Highlights of the International Consensus Statement on Major Depressive Disorder

David J. Nutt, DM, FRCP, FRCPsych, FMedSci

Neuropsychopharmacology Unit, Division of Experimental Medicine, Imperial College, London, United Kingdom

Experts in psychiatry gathered for the International Consensus Group on Depression to outline a universal treatment algorithm for depression with the purpose of merging the evidence base and standards of clinical practice from various countries, including the United States, Europe, the Middle East, China, and Japan. The topics addressed included screening for and diagnosing depression, treating depression in primary care or referring to a specialist, and using preferred treatments for depression while considering treatment availability, cost effectiveness, and optimal dosing strategies. To access the full text of the roundtable, see the supplement article “International Consensus Statement on Major Depressive Disorder.”1

Screening for Depression

To ensure accurate diagnoses and treatment, clinicians should periodically screen all patients for depression. One simple, cost-effective, and widely accepted screening tool is the PHQ-2,2 an assessment consisting of 2 questions to which patients’ answers signal whether or not a further clinical assessment regarding depression is necessary. Because some cultures may present with depression differently (eg, reporting more somatic than cognitive or emotional symptoms), other techniques, such as inquiring about the patient’s sleep and sexual functioning, may indicate that a further assessment for depression is warranted. For more information on screening tools, see the supplement article by Alan J. Gelenberg, MD, “Using Assessment Tools to Screen for, Diagnose, and Treat Major Depressive Disorder in Clinical Practice.3

Diagnosing Depression

After a patient screens positive for depression, an in-depth diagnostic examination is required. The consensus group recommended using measurement-based tools to diagnose depression and to determine the level of depressive severity, the presence of any co-occurring psychiatric or medical disorders, and the risk of suicidality. The PHQ-94 and the HADS5 diagnostic tools assess patients’ levels of anhedonia, depressed mood, and psychomotor retardation, and the PHQ-9 also evaluates patients’ sleeping and eating habits, self-esteem, and self-harm/suicidal thoughts. A clinical interview and differential diagnosis should always accompany the use of diagnostic tools to ensure a correct diagnosis.

Psychiatric and medical conditions that may be mistaken for, may co-occur with, or may mask major depression include adjustment disorder, bipolar disorder, psychosis, substance abuse, and medical illnesses, particularly thyroid conditions. A patient who has any of these conditions, a risk of suicide or harm to self or others, or treatment resistance (ie, a history of multiple unsuccessful treatment attempts) should be referred to a specialist.6 Further, a patient with extremely severe MDD should be hospitalized. For more information on using diagnostic tools, see the supplement article by Alan J. Gelenberg, MD, “Using Assessment Tools to Screen for, Diagnose, and Treat Major Depressive Disorder in Clinical Practice.”3

Treating Depression

Helping patients achieve symptomatic remission and full functional recovery is the ultimate goal of depression treatment. To aid in this process, the consensus group designed an algorithm of recommended treatment practices for physicians based on the current Japanese treatment algorithm for depression (see Figure 1 in the supplement article “International Consensus Statement on Major Depressive Disorder1).

After confirming a diagnosis of MDD, if the depression is mild or moderate, then clinicians should choose an appropriate treatment based on the individual patient’s needs and preferences while considering treatment availability, cost-effectiveness, safety, and optimal dosing strategies. Additionally, establishing a therapeutic alliance and educating patients are critical early steps in the treatment of depression.


Establishing a therapeutic alliance. A positive working relationship and strong therapeutic alliance between clinicians, patients, and families substantially increases the odds that patients will achieve remission.7 Patients should be educated about depression and its treatment, including the potential side effects and drug-drug interactions associated with antidepressant treatment and the importance of taking the medication as prescribed. Clinicians should immediately respond to any worries the patient has about taking medication, describe the follow-up plan, and reassure the patient that, as treatment progresses, any problems that arise will be promptly addressed. This collaborative dialogue is the most effective strategy to improve treatment adherence for patients with mood disorders.8

Nonpharmacologic treatments for depression. When educating patients about treatment options, clinicians should inform patients of pharmacologic as well as nonpharmacologic treatments. Available nonpharmacologic options include psychotherapy, ECT, rTMS, VNS, and DBS, all of which should be administered by a psychiatric specialist. Psychotherapy is an integral part of patients’ treatment and should be considered for initial therapy for mild depression and as augmentation to an antidepressant for moderate or severe depression or for patients with adherence problems.9 ECT, rTMS, VNS, and DBS stimulate brain activity by inducing neurophysiologic effects via electric currents or magnetic impulses. Generally, these treatments are reserved for patients with severe depression and are not considered a first-line treatment option for depression.

