Depressive Disorders

Definition AND EpidemiologyTop

The group of depressive disorders share a common set of symptoms including periods of either low mood or loss of pleasure (anhedonia) and are accompanied by sleep changes, feelings of guilt, low energy, poor concentration, appetite changes, psychomotor slowing or agitation, and suicidal ideation.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), depressive disorders are classified into:

1) Major depressive disorder (MDD), single and recurrent episodes.

2) Persistent depressive disorder (previously “dysthymia”).

3) Premenstrual dysphoric disorder.

4) Substance/medication-induced depressive disorder.

5) Depressivedisorder due to another medical condition.

6) Other specified depressive disorder.

7) Unspecified depressive disorder.

MDD (or “depression,” as it is commonly known) is a debilitating condition that affects many people worldwide. The average lifetime prevalence rates have been reported between 2% and 21%. Across the lifespan, MDD is more common among women.

In terms of disability, unipolar depression (depression in the absence of hypomania or mania) was ranked in 2021 by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) as the twelfth leading cause of years lost to disability (YLD), as well as the second highest source of all-cause disability-adjusted life years (DALYs) among all ages and sexes.Evidence 1Moderate Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Gutiérrez-Rojas L, Porras-Segovia A, Dunne H, Andrade-González N, Cervilla JA. Prevalence and correlates of major depressive disorder: a systematic review. Braz J Psychiatry. 2020 Nov-Dec;42(6):657-672. doi: 10.1590/1516-4446-2020-0650. PMID: 32756809; PMCID: PMC7678895. GBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024 May 18;403(10440):2133-2161. doi: 10.1016/S0140-6736(24)00757-8. Epub 2024 Apr 17. PMID: 38642570; PMCID: PMC11122111.

Clinical Features And DiagnosisTop

Screening for Major Depressive Disorder

1. It is important to accurately recognize, diagnose, and treat depression.

2. Depressed patients do not always present with mood complaints. A substantial proportion of depressed patients present only with somatic complaints.Evidence 2Moderate Quality of Evidence (moderate confidence that we know the true relationship). Quality of Evidence lowered due to unexplained heterogeneity among centers. Simon GE, VonKorff M, Piccinelli M, Fullerton C, Ormel J. An international study of the relation between somatic symptoms and depression. N Engl J Med. 1999 Oct 28;341(18):1329-35. PMID: 10536124.

3. Goals of assessment include establishing rapport, evaluating for safety, assessing for comorbidities, and providing patient education.

4. Screening for depression can be done using several tools, which have been shown to be moderately but equally effective. They include:

1) The 9-item and 2-item Patient Health Questionnaire (PHQ-9 and PHQ-2): Examples of these questionnaires: see mdcalc.com; Table 1; Table 2. The 2-item instrument is a highly sensitive screen for depression (98% sensitivity, 86% specificity), however the 9-item questionnaire allows for assessing the response to treatment at follow-up visits by showing the change in the total score.

2) Hamilton Depression Rating Scale (HDRS).

3) Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR).

4) Beck Depression Inventory first (BDI-I) or second (BDI-II) edition.

5) Zung Self-Rating Depression Scale (SDS).

6) Center for Epidemiologic Studies-Depression Scale (CES-D).

5. For specific populations, other screening tools include the Geriatrics Depression Scale (GDS), Cornell Scale for Depression in Dementia (CSDD), and the Edinburgh Postnatal Depression Scale (EPDS). 

Note that screening tests are not diagnostic. Positive screens should be followed by a clinical interview to confirm the diagnosis of depression.

Diagnosing Depression

According to the DSM-5-TR, a diagnosis of MDD requires the presence of ≥5 symptoms, of which ≥1 must be either depressed mood or anhedonia. Additional symptoms may include sleep changes, feelings of worthlessness or excessive guilt, low energy, poor concentration, appetite changes, psychomotor slowing or agitation, and suicidal ideation. These symptoms must continue for 2 weeks, cause significant distress or functional impairment, and not be better explained by other mental disorders, other medical disorders, or the effect of a substance. These criteria constitute a major depressive episode (MDE). One or more major depressive episodes make up MDD.

