Cognitive-behavior therapy

The most studied psychotherapy for depression ( ) and TRD ( ; ; ; ; ; ; ; ; ), cognitive-behavior therapy (CBT) has become a standard, widely available treatment. CBT methods are anchored in a collaborative-empirical therapeutic relationship in which therapists actively engage patients in a process of detecting and modifying maladaptive cognitions and reversing dysfunctional behavioral patterns ( ). The treatment is usually short-term (12–20 sessions), but briefer and longer courses of therapy have been studied and found to be useful ( ).

Because patients with TRD may have often tried many previous treatment options and feel demoralized about the chances of response to yet another treatment, the CBT approach to TRD typically focuses directly on hopelessness and treatment burnout ( ). With in-session demonstrations of the value of spotting and changing depressive thoughts and behaviors, and use of action plans for between sessions, therapists try to stimulate hope that progress is possible. Standard CBT methods such as identifying and changing negative automatic thoughts, behavioral activation, and problem solving are used, as in the treatment of acute depression. However, TRD is conceptualized as a deeply ingrained condition that may require higher levels of activity from the therapist, especially early in treatment. There is an emphasis on rehabilitation of patients who have lost much of their “conditioning” to work effectively, engage in interpersonal relationships, and enjoy pleasurable activities. Thus, behavioral methods such as activity scheduling and step-by-step plans to manage effortful tasks often have a central role in treatment of patients with TRD ( ). By gradually increasing activity level, social engagement, and involvement in pleasurable activities, the patient with TRD is participating in a process similar to physical therapy. CBT for long-standing depression also emphasizes a search for the patient’s strengths and positive features that have been obscured by chronic negativism but offer potential in a path toward recovery.

Another feature of CBT for TRD is the use of a comprehensive, multidimensional treatment plan. If both CBT and pharmacotherapy are delivered by a psychiatrist, the integration of both treatments is a fundamental principle of treatment ( ). When split treatment is delivered by a physician and a nonmedical therapist, effective communication and coordination is recommended ( ). The CBT elements of therapy can facilitate pharmacotherapy and other methods, such as engaging in physical exercise and getting full medical evaluations and treatment, by addressing hopelessness and the inertia of TRD that has prevented the patient from taking actions that could help reduce depression. Nonadherence to pharmacotherapy is a particularly important target of CBT for treatment-resistant depression. The cognitive-behavioral therapist can elicit automatic thoughts and core beliefs that may be interfering with adherence and can devise behavioral interventions to increase the likelihood that medications and other treatments will be used to their full potential ( ).

Interpersonal psychotherapy

Interpersonal psychotherapy (IPT) is a manualized, time-limited treatment focusing on life events, affects, and their connection ( ). This treatment method offers the patient two general principles: (1) depression is a debilitating but treatable medical illness that is not the patient’s fault; and (2) depression does not arise in a vacuum but has a social context: upsetting life events evoke negative emotions and can precipitate mood episodes in vulnerable individuals; and depressed mood and functioning induce negative life events ( ). The treatment defines a life crisis— complicated bereavement following the death of a significant other; a role dispute with a significant other; a major life event role transition ; or interpersonal isolation —for the patient to address within a brief time frame (generally 12–16 weeks), but assigns no formal homework. This time-limited approach helps patients to understand their depression in a social environmental context and, rather than avoiding painful negative effects ( ), to recognize them as useful social signals in order to resolve the painful life situation. In doing so, patients mobilize protective social supports and learn new social skills.

Although there has been no specific adaptation of IPT for TRD, IPT has been adapted for chronic depression (IPT-D) ( ; ). Beyond the standard IPT approach, some features of IPT-D may benefit patients with TRD. IPT-D focuses on the patient’s inevitable difficulty in distinguishing between chronic, often lifelong depression and his or her personality. These patients may see themselves as defective, depressive, hopeless, even toxic people whom no one can really like, leading them to maintain distance from others. The goal of therapy is, in part, an “iatrogenic role transition,” engineered by the therapy, to help the patient distinguish a healthy self beneath the mood syndrome and to recognize pessimism, resignation, and a sense of defectiveness as longstanding depressive symptoms, not who the patient actually is ( ).

