Once a patient with potential depression is identified, comprehensively assessed, and the subtype of his/her depression defined (Chapter 3), the next task is to engage the patient in developing a treatment plan composed of evidence-based interventions to be implemented at the appropriate stage of their depression. Providing a choice of interventions and their respective benefits versus side effects is one way to engage the patient in planning treatment and improves adherence and outcomes.¹ The timing of the intervention is also important; for example, patients with severe depression are often unable to fully engage in cognitive behavioral therapy (CBT) and profit more from CBT if it is introduced during milder stages of illness or once recovery has begun.

Aiming for complete remission and optimal functioning improves outcomes. Patients who experience residual subthreshold symptoms demonstrate a more severe course of illness and experience a relapse or recurrence three times faster than patients who achieve a full remission.²

Achieving full remission and optimal functioning improves the mental health prognosis, and may also improve the course of the comorbid medical disorders. Some examples are as follows:

• 
  

  Patients with depression following stroke are more likely to die from complications of their stroke.³

  
  
• 
  

  Patients with diabetes and depression have worse glycemic control and higher rates of diabetic complications.⁴

  
  
• 
  

  Patients with untreated depression are at greater risk of arrhythmia following myocardial infarction and other cardiac diseases than are those without depression (Chapter 7).

The care of patients with medical disorders and comorbid depression costs up to twice that of patients with chronic diseases who are not depressed.⁵ It is important to note that only a fraction of these increased costs (about 1%) are attributable to mental health care. Indirect costs are substantial and include lost income and employer costs due to missed work. Costs go well beyond the monetary and also include poorer quality-of-life and increased suicide rates.^6,7 Effective treatment of the depression is likely to lower overall healthcare costs. For example, older adults with major depression or dysthymic disorder who are managed using an integrated depression care model (Chapter 23) are twice as likely as those with nonintegrated care to have at least a 50% reduction in depression symptoms,⁸ and reduced total healthcare costs.⁸

In summary, treating depression to remission and minimizing risks for recurrence not only benefits patients and their families; it also has the potential to lower the costs of care and limit the other wider societal burdens of depression. In this chapter, we address methods for approaching and engaging the patient with medical illness and depression, the nuances of treating depression in the context of medical comorbidities, and the measurement of the patient’s progress during treatment.

The first step to successful treatment is in the approach to the patient, summarized by the checklist in Box 4-1.

STRIKE A BALANCE BETWEEN EMPATHY AND MOBILIZATION

It is fundamental to convey a genuine recognition and appreciation of the patient’s distress, despair, helplessness, and hopelessness. The challenge is to empathize with the patient, assure that he or she feels heard, yet gently resist the patient’s depressive tendency to dwell on the negative through redirecting the conversation. Otherwise, this risks reinforcing hopelessness and entrenchment. Aiming for a balance between genuine empathy with the patient’s despair while at the same time identifying and reinforcing any signs of desire for change, feeling better, and engaging in life is critical. As well, western medicine is disease-focused and problem-oriented. While this is valuable in facilitating an understanding of the underlying cognitive, behavioral, psychologic, and neurologic processes of psychiatric illness, it also risks promoting an externalized focus and intensifying passivity in a patient who may already be depleted, negative, and often immobilized. It is, therefore, up to the clinician to find ways to limit reinforcing the patient’s passivity without shaming or otherwise sending a message that could be interpreted by the patient as being blamed for his or her depression or trivializing its magnitude and impact. As discussed later in this chapter, continually promoting active engagement of the patient through self-care approaches and carefully timed evidence-based psychotherapies should be regarded as central. By implementing carefully identified interventions, and simultaneously aligning with any aspects of the patient that are hopeful and desiring change, more robust and sustainable progress can be made.

Motivational interviewing (MI) is a natural fit for patients with depression who are inclined to become disengaged, unmotivated, hopeless, helpless, and frankly overwhelmed.⁹ MI is a communication style that embraces the balance between empathizing with the distress and negativity while simultaneously helping patients to relinquish any ambivalence about feeling better (usually linked to the sense of being overwhelmed), and encouraging them to participate actively in alleviating their depression.

ADDRESS STIGMAS

Despite the growing public awareness of depression, the stigma of mental illness remains a destructive attitude lurking in the background for many patients, including those who have reached out for help. Sometimes the patient’s family or significant others unwittingly contribute to poor treatment adherence because of stigmatized or misinformed beliefs. Listening for and addressing this from the outset can keep treatment on track. Peer-led programs are a potent approach to neutralizing stigma and are increasingly available. These range from support groups to buddy programs for which formalized training programs are available.