Differential diagnosis includes grief, other psychiatric conditions, systemic medical conditions, medications, and substance use.

Mild depression is defined in the DSM-5-TR as “few, if any, symptoms in excess of those required” for the diagnosis. The intensity of symptoms is “manageable” and there is “minor impairment” in functioning.

Moderate depression according to the DSM-5-TR refers to situations where the intensity and impairment due to depressive symptoms fall between mild and severe.

Severe depression according to the DSM-5-TR refers to situations where “the number of symptoms is substantially in excess of that required” for the diagnosis, the symptoms are “seriously distressing and unmanageable,” and they “markedly interfere” with functioning.

Other Forms of Depression

Depressive symptoms occur in a number of psychiatric disorders. In medical settings, adjustment disorder with depressed mood and MDD are the most commonly seen. Adjustment disorders occur in response to a stressor, with symptoms of marked distress or impaired functioning. Symptoms must develop within 3 months of the stressor occurring and should resolve within 6 months of the stressor ending.

Although MDD can also occur after a stressor, the key difference between MDD and adjustment disorder is whether the patient perceives their low mood would remit if the stressor were removed. In adjustment disorder the removal of the stressor would lead to remission of depressive symptoms. In MDD the removal of the stressor might improve symptoms marginally but not completely.

Risk FactorsTop

Risk Factors in the Development of Depression

A number of risk factors have been identified in the development of depression. These include negative affectivity (neuroticism), adverse childhood experiences, female sex, low socioeconomic status, family history, non–mood related psychiatric disorders (eg, anxiety, substance use), and chronic or disabling systemic medical conditions (eg, diabetes mellitus, cardiovascular disease). Further information about the strength of those associations: Table 3.

In older adult patients, risk factors for depression include advanced age, female sex, being single (including being divorced or widowed), bereavement, chronic or disabling systemic medical conditions (including dementia), sleep disturbance, and institutionalized living. It should be also noted that older adults, particularly men, are also at high risk for suicide.

Depression due to Another Medical Condition

Some systemic medical conditions cause symptoms that overlap with those of depression and can be said to mimic depression (eg, hypothyroidism), while others appear to increase the risk of developing depression or may have a joint factor that causes depression (eg, multiple sclerosis).

It is important to screen each patient for other simple or reversible causes of depressive symptoms that are plausible within each patient’s own context and treat the underlying condition when possible. Treatment of depression should be considered when depressive symptoms appear to be interfering with functioning and persist despite treatment of the underlying systemic medical condition.

Medical conditions that may be associated with depressive symptoms include B12 deficiency (particularly in older adults), hypothyroidism, Cushing syndrome, Parkinson disease, Huntington disease, Alzheimer disease, traumatic brain injury, stroke, multiple sclerosis, systemic lupus erythematosus, neoplasm, HIV, cytokine-induced sickness behavior, and delirium.

Medication-Induced Depression

In the literature, there are reports of medications causing depression. However, most claims are not supported by high-quality evidence.

There are varying degrees of evidence suggesting that a number of medications are particularly likely to cause depression or be associated with depressive symptoms. These include antibiotics (eg, penicillins, quinolones), antiviral agents (eg, efavirenz), beta-blockers and calcium channel blockers, other selected antihypertensive medications (eg, clonidine, guanethidine, methyldopa), retinoic acid derivatives, anticonvulsants, glucocorticoids, interferon, L-dopa.

Because individual response to treatment varies between patients, if depressive symptoms are noted to occur temporally after initiation of a medication and remit when the medication is stopped, consider using another agent.

TreatmentTop

General Considerations

Please remember that depression is not simply “the blues,” and it is not a sign of a character flaw or weak will. The compassionate clinician recognizes that patients with depression will not improve by being advised to “pull themselves together” or to “just get over it.” Depression is a serious illness with profound consequences that can—and should—be treated in this modern era.

