Major depressive disorder in adults: Treatment with supplemental interventions

INTRODUCTION — Major depressive disorder (MDD) is highly prevalent and disabling. The estimated lifetime prevalence of depressive disorders is 12 percent [1], and they are the 13^th greatest cause of disability and mortality in the world [2]. In the United States, major depression ranks second among all diseases and injuries as a cause of disability, and persistent depressive disorder ranks 20^th [3,4].

Although treatment with antidepressants and/or in-person psychotherapy remains the cornerstone of treatment for individuals with MDD, patients with depression often ask about alternative treatment options, especially if they are reluctant to take medications or unable to access psychotherapy. This topic reviews supplementary and supportive care interventions for patients with MDD, including the use of physical and mindfulness-based interventions, such as exercise, yoga, and relaxation; online interventions (eg, internet-based psychotherapy); and other self-help measures. Other aspects of diagnosing and managing MDD are discussed separately, including the approach to initial treatment, pharmacotherapy and psychotherapy for initial treatment, continuation and maintenance treatment, the management of individuals with resistant depression, integrative medicine, and investigational treatments for depression.

●(See "Major depressive disorder in adults: Approach to initial management".)

●(See "Major depressive disorder in adults: Initial treatment with antidepressants".)

●(See "Unipolar depression in adults: Choosing treatment for resistant depression".)

●(See "Unipolar depression in adults: Continuation and maintenance treatment".)

●(See "Unipolar depression in adults: Clinical features".)

●(See "Unipolar depression in adults: Assessment and diagnosis".)

●(See "Diagnosis and management of late-life unipolar depression".)

●(See "Unipolar depression in adults: Investigational and nonstandard treatment".)

DEFINITIONS

●Major depressive disorder – MDD is diagnosed in patients with a history of at least one major depressive episode and no history of mania or hypomania (table 1) [5].

In this topic, the term "major depression" refers to MDD.

●Major depressive episode – A major depressive episode is a period lasting at least two consecutive weeks, with five or more of the following symptoms: depressed mood, anhedonia, insomnia or hypersomnia, change in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration or memory, thoughts of worthlessness or guilt, and recurrent thoughts about death or suicide. At least one of the symptoms must be depressed mood or anhedonia. (See "Unipolar depression in adults: Clinical features".)

●Severity of depression – To determine the severity of major depression, we use the number and severity of depressive symptoms (table 1); level of functional impairment; and the presence and severity of suicidal thoughts and behaviors, psychosis, and catatonia [5]. We typically use the nine-item Patient Health Questionnaire (PHQ-9) to rate the number and frequency of depression symptoms (table 2).

The PHQ-9 is a self-report assessment that is discussed separately. (See "Using scales to monitor symptoms and treat depression (measurement based care)".)

ROLE AND SELECTION OF SUPPLEMENTAL TREATMENTS

Role of supplemental treatments — The cornerstones of management for individuals with major depression are pharmacotherapy and in-person psychotherapy, referred to in this topic as "standard treatment." Supplemental interventions for the treatment of depression include exercise, mind-body interventions (eg, yoga, tai chi, relaxation, massage), internet-based psychotherapy (IBP), and other self-help interventions. Bright light therapy, which is a standard treatment for seasonal affective disorder, can also be used as a supplemental treatment for MDD. We typically use supplemental interventions as adjuncts to standard treatment; however, for individuals with mild major depression, these interventions can serve as alternatives to standard treatment.

●Adjunctive interventions for all patients – Supplemental interventions can augment standard treatment for individuals with any depression severity. However, patients with more severe depression may require additional support or supervision to engage in these interventions given their level of functional impairment and lack of energy. We incorporate most supplemental interventions into the ongoing management plan. However, in some situations, they may be time limited, such as the use of IBP as a "bridge" to in-person psychotherapy.

●Alternatives to standard treatments for those with mild depression – Supplemental interventions can serve as "stand-alone" treatment for the subset of individuals with mild depression who do not want or cannot access in-person psychotherapy and prefer not to start pharmacotherapy. These include individuals with a short duration of symptoms (eg, ≤3 months), no prior episodes of depression, and no major functional impairment. Patients who opt not to pursue standard treatments require close monitoring for symptom progression even if they pursue supplemental interventions.

We do not recommend supplemental treatments as "stand-alone" options for treating individuals with moderate to severe major depression.

Choosing an overall treatment regimen and details regarding standard treatment options for individuals with major depression are discussed separately. (See "Major depressive disorder in adults: Approach to initial management" and "Unipolar depression in adults: Choosing treatment for resistant depression".)

Selecting a supplemental treatment

●General approach and importance of patient preference – In selecting a supplemental treatment, we consider treatment efficacy and availability and patient preferences, comorbidities, and prior treatment experiences. We start by eliciting patients' preferences regarding whether to add a supplemental treatment and, if so, which to select. Because re-engaging in positive activities is an important component of depression treatment, we encourage patients to pursue the supplemental intervention(s) that appeal to them. The idea that individuals with depression benefit from pursuing positive activities that have ceased due to depression ("behavioral activation") is discussed separately. (See "Behavioral activation therapy for treating unipolar major depression".)