FOCUS ON TREATMENT ADHERENCE

The sense of depletion and hopelessness that accompanies depression may contribute to poor treatment adherence, compromising the patient’s capacity to engage actively in therapy, keep appointments, and take psychiatric and nonpsychiatric medications as prescribed. The expense of multidrug regimens and psychotherapy are contributing factors, leading some patients to skip doses or not fill prescriptions because of cost.¹⁰ In addition, a societal imperative for “quick fixes” can lead some patients to cease treatment when it doesn’t seem to help immediately. Thus, imperfect treatment adherence has become the rule rather than the exception.¹¹

From the outset, clinicians should engage in an open and honest dialogue about whether and how the medications are to be taken and tolerated. This can be facilitated by normalizing the likelihood that some doses will be missed, while nonjudgmentally emphasizing the importance of adherence and the consequences of nonadherence. Involve family members and significant others in these discussions whenever possible, with close attention to their concerns, belief systems, and understanding of the illness. Educating and supporting those closely involved with the patient improves outcomes for patients with depression.^12,13

SUPPORT AND EDUCATE CARETAKERS

Caring for a relative or friend with depression can be difficult and stressful, and it is not unusual for such individuals to become depressed themselves, or to engage in maladaptive coping with excessive use of alcohol, or insufficient sleep, exercise, social engagement, or other restorative activities. This, in turn, can adversely affect the patient.¹³ Caregivers, family, and friends may also not understand that the patient cannot help feeling and behaving as they are and cannot just “snap out of it.” It is, therefore, important to maintain contact with caregivers, to find ways of involving them in the treatment when clinically appropriate, and to remain attuned to their own signals of distress and refer them for treatment when indicated.

PREVENT CLINICIAN BURNOUT

Similarly, clinicians working with depressed individuals must continually be aware of their own responses, which can range from increasing hopelessness to anger when a patient’s depression is not responding to treatment. Working with patients with depression is often depleting; particularly at risk are clinicians who’ve yet to establish a healthy work–life balance. This risk is intensified when treating medically ill patients since the likelihood of treatment resistance and physical suffering and death is increased. Team-based care helps clinicians to tolerate this stressful work since it provides support and a sharing of clinical responsibility (Chapter 23).

MAINTAIN COMMUNICATION WITH ENTIRE CARE TEAM

It is essential in treating depression in the medically ill for all clinicians involved to be in close communication, given the heightened risk of adverse events, complications, and medication interactions. Ideally, treatment should be conducted in a setting where there is a common electronic medical record. But even when such continuity is available, some clinicians avoid documenting in the shared medical record due to confidentiality concerns. However, sophisticated information systems allow for heightened security. It is also important that only the most clinically relevant details are documented and process notes are never contained within the treatment record.

TREATING MULTICULTURAL POPULATIONS IN MEDICAL SETTINGS

Depression is a leading cause of disability among major ethnic groups in the United States and is one of the most common and underdiagnosed medical comorbidities in these groups. Research consistently has shown that non-European populations are much more likely to see primary care physicians than specialists for depression and are less likely to adhere to antidepressant therapy. The prevalence of depression in Chinese Americans seeking medical treatment is approximately 20%^14–16 and the prevalence among Hispanics, seeking treatment in urban medical centers, is 22%.¹⁷ Interestingly, the time spent in America as an immigrant seems to be a notable factor. Recent immigrants seem to be relatively more protected from the risk of psychiatric disorder. Having a “home” country with recent connections to family and friends seems to be a positive health advantage that diminishes over time with increasing isolation from home, low income, and other stresses related to minority status in the United States.¹⁸ Depression recurrence and chronicity are higher among Mexican Americans, Puerto Ricans, and African Americans than in the white population, and these groups are the most likely among all ethnic populations to receive inadequate depression treatment.¹⁹ These prolonged and recurrent depressions may be related to the lack of access to treatment. Because the most consistent care these patients receive is in the primary care or emergency setting, it is worth examining the emerging modalities of culturally sensitive depression treatment being used in primary care.

The biopsychosocial model of depression is not necessarily shared by all ethnic minorities. The notion of medicalizing the psychological reaction to chronic and intense emotional stress and loss may appear foreign to them.²⁰ The Engagement Interview Protocol (EIP) has been developed to help Chinese Americans to accept mental health treatment and a way to incorporate their worldviews into the psychiatric assessment.¹⁵ This interview allows the clinician to work with the patient by understanding their illness beliefs and taking their narratives of their illness experience into account. Because the primary care visit has multiple time constraints, the EIP uses a direct line of questioning to gain data on the patient’s developmental, immigration, educational and work history, current social environment, and stressors. Other goals include eliciting narratives on connections and networks within the host country, spiritual beliefs, marital status and issues with extended family members or cultural community members. Questions like “How do you like living in this country?” that are included in the EIP can bring about important disclosures about cultural- and immigration-related stressors through the patient’s story telling. Other questions like “What do you call your problem?,” “What do you fear most about this problem?,” and “What kind of treatment do you think you should receive?” can be helpful in conceptualizing the patient’s view of depression.¹⁵

The disclosure of a depression diagnosis should be done with sensitivity since these patients are less familiar with the biopsychosocial method and can find the diagnosis highly stigmatizing. Ask directly about what this diagnosis means to the patient and describe the illness using the patient’s words, perhaps with words like stress, tension, anxiety, or feeling overwhelmed and tired. Clarify misconceptions around diagnostic labels and describe the biology of depression in terms that are accessible to the patient. Elicit the patients’ worries about the diagnosis and prognosis, and provide reassurance.²¹