Because chronically depressed patients tend to be passive, conflict-avoidant, and uncomfortable with strong affects, IPT-D focuses on eliciting and validating negative effects such as anger, helping the patient to understand them as appropriate signals in reaction to mistreatment or unfairness in interpersonal encounters, rather than as “bad” emotions. Patients with persistent depression need encouragement and repeated role play to practice confronting others, something they may have avoided throughout life even when not clinically depressed. Discovering that one can own and use one’s feelings to set boundaries with others can be a liberating and mood-enhancing experience, providing mastery over one’s environment and a sense of personal control.

Another crucial aspect of IPT for patients with TRD is emphasis on the medical model. They are not defective themselves, but individuals with a tough illness that has not responded to prior treatments. They have not “failed the treatments,” the treatments have failed them. It’s important for the therapist to generate realistic therapeutic optimism that this next course, taking a very different, interpersonally focused approach from past pharmacotherapy or psychotherapy trials, may be the one that relieves them of TRD.

Psychodynamic psychotherapy

Although the theoretical underpinnings of contemporary psychodynamic treatment for depression vary widely ( ), most treatments focus on how past experiences and conflictual relationships affect current functioning, including how the relationship between the patient and the therapist reflects these conflicts. Psychodynamic treatments also aim to facilitate insight and address how patients avoid difficult topics. Themes that tend to emerge include the impact of perceived or actual losses, conflict about the expression of anger, and avoidance of shame ( ).

Short-term psychodynamic treatment for depression may include approximately 16–20 sessions, whereas long-term treatment may include 50 or more sessions. Regardless of the specific variant of psychodynamic treatment employed, shorter treatments tend to focus on symptom relief, whereas long-term treatment emphasizes changing core personality features and maladaptive interpersonal patterns.

The single completed trial of brief psychodynamic therapy for TRD used a manualized form of this treatment that emphasizes emotional factors that lead to, exacerbate, and perpetuate depression, as well as increasing the patient’s tolerance for anxiety ( ). The trial report did not discuss adaptations for persons who had not responded to other interventions for depression ( ). Although we found no work focused on specific adaptations of psychodynamic treatment to TRD, the guiding assumption may be that exploration of internal conflicts and unconscious issues are not addressed in other psychosocial treatment modalities or in pharmacotherapy, and thus may be used to facilitate change.

Problem-solving therapy

This evidence-based, CBT-related psychosocial intervention focuses on training in adaptive problem-solving attitudes and skills ( ). Sometimes referred to as structured problem solving, PST is a prescriptive model for solving and effectively coping with major and minor life stressors. Its two essential components are: (1) general orientation, and (2) problem-solving skills. Developing a problem-solving orientation is a meta-cognitive process that teaches individuals to see problems as challenges to be solved and thus serves a motivational function. Problem-solving skills are developed by working through real-life stressors with a structured four-pronged approach: (1) problem definition and formulation, (2) generation of alternative solutions, (3) decision-making strategies, and (4) solution implementation and verification ( ).

Although no randomized controlled studies have evaluated the effectiveness of PST in treatment-resistant depression, PST experts believe this approach can be adapted for this population. A positive problem-solving orientation can be used to build hope and view treatment resistance and core symptomatology as workable problems. Skill building in problem solving may thus focus on dealing with particular difficulties associated with not getting better. For example, the therapist and patient might work on identifying strategies to better handle disappointment, decreased motivation, and associated feelings of distress. Other common challenges in TRD such as interpersonal conflict, job loss, and financial stress can also be targeted in problem-solving therapy.

