Psychosocial treatment approaches to difficult-to-treat depression

Patients with depression, particularly those with chronic depression or DTTD, often have coexisting medical and psychiatric conditions.7,15,16 In patients with comorbid depression and medical conditions (eg, thyroid disorders, infections, neurological conditions), the depression is often untreated or unrecognised because of shared symptoms.7 The United States National Comorbidity Survey found most lifetime cases of depression were secondary to another psychiatric disorder and that 75% of people with depression had another psychiatric disorder.17 Anxiety and depression often coexist, so that patients with a diagnosis of depression commonly experience an anxiety disorder, such as generalised anxiety disorder, obsessive–compulsive disorder or panic disorder (see Tiller).18,19 Alcohol and other substance dependencies and personality disorders also frequently coexist with depression,1,18 and recent studies have begun to identify “hidden” bipolarity features as significant factors for treatment resistance.20 Complexity and comorbidity should be considered the norm.7,15 These comorbidities complicate the clinical picture, worsen the depression, and make it difficult to treat.

Patients with a diagnosis of depression, and specifically DTTD, often experience a range of negative environmental or contextual factors, such as family conflict, financial distress, work stress or job loss, poor-quality interpersonal relationships and social support, poor social adjustment, and other serious life events.1,4,5,15,21 Adverse health behaviour such as obesity, sedentary lifestyle and smoking are also identified risks for people with MDD.22 A recent systematic review of 25 primary studies involving 5192 patients with chronic depression identified that negative social interaction and low levels of social integration coexist with chronic depression.16 There is consensus that late onset of depression, family history of DTTD, and severity or chronicity of depression are also risk factors for treatment resistance.15,18

Depression in primary care appears in many guises. Two-thirds of patients with depression initially present with one or more physical symptoms,23 and comorbid anxiety, personality traits, addictive behaviour and bipolarity can all potentially alter the clinical presentation. Furthermore, although there are probably different types of depression, such as melancholic, hopeless or situational depression,24 these heterogeneous presentations are often treated as though they are the one condition.

If a patient has not responded fully to the first-line treatment, it is always necessary to review the diagnosis and the treatment. Antidepressant medication and psychotherapy are both recommended as first-line treatments, either alone or in combination, for patients with mild to moderate MDD.25 However, these treatments are not always equally efficacious. For example, there is evidence that depression characterised by severe hopelessness responds poorly to antidepressants.26 Coexisting psychiatric disorders and medical illnesses require treatment in their own right if the treatment for depression is to be successful.16

Similarly, persisting contextual factors need to be taken into account when making a comprehensive diagnosis of the situation. Continuing stressors, or poor resources and coping skills, have a ceiling effect on the level of improvement that can be expected from pharmacotherapy alone.2,6

Patients with depression often do not take, forget to take, or cannot be bothered to take their medication.18 This non-adherence to antidepressants is explained partly by personality characteristics,27 the strength of the doctor–patient alliance,28 intolerable side effects,18 and health beliefs and stigma.29 Patients’ attitudes and beliefs are at least as important as side effects in predicting adherence to medication.29 Furthermore, the depression, anhedonia and secondary demoralisation (the “giving up”, “can’t be bothered”, “it won’t help” attitude) that so often accompany depressive illness reinforce the likelihood of non-compliance.

Individuals with chronic depression that is difficult to treat tend to experience significant low self-esteem, anxiety, demoralisation, hopelessness, and lack of joy and drive (anhedonia).21,30 In some people, these may be lifelong traits; in others, they may be activated by the depression.30 Nevertheless, people with treatment-resistant depression have more negative affect and dysfunctional cognitions than those with non-resistant depression,31 and people who experience repetitive and unhelpful thinking about depression tend to have prolonged depressive symptoms.30,32 Severe and persistent depression occurs when there is a recurring reinforcing relationship between depressed mood and negative cognitive processing. This phenomenon, in which the symptoms of depression and secondary beliefs maintain each other, producing a continuous cycle of reinforcement, is described as cognitive reactivity or cognitive vulnerability.30,32

A recent systematic review of 13 articles, representing seven RCTs with a total of 592 patients, concluded that psychotherapy had utility in managing treatment-resistant depression.12 Six of the trials used cognitive therapy. CBT was mostly used to augment antidepressants, but in two trials it was a standalone treatment, delivered in 16 sessions. The review concluded that primary care providers should consider psychotherapy as a reasonable treatment option for treatment-resistant depression.12 In another study, improvements in social functioning and reductions in depressive symptoms were observed after group CBT, and were maintained at 12-month follow-up.11 A combination of CBT and medication was found to be effective in patients with chronic depression and those with residual symptoms.38

CBT techniques are useful in dealing with some of the specific risk factors associated with DTTD.12,16,21,35 For example, the maladaptive cognitions and behaviour that perpetuate chronic depressive symptoms can be modified by CBT techniques such as cognitive restructuring.12,21,35 Activity scheduling, social skills training and other behavioural interventions can help overcome anhedonia, interpersonal or social problems, and coexisting anxiety.12,21,36

There is considerable evidence that IPT is effective in treating depression, particularly around improving the quality of social relationships and interpersonal skills.10 There is little research about the effectiveness of IPT in DTTD, but it has been recommended for the treatment of chronic depression.39 IPT, as an additional or standalone treatment, has been found to be beneficial in people with recurrent MDD.40 Features of IPT that make it potentially beneficial in treating people with DTTD or chronic depression include: attention to the therapeutic alliance and the patient’s readiness to change; the case formulation that considers issues of attachment, culture, self-definition and interpersonal relatedness; and its addressing of effects of trauma, abuse or insecure attachment on patterns of relating and interpersonal sensitivity.41 IPT can also help deal with aspects of grief, relational conflict and role transition that may be intrinsic parts of the depression or consequences of it.

FBT is designed to improve communication and resolve conflicts between family members. There is considerable evidence that family therapy is effective in treating depression, particularly as individuals with depression report significant problems in multiple areas of family functioning.10 However, there is little research evidence regarding its efficacy in DTTD. Family members of patients with depression experience change in their own lives because of the depression.2 The way in which family members respond to the depression can have a significant effect on whether the patient will engage in treatment, as well as the duration of the depressive episode.2 There is a need for research to identify the precise mechanisms of change activated through FBT. A meta-analysis of research conducted in a related area — family therapy as an adjunct treatment for chronic disease interventions — showed it was efficacious, but which components of the therapy led to the change are still not understood.2 Nevertheless, outcome benefits of FBT have been found after five sessions.2

There is considerable evidence that BPP is effective in treating depression, particularly in helping patients overcome problems in regulating complex feelings,10 but there is little research about its effectiveness in DTTD. In a small sample of 10 patients with treatment-resistant depression who were provided with about 12 sessions of BPP, substantial functional and symptomatic gains were associated with the therapy.35

Studies have shown that MBCT, which combines CBT with mindfulness techniques, is effective in reducing relapse rates in people with multiple episodes of depression.42 MBCT has also been shown in pilot studies to be useful in people with DTTD.31,32,36 A single RCT showed MBCT to be effective in chronic depression.43 MBCT is useful in decreasing ruminative thinking, as well as in changing the relationship the patient has with his or her unhelpful depressive thoughts and feelings, anhedonia, low self-esteem and feelings of hopelessness.31