After the diagnosis is made, it is important to look at how clinicians initiate and follow up with standard depression care. Collaborative care centers that use Depression Care Managers (DCMs) to follow up with patients after they are diagnosed with depression are helpful in providing standard care (see Chapter 23). However, while collaborative care has improved treatment among all socioeconomic classes it has not been shown to overcome racial/ethnic barriers to accessing mental health care.²² Incorporating cultural tailoring into the collaborative care model, as in the Blacks Receiving Interventions for Depression and Gaining Empowerment (BRIDGE) study, has been shown to be beneficial among African Americans. Cultural tailoring is a minority patient centered care that provides intense psychoeducation and supportive counseling that is culturally understandable. This study and a few others have shown that these patients react significantly more positively to their DCMs and find them more helpful and supportive. These patients were more likely to become connected to psychotherapy as well.^23,24

Adherence to antidepressants can be a major issue in minority populations, especially if the patient’s ambivalence about taking medication is not explored. Motivational interviewing has been shown to be helpful for Latino patients taking medications and has improved antidepressant adherence.^25,26 A method called Motivational Enhancement Therapy for Antidepressants (META) and other techniques like this are used to motivate the patient by empathizing with the patient’s struggle, addressing concerns about pharmacotherapy, validating reasons for not taking the medications, and allowing the patient to decide about the regimen. This type of motivational therapy helps patients adhere to treatment and increases trust in the clinician, improvement in symptoms, daily functioning, and quality-of-life.²⁵ Although the studies done on culturally sensitive depression treatment have shown positive effects, relatively few have been done for selected ethnic populations. The emergence of collaborative care provides the impetus to study these techniques more rigorously, but there is much left to study. Table 4-1 summarizes a selected group of new treatment modalities addressing cultural barriers in depression treatment.^{15,17,23,24,26,27}

THE BASICS

Basic lifestyle measures for patients with comorbid medical illness and depression are an integral part of treatment, as they affect treatment response²⁸ and are often disrupted in patients who are medically ill. These include sleep, daylight exposure, nutritional needs, and physical activity.

Sleep

Insomnia and hypersomnia are extremely common in depression. Compared to the general population, patients with medical illness are more likely to suffer from a sleep disturbance,²⁹ experience physical symptoms, such as pain that interfere with sleep quality, and/or be taking a medication that affects sleep. Sleep problems are associated with general medical comorbidity and poorer cognitive function in the elderly^30,31 and with chronic illnesses in nongeriatric populations, including obesity,³² hypertension,³³ cardiovascular disease,³⁴ hypercholesterolemia,³⁵ and diabetes.³⁶ There may be an association between abnormal sleep duration (either short sleep or long sleep) and higher mortality,³⁷ though this is controversial and there is little consensus on how to interpret such an association.³⁸ Regardless, it is clear that caring for patients with depression and comorbid medical conditions is likely to include management of sleep complaints.

Take a thorough sleep history, consider a primary sleep disorder (discussed in Chapter 18), and address contributing medical issues including medications, primary sleep disorders, and psychiatric and medical illnesses that may contribute to insomnia. Next, address factors and behaviors that contribute to poor sleep. Some of the most important modifiable factors include use of alcohol, caffeine, smoking, and noise and light pollution. Many commonly prescribed antidepressants have a deleterious effect on sleep architecture, ultimately suppressing deep, restorative, non-REM sleep and REM sleep. Easily implementable sleep hygiene interventions (Box 4-2) and specific behavioral therapies, such as sleep restriction, CBT, and structured relaxation training can be helpful for many patients.³⁹ If these measures are not affective or implementable, consider pharmacologic intervention for the sleep problem.

Benzodiazepines for Insomnia

Risk of respiratory depression associated with benzodiazepines is the first consideration, and these agents should be used sparingly in patients whose respiratory functions are already compromised by, for example, pulmonary disease, sleep apnea, or chronic opioid use. In the elderly, benzodiazepines are also associated with increased risks of cognitive decline and falls.⁴⁰

Benzodiazepines and benzodiazepine receptor agonists have been associated with an increase in mortality,^39,41 but this association remains controversial and may not be causal. Despite these uncertainties, since a causal relationship between hypnotics and mortality has been suggested, clinicians are advised to use caution when prescribing hypnotics or other sedatives for patients who are medically ill.

Nonbenzodiazepine Hypnotics

Nonbenzodiazepine hypnotics such as zolpidem, zaleplon, and eszopiclone appear less likely to suppress respiration than benzodiazepines.⁴² Nonetheless, they carry risks of altered mental status similar to those of the benzodiazepines. Zolpidem has been associated with parasomnias, and falls, and so particular caution is warranted with these agents.⁴³

Sedating Antidepressants for Insomnia

Because of its sedating properties, mirtazapine is often useful in depressed patients with prominent sleep problems, provided that weight gain is not of special concern. Trazodone is often used for sleep in doses that are subtherapeutic for depression. The most common medical concern with trazodone, and with the tricyclic antidepressants, is the increased risk of falls. The risk of falling associated with trazodone and SSRIs in the elderly is similar to, and may even be higher than, with tricyclic antidepressants.⁴⁴ Trazodone-induced QTc prolongation is usually mild and clinical reports of this have appeared exclusively in the context of overdose.⁴⁵

Antipsychotics for Insomnia

Use of antipsychotics, most importantly quetiapine, for insomnia has become commonplace for patients with and without major psychiatric illness.⁴⁶ However, these have a risk of adverse metabolic effects and movement disorders, even when used at low doses. These concerns, as well as the increased risk of sudden cardiac death in the elderly,⁴⁷ should prompt caution about their use for insomnia in depressed, medically ill patients. They should be reserved for cases in which other agents have clearly failed or other indications exist, for example, psychotic symptoms.

