Depression relapse while on antidepressants is a significant concern in clinical psychiatry, especially for individuals with major depressive disorder who are undergoing antidepressant treatment.
While antidepressant medication can be highly effective in reducing depression symptoms in teens, research shows that some patients still experience a depressive relapse despite ongoing care.
What Is Depression?
Depression is more than just feeling sad or having a bad day. It’s a serious mental health condition that can affect how a person thinks, feels, and functions in daily life. At its core, depression is marked by persistent feelings of hopelessness, emptiness, or loss of interest in activities that once brought joy.
There are different types of depression, each with its own patterns and challenges:
- Major Depressive Disorder (MDD): Characterized by deep sadness, lack of energy, and difficulty functioning for weeks or months at a time. Because major depression is often treated with antidepressants, patients may face a higher risk of relapse if medication alone does not fully address underlying causes.
- Persistent Depressive Disorder (Dysthymia): A longer-lasting form of depression where symptoms may be less severe but can stretch on for years, often interfering with work, relationships, and overall quality of life. Relapse is often harder to detect here because the overall symptoms can fluctuate between mild and more severe.
- Bipolar Disorder (formerly manic depression): Involves alternating episodes of depression and mania (periods of high energy or irritability), making it a complex mood disorder. Even when depressive symptoms improve, shifts in mood can increase vulnerability to relapse.
- Seasonal Affective Disorder (SAD): Depression that tends to occur during certain times of the year, often in the winter months when daylight is limited. Even with antidepressant treatment, symptoms may return when environmental triggers reappear.
- Postpartum Depression: A form of depression that can affect new mothers (and sometimes fathers) after the birth of a child, often linked to hormonal changes and the challenges of new parenthood. Relapse may occur if hormonal shifts or life stressors continue beyond the initial treatment period.
Understanding these types of depression is important because while medication and therapy can help to reduce symptoms, the nature of depression means that relapse is still possible, even during treatment. At Key Healthcare, we take the time to carefully assess each individual’s unique situation so that the treatment plan is tailored, compassionate, and designed to support long-term healing.
What is a Depression Relapse?
A depression relapse occurs when a person who has been improving on antidepressant treatment begins to experience depressive symptoms again. This is different from a recurrence, which happens after someone has fully recovered for a longer period. Relapse can happen weeks or months into treatment and is especially challenging because it may leave patients feeling discouraged, even when they are still taking medication as prescribed.
Relapse risk can be influenced by several factors, like:
- The severity of the original major depressive disorder (MDD) episode.
- Co-occurring conditions such as anxiety disorders o substance use issues.
- Stressful life events or changes in environment.
- Inconsistent medication use or other medical complications.
Having a clinical team that works closely to monitor your progress with both therapy and antidepressant medication helps individuals recognize the early signs of relapse and adjust treatment strategies quickly.
Symptoms of a Depression Relapse
The signs of a relapse often look like the return of familiar depressive symptoms, even if the person had been responding well to medication.
Common symptoms include:
- A noticeable drop in energy and motivation.
- Return of persistent sadness or hopelessness.
- Withdrawal from social connections or favorite activities.
- Changes in sleep or appetite.
- Struggles with concentration, memory, or decision-making.
- Increased feelings of guilt, worthlessness, or emptiness.
- Re-emergence of thoughts of self-harm or suicidal ideation.
Relapse does not mean treatment has failed; rather, it sends a signal that your care plan may need adjusting. Early recognition of these symptoms allows for timely interventions that can work to reduce the severity and duration of your relapse.
At Key Healthcare, we know how isolating and exhausting these symptoms can be. We offer personalized care, therapy, and medical support to help individuals rebuild their confidence, reconnect with loved ones, and rediscover purpose in their daily lives.
What Research Tells Us About Relapse
A recent systematic review and meta-analysis looked at how often people experience a return of depression symptoms. The researchers found that those in the discontinuation group—patients who stopped taking their antidepressant medication—had a much higher risk of relapse compared to people who continued with maintenance therapy.
This paper contributes to our understanding of how long-term treatment can protect against relapse, but it also highlighted gaps in what we know. There are still few studies that focus on certain populations, and overall there remains little research on how other groups may respond to antidepressants over time.
At Key Healthcare, we stay up to date with the latest research so we can tailor care to each individual’s needs, helping patients find a plan that supports their long-term stability and well-being.
Antidepressants as a Form of Depression Treatment
For many individuals living with depression or major depressive disorder, antidepressant medication can be a lifeline. These medications work by balancing brain chemicals that influence mood and emotions, helping to reduce persistent sadness, restore energy, and improve overall functioning.
There are several common types of antidepressants used in treatment today:
- Selective Serotonin Reuptake Inhibitors (SSRIs): Often the first-line treatment, SSRIs increase serotonin levels in the brain and are generally well tolerated.