We prioritize patient preference in selecting a supplemental treatment because few studies directly compare different supplemental treatments. Evidence for the efficacy of supplemental interventions for treating depression varies in quality and limits the strength of recommendations for using them. Common study limitations include the use of "wait list" controls, a paucity of studies comparing supplemental interventions with standard treatments, study populations defined by the presence of depressive symptoms rather than a diagnosis of major depression, and study outcomes that are based on symptom improvement rather than depression response or remission.

●Exercise for all – For all individuals with depression who are willing and able to engage in physical activity, we suggest exercise as a first-line intervention because substantial evidence supports its efficacy (see 'Exercise and physical activity' below). Because exercise also provides cardiovascular and fitness benefits, we especially encourage it in patients with depression and comorbid conditions for which exercise improves outcomes, such as diabetes, cardiovascular disease, and osteoarthritis.

●Mind-body interventions for patients who cannot exercise – For individuals who are unwilling or unable to engage in aerobic or resistance exercise, we encourage mind-body interventions (eg, yoga and tai chi). Patients can also combine mind-body interventions with exercise and other supplemental treatments. Although we discuss these interventions with all patients with depression, those with some prior experience of mindfulness-based interventions, such as meditation, may be most open to them. Individuals with comorbid anxiety disorders may particularly benefit from mindfulness-based interventions [6].

The incorporation of mindfulness techniques into cognitive behavioral therapy (ie, mindfulness-based cognitive therapy) is a type of standard psychotherapy for MDD and is discussed separately. (See 'Mind-body interventions' below and "Unipolar major depression: Treatment with mindfulness-based cognitive therapy".)

●Patients who are open to psychotherapy – We encourage IBP for all individuals who want psychotherapy but are unable to find or access a therapist. We also discuss IBP with patients who express interest in self-help interventions. (See 'Internet-based psychotherapy' below.)

As with other supplemental interventions, patients with mild MDD can use IBP as either an alternative or an adjunct to standard treatment or a bridge to in-person psychotherapy. Using IBP as a bridge to in-person psychotherapy makes the most sense if the online intervention uses an approach based in cognitive behavioral or other evidence-based psychotherapy for treating depression. Those who use IBP as an alternative or bridge to standard treatment require close follow-up to monitor for worsening symptoms.

Individuals with moderate to severe MDD can use IBP as an adjunct to standard treatment. (See 'Role of supplemental treatments' above.)

●Choice between other supplemental treatments – We rely on patient preference to inform the selection of other supplemental interventions, including bright light therapy, meditation, relaxation, massage, and other self-help modalities (eg, support groups, bibliotherapy, and smartphone applications). (See 'Bright light therapy' below and 'Other self-help modalities' below and 'Other interventions' below.)

EXERCISE AND PHYSICAL ACTIVITY — We encourage all patients to engage in exercise and increase their general level of physical activity. Exercise is a form of physical activity that is planned, structured, and repetitive and has the objective of improving or maintaining one or more components of physical fitness [7]. Multiple randomized trials suggest that exercise is the best-established supplemental intervention for treating individuals with MDD.

The general health benefits and risks of aerobic exercise and strength training are discussed separately. (See "The benefits and risks of aerobic exercise", section on 'Benefits of exercise' and "Strength training for health in adults: Terminology, principles, benefits, and risks", section on 'What medical conditions improve with strength training?'.)

Suggested regimen

Type, intensity, and frequency — We suggest exercise as adjunctive treatment for all individuals with MDD, based upon randomized trials that suggest a moderate impact of exercise on depressive symptoms and limited harms. Prescribing exercise as adjunctive treatment or monotherapy is consistent with multiple practice guidelines [8-14].

●Patients who already exercise – For individuals who are already physically active or engage in some exercise, we typically prescribe moderate to vigorous aerobic exercise for depression treatment. However, resistance exercise is a reasonable alternative [15]:

•Moderate or vigorous aerobic exercise (eg, brisk walking, running, or cycling) to achieve 50 to 85 percent maximum heart rate

•Resistance training (upper and lower body weightlifting involving all major muscle groups)

We typically encourage patients to exercise in 30- to 60-minute sessions at least three times weekly because this is consistent with the regimens evaluated in many randomized trials [16]. We encourage vigorous aerobic exercise if possible because most trials of exercise for depression have evaluated aerobic exercise and more intense exercise may produce larger benefits [16,17]. As an example, a 2024 network meta-analysis found a positive dose-response relationship between the level of exercise intensity and improvement of depression, with vigorous exercise (eg, running or interval training) producing larger effects than light physical activity (eg, walking or yoga) [18]. By contrast, earlier meta-analyses of randomized trials suggested similar efficacy for different intensities (ie, light, moderate, and vigorous) of exercise interventions [19,20].