Antihistamines for Insomnia

Many patients try antihistamines such as diphenhydramine prior to seeking a prescription for sleep problems, as these are the key ingredients in most over-the-counter sleep-aids. However, their anticholinergic properties increase the risk of confusion and other systemic anticholinergic effects (urinary retention, constipation, dry mouth, blurred vision, and confusion), particularly in the elderly or patients with central nervous system compromise.⁴⁸

Melatonin and Ramelteon

Melatonin might be an ideal option for treating sleep problems because of its virtually nonexistent toxicity. Unfortunately, its hypnotic effects are limited in patients who are elderly or have a medical illness.⁴⁹ The melatonin receptor agonist ramelteon appears to be effective for insomnia across all adult age groups, and without a consistent pattern of adverse events, although data remain limited.⁵⁰ Interestingly, melatonin seems helpful in reversing sleep disruption induced by beta-blockers.⁵¹ This class of agents is preferentially useful in treating difficulties with sleep initiation as opposed to sleep maintenance.

Light Exposure

Exposure to light, natural or artificial, is useful in treating patients with seasonal affective disorder.⁵² Evidence for prescribing light exposure to patients with nonseasonal depressive disorders is mixed.^53,54 However, recommending increased exposure to light, such as a morning walk or other daytime activities that require going outside, as part of a comprehensive treatment plan carries minimal risk. It may be especially beneficial for depressed patients who have a shifted sleep/wake cycle, stay inside most of the day, or prefer a naturalistic treatment model.

If artificial light is used, it is important that the patient be guided to reputable light box distributers and the light box should be used as recommended. Typically, patients should use the light box soon after they wake up (to correlate with natural morning light exposure) and for no more than 45 minutes per day. Although guidelines have historically instructed patients to use a light box that provides a high “dose” (as measured in photopic lux) of at least 10,000 lux, more recent evidence indicates that lower doses can also be effective.⁵⁵ The cost of these devices is modest and adverse effects are unlikely. The risks are primarily those of activation, insomnia, and mania in the context of a bipolar diathesis.⁵⁶ To date there are no established ocular/vision risks though it is generally recommended that periodic eye examinations be conducted.⁵³

Nutrition

Good general nutrition appears to be associated with better outcomes for depression, and obesity is strongly associated with a higher risk of depression.⁵⁷ People who consume diets high in processed and sweetened foods are at higher risk for depression compared to those on nutrient-rich diets, such as the Mediterranean diet and whole foods diets.^58–60 And among patients with depression, better nutritional intake is associated with higher global assessment of functioning (GAF) scores.^47,61 However, a causal relationship between poor general nutrition and depression is not firmly established. Potential causal mechanisms include a relationship between dietary factors and brain-derived neurotrophic factor (BDNF),⁶² as well as several specific nutritional deficiencies that have independent causal associations with depression.

A comprehensive intervention for depression in patients with suboptimal nutrition might include consideration of the following specific nutritional needs:

Fish Oil

Although the evidence for the efficacy of fish oil is stronger for bipolar depression, it may also be effective as an adjunct to conventional treatment for major depression. Fish oil appears to be most helpful when it contains a ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) that exceeds 60%.⁶³ Typical therapeutic doses for EPA + DHA lie in the 1,000 to 4,000 mg per day range.

Vitamin D

Vitamin D deficiency is associated with depression. However, there is insufficient evidence to support that vitamin D supplementation in patients who are deficient improves depression outcomes.^64,65 In a recently published small randomized placebo-controlled trial involving 36 individuals with severe depression and vitamin D deficiency at baseline, the group randomized to receive 50,000 units of Vitamin D3 weekly showed significantly more improvement in their depression as measured by Beck Depression Inventory.⁶⁶ Given the low risk, potential mood benefits, and other medical benefits of correcting the deficiency, supplementation should still be considered.