Supportive psychotherapy

Supportive psychotherapy (SP) is often thought of as an ambiguous therapeutic entity in which the therapist provides empathy, kindness and encouragement with the aim of supporting patients in an atmosphere of safety through the symptoms of psychiatric illness or life struggles. It is typically poorly defined, not implemented methodically, and is rarely investigated as the primary treatment intervention for any psychiatric disorder ( ). Although many clinicians say they provide supportive psychotherapy, they may be offering an eclectic, potentially confusing amalgam of various therapeutic techniques. In its best form, SP is a specific therapeutic approach based on a solid theoretical framework ( ; ; ).

Supportive psychotherapy can be a manualized, affect-focused approach that typically involves identifying and reinforcing mature defense mechanisms, strengthening reality testing, encouraging use of adaptive coping mechanisms, and bolstering self-esteem, all within a holding environment that fosters trust, structure, and physical and emotional safety ( ; ). Specific techniques may include reflecting the patient’s concerns, helping the patient name conscious emotions, highlighting the patient’s strengths, providing reassurance, and gentle reframing.

Several manualized versions of SP have been developed including Brief Supportive Psychotherapy, a time-limited affect-focused treatment focusing on the “common factors” inherent to most forms of psychotherapy including empathy, therapeutic alliance, and optimism for improvement; and Short Psychodynamic Supportive Psychotherapy, a time limited approach rooted in psychoanalytic theory and technique but focusing on affective and relational content from the supportive side of the supportive-exploratory continuum. These versions offer uniform and replicable forms of SP for both clinical and research use ( ; ).

Despite the lack of empirical research for supportive psychotherapy in TRD, other considerations may lend credence to the use of this approach. It is well known that comorbid diagnoses, of which personality disorders, substance use, and medical illness are common in the TRD population ( ; ), may influence outcome. Though not studied directly with TRD, evidence supports the efficacy of SP in depressive disorders with comorbid personality disorders ( ; ), alcohol use ( ), and medical/neurologic illness including breast cancer ( ), diabetic foot syndrome ( ), and TBI ( ). In addition, SP may be more acceptable for patients with severe symptoms or marked functional impairment. postulates that SP is specifically helpful for patients with chronic or recurring disability because the goals of minimizing deterioration and maximizing competence can be performed within the limitations of the illness, almost irrespective of severity. Supportive psychotherapy does not require the insight, curiosity or motivation necessary in other modalities and may be more tolerable than other forms of therapy which focus on exploration of the unconscious, challenging firmly held beliefs, addressing avoidance behaviors, or completing homework ( ).

Finally, there is the benefit of accessibility. In a survey of psychiatrists, SP was the most commonly used psychotherapy with 36% saying they provided it in their practice ( ). Though the definition of SP was vague, usage patterns have likely changed since this survey was conducted, and therapists’ subjective self-report of their treatment have limited reliability, SP still may be more likely to be available in clinical practice than other forms of psychotherapies for TRD.

Mindfulness-based cognitive-behavior therapy

When first developed for mood disorders, mindfulness-based cognitive therapy (MBCT) was applied only for relapse prevention in patients who had little or no active depression. The rationale was that persons with symptoms such as psychomotor agitation, poor concentration, and low energy would have difficulty participating in mindful meditation ( ; ). Subsequently, MCBT was adapted for the treatment of acute depression and found to be effective for short-term symptom relief ( ). The key differences between standard CBT and MBCT are the use of mindfulness practices in the latter to increase awareness and attentional control. Instead of attempting to question ruminative, self-condemning thoughts and modify them as in standard CBT, patients are taught to disengage from such thoughts as a way of interrupting ruminative, depression-inducing thinking ( ).

Modifications of MCBT for treating persons with TRD have been described by who recommend that mindfulness be used to help patients focus on “noticing and accepting that which is in the present moment.” Patients learn that their thoughts and feelings are “mental events rather than aspects of self or direct reflections of truth.” Because patients with TRD have often withdrawn from activities that can offer positive reinforcement, MBCT also teaches skills to help patients engage in constructive, positive behaviors ( ).