Be sure to listen attentively to your patient with compassion and sensitivity, and do not underestimate their complaints. Be advised that the safety of your patient is paramount, and thus, any declaration of suicidal ideation should be assessed carefully, and appropriate action taken when necessary.

It is important to note that there are multiple management options to treating depression, including lifestyle interventions, psychotherapy, pharmacotherapy, neuromodulation (eg, electroconvulsive therapy [ECT] and repetitive transcranial magnetic stimulation [rTMS]; see below); or a combination of these modalities. The following is a more in-depth explanation of management approaches based on the severity of symptoms.

Appropriate management should be individualized to each patient according to:

1) The nature of the disorder (that is, confirm the diagnosis of depression, exclude other causes).

2) The severity of symptoms.

3) Any medical or psychiatric comorbidities (including the possibility of drug-drug interactions and pregnancy).

4) Previous response to treatment (in the patient or other family members).

5) The existing support, resources, preferences, and psychosocial environment of the patient.

The assessment of efficacy of pharmacologic treatment of depression is hampered by short duration of trials, large number of patients not completing studies, and confounding of treatment effect by spontaneous remissions. The treatment effect is also influenced by the various methods of measurement of depressive disorder and outcomes of interests adding to the limitations of the generalizability of trial findings. The overall body of evidence suggests shortening of depressive episodes and possibly prevention of recurrent episodes, especially among patients with previous recurrences. The suggestions include continuation of treatment for up to 6 to 12 months after remission and possibly longer or permanently after consecutive relapses. Such relapses are common, and after discontinuation of treatment about one-third of patients will experience relapse of symptoms within 1 year.

Management of Mild Depression

1. Self-care is recommended: NEST-S: “Nutrition, exercise, sleep, time for self, and social support” are helpful in the management of mild depression, and there is good evidence for exercise in particular.

2. Psychotherapy and pharmacotherapy are similarly effective in the management of mild depression, however, psychotherapy is preferred due to a low risk of adverse effects. First-line psychotherapy treatment may involve:

1) Cognitive behavioral therapy (CBT): CBT involves 12 to 16 sessions of psychotherapy treatment that identifies and treats maladaptive behaviors, cognitive distortions, negative schemas, and the cognitive triad of a negative view of self, the world, and the future in order to improve mood symptoms.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). National Institute for Health and Clinical Excellence. Depression in adults: recognition and management (CG90). Evidence. https://www.nice.org.uk/guidance/cg90/evidence. Published October 2009. Updated April 2016. Accessed August 17, 2016.

2) Behavioral activation therapy (BAT): It is a brief structured therapy that includes a number of sessions (from 2 to 24, usually 12) provided weekly or twice a week in an individual or group format. BAT is a component of CBT; however, the focus is on actions to increase engagement of the patient with their world and increase rewarding behaviors based on the principle that “what you do affects how you feel.” The effects of BAT and CBT on depression are similar.Evidence 4Moderate Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Uphoff E, Ekers D, Robertson L, et al. Behavioural activation therapy for depression in adults. Cochrane Database Syst Rev. 2020 Jul 6;7(7):CD013305. doi: 10.1002/14651858.CD013305.pub2. PMID: 32628293; PMCID: PMC7390059.

3) Interpersonal therapy (IPT): Interpersonal therapy is a 12- to 16-session psychotherapy treatment that focuses on improving mood symptoms by identifying and working through distressing life events, which include complicated bereavement (grief), role disputes (interpersonal conflicts), and role transitions.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision. National Institute for Health and Clinical Excellence. Depression in adults: recognition and management (CG90). Evidence. https://www.nice.org.uk/guidance/cg90/evidence. Published October 2009. Updated April 2016. Accessed August 17, 2016.