Folate

Individuals with folate deficiency are more likely to experience depression,⁶⁷ and hypofolatemia has been associated with treatment resistance.⁶⁸ Risks for folate deficiency are significantly higher in the context of pregnancy, alcoholism, and gastrointestinal disorders. Folate ultimately regulates the synthesis of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. Some anticonvulsant-class mood stabilizers such as lamotrigine and valproate interfere with conversion of folate to l-methylfolate, its biologically active metabolite. A link has been identified between a genetic mutation in the enzyme 5-methyltetrahydrofolate (-MTHF) reductase (which converts folate to l-methylfolate), and major depressive disorder, as well as other neuropsychiatric conditions.⁶⁹ Given the reductase mutation findings, and studies linking excessive folic acid (synthetic folate) supplementation with heightened risk for some cancers, supplementing specifically with l-methylfolate is ideal.⁷⁰ There appears to be stronger evidence for folate as adjunctive treatment for depression in women specifically.⁷¹

Heavy Metals

There is little evidence that supplementation with heavy metals such as selenium and chromium improves depression outcomes,^72,73 though for some patients with depression who lack access to nutritious food, attention to this problem such as enrollment in a food assistance program has a positive effect.⁷⁴

Physical Activity and Relaxation

There is an association between depression and lower levels of physical activity,⁷⁵ but the extent to which prescribed exercise augments depression treatment remains a matter of debate.^76,77 It appears to improve depression outcomes to at least some extent,⁷⁸ in addition to its well-established benefits for other health parameters, including sleep. A formal exercise regimen must be tailored to the physical limitations resulting from the medical illness.

Relaxation training may also be beneficial, but the evidence supporting it arises primarily from interventions that combine psychotherapy with relaxation training and/or physical activity, rather than from these practices alone.⁷⁹ The relaxation response is a state of relaxed consciousness that is associated with decreases in physiologic indicators of stress, for example, heart rate and oxygen consumption. It can be induced by various spiritual, deep breathing, and attention-focusing techniques,⁸⁰ is virtually without risk, and has been associated with a positive effect on depressive and some medical symptoms.⁸¹ However, its efficacy in the treatment of depressive disorders remains unproven.⁸²

PSYCHOTHERAPY

Evidence-based psychotherapy is an important component of depression treatment in the medically ill patients. Many medical patients prefer psychotherapy to adding psychotropic medications to their regimen⁸³ Depressed patients have the tendency to engage in unhealthy behaviors and poor self-care, which may intensify the medical illness or increase the risk of additional medical problems.⁸⁴ For those with medical illness, psychotherapy for depression can also specifically target problematic health behaviors contributing to worsening medical conditions (such as withdrawing from social support, smoking, sedentary lifestyle, poor medication and treatment adherence).

Depression in the presence of medical illness is associated with more severe psychological, cognitive, and physical impairment⁸⁵ making psychotherapeutic treatment more complicated, associated with less robust benefits, and requiring adaptation. Despite the complex interactions between depression and medical illness, several forms of structured psychotherapy are effective in treating depression and associated problematic health behaviors, including nonadherence.^85,86 These include interpersonal psychotherapy, CBT, and mindfulness-based therapies.^87–90

Interpersonal Psychotherapy

Interpersonal psychotherapy (IPT) has been adapted and studied for the treatment of depressed patients in primary care,⁹¹ and for patients with coronary artery disease,⁹² HIV,⁹³ and breast cancer.^87,94 IPT focuses on interpersonal stressors, changes, and difficulties,⁸⁷ since these often serve as causal or maintenance factors. Depression often follows a negative or stressful change in one’s interpersonal environment, such as the death of a loved one, conflict with a significant other, a career change, the beginning or ending of a marriage or other relationship, or becoming medically ill.⁹⁵ Subsequently, depressive symptoms jeopardize interpersonal functioning, resulting in additional negative life events. For example, medical treatment related demands may lead to decreased social contact and support resulting in interpersonal deficits over time. Additionally, changes in roles may also result from medical illness, commonly seen as decreased ability to work or loss of work productivity.⁸⁷

There are two key principles guiding IPT. First, depression is a medical illness. This first principle defines the problem to be solved and counteracts any tendency for the patient to blame him/herself. The second principle is that depressed mood is related to life events, and situational context. IPT makes the connection between mood and distressing life events that either precede or follow onset of depressive disorder.⁹⁶ In particular, IPT targets four core problem areas: grief, role disputes, role transitions, and interpersonal deficits.⁸⁷

IPT is a time-limited psychotherapy comprised of three phases with a typical treatment course ranging between 8 and 20 sessions. The initial phase (sessions 1–3) involves assessment of depression severity, the interpersonal context in which the depression occurs, the patient’s relationship history and patterns, capacity for intimacy, and current relationships (is to substantiate depression as an illness rather than a flaw or defect within the patient).⁹⁵ In diagnosing depression, the IPT therapist employs symptom severity measures, such as the Beck Depression Inventory (BDI-II; additional measure information provided toward the end of this chapter).⁹⁷ Further clarification of how the four problem areas relate to depression (grief, role disputes, role transitions, and interpersonal deficits) also occurs during the initial treatment phase.