●Patients who do not exercise – We encourage individuals with depression who do not currently exercise or cannot exercise at this level of intensity to increase their physical activity by any amount possible with the ultimate goal of moderate to vigorous aerobic exercise or resistance training at least three times weekly. We encourage them to incorporate increased physical activity into a daily routine and establish a sustainable practice of regular exercise that they can build on over time. Walking, dance, and mind-body types of exercise (eg, yoga, tai chi) are reasonable options for these patients (see 'Mind-body interventions' below). To enhance adherence and effectiveness, we also encourage patients to engage in supervised exercise, if possible. (See 'Enhancing adherence' below.)

Even modest physical activity can improve depressive symptoms. As an example, a 2024 network meta-analysis of 218 studies found moderate reductions in depression with walking or jogging, dance, yoga, and tai chi or qigong, compared with active controls [18]. The certainty of these findings is limited by a high risk of bias in most included trials [21].

Earlier meta-analyses of randomized trials suggest similar efficacy for different types (ie, aerobic, resistance, and mixed) of exercise interventions [19,20]. Trials of exercise interventions in older adult populations have also demonstrated similar efficacy for aerobic, resistance, and mind-body (eg, yoga, tai chi, qigong) types of exercise [22,23]. (See 'Efficacy in special populations' below.)

Different exercise regimens may provide optimal benefit for preventing or treating specific health conditions (eg, more intense aerobic exercise for optimal cardiovascular health). Additional information about the benefits and risks of exercise and specific exercise regimens is discussed separately. (See "The benefits and risks of aerobic exercise", section on 'Benefits of exercise' and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease", section on 'Our approach' and "Exercise prescription and guidance for adults" and 'Expected benefits' below.)

Duration of intervention — We encourage patients to exercise indefinitely. Although exercise regimens evaluated in clinical trials generally last between 6 to 12 weeks [24], we believe that the overall benefits of continued exercise justify encouraging its continued use.

The long-term impact of exercise on depression outcomes is unclear. Continued exercise beyond the acute intervention may maintain its benefits [9]. However, meta-analyses have reported conflicting results regarding the durability of exercise's effect on depressive symptoms posttreatment, with two meta-analyses finding no posttreatment benefit [24,25] and a third finding a small to moderate benefit of exercise at up to 26 months posttreatment [20].

Enhancing adherence — To optimize adherence, we suggest exercising in a supervised setting (eg, group class or with a trained professional) because the evidence that exercise improves depressive symptoms is most robust for supervised exercise. Other strategies for improving adherence include using patient preferences to guide the type and frequency of activity, setting exercise goals and providing feedback, and motivational interviewing (motivating the patient to exercise by eliciting both the patient's reasons to do so and the patient's ambivalence about change). Motivational interviewing is discussed separately. (See "Overview of psychotherapies", section on 'Motivational interviewing'.)

●Rates of adherence to exercise – Although adherence to exercise interventions in clinical trials varies, some studies report that adherence rates are comparable to those with antidepressants or psychotherapy [15,26]. As an example, a meta-analysis of adherence to lifestyle interventions for depression treatment (eg, changes in diet and physical activity), reported pooled intervention completion rates of 53 percent [27]. In comparison, poor adherence to antidepressants occurs in approximately 50 percent of individuals [28,29]. Among patients with depression who receive psychotherapy, 20 to 70 percent prematurely discontinue treatment [30].

By contrast, a meta-analysis of 21 trials found higher rates of dropout with exercise interventions compared with antidepressant treatment [31]. Adherence rates between different types of exercise (eg, aerobic, resistance, and mindfulness-based) appear similar, at least in older populations [23].

●Importance of supervision – We suggest supervised exercise because it may motivate patients, reduce injuries, and enhance adherence to exercise [32,33]. Supervision can occur in a group or one-on-one [31,34]. Clinician guidance and support may help those individuals who cannot participate in a supervised exercise program. As an example, clinicians can review data that patients provide from wearable devices that track their daily activity levels [35]. Meta-analyses of randomized trials have generally found larger benefits from supervised, compared with unsupervised, exercise interventions [17,19,32,36].

Expected benefits

Improvement of depression — Evidence from meta-analyses of randomized trials supports the use of exercise as a "stand-alone" treatment for individuals with mild major depression and as an adjunct to standard treatment for all individuals with major depression, including older individuals and those with chronic medical conditions, as well as individuals with depressive symptoms who may not meet criteria for a diagnosis of MDD.

●As "stand-alone" treatment – For individuals with mild major depression, exercise is a reasonable alternative to treatment with psychotherapy or antidepressants, although clinicians should regularly monitor patients for worsening symptoms (eg, every four weeks). Meta-analyses of randomized trials evaluating exercise as a "stand-alone" treatment suggest that it is superior to control interventions and may be comparable to treatment with antidepressants or in-person psychotherapy; however, variability in study design and quality limits the certainty of these conclusions.