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): These medications target both serotonin and norepinephrine to help with mood and sometimes physical symptoms like pain.
- Norepinephrine Reuptake Inhibitors (NRIs): Used less commonly, these can benefit certain patients who don’t respond to SSRIs or SNRIs.
- Monoamine Oxidase Inhibitors (MAOIs): An older class of antidepressants that may be effective for treatment-resistant depression but require dietary restrictions and careful monitoring.
While antidepressants are highly effective for many people, they are not a “one-size-fits-all” solution. Some may need to try more than one medication before finding the right fit, and others may find that medication alone does not fully resolve their symptoms.
For this reason, antidepressants are often combined with therapy, lifestyle changes, and ongoing mental health support.
Risk Factors for Depression Relapse While on Antidepressants
While antidepressants are essential in depression treatment, other factors can increase the likelihood of relapse:
- Previous depressive episodes and chronic depressive disorders
- Partial or incomplete initial response to antidepressant drug treatment
- Co-occurring mental health conditions such as anxiety or bipolar spectrum disorders
- Inconsistent continued treatment or poor medication adherence
- Major life stressors affecting daily life
- Biological factors such as inflammation or neurotransmitter imbalance
- Changes in eating habits and sleep patterns
- Substance use or chronic illness
Recognizing these risk factors is the first step toward prevention, and at Key Healthcare, we help individuals create personalized strategies to manage these challenges and strengthen their path toward lasting recovery.
Maintenance Treatment and Relapse Prevention
Maintenance treatment, also known as maintenance therapy, is an essential part of preventing a depression relapse, especially for individuals living with major depressive disorder or other mood disorders. It focuses on long-term care to stabilize symptoms, reduce risk factors, and support lasting wellness.
Maintenance strategies may include:
- Antidepressant medication management at a therapeutic dose, carefully monitored to ensure effectiveness and minimize side effects.
- Mood stabilizers or other psychiatric medications when needed, particularly for those with severe depression or co-occurring affective disorders.
- Regular psychiatric evaluations and follow-ups to assess progress, adjust medications, and track depression scores.
- Individual and group therapy, where patients learn to challenge negative thoughts, strengthen coping strategies, and build confidence.
- Lifestyle interventions such as nutritional guidance, exercise planning, and stress-reduction practices that improve overall mental health and well-being.
- Family therapy and support systems to create a stronger foundation for ongoing stability.
Guidelines from the National Institute for Health and Care Excellence (NICE) recommend continuing treatment for at least six months after a first depressive episode, and for longer periods in cases of recurrent depression or individuals with high relapse risk.
The Role of Ongoing Support in Depression Treatment
Long-term recovery from depression involves much more than taking an antidepressant every day. At Key Healthcare, we understand that each person’s journey looks different. That’s why we take a personalized approach to design a treatment plan that not only manages symptoms but also builds resilience for the future. Our compassionate team is committed to guiding you through every stage of recovery with care and support.
If you or a loved one is experiencing a depression relapse while on antidepressants, don’t wait. Contact Key Healthcare today to learn more about our evidence-based treatment programs and take the first step toward lasting stability, healing, and hope.
Sources
Kalfas M, Tsapekos D, Butler M, McCutcheon RA, Pillinger T, Strawbridge R, Bhat BB, Haddad PM, Cowen PJ, Howes OD, Joyce DW, Nutt DJ, Baldwin DS, Pariante CM, Lewis G, Young AH, Lewis G, Hayes JF, Jauhar S. Incidence and Nature of Antidepressant Discontinuation Symptoms: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2025 Jul 9:e251362. doi: 10.1001/jamapsychiatry.2025.1362. Epub ahead of print. Erratum in: JAMA Psychiatry. 2025 Jul 22. doi: 10.1001/jamapsychiatry.2025.2398. PMID: 40632531; PMCID: PMC12242823.
National Institute of Mental Health. (2024, December). Depression.
National Institute for Health and Care Excellence. (2022, June 29). Depression in adults: Treatment and management (NICE Guideline No. NG222).
O’Connor, E. A., Whitlock, E. P., Gaynes, B., et al. (2009, December). Screening for depression in adults and older adults in primary care: An updated systematic review (No. 75, Evidence Syntheses) [Table 2, List of antidepressants and their categorizations]. Agency for Healthcare Research and Quality (US).
Preventing recurrent depression: long-term treatment for major depressive disorder. Prim Care Companion J Clin Psychiatry. 2007;9(3):214-23. PMID: 17632654; PMCID: PMC1911177.
Unützer, J., Harbin, H., Schoenbaum, M., & Druss, B. (2021). Re-evaluating the role of antidepressants in long-term depression care. American Family Physician, 103(1), 16–23.
