Remarks y The term “depression” refers to moderate to severe depressive episode or disorder. y There were no studies identified in the review that included comparisons by severity of depression (e.g. moderate versus severe). However, there was no evidence of an association between baseline severity and the network estimates in meta-regression analysis. y TCAs are generally less well tolerated than SSRIs and are also generally considered less safe, due to anticholinergic side-effects, toxicity, psychomotor and cognitive impairment risks, and lethality risks in cases of acute intoxication or overdose. TCAs are therefore recommended for consideration in cases where SSRIs are not available for adults with panic disorder. y TCAs should be avoided in older adults and in people diagnosed with glaucoma, heart conditions, prostatism or other prostate conditions, or at risk of these conditions. y Consider increased risk of bleeding associated with SSRIs, particularly for older people or people taking other medicines that can damage the gastrointestinal mucosa or interfere with clotting (e.g. NSAIDs).

Implementation considerations y Service providers should only consider antidepressant medicine alone for adults with depression when psychological interventions are not available. y Service providers should assess psychosocial stressors (e.g. domestic abuse, unemployment) associated with depression and include appropriate psychosocial interventions in their treatment plan. y Providers should keep in mind the possible adverse effects associated with antidepressants, the ability to deliver either intervention (in terms of expertise and/or treatment availability) and individual preferences. Discontinuities in drug availability (common in LMICs) may interfere with continuation of treatment. y Generic TCAs and many generic SSRIs are associated with low acquisition costs. Cost of daily dose of generic antidepressants varies from region to region throughout the world ranging between 3% and 9% of minimum wage (131). y For the treatment of depressive disorder, the WHO EML (13) includes:

• TCA: amitriptyline;
• SSRI: fluoxetine (therapeutic alternatives: citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). y The Interagency health kit 2017 includes fluoxetine (133). y Specific types of antidepressants selected should carefully consider factors such as demographic characteristics (e.g. higher risks and side-effects that may be associated with pregnancy or older age), side-effects profiles (e.g. sexual dysfunction, sleep problems, weight gain) and availability (e.g. continuous availability, costs). y Explain rationale for prescribing and provide written and verbal information on benefits and harms, side-effects, drug interactions, the importance of taking medicines as prescribed and the likely time to improvement in symptoms. y Regularly review the effectiveness of the medicine and side-effects with the person during the first three months of treatment and every three months afterwards. For adults who experience side-effects after starting medicine, consider closer monitoring of their symptoms, reducing the dose of the medicine or stopping the medicine gradually and offering alternative interventions.