have relatively severe and incapacitating discontinuation symptoms. For this reason, tapering antidepressants with self-monitoring and provider oversight is recommended.24-26
“When should I come back?” asks A.W. “I am feeling healthy and have energy, and I’m OK staying on the medicine now.”
“How are you doing with exercise?” asks the provider.
“Excellent,” replies A.W. “I still walk at work with a small group and I run with my husband and kids on the weekend. It’s fun — and good for all of us.”
The provider smiles. “We can wait about three to four months for you to check back in. What do you think about using your journal to monitor your overall progress? If you find sleep is starting to deteriorate or any other symptoms beginning to emerge, come in sooner.”
Clinical Pearls
- Monitor for symptoms of relapse during the continuation phase and engage the patient in self-monitoring techniques.1,3,4
- Check for medication compliance.1,3,4
- If a relapse occurs, consider increasing the dosage of medication and/or therapy and/or lifestyle interventions until the symptoms remit.1,3,4,10
- Continue to check for comorbidities and diagnostic accuracy during the continuation phase.1,3,4,10
Maintenance Phase and When to Deprescribe
A year and a half later, A.W., now 42 years of age and recently divorced, presents for a refill of 100 mg sertraline, saying, “Sorry for all the cancellations — it has been hard to find the time to make appointments. I know you said I should be able to taper off the sertraline about nine months after my symptoms improved, but it has been a very difficult year.” Her PHQ-9 score has risen to 9, along with her response to item 10, reflecting “somewhat difficult” functioning. She does not endorse any thoughts of self-harm or suicide.
Antidepressant therapy should be maintained after symptoms remit and the patient returns to baseline functioning. Although treatment guidelines vary regarding the optimal duration to reduce the risk of relapse, most agree that the highest risk period is within the first six months post-remission and that treatment should continue throughout this time.24-27
Supporting this approach, a recent meta-analysis showed a 40% relapse rate when antidepressants were discontinued immediately following remission, compared to a 20% relapse rate when medication was continued for at least six months.23 Continuing treatment for a full year further reduces relapse risk, although less dramatically. Patients at high risk for relapse because of factors such as medical comorbidities, a history of recurrent depressive episodes, or a strong family history of depression, should be monitored on antidepressants for two years post-remission to minimize relapse risk.24-28
“Divorce is a major stress,” responds the provider. “How do you think it has affected you?”
A.W. tears up. “When I first found out about my husband, I did have that feeling again — wanting to disappear. I started drinking — a lot — for the first time in years.” Looking more composed, she continues. “I reached out to my therapist from the online group, and he connected me with a local therapist. I think I’m OK. My sleep is pretty good. I can see some positives and I’m committed to staying sober — I haven’t had a drink in 24 days. I don’t think I want to increase the sertraline, but I don’t want to go off it.”
The chronic use of antidepressants raises important considerations. Current guidelines recommend reserving long-term antidepressant treatment for individuals with severe, recurrent depression with significantly impairing symptoms, such as suicide attempts.29,30
Interestingly, several studies suggest that the rise in antidepressant prescribing is more attributable to long-term use than to an increase in a new depression diagnosis. This trend suggests that tapering patients off these medications is challenging for providers.29,30 However, deprescribing guidelines remain limited to nonexistent. In a literature review, Romagnoli et al concluded “… there is not yet a clear and sufficient body of evidence to fully support antidepressant deprescription interventions,” echoing the findings of a 2021 Cochrane review on the topic.25,28
One of the challenges of deprescribing antidepressants is distinguishing withdrawal or discontinuation symptoms from re-emergence of underlying depression.28-30
Although generally well-tolerated, antidepressants can have concerning side effects, including weight gain, upper gastrointestinal bleeds, sexual dysfunction, emotional numbing, and the risk of falls and fractures, particularly in older adults.32,33 Most recommendations advocate for an individualized approach to tapering (starting no earlier than six months after remission). For those with higher risk factors of relapse, a full two years of maintenance therapy may be warranted. Tapering should be gradual, allowing sufficient time to differentiate between withdrawal effects and a new episode of depression, underscoring the need for close provider monitoring during this time.1,4,10,32-34
The provider and A.W. decide to meet every one to two months until symptoms remit. She will focus on optimizing a healthy lifestyle, with attention to exercise, sleep, and diet during this time, and keep an open mind about the sertraline dose moving forward, depending on the clinical course.