4) Problem-solving therapy (PST): The theory behind problem-solving therapy is to improve mood by improving patients’ problem-solving skills. The goal of this psychotherapy is to identify the patient’s problems, consider various solutions, decide on the most appropriate solution, prepare a plan to carry out that solution, and assess whether the solution was effective.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (especially against or in addition to antidepressants) and heterogeneity of results against different comparators. National Institute for Health and Clinical Excellence. Depression in adults: recognition and management (CG90). Evidence. https://www.nice.org.uk/guidance/cg90/evidence. Published October 2009. Updated April 2016. Accessed August 17, 2016.

5) Self-management resources such as workbooks and websites are suggested when low resources exist for traditional psychotherapy.

3. Free examples developed at Simon Fraser University (sfu.ca) include:

1) Antidepressant Skills Workbook (for adults).

2) Antidepressant Skills at Work: Dealing with Mood Problems in the Workplace.

3) Positive Coping with Health Conditions.

4) Managing Depression: A Self-help Skills Resource for Women Living With Depression During Pregnancy, After Delivery, and Beyond.

5) Dealing with Depression (for adolescents).

4. Resources available at cost include:

1) Greenberger D, Padesky, CA. Mind Over Mood: Change How You Feel by Changing the Way You Think. 2nd ed. New York: Guilford Publications; 2015.

2) Beating the Blues (website): beatingtheblues.co.uk.

3) moodgym training program (website): moodgym.com.au.

Management of Moderate Depression

Psychotherapy and pharmacotherapy are similarly recommended in the treatment of moderate depression; however, pharmacotherapy may be preferred to better treat depressed mood, somatic symptoms, and suicidality in the acute phase. Combination therapy may also be recommended in some cases. First-line pharmacologic treatment may involve drugs from different classes: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs; mirtazapine), a norepinephrine-dopamine reuptake inhibitor (NDRI) (bupropion), other serotonin modulators and stimulators (eg, vilazodone, vortioxetine), and a melatonin agonist (agomelatine), with some suggestion that escitalopram, vortioxetine, and agomelatine have the best balance between efficacy and acceptability.Evidence 7Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the small number of direct comparisons and short duration of many studies. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. Epub 2018 Feb 21. PMID: 29477251; PMCID: PMC5889788. Other useful modalities include different types of psychotherapy (BAT, CBT, IPT, PST), as outlined above.

Management of Severe Depression

1. Combination therapy of pharmacotherapy and psychotherapy is recommended to increase the probability of remission.

2. Major depressive episodes with psychotic features can be treated with a combination of an antidepressant and an antipsychotic medication.

3. ECT should be considered for severe, treatment-resistant depression or depression with psychotic features.

Management of Depression in Older Adults

1. Exercise and mind-body interventions (eg, yoga, tai-chi) have growing evidence for monotherapy in mild depression, or as adjunct treatment. For example, moderate-intensity exercise and combination exercise (ie, aerobic and strength training) can be effective.

2. Psychotherapy: CBT and PST are two of the most effective psychotherapies for older adults, but there is still evidence for BAT and IPT too.

3. Sertraline and duloxetine are considered first-line antidepressant treatments for older adults because of efficacy and tolerance.

4. Be mindful of adverse effects, which may be exaggerated in older adults (eg, polypharmacy interactions, anticholinergic adverse effects, hyponatremia, gastrointestinal bleeding, and QTc prolongation). In general, older adult patients should be started on lower doses of psychotropic medications and dose escalation should occur slowly, with the goal of attaining a therapeutic dose.

Pharmacotherapy

1. Choosing an antidepressant medication: The choice of an antidepressant, when indicated, should be discussed with the patient. The selection should be based on the patient’s preference, type of symptoms, adverse effect profile of the medication, comorbidities, and concomitant medication use. When selecting an antidepressant, most clinicians start with an SSRI, as this class is well tolerated and effective.

1) SSRIs, SNRIs, and newer antidepressants such as bupropion, mirtazapine, or vortioxetine are considered first-line medications for depression.

2) Generally, quetiapine, trazodone, and TCAs are considered second-line treatment and monoamine oxidase inhibitors (MAOIs) are considered third-line agents due to their adverse-effect profiles.