•Compared with control interventions – Meta-analyses of randomized trials suggest that exercise has a small to moderate effect on depression symptoms compared with control interventions; however, conclusions are limited by variability in study design and risk of bias in many studies [6]. Although earlier studies found no benefit from exercise [15,24,37,38], subsequent meta-analyses suggest that exercise is beneficial in reducing depression symptoms [20,25,32,39-42].

As an example, in a meta-analysis of 41 randomized trials (2264 participants), exercise interventions improved depression symptoms compared with nonactive controls, and the clinical effect was large (standardized mean difference [SMD] -0.946, 95% CI -1.18 to -0.71) [19]. The effect size was comparable to that found in meta-analyses of psychotherapy and antidepressants, and the estimated number needed to treat to produce a clinically meaningful improvement in symptoms was two. Similar results were seen for both aerobic and resistance exercise. The study found smaller effects when restricting analyses to trials with low risk of bias. Included trials demonstrated substantial clinical and statistical heterogeneity.

Exercise may improve outcomes in individuals with depressive symptoms who do not have an established diagnosis of MDD [43-45]. As an example, in a meta-analysis of 14 trials of 1737 adults without clinical depression from eight countries, exercise reduced depressive symptoms more than control interventions, and the clinical benefit was small to moderate (SMD -0.34, 95% CI -0.52 to -0.27); however, the quality of evidence was low [44].

•Compared with antidepressants – For individuals with mild to moderate major depression, aerobic exercise may be comparable to treatment with antidepressants; however, the certainty of evidence is low. As an example, a network meta-analysis of 21 trials of participants with mild to moderate major depression found no significant differences between antidepressants, exercise, or combination interventions (ie, exercise plus antidepressants) for improving depressive symptoms [31]. All three treatment approaches demonstrated superior efficacy compared with control conditions.

Similarly, in a network meta-analysis of three trials of 430 participants with major depression, aerobic exercise achieved similar rates of remission as sertraline, although the relatively small sample limits the certainty of this finding [46]. Other meta-analyses have reported similar results [16,20].

•Compared with psychotherapy – Randomized trials suggest that exercise may be comparable to psychotherapy. As an example, a meta-analysis of seven trials with 189 participants found comparable improvement in depressive symptoms with exercise and psychologic interventions (SMD -0.03, 95% CI -0.32 to 0.26) [20].

●As an adjunctive treatment – Evidence supporting the efficacy of exercise as an adjunct to standard treatment is less robust because most trials have compared exercise with placebo or control interventions [20,47]. Limited data suggest that adding exercise to antidepressant monotherapy offers little additional benefit compared with antidepressant treatment alone [25,31]. As an example, in a network meta-analysis of three trials of 430 participants with major depression, rates of depression remission were comparable between sertraline plus exercise compared with sertraline alone (relative risk 1.23, 95% CI 0.89 to 1.70), although imprecision limited the certainty of evidence [46].

Efficacy in special populations

●Older patients – Exercise appears to reduce depressive symptoms in older individuals with and without established major depression [23,45,48,49]. As an example, in a meta-analysis of 15 trials of 596 participants aged ≥65 with clinical depression, exercise interventions were superior to control interventions for achieving symptom improvement, and the clinical benefit was moderate to large [22]. Aerobic exercise, resistance exercise, and mind-body interventions each appeared equally efficacious. A separate meta-analysis found similar results in older adults with mild cognitive impairment [50]. Mind-body interventions for treating depression are discussed below. (See 'Mind-body interventions' below.)

●Patients with chronic medical illnesses – Exercise also appears efficacious for treating depression in individuals with coexisting general medical illnesses [36]. As an example, in a meta-analysis of 90 trials in 10,534 participants with chronic illnesses (eg, cardiovascular disease, fibromyalgia, or obesity), participants randomized to exercise had greater improvements in depressive symptoms than control group participants, although variability across studies limited the certainty of evidence [43].

In addition to improving the depressive syndrome, exercise may improve comorbid general medical illnesses. (See "The benefits and risks of aerobic exercise", section on 'Benefits of exercise' and "Strength training for health in adults: Terminology, principles, benefits, and risks", section on 'What medical conditions improve with strength training?'.)

●Patients hospitalized for depression – Limited evidence suggests that exercise may be less effective in individuals who are hospitalized for depression treatment. A meta-analysis of 25 trials found that exercise improved depressive symptoms and that the clinical effect was moderate in the subgroup analysis of three trials of inpatients [32]. Small, open-label trials in patients hospitalized for severe MDD suggest that exercise may augment responses to standard treatments [51-53].