In the second phase of treatment, the IPT therapist is explicit and transparent with the patient in describing the IPT model of depression and the case formulation.⁹⁵ The IPT therapist collaborates with the patient in a partnership while maintaining a relaxed and supportive therapeutic stance. During session, the events of the past week are reviewed. When the patient demonstrates success or skillful behavior in an interpersonal situation, the therapist acts as a cheerleader, reinforcing these pro-social skills. With negative outcomes or missed opportunities, the therapist empathizes, works with the patient to analyze what went wrong in the situation, generates new interpersonal options, and rehearses them with the patient. Common interpersonal skills targeted in IPT include assertion of needs and wishes, promoting effective expression of anger, and taking social risks. Then the patient tests out these new options/skills in between sessions. Thus, over time, depressed patients develop a repertoire of new, adaptive interpersonal skills.⁹⁵

In the final phase of treatment (last three sessions), the therapist reviews the patient’s accomplishments to highlight the patient’s competency and discusses that ending therapy is another role transition, encompassing both negative and positive aspects.⁹⁵

IPT has been modified to specifically address the needs of medically ill patients. These modifications include decreasing session time to 45 minutes, phone sessions if the patient is too ill to travel, psychoeducation about both depressive and medical symptoms, and adaptations to the content within the four interpersonal problem areas.⁹⁸ For instance, within the psychoeducation component, patients are informed they have two medical illnesses and the “sick role” is adapted to include both illnesses.

IPT has been conducted with and without medication augmentation.^99–101 The combination of medication and IPT produces the best outcomes, making it optimal for prescribers to simultaneously provide IPT.⁹⁵ Although IPT is comparable to medication, it takes longer to achieve these benefits. IPT training resources can be found at www.interpersonalpsychotherapy.org; the International Society for Interpersonal Psychotherapy’s website.

Cognitive Behavior Therapy

Cognitive behavior therapy (CBT) for depression has been adapted and studied for treating patients in primary-care¹⁰² and in those with diabetes,^103,104 HIV,¹⁰⁵ cardiovascular disease,¹⁰⁶ chronic obstructive pulmonary disease,^107,108 Parkinson disease,¹⁰⁹ multiple sclerosis,^110,111 inflammatory bowel disease,^112,113 rheumatoid arthritis,¹¹⁴ end-stage renal disease,^115,116 and cancer.^117,118 Behavioral activation and cognitive restructuring are key components of CBT for depression.

Behavioral activation improves mood by fostering involvement in activities that bring patients into contact with reinforcing contingencies and by decreasing behaviors, such as avoidance, that perpetuate depression, such as avoidance.^88,89 Key behavioral targets include reducing reinforcement for depressive behaviors and increasing reinforcement for healthy/pro-social behaviors.⁹⁰ Particularly relevant to medical patients, behavioral activation generates nondepressed, approach-oriented behavior through behavioral scheduling, problem solving, and prioritizing, all of which contribute to an increasing sense of control over life.^89,119 These structured activation approaches target social support, emotional expression, and stress management.¹²⁰ For example, development of social skills, graduated exposure to social situations, and social anxiety reduction strategies increase positive social reinforcement and decrease negative affect.

At the beginning of treatment, in addition to establishing a strong therapeutic alliance, discussion is devoted to the function of depression and the treatment rationale. Weekly self-monitoring is the first step in systematically increasing nondepressive activities. Self-monitoring of daily activities and mood serves multiple functions: (1) to highlight current daily activities, (2) to identify potential activities to target, and (3) to obtain baseline measurement. The next treatment component focuses on identifying patients’ values within a range of life domains. Then an activity hierarchy is constructed in which new values-based activities are rated from “easiest” to “most difficult” to accomplish. Patients then progress from the easiest activity through the hierarchy to the most difficulty. Both the therapist and patient thoughtfully consider the frequency and duration of each activity per week. The activity engagement is reviewed at the next session, and barriers or problems with engaging the activation plan are thoroughly discussed.⁸⁸

The cognitive component of CBT focuses on identifying and challenging negatively biased thoughts that cause or maintain depression.¹²¹ Therapists guide patients through structured learning experiences with techniques, such as psychoeducation, guided discovery using use of Socratic questioning, role playing, the downward arrow technique for uncovering core beliefs, and behavioral experiments to empirically test their maladaptive automatic depressive thoughts.¹²¹ Cognitive restructuring is then used to challenge the validity of the patient’s assumptions and to develop more realistic appraisals of daily situations. In addition, behavioral experiments are developed to test out unhelpful and/or rigidly held beliefs. These challenging strategies are applied in real time (daily, weekly) to help patients develop more realistic, alternative thoughts and beliefs that improve mood. Typically, about eight sessions are needed for patients to sufficiently learn the cognitive model and skills and a significant reduction in depression often occurs within this first stage of therapy. The next phase of therapy (sessions 9–16) focuses on modifying dysfunctional core beliefs and learning skills to prevent relapse.¹²¹

Although somewhat distinct, problem-solving therapy (PST) is derived from CBT and is thought of as a type of CBT. PST involves training patients to adopt adaptive problem-solving attitudes (e.g., increase positive problem orientation) and skills (e.g., increasing rational problem solving and decreasing impulsive and avoidant problem-solving).¹²² PST is short-term and present-focused, ranging from 6 to 16 1-hour sessions. PST has strong empirical support for treating depression provided that the course of treatment includes training in problem-orientation and assignment of homework.¹²³ PST has demonstrated promise as an effective treatment for psychological distress and depression among medically ill patients,^123,124 including depressed patients with cancer,^125,126 cardiac disease,¹²⁷ and diabetes.^128,129

PST teaches patients to address current life difficulties by appraising problems as solvable challenges,¹³⁰ breaking larger problems into smaller pieces and identifying specific steps toward positive change, similar to the process of change engendered by behavioral activation.¹³¹ Patients are taught to identify emotions as cues for the presence of a problem and to inhibit automatic/impulsive responses to the problem(s). Instead, patients are taught to practice rational problem-solving skills (see Table 4-2 for rational problem-solving activities).¹²⁰ The PST model identifies problem-solving skill as the ability to define a problem, identify solutions, and verify the effectiveness of the employed solutions and that one’s problem-solving repertoire mitigates how one experiences psychological distress leading to depression.