A network meta-analysis comparing different antidepressants ranked the following antidepressants as the top 5 based on their efficacy and tolerability: mirtazapine, escitalopram, sertraline, vortioxetine, and agomelatine.

Other treatment options exist, such as the addition of third- or second-generation antipsychotics (eg, aripiprazole, brexpiprazole, quetiapine) along with other classes of antidepressants. However, more complex treatment regimens should be used under the supervision of a psychiatrist.

2. Major adverse effects and interactions of antidepressant agents: Table 4.

3. Suggestions for initiating antidepressant medications:

1) Before starting any antidepressant agent, consider completing serum sodium tests (eg, in older adults), baseline liver function tests, and a metabolic workup, such as screening for diabetes mellitus, dyslipidemia, and thyroid disease.

2) Obtain an electrocardiogram (ECG) to determine any baseline arrhythmias as well as the QTc (which can be prolonged with psychotropic use) prior to initiation of a medication.

3) Consider follow-up every 1 to 2 weeks when titrating an antidepressant. The frequency can then be reduced to every 2 to 4 weeks when a therapeutic dose is reached, depending on the severity of depression and response to treatment.

4) In selecting the appropriate antidepressant agent, patient comorbidities should be taken into account along with any adverse effects of the medications. For example, mirtazapine is associated with increased appetite and weight gain, and therefore may be avoided in patients with obesity and diabetes mellitus.

4. Dosing of common first-line medications effective in treating major depression: Table 5.

5. Assessing treatment response:

1) Initial treatment response: Most clinical trials define clinical response as a ≥50% reduction in the score on a depression rating scale, while clinical remission is defined as a score within the normal range of the scale. Improvement may begin within 1 to 2 weeks of treatment; however, it can take >8 weeks for response and/or remission.

2) Adjusting medication treatment:

a) If there is <20% improvement on one of the depression scales after 2 weeks, consider increasing the dose of medication.

b) If there is ≥20% improvement after 4 to 6 weeks (but not remission), consider an additional 2 to 4 weeks of the same treatment.

c) If there is no further improvement, consider other treatment strategies: psychotherapy such as CBT and IPT; switching antidepressants; augmentation (combining an antidepressant with a second medication) under the supervision of a psychiatrist in some cases; neuromodulation under the supervision of a psychiatrist.

6. Length of therapy: Pharmacotherapy should be continued for ≥6 months after remission. For those with recurrence of depression or risk factors for recurrence, treatment is recommended to be continued for ≥2 years. Depending on the number of recurrent episodes, longer treatment courses can be considered. Dosing should be continued at the same effective dose, not a reduced dose.

7. Switching antidepressant medicationsEvidence 8Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity of findings, indirectness to today’s modalities, and observational nature of some data. Ruhé HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. 2006 Dec;67(12):1836-55. Review. PubMed PMID: 17194261. Han C, Wang SM, Seo HJ, et al. Aripiprazole augmentation, antidepressant combination or switching therapy in patients with major depressive disorder who are partial- or non-responsive to current antidepressants: a multi-center, naturalistic study. J Psychiatr Res. 2014 Feb;49:75-82. doi: 10.1016/j.jpsychires.2013.11.001. Epub 2013 Nov 12. PubMed PMID: 24268719.: No difference exists between switching within the same class of medications versus switching to a different class of medications. However, if a patient fails 2 antidepressants of the same class, consider switching to a different class.

1) The technique for safe switching to a different class of antidepressant agents depends on drug-drug interactions and the pharmacologic properties of the medications. For example, when switching from SSRIs to MAOIs, withdraw SSRIs first and wait for 2 weeks (in the case of fluoxetine, wait for 5 to 6 weeks) before starting MAOIs.

2) If switching an SSRI to venlafaxine, cross-taper cautiously and start venlafaxine at a smaller dose of 37.5 mg.