Prevention of depression — We also encourage patients to exercise because it may prevent future depressive symptoms [54,55]. Evidence supporting this approach includes prospective observational studies:

●In a meta-analysis of 15 studies comprising 191,130 participants, individuals who performed half or all of the total recommended weekly amount of physical activity (4.4 or 8 marginal metabolic equivalent task hours/week) demonstrated 18 and 25 percent lower relative risks of depression, respectively, compared with those with lower levels of activity [56].

●In a meta-analysis of 35 studies of over 170,000 participants without depression, those with high levels of baseline physical activity had lower odds of developing depression, compared with those with low levels of activity (adjusted odds ratio 0.84, 95% CI 0.79-0.88) [57].

MIND-BODY INTERVENTIONS — Mind-body interventions are a form of multicomponent exercise that integrates specific movement sequences with breath control and focused attention (or meditation) [58]. Mind-body interventions that may have a potential role in the treatment of MDD include yoga, tai chi, relaxation, and massage. However, data supporting their efficacy are often of low quality, and isolating the effective components of these interventions is difficult given variability between practitioners and types of interventions and the possible benefit of the group setting itself [6].

Yoga — Yoga is a reasonable adjunctive intervention for individuals with major depression [9]. We typically discuss yoga with patients who have prior experience with it or express an interest in mind-body interventions.

Yoga has three main components: physical postures or poses (āsanas), breath control/regulated breathing (prānāyāma), and meditation/relaxation (dhyāna). Yoga differs from exercise by incorporating a meditative focusing of one's mind upon the postures [59]. Many styles of yoga exist with varying levels of exertion, and the preferred style for treatment of depression is unclear. Most studies have evaluated Hatha yoga, which incorporates meditation, strength building, and flexibility training. The optimal duration of yoga therapy for treating depression is also unclear, although most study interventions range from 4 to 12 weeks [60]. General information about yoga is discussed separately. (See "Overview of yoga".)

Yoga has minimal adverse effects (eg, musculoskeletal soreness and injuries). Although yoga may improve depressive symptoms, the magnitude of possible benefit is likely small to moderate. Only low certainty data support its use, with some meta-analyses finding that yoga reduces depressive symptoms and others reporting no significant changes in depression outcomes, particularly in studies comparing yoga with active control interventions.

Meta-analyses of randomized trials support the role of yoga in treating depression [59-62]. As an example, in a 2024 network meta-analysis of 1047 adults with MDD, yoga reduced depressive symptoms, compared with active controls (standardized mean difference [SMD] -0.55, 95% CI -0.73 to -0.36, a moderate effect) [18]. Two earlier meta-analyses found similar results, one of which suggested that more frequent yoga sessions may produce larger reductions in depressive symptoms [63,64]. However, the overall certainty of evidence from meta-analyses is low given high risk of bias and trial heterogeneity (ie, wide range of types of yoga and control interventions).

Tai chi — Tai chi may be a useful adjunctive treatment in individuals with major depression. We typically discuss tai chi with patients who have prior experience with it or express an interest in mind-body interventions.

Tai chi is a mind-body practice that involves mental focus on continuous, slow movements. Although tai chi may reduce depressive symptoms in the general population, its role in treating individuals with major depression is less clear.

Limited evidence supports the use of tai chi in individuals with major depression. As an example, in a network meta-analysis of 343 participants with MDD, tai chi or qigong reduced depressive symptoms compared with active control interventions (SMD -0.42, 95% CI -0.65 to -0.21, a moderate effect) [18]. Similarly, in a trial of 52 individuals with major depression, response (reduction of baseline symptoms ≥50 percent) occurred more frequently in those randomized to tai chi than in those assigned to education or a wait list control (56 versus 21 and 25 percent) [65].

Data from meta-analyses of randomized trials suggest that tai chi may also improve depression outcomes in individuals with depressive symptoms (ie, who do not necessarily have a diagnosis of major depression) [66-68]. As an example, in a meta-analysis of 14 trials of 1959 participants, tai chi interventions seemed moderately more effective for reducing depressive symptoms than nonmindful exercise interventions [66].

Tai chi may also augment the effects of standard treatment with antidepressants. As an example, in a meta-analysis of four trials of 837 participants, those randomized to combination treatment with tai chi and antidepressants experienced greater reductions in depressive symptoms than those assigned to antidepressants alone (SMD -0.58, 95% CI -1.13 to -0.03, a moderate effect size) [68].

Results from these meta-analyses should be interpreted with caution given high levels of study heterogeneity and concerns about risk of bias in the included trials.

Additional information about tai chi is available through the National Center for Complementary and Integrative Health, which is part of the United States National Institutes of Health.

Other interventions

●Meditation – The use of meditation and mindfulness interventions as part of psychotherapy (ie, mindfulness-based cognitive therapy) is discussed separately. (See "Unipolar depression in adults: Investigational and nonstandard treatment", section on 'Meditation' and "Unipolar major depression: Treatment with mindfulness-based cognitive therapy".)