Selecting an antidepressant. Because the availability of depression treatments varies from country to country, antidepressants are discussed as a class rather than recommendations being made for specific agents. For patients with moderate or severe depression, clinicians should routinely recommend antidepressant therapy. Because of their superior tolerability and safety profiles, the use of newer antidepressants such as SSRIs, SNRIs, or NDRIs are encouraged over the use of MAOIs or TCAs, if costs permit (see Table 2 in the supplement article “International Consensus Statement on Major Depressive Disorder1). Although several agents in each of these classes are currently available, robust differences in overall efficacy between contemporary antidepressants do not appear to exist.6 Therefore, the consensus group recommended that clinicians become familiar with 2 or 3 antidepressants from each class, including knowing the side effect profiles, dosing strategies, and drug-drug interactions, which will help in selecting an appropriate medication based on each individual patient’s needs. Additionally, although benzodiazepine monotherapy is commonly practiced for MDD in some regions, it is not a standard treatment approach and should be avoided.

Antidepressant safety and tolerability. All antidepressants carry some risk of side effects, including nausea, sedation, insomnia, sexual dysfunction, and weight gain. Clinicians should disclose the potential for the emergence and/or worsening of suicidal ideation during antidepressant therapy for patients aged 24 years or younger. While the presence of these side effects may deter some patients from seeking or accepting treatment for their depression, clinicians should stress to patients that the risks of untreated depression, on average, greatly outweigh the risks associated with antidepressant therapy (including the risk of emergent/worsening suicidal ideation). For more in-depth information on antidepressants, see the supplement article by George I. Papakostas, MD, “The Efficacy, Tolerability, and Safety of Contemporary Antidepressants.”10

Optimizing antidepressant dosages. The goal of a successful dosing strategy for MDD is to achieve an effective and tolerable dose as soon as possible. Upon reaching an effective dose, clinicians should assess patients’ symptomatic improvement and medication tolerability before adjusting the dosage or switching to another agent. As a reference point, clinicians should consult the starting, initial target, and maximum daily doses as well as titration schedules for SSRIs, SNRIs, and NDRIs as recommended by the APA,9 the TMAP,11 and the WFSBP12 (see Table 3 in the supplement article “International Consensus Statement on Major Depressive Disorder1).

If a medication is inefficacious or intolerable, reasonable treatment options include modifying the antidepressant dose, augmenting or combining the current antidepressant with another medication, or switching to a different antidepressant. Before employing augmentation or switching strategies, if possible, refer the patient to an expert primary care physician or psychiatric specialist who is accustomed to and comfortable with implementing complex treatment strategies for patients with depression.

If remission is achieved during the course of therapy, the consensus group recommended continuing that medication regimen for at least 6 months to help maintain remission and prevent relapse.

Monitoring antidepressant treatment. During all phases of treatment, clinicians should actively monitor a patient’s course of illness with measurement-based assessments such as the PHQ-9,4 the CGI,13 HDRS,14 or QIDS-SR.15 For more information on monitoring tools, see the supplement article by Alan J. Gelenberg, MD, “Using Assessment Tools to Screen for, Diagnose, and Treat Major Depressive Disorder in Clinical Practice.”3 Generally, physicians should choose a tool that is convenient and inexpensive and then use it consistently throughout treatment; patient-rated scales save time and can be completed on paper, by telephone, or by computer.


This International Consensus Statement on Major Depressive Disorder outlines the basic strategies for detecting, diagnosing, and treating MDD. Of critical importance are screening all patients for depression, accurately diagnosing the disorder using appropriate tools and clinical judgment, and treating patients with depression with an antidepressant. Physicians need to become very familiar with the dosing, potential side effects, and costs of a few antidepressants in each class that are available in their countries.

For Clinical Use

  • Use measurement-based tools to screen for and diagnose depression
  • Assess patients’ depressive severity, co-occurring disorders, and suicidality
  • Refer patients to psychiatric specialists when appropriate
  • Establish a therapeutic alliance with patients and their families and educate them about the disorder and its treatment
  • Consider psychotherapy as monotherapy for milder depression and as adjunctive therapy for moderate or severe depression
  • For moderate or severe depression, begin treatment with an antidepressant, such as an SSRI, SNRI, or NDRI
  • Treat patients to remission and monitor their progress after remission has been achieved


APA=American Psychiatric Association, CGI=Clinical Global Impressions, DBS=deep brain stimulation, ECT=electroconvulsive therapy, HADS=Hospital Anxiety and Depression Scale, HDRS=Hamilton Depression Rating Scale, MAOI=monoamine oxidase inhibitor, MDD=major depressive disorder, NDRI=norepinephrine-dopamine reuptake inhibitor, PHQ-2=2-item Patient Health Questionnaire, PHQ-9=9-item Patient Health Questionnaire, QIDS-SR=Quick Inventory of Depressive Symptomatology-Self Report, rTMS=repetitive transcranial magnetic stimulation, SNRI=serotonin-norepinephrine reuptake inhibitor, SSRI=selective serotonin reuptake inhibitor, TCA=tricyclic antidepressant, TMAP=Texas Medication Algorithm Project, VNS=vagus nerve stimulation, WFSBP=World Federation of Societies of Biological Psychiatry,

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