. 2022 Apr 1;12(4):e051918. doi: 10.1136/bmjopen-2021-051918

Table 2.

Strategies for inadequate response to first-line treatment of depression according to the most relevant CPGs

CPG; author, year	Terminology for responsiveness	Recommended strategies
Ministerio de Salud (Chile), 2012²⁴	Refractory or resistant to treatment: no appropriate response to pharmacotherapy under usual dosage or when there is poor or inadequate response to one or more treatments. Remission: absence of signs and symptoms for 2 months	Reevaluation of the diagnosis Adjusting dosage Switching to a different antidepressant Augmentation with a second medication (lithium, liothyronine or second antidepressant) Combining antidepressants
Ministerio de Salud (Colombia), 2015²⁵	Refractory or resistant to treatment: absence of substantial remission of depressive symptoms or no improvement of social functioning with trial of pharmacotherapy at adequate duration and dosage. Remission: the patient responds to treatment in the initial or acute phase (within 12 weeks) and does not present further relapses in the continuation and follow-up phase. Response: defined as a 50% decrease in the score on a symptom scale depressives	Reevaluate adherence diagnosis and adverse events, adjusting dosage, add psychotherapy, switching to a different antidepressant, combining antidepressants, augmentation with a second medication (lithium or thyroid hormone)
NICE, 2018²⁶	Inadequate response: no clear definition is presented. Remission: complete relief of symptoms	Check adherence and adverse events Increase the frequency of appointments and monitor results Consider reintroducing previous treatments (increase the dose) Consider switching to an alternative antidepressant Combining medications or augmentation Combined psychological and drug treatment
Trangle et al, 2016²⁷	Partial response: 25%–50% reduction in symptoms Response: >50% reduction in symptom Remission: devoid of symptoms.	Reassessment of patient/family engagement and adherence Optimise antidepressant dose Switching to a different antidepressant Adding, switching or substituting treatment modality Adding cognitive psychotherapy or adding another medication (buspirone or bupropion) Reevaluating the diagnosis and the possibility of a bipolar diagnosis Check comorbidities and/or substance abuse (inclusion referral to specialised care) Augmentation therapy: augmentation with lithium, antipsychotics or triiodothyronine (T3) and combination of antidepressants adding bupropion or buspirone, mirtazapine +SSRI, TCA+SSRI Other strategies such as electroconvulsive therapy and hospitalisation
APA-Psychology, 2019²⁸	Partial response and no response: no clear definition is presented. Remission: no longer having symptoms Response: reduction in depressive symptoms	Switch from antidepressant medication alone to cognitive therapy alone Switch from antidepressant medication alone to another antidepressant medication Add psychotherapy (interpersonal psychotherapy, cognitive-behavioural therapy, or psychodynamic therapy) Augment with another antidepressant medication (do not include augment with other medicines)
VA/DoD, 2016²³	Partial response:<50% improvement in symptoms Response: improvement >50% PHQ scores Remission: PHQ score <4 for at least 1 month No response: no clear definition is presented.	Reevaluation of the diagnosis, comorbidities and adherence, adjusting dosage, augmentation of drugs, switching to another monotherapy (medication or psychotherapy), augmentation with a second medication including antidepressant, antipsychotic, lithium, T3 or psychotherapy.
Kennedy et al, 2016²¹ (CANMAT)	Partial response: 25%–49% reduction in symptom scores. No response: <25% reduction in symptom scores. Inadequate response: partial response and no response	Optimise antidepressant by increasing dose. Consider adjunctive use of psychological and neurostimulation treatments. Switch to an antidepressant with superior efficacy. Add an adjunctive medication, either combination with other antidepressant or augmentation with other medication (eg, triiodothyronine). Consider switch to a second-line or third-line antidepressant. Consider longer evaluation periods for improvement. Increase dose if not at maximal doses. Consider a chronic disease management approach, with less emphasis on symptom remission and more emphasis on improvement in functioning and quality of life.
Gelenberg et al, 2010²² (APA-Psychiatry)	No response and partial response: no clear definition is presented.	During initial weeks—assess adherence, consider increasing medication dosage, and increase intensity of psychotherapy. For severe cases consider electroconvulsive therapy. At 4–8 weeks—Switch to a different antidepressant, change to or augmentation with psychotherapy, augmentation therapy with other antidepressant or other medicine, or electroconvulsive therapy.

AGREE II, Appraisal of Guidelines for Research and Evaluation II; APA-Psychiatry, American Psychiatric Association; APA-Psychology, American Psychological Association; CANMAT, Canadian Network for Mood and Anxiety Treatments; CPG, Clinical Practice Guideline; ICSI, Institute for Clinical Systems Improvement; MS, Ministerio de Salud; NA, not available; NICE, National Institute for Health and Care Excellence; PHQ, Patient Health Questionnaire; SSRI, Serotonin Selective Reuptake Inhibitor; TCA, Tricyclic Antidepressants; VA/DoD, US Department of Veterans Affairs (VA).