Applying the PST model to medical conditions means that medical patients can experience their medical problems as ongoing stressors and problem-solving skills can decrease the likelihood that one will experience heightened distress when facing ongoing medical stress. The PST manual and training tools and videos can be found on the IMPACT Collaborative Care for Depression website (http://impact-uw.org/tools/pst_manual.html).

Mindfulness-Based Therapy

Mindfulness-based therapies aim to teach mindfulness skills so that depressed patients can better connect to their experiences and their environment in real time. Here, mindfulness is defined as the skill of nonjudgmentally observing one’s experiences, such as bodily sensations, emotions, and thoughts, in the present moment.¹³¹ Most learning within mindfulness-based therapies is experiential and involves first learning basic mindfulness practices, such as mindful breathing, body scan, and mindful movement. Then mindfulness is applied in a more sophisticated way to emotions, thoughts, one’s sense of self, and interpersonal processes.

The first two mindfulness treatments discussed here (mindfulness-based stress reduction [MBSR] and mindfulness-based cognitive therapy [MBCT]) utilize and require formal mindfulness meditation (i.e., sitting in silence and meditating). The latter two treatment programs (emotion regulation and acceptance and commitment therapy) involve mindfulness skills training but typically do not require that the patient employs sitting meditation practice. MBSR, developed by Jon Kabat-Zinn,¹³¹ is a group treatment for psychological distress, depressive symptoms, and anxiety for patients with chronic disease. Originally developed for chronic pain, its effect on alleviating depression has subsequently been tested in patients with a range of medical conditions, such as cancer, heart failure, and rheumatoid arthritis.^90,132 A meta-analysis of six studies found that MBSR has significant but small effect sizes (Hedges g= 0.26) in treating depression in patients with various medical and somatic conditions⁹⁰ and may be most useful when integrated into a CBT program. However, among patients with recurrent and treatment-resistant depression but without major medical comorbidities, mindfulness appears to be more beneficial than either CBT or education alone.¹³³ MBCT is a form of MBSR, also delivered in a group format. It includes mindfulness skills training (i.e., sitting mindfulness meditation) as well as cognitive therapy exercises to improve awareness of depressive cognitions and the connection between depressive thinking patterns and behavior and mood. MBCT helps patients develop a different mode of mind to best work with these thoughts and feelings when depression threatens to overwhelm them.^134,135 MBCT has led to significant improvement in depressive symptoms among HIV-infected patients,¹³⁵ vascular disease,¹³⁶ cancer,¹³⁷ traumatic brain injury,¹³⁸ and for patients who have had a stroke.¹³⁹

Other forms of mindfulness-based behavior therapies show promise for treating depression in medically ill patients. One such treatment is a mindfulness and emotion regulation intervention, adapted from MBCT¹¹⁴ and MBSR. This treatment aims to improve emotion regulation and promote awareness and acceptance of the entire spectrum of emotional experience through training in mindfulness meditation.¹³³ It has been employed in patients with rheumatoid arthritis to improve regulation of negative affective responses to stressful life events, and to encourage positive affective engagement (e.g., social engagement). Adaptations in the medically ill include reducing duration of meditation times to 10 minutes. Aside from the mindfulness meditation component, the other treatment elements are based on CBT. These include emphasizing emotional clarity, accepting and reframing of negative thoughts, cultivating positive emotions through pleasant event scheduling, and enhancing social relations.

Acceptance and commitment therapy (ACT) also relies heavily on mindfulness and acceptance, and includes other core components such as values-based behavioral change and activation.¹⁴⁰ ACT has a moderate evidence base for treating depression. It is empirically supported for treatment of chronic pain and has some evidence for improving psychological functioning, medical symptoms, and health behaviors among patients with diabetes, epilepsy, obesity, and irritable bowel syndrome. Both of these mindfulness-based CBTs place a primary emphasis on learning to relate differently to unwanted thoughts and feelings during times of negative affect such that the function of negative thoughts and emotions is altered.^133,140

Common Features of Psychotherapy

All three psychotherapy types (IPT, CBT, mindfulness) are effective for depression among medically ill patients and have common treatment elements, principles, and goals. All aim to preserve effective and rewarding social relationships and interpersonal connections despite facing medical-related burdens while learning new ways of responding or relating to depressive symptoms. In addition, they are structured, short-term (i.e., ≤20 sessions), rely on multiple components, are present-focused, and are designed flexibly to accommodate the medical condition. All therapeutic modalities are directive with agendas and a path to follow, skills to learn, and continuous assessment of depressive symptom change.

