Common Residual Symptoms Including Anhedonia: Impact on Quality of Life for Patients With MDD
Residual symptoms, such as anhedonia, may persist in patients with major depressive disorder despite ongoing treatment and can negatively impact quality of life. It is important for healthcare providers to recognize residual symptoms and implement strategies to manage them in patients with MDD.
Transcript:
Well, hello, and welcome to Psych Navigator’s Clinical Insights series. Today, we’ll be talking about Common Residual Symptoms Including Anhedonia: Impact on Quality of Life for Patients With MDD, Clinical Insight Video. I am Dr Rakesh Jain, a Clinical Professor of Psychiatry at Texas Tech University School of Medicine in Midland, Texas. I am also a practicing psychiatrist in Austin, Texas.
Today, we will take a closer look at common residual depressive symptoms in patients with major depressive disorder (MDD) and consider how they may affect their quality of life. We will also discuss why recognizing and managing residual symptoms early in the treatment process can be clinically important. Lastly, we will explore strategies that healthcare providers can use to offer support.
The primary goal of managing MDD is to help patients achieve remission of depressive symptoms and help improve their overall quality of life.1
The recommended initial pharmacological treatment for patients with MDD is antidepressant monotherapy.2 However, even with antidepressant therapy, some patients may find that their treatments do not fully address their depression, leaving them with lingering symptoms of depression, referred to as residual depressive symptoms.
Studies show that residual symptoms of depression can be found in a high proportion of MDD patients, even in those who have achieved remission. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, at least one residual symptom was reported by more than 90% of patients who achieved remission.3 Residual depressive symptoms can include low mood, anhedonia, cognitive impairment, and fatigue.1,4,5
These symptoms can negatively impact the patient’s daily life and well-being.1
In fact, the presence of residual symptoms has been associated with significantly higher levels of disability, making depression a leading cause of disability.1 In a long-term follow-up study of MDD patients, patients with chronic MDD, whose depressive symptoms were not adequately managed by their treatments, experienced significantly more disability than those without chronic MDD, as indicated by nearly five-fold higher WHO Disability Assessment Schedule 2.0, also known as WHODAS 2.0, scores in patients with chronic MDD compared to those in individuals without. Of note, the increased level of disability in patients with chronic MDD persisted for 6 years.6
Moreover, research suggests that untreated residual depressive symptoms may also increase the risk of relapse. In a study that followed MDD patients for 10 months, 76% of patients with residual symptoms relapsed, while only 25% of those without residual symptoms relapsed.7 A large cohort study also showed that patients with residual symptoms relapsed earlier, at approximately 28 weeks, compared to those without residual symptoms, who, on average, relapsed at 157 weeks.8
Among the most common and disabling residual symptoms is anhedonia. Anhedonia, defined as the loss of pleasure, motivation, or interest in activities that were once enjoyable, is a core diagnostic symptom of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.5
Research has linked anhedonia to dysfunctions in the brain’s reward systems, particularly in the mesocorticolimbic dopamine pathway, where decreased dopamine signaling in the ventral striatum is thought to lead to impaired reward anticipation and reduced motivation or pleasure.9
In terms of patient outcomes, the presence of anhedonia symptoms can be associated with a more complex and severe presentation of MDD, increased risk of suicidality, reduced response to selective serotonin reuptake inhibitors, and decreased health-related quality of life.10
Together, these findings suggest that residual depressive symptoms, such as anhedonia, can be clinically significant indicators of disease burden.
To help address the challenges associated with residual depressive symptoms, identifying the presence of residual symptoms in MDD patients following their initial course of treatment is critical. Early recognition can help healthcare providers (HCPs) to adjust treatment strategies and potentially lessen the overall impact on a patient’s quality of life.1
In clinical practice, patient probes during a clinical visit can be key in identifying ongoing depressive symptoms such as anhedonia.
HCPs might ask patients probing questions such as:
- “Are there things you used to enjoy that just don’t feel the same anymore?”
- Another question might be, “Do you still look forward to things you used to really like—such as hobbies, time with friends, even food?”
- Another question might be, “When was the last time you felt genuinely excited or happy about something?”
