Depression is a common and treatable mental health condition, associated with immunosuppression, which is often unrecognized and undiagnosed in individuals with TB and results in poor treatment outcomes, including treatment failure, loss to follow-up and death (17).
People with depression experience a range of symptoms, including persistent depressed (or low) mood or loss of interest and pleasure, for at least two weeks, and also have considerable difficulty with daily functioning in personal, familial, social, educational, occupational or other areas (32). When considering whether a person with TB has depression, it is essential to assess not only the symptoms of depression, but also difficulties in day-to-day functioning due to the symptoms, beyond those that can be attributed to TB and/or its treatment (see Table 1 and WHO mhGAP Intervention Guide 2.0 protocol for Depression) (32).
Identifying depression among individuals with TB can be difficult since some symptoms, such as marked change in appetite or weight (even when food is available), fatigue or loss of energy, and disturbed sleep, may also be commonly present in TB, thus making identification difficult. Identifying symptoms of depression can be done using screening tools such as the Patient Health Questionnaire (PHQ-9) (41). Such tools do not establish a diagnosis of a mental disorder but provide an indication of the severity of symptoms. They remain a useful tool as people with symptoms of depression can be supported by lower intensity, non-pharmacological approaches, as described below. If a health worker suspects depression, a person can be referred to a health worker trained in the assessment of mental health conditions, where available, such as a mental health specialist or health worker trained in WHO mhGAP (32).
Several symptoms of depression (depressed mood, diminished interest or pleasure in activities, beliefs of worthlessness or guilt and hopelessness) may be perceived as part of common reactions to TB diagnosis, stigma and discrimination, and/or worries about the likelihood of being cured. People exposed to such severe stressors often experience psychological difficulties consistent with symptoms of depression that may not necessarily meet the criteria for a diagnosis of depression (31). Even so, such common reactions may cause distress, which can be mitigated through lower intensity approaches such as education or guided or unguided self-help for stress management. Initial support can also include social support to address stressors, such as for finance or housing.
In circumstances in which people demonstrate symptoms of significant distress, provision of brief psychological interventions in a stepped care approach, including guided self-help, may be warranted. If trained and supervised psychological-intervention providers are available, approaches may include WHO Problem Management Plus (PM+) – a brief psychological intervention delivered in individual or group format for people with high distress and impaired functioning (42); or WHO Self-Help Plus (SH+) – a brief guided self-help package (43, 44). If symptoms of depression persist even after TB symptoms improve and external stressors have been effectively addressed through social support and social protection interventions, a referral to mental health specialists may be indicated.
Another method for identifying depression is through assessment conducted by a mental health specialist or health worker trained in such an assessment, for example following the depression protocol in the mhGAP Intervention Guide 2.0 (32). This type of assessment can also be conducted following positive identification via a screening tool.
People living with depression should be regularly monitored. Management of depression should be initiated through psychosocial interventions such as psychoeducation, stress reduction, strengthening social support and promotion of daily activity functioning. Management of depression also includes offering brief evidence-based psychological interventions such as interpersonal psychotherapy, cognitive behavioural therapy, behavioural activation and problem-solving counselling, where these are available (45). WHO Problem Management Plus (42) is a brief psychological intervention which can be delivered by trained non-mental health specialists under adequate supervision. For people with moderate to severe depression, pharmacological interventions can also be considered in the management of depression. Two recommended interventions include selective serotonin reuptake inhibitors (SSRIs), like fluoxetine, and tricyclic antidepressants like amitriptyline (46). While generally safe to use among people receiving treatment for drug-susceptible TB, evidence suggests that their combination with rifampin can lead to reduced efficacy of these drugs and therefore dosing should be monitored closely. For people receiving treatment for drug-resistant TB, moderate drug-drug interactions have also been observed with levofloxacin, bedaquiline and delamanid, specifically an increased risk for QT-prolongation and/or arrhythmias (38). People who experience these moderate drug interactions may use SSRIs and tricyclic antidepressants but require closer monitoring.