●Relaxation – Relaxation techniques may augment standard treatment for individuals with major depression. Relaxation techniques include progressive muscle relaxation, relaxation imagery (imagining beautiful or peaceful places), or autogenic training (visualizing and inducing a state of warmth and heaviness throughout the body).

Data from meta-analyses of randomized trials suggest that relaxation techniques may be superior to no treatment but less effective than standard treatment. As an example, a meta-analysis of five trials of 136 participants found a moderate reduction in depressive symptoms with relaxation, compared with no treatment [69]. However, in a meta-analysis of nine trials of 286 participants, relaxation was less effective than psychotherapy (primarily cognitive behavioral therapy) [69].

●Massage – Based upon randomized trials, massage therapy may improve depressive symptoms. A meta-analysis of 17 trials compared massage therapy with control conditions (eg, progressive muscle relaxation) in patients with depressive symptoms (n = 786) and found a significant, clinically large effect favoring massage therapy [70].

Information about massage therapy for mild to moderate antenatal depression is discussed separately. (See "Mild to moderate episodes of antenatal unipolar major depression: Choosing treatment", section on 'Adjunctive treatments'.)

●Auricular acupuncture – Auricular acupuncture is safe and possibly effective as an adjunctive treatment for individuals with major depression [71-73]. As an example, in a randomized trial of 74 adults with clinically significant depression symptoms (Patient Health Questionnaire-9 score of ≥10), auricular acupuncture was safe and resulted in higher rates of depression remission at three months, compared with nonspecific ("sham") auricular acupuncture (46 versus 13 percent; relative risk 2; 95% CI 1.2-3.3) [71]. These results await confirmation in larger randomized trials.

General information about acupuncture is discussed separately. (See "Overview of the clinical uses of acupuncture".)

SELF-HELP INTERVENTIONS — Self-help interventions for treating depression include a wide variety of adjunctive therapies, which can range from internet-based psychotherapy (IBP) to structured workbooks, mobile apps, and/or online resources. Self-help therapies can be clinician guided or unguided. Patients with moderate to severe depressive symptoms benefit at least as much from adjunctive self-help interventions as those with milder levels of depression [74].

The use of clinician-guided interventions for treatment of mild episodes of depression is consistent with multiple practice guidelines [12,75].

Internet-based psychotherapy — We typically select IBP as an adjunct to standard treatments or a "stand-alone" alternative to standard treatment in individuals with mild symptom severity. (See 'Selecting a supplemental treatment' above.)

Common features and treatment duration

●Types of interventions – IBP can be clinician guided or unguided. Although both clinician-guided and unguided interventions can improve depressive symptoms, we generally suggest that patients who are interested in internet-based interventions use clinician-guided IBP, if available. Clinician-guided interventions usually involve minimal, intermittent contact with a clinician or paraprofessional who monitors progress and provides support via email, telephone, or virtual visit [76,77]. Although different internet-based interventions exist for depression treatment, they are generally based upon established types of psychotherapy. Internet-based cognitive behavioral therapy (iCBT) has been the most widely studied [78].

●Common features – Common features of internet-based interventions include:

•Behavioral activation

•Cognitive modification

•Relaxation, physical exercise, and lifestyle modification

•Acceptance and mindfulness

•Problem solving

•Interpersonal skills

The order and depth of each module is individually tailored to meet the patient's specific needs and preferences, which are assessed at the beginning [79]. Each module can be completed in 10 to 60 minutes, depending upon reading speed, motivation, and the tailored content that is presented [80,81].

●Duration and number of sessions – Although the structure of individual interventions varies, most have 8 to 18 sessions or modules that take approximately 15 to 60 minutes to complete [80-82]. Some programs offer modules that are individually tailored to meet the patient's specific needs and preferences [79].

Although the optimal number of sessions for improving depression outcomes is unclear, we suggest that individuals who do not respond after six to eight sessions pursue more intensive treatment. Some data suggest that patients who experience minimal improvement after six sessions are unlikely to respond with further treatment [77].

Expected benefits

●As a "stand-alone" intervention – Meta-analyses of randomized trials suggest that IBP results in short-term improvements in depression symptoms and may be useful for individuals with major depression [79,81-93]. Most studies and meta-analysis show greater efficacy for clinician-guided interventions, compared with self-guided interventions [76,77,85,94]. Support for the efficacy of IBP comes primarily from trials that compare it with control conditions rather than standard treatments, such as antidepressants or in-person psychotherapy. Representative meta-analyses include:

•In a network meta-analysis of 36 trials of 8107 participants, participants randomized to guided and unguided iCBT interventions had higher response rates than those who received either treatment as usual or wait list control interventions (mean difference in Patient Health Questionnaire-9 [PHQ-9] scores ranging from -3.3 to -0.9, depending on comparison) [82]. Posttreatment follow-up revealed higher response rates for clinician-guided iCBT compared with self-guided iCBT (mean difference -0.68; 95% CI -1.1 to 0.27; response rates 48 versus 37 percent), especially among participants with PHQ-9 scores of 10 or higher (52 versus 35 percent). Some treatment effects persisted at 6- and 12-month follow-up.