The implementation of standardized tools in clinical practice can also help quantify and track changes in depressive symptoms over time, helping to monitor for residual symptoms. One instrument that can be used in clinical practice to monitor depressive symptoms and treatment progress is the Patient Health Questionnaire-9, also widely known as the PHQ-9. The PHQ-9 is a brief, self-rated questionnaire consisting of 9 items derived from the diagnostic criteria for a depressive episode in the DSM-4. Using the questions shown here on the screen, the PHQ-9 is used to screen for symptoms of depression over the past two-week period.11
Another possible instrument is the 14-item, self-administered, Snaith–Hamilton Pleasure Scale (SHAPS). The SHAPS is an assessment tool commonly used to evaluate anhedonia symptoms by measuring the capacity to experience pleasure. As you can see here, it contains 14 questions that cover four domains of pleasure, including social interactions, food and drink, sensory experiences, and hobbies.5
As I mentioned earlier, about 50% of patients with depression respond to the initial antidepressant monotherapy, according to the STAR*D study, which suggests some patients are left with residual depressive symptoms.12
If the initial antidepressant treatment does not provide an adequate response, patients may be switched from one antidepressant to another. However, persistent antidepressant treatment cycling has been shown to negatively impact the overall treatment course in patients with MDD.
First, persistent cycling may prolong depressive episodes and delay remission. Studies show that the likelihood of remission decreases with each additional treatment step, while intolerance to treatment increases.13 As mentioned earlier, inadequate response to treatment and residual symptoms can also increase the risk of relapse.1,5
Second, undertreated depression can be associated with developing comorbidities such as cardiovascular diseases and stroke, and it may also increase the risk of self-harm.14
In addition, research suggests that many patients with an inadequate response to antidepressants report high levels of frustration with their HCPs, which may impact treatment adherence and the patient-HCP relationship. Some patients may even lose motivation to pursue additional treatment options.15
Beyond the clinical impact, persistent treatment resistance can increase healthcare resource use and overall economic burden through direct medical costs and productivity losses.14,16
Lastly, cycling through multiple antidepressant monotherapies may delay the initiation of other treatment strategies, such as augmentation, which can include adjunctive therapies, such as atypical antipsychotics.17
For patients who have not shown at least a partial response to their initial antidepressant therapy, defined as those with a decrease of <50% but ≥25% from baseline depression scale scores,18 the American Psychiatric Association recommends switching to another non-monoamine oxidase inhibitor antidepressant.2
In cases of partial response, augmentation or combination strategies are recommended. These may include psychotherapy, adjunctive treatment with a non-monoamine oxidase inhibitor antidepressant, or an adjunctive non-antidepressant medication, such as a mood stabilizer, thyroid hormone, an anticonvulsant, a psychostimulant, or an atypical antipsychotic.2
Atypical antipsychotics have been studied systematically and in randomized controlled trials as an option for adjunctive pharmacotherapy for patients with partial response.2 In the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, which evaluated second-step treatment strategies for patients not responding to their initial antidepressants, augmenting with an atypical antipsychotic was shown to be more effective in achieving remission than switching to or augmenting with another antidepressant.19
Augmentation therapy may help avoid unnecessary switching between antidepressants and can potentially allow the patient to start an appropriate therapy earlier, which may help improve their quality of life.19,20
In fact, the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults recommends considering the use of atypical antipsychotics after inadequate response to initial pharmacotherapy with a first-line antidepressant. The 2023 Guidelines Update recommends adjunctive therapies, particularly atypical antipsychotics, as a potential treatment option to help improve outcomes for patients who have had a partial response to their first or second antidepressant trial. Additionally, it recommends an earlier use of adjunctive strategies for patients with a partial response, while factoring in individual risks, benefits, and preferences.17,21
As we have seen today, residual depressive symptoms—such as anhedonia—can persist in patients with MDD despite ongoing treatment or symptomatic remission. This may lead to impaired quality of life and poor long-term outcomes.
The presence of anhedonia symptoms, in particular, can signal a more severe, complex presentation of MDD, and residual anhedonia symptoms may reduce a patient’s ability in social, emotional, and cognitive realms, impacting quality of life.
Utilizing patient probes and standardized tools such as the PHQ-9 and SHAPS can help HCPs evaluate and monitor persistent residual depressive symptoms such as anhedonia and can help in adjusting the management strategy if needed.
Persistent cycling of antidepressant treatments may delay appropriate treatment for patients and reduce patient engagement and trust in their HCPs. Therefore, it is important to understand that adjunctive strategies, including atypical antipsychotics, for patients with MDD who experience partial response to their antidepressants can potentially help improve patient outcomes.
I hope that you found this discussion on residual symptoms in MDD helpful for your clinical practice and patient care. Thank you for joining me today! My name is Rakesh Jain, and this was a presentation from Psych Navigator’s Clinical Insight Series, titled "Common Residual Symptoms Including Anhedonia: Impact on Quality of Life for Patients With MDD," Clinical Insights. Good-bye for now.
