Implementing Guideline-Based Strategies to Avoid Relapse and Recurrence in Depression

Roger S. McIntyre, MD, FRCPC

Department of Psychiatry, University of Toronto, and the Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada

Major depressive disorder is a prevalent and debilitating condition, projected to rise from third in years of life lost and early mortality in 2004 to first by 2030.1 Although many treatments are now available for depression, patients often do not achieve the goals of therapy, which are asymptomatic remission, functional recovery, and prevention of relapse and recurrence.

Contributors to Nonremission

Factors that contribute to nonremission include failure to establish a diagnosis, absence of measurement-based care, presence of complex illness presentations, and lack of early improvement. A meta-analysis2 of studies of diagnosis of depression in adults in primary care settings reported that about half of the cases were missed (AV 1AV 1). However, when patients were evaluated over time, accuracy of diagnosis improved. Systematic screening for depressive symptoms can increase rates of diagnostic accuracy.

Measurement-based, algorithm-driven care is not a new technique but is less commonly used in treating MDD than in managing other chronic diseases. To increase the probability of achieving remission in patients with depression, clinicians should use: (1) treatment guidelines; (2) metrics that quantify symptoms, side effects, and functional improvement; and (3) algorithm decision points to inform the selection and sequencing of treatment.3 Compared with treatment as usual, use of the TMAP algorithm led to significantly greater improvement in mental functioning, as measured by the SF-12 mental health summary score (P = .046), as well as greater symptom reduction, as measured by the 30-item IDS-C (P = .002).4

Complex illness presentations also contribute to nonremission. In clinical practice, patients often present with depression as well as other psychiatric or medical conditions that may impede treatment progress.2 Such patients are frequently excluded from clinical trials and may have more difficulty achieving remission than typical trial participants. For example, patients with depression and anxiety have a lower probability of achieving remission than those with nonanxious depression.5

Additionally, patients who have no response to antidepressant treatment in the first 2 weeks appear to have a lower probability of achieving remission with that medication when compared with patients who do experience some degree of benefit in the first 2 weeks of therapy. Although many treatment guidelines recommend not changing therapy for at least 4 to 6 weeks, a meta-analysis6 showed that early improvement (ie, a 20% or greater improvement in HDRS-17 scores by week 2) is a highly sensitive predictor of remission at weeks 4 to 8.

Consequences of Nonremission

Consequences of nonremission of depression can be psychiatric, medical, and neurobiological. Psychiatric consequences of nonremission include increased likelihood of relapse and recurrence of depression, reduced likelihood of returning to full psychosocial functioning, and, in depressed patients who are also parents, increased risk of psychiatric diagnoses in their children. In a naturalistic study,7 patients with residual depressive symptoms remained well for a median of 68 weeks, but those treated to asymptomatic remission remained well for a median of 231 weeks (4.4 years). Regarding psychosocial functioning, individuals with asymptomatic remission attained functioning almost comparable to that of community samples, but patients with residual symptoms showed continued psychosocial impairment in most areas.8 Adverse consequences of nonremitted depression occur not only in patients with the disorder but also in their children. Rates of depression, anxiety, and disruptive behavior decreased by 11% among children of mothers who achieved remission but increased by 8% in children of mothers with continuing depression.9

Nonremission of depression may also have medical consequences. For example, a bidirectional relationship exists between depression and metabolic conditions such as hyperglycemia, hyperinsulinemia, type 2 diabetes mellitus and insulin resistance, as well as overweight and obesity.10 When patients with depression are treated to full remission, the probability of insulin signaling returning to normal rises.11 Depression is also proinflammatory, which may contribute to allostatic changes such as cardiovascular disorders, obesity, and low bone mineral density, but treatment to remission appears to normalize inflammatory cytokines.12–14

Nonremission of depression may cause detrimental changes in the brain. A high number of episodes of depression was found to be associated with increased reduction in hippocampal volume and function15 and increased risk of dementia (AV 2AV 2).16 However, patients with major depression who were in stable remission had lower rates of brain volume decline than those who did not achieve remission.17


Strategies to Improve Outcomes

Because nonremission of depression has such negative consequences, the goals of treatment are remission, functional recovery, and prevention of relapse and recurrence. From a patient perspective, according to a survey18 of 535 outpatients receiving treatment for MDD, remission means not only the absence of depressive symptoms but also the presence of positive feelings such as self-confidence and optimism, a return to feeling like themselves, and a return to the usual level of functioning (AV 3AV 3).

Patients with MDD may respond to therapy and say they feel “better,” but clinicians must help patients achieve remission, not just response. To help patients achieve remission, clinicians need to incorporate measurement-based care and evidence-based guidelines and algorithms into treatment. Measurement tools are available to help clinicians bring about remission and functional recovery in patients with depression.19 Some tools, like the PHQ-9, can be used for screening, diagnosis, and monitoring symptom severity; others are better suited to 1 task than another (eg, the IDS is used for measuring symptom severity, while the SDS is a useful measure of functional outcomes). Tools may be clinician-rated or patient-rated and vary in length. Response is generally defined as a ≥ 50% reduction in symptoms according to the HDRS or the MADRS, which means that a patient may still have substantial residual symptoms depending on baseline severity. Remission is typically defined as a score ≤ 7 on the HDRS or ≤ 9 on the MADRS, with minimal residual symptoms, maintained for at least 3 weeks.20 Evidence-based guidelines such as the recently updated APA treatment guideline for MDD3 and algorithms such as TMAP21 are available.

Measurement tools should be systematically employed with measurement-based care strategies to monitor progress and guide treatment choices.22 Strategies include setting a visit schedule; regularly monitoring symptom improvement, side effects, and medication adherence; and using a set dose titration schedule. Treatment algorithms provide critical decision points at which measurement tool results are used to sequence treatment steps.21 Continuation and maintenance treatment phases are necessary to prevent relapse and maintain recovery. Implementing these strategies to achieve remission and avoid relapse and recurrence of depression can help optimize patients’ psychiatric, medical, and neurobiological health and return patients to “their old selves.”

For Clinical Use

  • Regularly screen patients for depression to provide a timely diagnosis
  • Use measurement-based care strategies to manage cases, paying particular attention to complex illness presentations and lack of early improvement
  • Treat depression using measurement tools, guidelines, and algorithms to improve the probability of asymptomatic remission and recovery, and monitor patients for relapse and recurrence

Drug Names

No drugs were mentioned in this activity


APA=American Psychiatric Association, HDRS-17=17-item Hamilton Depression Rating Scale, MADRS=Montgomery-Åsberg Depression Rating Scale, IDS-C=Inventory for Depressive Symptoms–Clinician-Rated, MDD=major depressive disorder, PHQ-9=9-item Patient Health Questionnaire, SDS=Sheehan Disability Scale, SF-12=Medical Outcomes Study 12-item Short-Form Health Survey, TMAP=Texas Medication Algorithm Project

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