•A 2022 meta-analysis of 19 trials evaluated the efficacy of cognitive behavioral therapy-based computer or internet interventions with minimal clinician guidance (≤10 minutes weekly). Cognitive behavioral therapy-based interventions demonstrated superiority over control interventions (mostly wait list control; standardized mean difference [SMD] in depression symptoms -0.64; 95% CI -0.84 to -0.45), with a moderate effect size [83]. Interventions with combined guidance (ie, telephone plus email) showed greater efficacy than those using only a single strategy. IBP may be effective for individuals with chronic medical conditions, such as hypertension and diabetes [78,89].

●As an adjunct to standard treatment – IBP may also augment the efficacy of face-to-face psychotherapy. As an example, in a 12-week trial of 98 individuals with major depression, the combination of standard (in-person) psychotherapy plus a cognitive behavioral therapy-based internet psychotherapy intervention resulted in greater improvement in depression symptoms compared with standard psychotherapy alone [95].

●Risk of relapse – The durability of benefit from clinician-guided self-help interventions appear time limited, and relapse often occurs [77,96]. As an example, in a prospective study of 439 patients who were successfully treated for depressive and/or anxiety symptoms with a cognitive behavioral therapy-based intervention, relapse occurred in over 50 percent at one year follow-up, typically within six months [97].

●Clinician-guided versus self-guided – Although clinician-guided IBP is generally more efficacious than self-guided IBP, the latter can also improve depression outcomes [79-81]. As an example, in a meta-analysis of 13 trials of 3876 participants with depression symptoms, self-guided iCBT (5 to 11 sessions) resulted in greater improvements in depressive symptoms and rates of treatment response compared with control interventions (eg, waiting list or usual care) [86]. However, the clinical benefit was small, and heterogeneity across studies was large. In a subsequent trial of 376 individuals with MDD, response (reduction of baseline symptoms ≥50 percent) occurred more frequently in participants randomized to an eight-week, self-guided, IBP-type program than in those randomized to usual care (44 versus 6 percent) [81].

●Limitations of the evidence – Existing studies may overestimate the efficacy of internet and other self-help interventions. Most studies compare internet-based interventions for depression with wait list, rather than "active," controls, which may overestimate efficacy estimates. In systematic reviews, IBP demonstrates greater efficacy when compared with wait list controls than with usual care or active controls [82,85,87].

Few studies compare internet-based interventions with in-person psychotherapy or antidepressant treatment [85]. Moreover, randomized trials of IBP may include participants with better prognoses than those included in trials of in-person psychotherapy [98]. As an example, studies often recruit individuals in the community rather than from clinical settings, and the former may have less severe or chronic depression [82,96]. Low-intensity psychotherapy interventions may also have limited effectiveness for preventing relapse [77,96,97]. Additional methodologic issues that may limit the certainty of evidence include study heterogeneity (ie, variability between studies) and incomplete allocation concealment (ie, investigators were not blinded to how participants were randomized) [77,88].

Other self-help modalities — A variety of other types of self-help interventions exist for the treatment of depression, including community support groups, smartphone applications, and bibliotherapy [74,99].

Community support groups — Multiple community groups composed of patients and family members provide education and support for each other with regard to mental illnesses such major depression [100]. Examples of national organizations with local chapters include the National Alliance on Mental Illness and the Depression and Bipolar Support Alliance [101,102].

Smartphone applications — Smartphone applications (apps) are a reasonable addition to standard treatment for depression. Smartphone apps may cause a small to moderate improvement in depression symptoms, although the quality of randomized trials supporting their use is variable [103]. As an example, in a meta-analysis of 18 trials of 3414 participants with depressive symptoms, those randomized to smartphone apps had greater symptom improvement than those randomized to control groups [87]. The 22 studied apps varied in duration (4 to 24 weeks). Heterogeneity across studies was large.

A subsequent meta-analysis suggests that smartphone apps may have efficacy in individuals with moderate major depression (not simply depressive symptoms) [104]. The meta-analysis of 13 studies of 1407 individuals with at least moderate depression revealed a moderate reduction in depressive symptoms in those randomized to mobile apps compared with control interventions (SMD 0.50, 95% CI 0.40-0.61). However, the use of inactive controls, high risk of bias in some trials, and moderate heterogeneity limit the certainty of this evidence.