Although MBCT for TRD is based on a standard manual for depression ( ), several modifications are recommended ( ). Psychoeducation is provided on the natural course of depression with an emphasis on avoiding self-blame ( ). Another key modification is reduced reliance on sitting meditation that patients with TRD may have difficulty in sustaining. Mindful movement such as walking meditation, yoga, and brief “breathing spaces” can take the place of longer sitting meditations when needed. Metaphors and exercises drawn from acceptance and commitment therapy are used to help patients effectively use mindfulness meditation and to distinguish between the useful process of acceptance and the negative effects of resignation ( ).

Definition of adequate treatment with psychotherapy

Clinical researchers assessing treatment resistance and defining TRD often attempt to define an adequate course of pharmacotherapy and the needed number of failed medication trials ( ; ; ; ; ; ). Most such systems have not considered psychotherapy in categorizing the level of treatment resistance ( ; ; ; ; ; ). Nor has defining the adequacy of a course of psychotherapy received sufficient attention. Such a definition would be useful in both TRD research and in treatment planning with patients with depression unresponsive to previous pharmacotherapy trials. Although constructing such a definition is more complex than for psychopharmacotherapy, we outline an approach here.

We cannot absolutely define an adequate psychotherapy course because numerous factors such as psychiatric comorbidity, interpersonal problems, medical illnesses, and presence or absence of personal resources may influence the need for intensity and duration of treatment. Different therapies have also been tested at different durations and doses. Limited evidence hints that patients may require varied amounts of psychotherapy to achieve remission ( ; ; ; ). However, studies that compared varying lengths of CBT or short-term psychodynamic therapy (8 vs 16 sessions) for depression reported no advantage for increased duration of treatment ( ; ; ; ). Perhaps the most telling report on the influence of length of therapy was a meta-regression analysis of 70 studies which discovered no significant relationships between number of psychotherapy sessions and treatment outcome ( ).

The mean number of sessions actually completed in psychotherapy RCTs may yield the best available information on how many sessions are needed for a reasonable trial. Because a Cochrane review of psychotherapy for TRD ( ) reported the mean number of sessions completed were 9–15 for CBT, 11 for IPT, and 16 for short-term dynamic therapy, we conclude that a range of 9–16 sessions may constitute an adequate course of psychotherapy. Longer or shorter treatment courses may be appropriate depending on treatment type, complexity of comorbid illnesses, and other potential influences on treatment outcome.

A definition of adequacy of a psychotherapy trial could include whether or not the therapist has been trained in the approach, follows the basic methods for the respective treatment, and is competently delivering therapy. For some therapies such as CBT and IPT, certification is available, and measures of competence have been developed ( ). Yet such standards may set an impractically high bar for delivering evidence-based psychotherapy to large numbers of patients. Lacking measures of training adequacy and therapist competence, clinicians assessing patients’ prior treatment experience can ask targeted questions to determine if the patient actually did participate in a therapy such as CBT, IPT, or MBCT. Questions could include: “What did you learn in the therapy?” “What methods did the therapist use?” “Did you do ‘homework’ between sessions?” “Can you describe the key elements of the therapy?” “What principles of the therapy are you using now?”

Determination of psychotherapy adequacy also may be influenced by the large number of computer-assisted CBT (CCBT) studies, which greatly reduced the amount of clinician time without impairing treatment effectiveness ( ; ; ; ). Investigations comparing CCBT with standard face-to-face CBT for depression have found no differences in outcome ( ; ). In addition CCBT has performed as well as standard CBT in patients with chronic or severe depression ( ). Engagement in CCBT provides patients a degree of standardization and “quality control” of therapy that may be absent from traditional psychotherapy. Patients participate in online exercises and skill-building practices that provide core CBT learning experiences in a reliable and measurable way ( ).