It is important to note that insight-oriented therapeutic approaches and nondirective supportive psychotherapy are not recommended as a stand-alone treatment for depression among the medically ill. Research, although limited, suggests poorer outcomes with insight-oriented and nondirective supportive approaches in the medically ill.^82,103 Support, ventilation, clarification, and insight are all valuable, but do not in and of themselves appear to be effective treatments for depression in medically ill populations. Rather, they should be included as part of the evidence-based therapies described above. There is, however, one empirically informed exception: among HIV patients with depression, group supportive psychotherapy and psychoeducational groups have shown equivalent benefits as CBT.¹⁴¹ Medically ill patients seeking treatment for depression should be informed about recommended evidence-based psychotherapies and offered these treatments as the first-line approach.

PHARMACOLOGIC INTERVENTIONS

Approaching pharmacologic interventions for the patient diagnosed with medical illness and depression involves following general guidelines for treating depression in conjunction with special consideration of the interactions among medical illness, aging, and the medications being prescribed.

General Considerations

Start by carefully establishing the depressive diagnosis and assessing the roles of concurrent medications, medical disease, and substance abuse. False-positive diagnoses of depression are common, perhaps even more common than false negatives, particularly in busy primary care practices where standardized assessments, re-assessments, and/or rating scales are not routinely used.¹⁴² When considering pharmacologic treatments, differentiating between bipolar and unipolar depression is important (Chapter 3) as pharmacologic treatment guidelines for bipolar depression are substantially different.

Evidence-based treatment guidelines for nonbipolar depression^143–145 support starting with any of the newer antidepressant agents, namely selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, or bupropion. Most evidence suggests that all of these agents are roughly equal in efficacy when applied to the general population;¹⁴⁶ there is some evidence that SNRIs are more effective than SSRIs in inducing remission, particularly among the more severely depressed.¹⁴⁷ Remission is typically defined as PHQ-9 total score <5 or when the individual is close to symptom-free and back to functioning at his or her peak level.

Identify two or three agents that would likely have favorable side-effect profiles for the individual, and then present the menu of options and side effects to the patient. While many patients will ask the clinician to choose the “best” medicine for them, it is important to educate the patient that there is no perfect medication, none without potential side effects, and no significant differences in efficacy (though evidence has emerged over the last decade that patients with severe comorbid anxiety tend to have worse outcomes and also more difficulty tolerating the side effects of medications).¹⁴⁸ Patients educated on these fundamentals often find it easier to engage actively in making a decision on which medication to try.

Once the patient has identified a medication, it is generally most prudent to start with the lowest dose possible for at least the first few doses in order to assess the patient’s sensitivity to the agent. Otherwise, one risks the patient having a negative experience with the medication and reduces odds of the patient persisting with a medication trial. As it appears, the patient is tolerating the medication, increase the dose as tolerated to the lower threshold for a therapeutic response. In the context of significant comorbid anxiety, it is especially important to start low and gradually titrate the dose as this population has a heightened sensitivity to the adverse effects of antidepressant class medications. Tracking response, side effects, and adherence to the regimen, while continually encouraging the patient to partner with the clinician and persevere with the medication, are all key factors. If a partial or no response is observed after 4 to 6 weeks at a therapeutic dose, switch or augment the medication. Generally the clinician will switch antidepressants if there is no response or if a partial response, consider augmenting with a complementary antidepressant. If the patient continues to respond inadequately, review the history to assure nothing has been overlooked, reassess for adherence, and then sequentially revise the regimen, including consideration of other somatic therapies, psychotherapies, and even of complementary and alternative agents. Once the patient has achieved a full remission or as close to full remission and optimal functioning as possible, prevent relapse with continuation therapy and depending on past history, consider whether maintenance therapy is indicated.

Complementary and Alternative Agents

Alternative medicines remain popular with patients who suffer from depressed mood and prefer to avoid prescription antidepressants. These agents can be difficult to manage due to a limited understanding of optimal dosing, pharmacologic mechanisms and safety profiles, and a tendency for the contents to vary. Nonetheless, they can be part of a psychiatric regimen for depression.

St. John wort and S-adenosyl methionine (SAMe) show a potential benefit for the treatment of mild depression,^149–151 but the evidence supporting their efficacy is still limited. St. John wort appears to be most promising for the treatment of mild depression,^150,151 while SAMe appears useful as an adjunctive therapy for patients who do not respond to SSRI monotherapy.¹⁵²

St. John wort can induce the P450 enzyme CYP3A and thus affect the metabolism of other medications, including lowering serum levels of hormonal contraceptives and antiretroviral agents. St. John wort should also not be taken in conjunction with conventional antidepressants due to the risk of serotonin syndrome.¹⁵³ SAMe may affect sleep or precipitate mania in individuals with underlying bipolar disorder¹⁵⁴ and also has risk for serotonin syndrome when used in tandem with conventional antidepressants.¹⁵⁵