Bibliotherapy — Despite its uncertain efficacy, bibliotherapy is a reasonable addition to standard treatment for depression given that it entails few, if any, adverse effects. Bibliotherapy is the use of structured workbooks for depression treatment. The books are often based on the principles of cognitive behavioral therapy and provide education and structured exercises to help readers manage depressive symptoms, identify and reframe negative thoughts, and re-engage in positive activities. Weak evidence from small randomized trials supports the efficacy of bibliotherapy for reducing depressive symptoms [105-108]. Representative examples include the following books: Overcoming Depression One Step at a Time: The New Behavioral Activation Approach to Getting Your Life Back and The Feeling Good Handbook [109,110].

BRIGHT LIGHT THERAPY — Bright light therapy (or phototherapy) is a standard treatment for seasonal affective disorder that can be used as a supplemental treatment for individuals with MDD. Meta-analyses of randomized trials support the efficacy and safety of bright light therapy for treating nonseasonal MDD. The use of bright light therapy for the treatment of nonseasonal MDD and seasonal affective disorder is discussed separately. (See "Unipolar depression in adults: Investigational and nonstandard treatment", section on 'Bright light therapy' and "Seasonal affective disorder: Treatment", section on 'Bright light therapy'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Depressive disorders" and "Society guideline links: Exercise in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Depression in adults (The Basics)" and "Patient education: Exercise and movement (The Basics)" and "Patient education: Exercise and movement as you get older (The Basics)")

●Beyond the Basics topics (see "Patient education: Depression in adults (Beyond the Basics)" and "Patient education: Depression treatment options for adults (Beyond the Basics)" and "Patient education: Exercise (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Role of supplemental interventions in major depression – Standard treatments for managing major depression are pharmacotherapy and in-person psychotherapy. Supplemental interventions for treating depression include exercise, mind-body interventions (eg, yoga, tai chi, relaxation, and massage), internet-based psychotherapy (IBP), light therapy, and other self-help interventions.

•Patients with mild episodes – Supplemental interventions can serve as alternatives to standard treatment in patients with mild depression if they have a short duration of symptoms (≤3 months), no prior episodes of depression, no major functional impairment, and are closely monitored (ie, every two to four weeks) for symptom progression. Other patients with mild depression can use supplemental interventions as adjuncts to standard treatment. (See 'Role of supplemental treatments' above and "Major depressive disorder in adults: Approach to initial management", section on 'Choosing a treatment regimen for patients with major depression'.)

•Patients with moderate to severe episodes – Supplemental interventions are useful adjuncts to standard treatment with antidepressants and/or psychotherapy for all individuals with major depressive disorder. We do not substitute supplemental interventions for standard treatment in individuals with moderate to severe episodes. (See 'Role of supplemental treatments' above and "Major depressive disorder in adults: Approach to initial management", section on 'Choosing a treatment regimen for patients with major depression'.)

●Selecting a supplemental intervention – In selecting a specific supplemental treatment, we take into account treatment efficacy, cost, availability, and ease of use and patient preferences and comorbidities. (See 'Selecting a supplemental treatment' above.)

•First line – We suggest exercise as a first-line supplemental intervention (Grade 2C). Exercise has demonstrated efficacy in reducing depressive symptoms in a wide range of adults, including older individuals and those with chronic medical conditions. However, most studies of exercise for depression are small, with risk of bias and a wide range of heterogeneity across studies.

We encourage patients to increase their physical activity with an ultimate goal of at least 30 and up to 60 minutes of moderate to vigorous physical activity at least three times weekly, if possible. Resistance exercise is an acceptable alternative. We encourage patients who cannot engage in this level of exercise to increase their physical activity as much as possible. To optimize adherence, we encourage patients to participate in supervised exercise (eg, group classes or sessions with a trainer). We typically encourage patients to continue exercise indefinitely, given its overall health benefits. (See 'Exercise and physical activity' above.)

•Reasonable alternatives or additions – For individuals who are not able or willing to exercise or who want additional supplemental interventions, options include the following:

-Mind-body interventions – Mind-body interventions, such as tai chi and yoga, are reasonable alternatives to aerobic or resistance exercise, but the evidence supporting their use is less robust. Mind-body interventions integrate specific movement sequences with breath control and focused attention (or meditation). Interventions with a potential role for depression treatment include yoga, tai chi, and relaxation. (See 'Mind-body interventions' above.)

-Self-help interventions – Self-help interventions include IBP, community-based support groups, smartphone applications, and bibliotherapy.

IBP has demonstrated efficacy for improving depressive symptoms. It can be used as an adjunct to standard treatment for any patient or as an alternative to standard treatment for selected patients with mild symptom severity. Individuals who may be most suited for IBP include those who want psychotherapy but are unable to find or access a therapist or who are interested in self-help interventions. For patients who are interested in this modality, we typically encourage an intervention that is clinician guided (rather than self-guided) and based in principles of cognitive behavioral or other evidence-based psychotherapy. (See 'Internet-based psychotherapy' above.)

Modest evidence supports the use of other self-help approaches, including community support groups, smartphone applications, and bibliotherapy.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Gregory Simon, MD, MPH, who contributed to an earlier version of this topic review.