3) If switching from mirtazapine to a TCA, withdraw mirtazapine first and then start the TCA.

4) When stopping antidepressants, consider reducing the dose gradually over 4 weeks.

8. Tapering medications: Abrupt discontinuation of antidepressant agents can lead to discontinuation symptoms. Common antidepressant discontinuation symptoms include nausea, headache, light-headedness, chills, body aches, insomnia, neurologic symptoms such as paresthesias, and “electric shock-like” phenomena. When stopping antidepressants, consider reducing the dose gradually over 4 weeks if tolerated. Some patients may need a slower reduction over a longer period. Some discontinuation symptoms may mimic the underlying depressive symptoms, which may recur on reducing and stopping medications. Medications associated with the highest risk of discontinuation symptoms include paroxetine and venlafaxine. Examples of medications with lower risk of withdrawal symptoms include fluoxetine, mirtazapine, vortioxetine and bupropion.

Neuromodulation

There is also evidence for the use of neuromodulation in treating depression. rTMS, ECT, magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagal nerve stimulation (VNS) are all neuromodulation techniques that can be used to treat depression. These interventions generally change central nervous system activity by applying magnetic or electrical stimulation. Two common examples of noninvasive interventions include rTMS and ECT. Amongst different types of neuromodulation in Canada, rTMS is considered first line for treatment-resistant depression, and ECT could be considered first line for severe major depressive episodes and can also be used for treatment-resistant depression. In comparison with ECT, rTMS does not require general anesthesia and there are no known cognitive adverse effects. Neuromodulation typically requires referral to a specialized psychiatric service to determine eligibility and to deliver treatment sessions.

Novel Pathway Therapeutics: Ketamine and Serotonergic Psychedelics

There is evidence for the use of ketamine (an N-methyl-D-aspartate [NMDA] receptor antagonist) in treatment-resistant depression.Evidence 9Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and the risk of bias. Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med. 2023 Jun 22;388(25):2315-2325. doi: 10.1056/NEJMoa2302399. Epub 2023 May 24. PMID: 37224232. IV racemic ketamine administered in a single dose may produce rapid antidepressant effects which, in some patients, may last several days. Therefore, a critical aspect of further research is sustaining the antidepressant effects of ketamine. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Some have suggested the approach of administration of ketamine to elicit the rapid antidepressant effects, followed by specific targeting of the downstream signaling pathway to extend the antidepressant effects without the need for repeated ketamine dosing that may be required for the treatment of depression in the long term.

There is also growing evidence for the use of serotonergic psychedelics such as psilocybin for the treatment of depression.Evidence 10Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness. Raison CL, Sanacora G, Woolley J, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530. PMID: 37651119; PMCID: PMC10472268. Psilocybin trials are often combined with supportive psychotherapy to help prepare patients for treatment, monitor their treatment sessions, and integrate their experiences afterwards. Similar to neuromodulation, these interventions also generally require a referral to a specialized psychiatric clinic. Unlike rTMS and ECT, these alternative treatments are still experimental, or are only available through special drug access programs within countries. For both therapeutics, issues with proper controls and regulation still need to be addressed before more widespread implementation. Future studies aimed at other effective treatments for depressive disorders, especially those with rapid onset, sustained efficacy, and fewer adverse effects are needed.

PrognosisTop

Remission is defined as a period of ≥2 months with no symptoms, or only 1 to 2 symptoms present to no more than a mild degree. It can be expected after 2 months for 50% of patients and within 1 year for 80% of patients, regardless of whether the depression is treated.

Decreased rates of remission are expected if the patient has persistent depressive disorder, comorbid psychiatric conditions with poor response (eg, anxiety, trauma related, substance use, and personality disorders), comorbid medical conditions that are untreated or undertreated (eg, sleep apnea, thyroid disease), or stressors.

The risk of recurrence is higher in individuals with previous multiple episodes, in patients whose previous episodes were considered severe, in those who still have residual symptoms of depression, and in those with chronic depression.

TablesTop