Rakesh Jain, MD, MPH
Rakesh Jain, MD, MPH, has extensive experience in mental health, particularly focusing on the recognition and treatment of depression and other mood disorders. He serves as a steering committee member for both Sana Symposium and Psych Congress and holds the position of clinical professor in the Department of Psychiatry at Texas Tech University School of Medicine. He has contributed to multiple radio interviews regarding mental health and wellness across various stations.
References
- Li Y, Wang D, Fang J, et al. Factors influencing the tendency of residual symptoms in patients with depressive disorders: a longitudinal study. BMC Psychiatry. 2024;24:557. doi:10.1186/s12888-024-05915-9
- American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010.
- Nierenberg AA, Husain MM, Trivedi MH, et al. Psychol Med. 2010;40(1):41-50. doi:10.1017/S0033291709006011
- Pastuszak M, Cubała WJ, Kwaśny A, Mechlińska A. The search for consistency in residual symptoms in major depressive disorder: a narrative review. J Pers Med. 2024;14(8):828. doi:10.3390/jpm14080828
- Wu C, Mu Q, Gao W, Lu S. The characteristics of anhedonia in depression: a review from a clinically oriented perspective. Transl Psychiatry. 2025;15(1):90. doi:10.1038/s41398-025-03310-w
- Iancu SC, Wong YM, Rhebergen D, van Balkom AJLM, Batelaan NM. Long-term disability in major depressive disorder: a 6-year follow-up study. Psychol Med. 2020;50(10):1644-1652. doi:10.1017/S0033291719001612
- Paykel ES, Ramana R, Cooper Z, et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995;25(6):1171-1180. doi:10.1017/s0033291700033146
- Israel JA. The impact of residual symptoms in major depression. Pharmaceuticals. 2010;3(8):2426-2440. doi:10.3390/ph3082426
- Phillips RD, Walsh EC, Zürcher NR, et al. Striatal dopamine in anhedonia: a simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation. Psychiatry Res Neuroimaging. 2023;333:111660. doi:10.1016/j.pscychresns.2023.111660
- Wong S, Le GH, Phan L, et al. Effects of anhedonia on health-related quality of life and functional outcomes in major depressive disorder: a systematic review and meta-analysis. J Affect Disord. 2024;356:684-698. doi:10.1016/j.jad.2024.04.086
- Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.x
- Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-17. doi:10.1176/ajp.2006.163.11.1905
- Fava GA. May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance. Ther Adv Psychopharmacol. 2020;10:1-11. doi:10.1177/2045125320970325
- Chan VK, Cheung EC, Chan SS, et al. Mortality-causing mechanisms and healthcare resource utilisation of treatment-resistant depression: a six-year population-based cohort study. Lancet Reg Health West Pac. 2022;22:100426. doi:10.1016/j.lanwpc.2022.100426
- Mago R, Fagiolini A, Weiller E, et al. Understanding the emotions of patients with inadequate response to antidepressant treatments: results of an international online survey in patients with major depressive disorder. BMC Psychiatry. 2018;18:33. doi:10.1186/s12888-018-1625-y
- Jain R, Laliberté F, Germain G, et al. Treatment patterns, health care resource utilization, and costs associated with use of atypical antipsychotics as first vs subsequent adjunctive treatment in major depressive disorder. J Manag Care Spec Pharm. 2023;29(8):896-906. doi:10.18553/jmcp.2023.29.8.896
- Jha MK, Matthew SJ. Pharmacotherapies for treatment-resistant depression: how antipsychotics fit in the rapidly evolving therapeutic landscape. Am J Psychiatry. 2023;180(3):190-199. doi:10.1176/appi.ajp.20230025
- Nierenberg AA, DeCecco LM. Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression. J Clin Psychiatry. 2001;(62 suppl 16):5-9.
- Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318(2):132-145. doi:10.1001/jama.2017.8036
- Lenze EJ, Mulsant BH, Roose SP, et al. Antidepressant augmentation versus switch in treatment-resistant geriatric depression. N Engl J Med. 2023;388(12):1067-1079. doi:10.1056/NEJMoa2204462
- Lam RW, Kennedy SH, Adams C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 update on clinical guidelines for management of major depressive disorder in adults. Can J Psychiatry. 2024;69(9):641-687. doi:10.1177/07067437241245384
This resource is intended for educational purposes only and is intended for US healthcare professionals. Healthcare professionals should use independent medical judgment. All decisions regarding patient care must be handled by a healthcare professional and be made based on the unique needs of each patient.
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