Clinical Pearls
- Maintain antidepressant therapy for at least six months after symptom remission.1,3,4,10,32
- Consider further maintenance depending on risk factors, comorbidities, psychosocial factors, and patient preference.1,3,4,10,27,32
- Educate patients regarding what is known about the risks and benefits of long-term antidepressant use.30,31
- Monitor the patient periodically throughout the maintenance phase.1,3,4,32,33
Conclusion
The case presented here underscores the complexities and nuances of long-term treatment of depression. From the initial decision to begin antidepressants to navigating the challenges of sustained use and potential tapering, this case highlights the importance of individualized care, continuous monitoring, and holistic treatment. The critical role of tailoring treatment plans to accommodate life changes, patient preferences, and emerging evidence toward a shared goal of sustained remission and improved quality of life is key. This approach not only optimizes clinical outcomes but also empowers patients to actively participate in their care, fostering confidence, resilience, and long-term well-being.
Author Ellen Feldman, MD, is with Altru Health System, Grand Forks, ND. Peer reviewer Glen D. Solomon, MD, MACP, FRCP (London), CTTS, NCTTP, is Professor and Chair, Department of Internal Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH.
References
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- Karrouri R, Hammani Z, Bourazza A, et al. Major depressive disorder: Validated treatments and future challenges. World J Clin Cases. 2021;9(31):9350-9367.
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- O’Donovan C, Alda M. Depression preceding diagnosis of bipolar disorder. Front Psychiatry. 2020;11:500.
- Sapra A, Bhandari P, Sharma S, et al. Using Generalized Anxiety Disorder-2 (GAD-2) and GAD-7 in a primary care setting. Cureus. 2020;12(5):e8224.
- Hunt G, Malhi G, Cleary M, et al. Prevalence of comorbid substance use in major depressive disorder in community and clinical settings, 1990-2019: Systematic review and meta-analysis. J Affect Disord. 2020;266:288-304.
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- Hershberger PJ, Martensen LS, Christensen DM, et al. Promoting motivational interviewing in primary care: More than intention. PRiMER. 2021;5:7.
- Agency for Healthcare Research and Quality. Motivational interviewing strategies to engage patients. Last reviewed November 2018. https://www.ahrq.gov/evidencenow/tools/motivational-interviewing.html
- Hyde J, Carr H, Lee R, et al. Efficacy of neurostimulation across mental disorders: Systematic review and meta-analysis of 208 randomized controlled trials. Mol Psychiatry. 2022;27:2709-2719.
- Sobule R, Ithman M. Ketamine: Studies show benefit. Mo Med. 2023;120(1):29-30.
- Meshkat S, Haikazian S, Di Vincenzo JD, et al. Oral ketamine for depression: An updated systematic review. World J Biol Psychiatry. 2023;24(7):545-557.
- Lewis G, Marston L, Duffy L, et al. Maintenance or discontinuation of antidepressants in primary care. N Engl J Med. 2021;385(14):1257-1267.
- Romagnoli A, Zovi A, Santoleri F, et al. Antidepressant deprescribing: State of the art and recommendations — A literature overview. Eur J Clin Pharmacol. 2024;80(3):417-433.
- Kato M, Hori H, Inoue T, et al. Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: A systematic review and meta-analysis. Mol Psychiatry. 2021;26:118-133.
- Henssler J, Schmidt Y, Diefenbacher A, et al. Incidence of antidepressant discontinuation symptoms: A systematic review and meta-analysis. Lancet Psychiatry. 2021;11(7):526-535.
- Van Leeuwen E, van Driel ML, Naunton M, et al. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev. 2021;4(4):CD013495.
- Royal College of Psychiatrists. Position statement on antidepressants and depression. Published May 2019. https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19---antidepressants-and-depression.pdf?sfvrsn=ddea9473_5
- Ormel J, Hollon SD, Kessler RC, et al. More treatment but no less depression: The treatment-prevalence paradox. Clin Psychol Rev. 2022;91:102111.
- Horowitz MA, Taylor D. Distinguishing relapse from antidepressant withdrawal: Clinical practice and antidepressant discontinuation studies. BJPsych Adv. 2022;28(5):297-311.
- Edinoff AN, Akuly HA, Hanna TA, et al. Selective serotonin reuptake inhibitors and adverse effects: A narrative review. Neurol Int. 2021;13(3):387-401.
- Zhao Y, Zhang Y, Yang L, et al. Safety profile of selective serotonin reuptake inhibitors in real-world settings: A pharmacovigilance study based on FDA Adverse Event Reporting System. Ann Pharmacother. 2024; Feb 26. doi:10.1177/1060028023115005. [Online ahead of print].
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In the vast mosaic of primary care, depression often remains in the shadows, embedded in patient care but easily overlooked. Left unrecognized, the prognosis worsens and complicates the management of other chronic conditions. However, with timely identification and effective treatment, the course of depression can be altered significantly. A comprehensive understanding of this condition, coupled with effective treatment strategies, empowers the primary care physician to mitigate the potentially debilitating effects of this condition.
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