Tx Response in MDD

Posted on Apr 13, 2010 in Expired CME | 2 comments

Getting Better Is Not Good Enough: Assessing and Addressing Treatment Response in Major Depressive Disorder 

 

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Learning Objectives

As a result of this activity, the learner will be able to

1. List 2 consequences of untreated or undertreated major depressive disorder (MDD)
2. Develop and implement monitoring strategies for patients with MDD who are receiving treatment

Introduction

Up to 40% of primary care patients will seek treatment for depression at some time in their lives; 14.4% of Americans will have major depressive disorder (MDD).[1,2] The economic impact of depression is significant, with annual direct costs of treatment and indirect costs due to loss of productivity estimated at $83 billion.[3] No less noteworthy are the incalculable personal costs resulting from social stigma, general ill health, disability, loss of interpersonal and occupational functioning, and mortality from suicide and accidents. Depression and other mood disorders make considerable demands on our healthcare resources, accounting for 8.5 million visits to primary care offices and hospital outpatient and emergency departments each year.[4] In 2006, of 459,000 hospital discharges, MDD was the first-listed diagnosis.[4]

Most patients with depression can be treated successfully; data show that a combination of appropriate pharmacologic therapy and psychotherapy is most effective.[5] With increased understanding over the last decade of the impact of depression on a number of domains of patient health and functioning, the treatment paradigm for MDD has shifted from achieving symptom relief or response to achieving remission in all patients. However, approximately one-third of primary care patients do not receive any treatment for their condition[6]; many who do receive treatment do not receive enough.[6] While screening remains important, clinicians must be able to do more than just recognize MDD; they also must be able to initiate therapy, monitor clinical response on a continual basis, and make therapeutic adjustments as necessary.

This article will provide primary care clinicians with a review of evidence-based strategies for identifying and managing MDD over the long term, with the goal of achieving symptomatic remission in each patient. The first part of the article will focus on identifying depression and initiating treatment. Results from recent clinical studies on achieving remission through each of the 3 strategies for nonresponse to antidepressant trials― switching, augmentation/combination therapy, and increase in dose of the original agent―will be presented. Many of these studies come from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, a large, multicenter, multistage research project funded by the National Institute of Mental Health with the specific purpose of evaluating treatment options for patients with MDD in both the primary care and secondary care settings.[7,8] The largest and longest study to evaluate depression treatment ever conducted, the STAR*D trial encompassed 4 “levels,” in each of which a different medication or combination of medications was tested.[7,8] All patients in the study were initially given citalopram, a drug from the most commonly prescribed antidepressant class, the selective serotonin reuptake inhibitors (SSRIs). Patients who failed to achieve symptomatic remission had their therapy augmented or switched in a subsequent level until remission was achieved.

In the second part of the article, a number of relatively simple yet effective strategies will be presented to improve the management of patients with MDD within the primary care clinician’s individual practice. Thus, the goal of this activity is multifold: present the rationale for treating every patient with depression to symptomatic remission; explore therapeutic strategies that can be utilized to achieve that goal; and provide clinicians with examples of relatively small changes that can be made within their practices to better pave the way for the therapeutic strategies to be implemented.

Detecting Depression: A Difficult Task

The American College of Preventive Medicine maintains that primary care providers should screen all adults for depression and should have systems in place, either within the primary care setting itself or through collaboration with mental health professionals, to ensure the accurate diagnosis and treatment of this condition[9]; these recommendations are in line with those of the US Preventive Services Task Force.[10] However, making an accurate diagnosis of depression can be challenging. Somatic symptoms often predominate and chronic illness may be present; in addition, patients may even deny the depressed mood.[11] Higher rates of depression may be found in patients with specific medical disorders. For example, diabetes, cardiovascular disease, and thyroid disorders are associated with an increased risk of depression.[12-15] Depressive symptomatology also has been associated with the use of certain medications, such as β-adrenergic blockers,[16] glucocorticoids,[17] phenobarbital,[18] and levodopa.[19]

Symptoms of depression also may be a component of bipolar disorder or a nonmood psychiatric disorder, such as anxiety, an eating disorder, or alcohol or drug abuse. Grief reactions or bereavement share many symptoms of MDD and, if prolonged, may cause substantial morbidity, particularly among the elderly.[20]

Certain complaints and presentations of symptoms should prompt clinicians to suspect an underlying depressive disorder.[11] Sleep disturbances, fatigue, multiple or nonspecific musculoskeletal complaints, shortness of breath, and back pain are highly predictive of clinically significant depression in up to 60% of patients.[21]

Tools for Identifying Depression

A number of self-report questionnaires and clinician-completed rating scales are available to screen patients for depression in primary care practices.[22] These tools are easily administered, inexpensive, and though not diagnostic, can detect milder mood conditions.[10,23,24] The US Preventive Services Task Force suggests primary care clinicians need only ask patients 2 simple questions: “Over the past 2 weeks, have you felt down, depressed, or hopeless?” and “Over the past 2 weeks, have you felt little interest or pleasure in doing things?” An affirmative answer to either question is considered a positive screen for depression.[10]

A more detailed patient-rated instrument, the World Health Organization’s WHO-Five (WHO-5) Well-Being Index, contains 5 statements about the frequency of well-being, scored from 0 to 5, over the past 2 weeks. A sum of less than 13 for all 5 questions is indicative of poor well-being and further testing for depression is warranted.[23]

The Patient Health Questionnaire (PHQ)-9 captures the frequency of 9 depression criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), rated 0 to 3, also over the previous 2 weeks. With this instrument, a score of 4 or less is not suggestive of depressive illness, but a score of 15 or higher indicates major depression; scores from 5 to 14 suggest mild or moderate depression.[24]

Another patient-rated questionnaire, the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) rates the severity of each of 9 depressive symptoms from the DSM-IV on a scale of 0 to 3.[25]

The Beck Depression Index (BDI) is a widely used screening tool and consists of 21 items to assess the intensity of depression. Each item is a list of 4 statements arranged in increasing severity about a particular symptom common in depression (eg, hopelessness, irritability, guilt, and feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex).[26]

The Zung Self-Rating Depression Scale is a 20-item, self-reported questionnaire that is widely used as a screening tool.[27] The questionnaire takes about 10 minutes to complete, and items are framed in terms of positive and negative statements covering the affective, psychological, and somatic symptoms associated with depression. The Zung scale can be useful for monitoring changes in depression severity over time; however, the scale cannot take the place of a comprehensive clinical interview for confirming a diagnosis of depression.[27]

Clinician-completed assessments have greater sensitivity to detect depression than self-reports and can rate the functional impact of depressive symptoms.[10] The Hamilton Rating Scale for Depression (HAM-D) grades 17 to 21 variables on scores of 0 to 2 or 0 to 4 to detect the presence and severity of depressive symptoms.[28] Previously considered the “gold standard” of depression rating scales in clinical trials, it has been increasingly suggested in recent years that the instrument is flawed both as a test instrument and in its conceptual basis.[29]

The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-administered instrument that is moderately time-consuming and requires special training. The findings from the MADRS are based on a clinical interview using a 10-item questionnaire to measure the severity of depression on a scale of 0 to 6.[30]

Sidebar: Resources for Depression Management

A number of resources are now available to help primary care clinicians in diagnosing and achieving remission in MDD. Some are listed below.

Diagnosis and Screening Tools

PHQ-9: English
PHQ-9: Spanish
HAM-D
CES-D
Inventory of Depressive Symptoms-SR
WHO-5 (in English and Spanish)
MADRS
Depression Evaluation: Initial Visit
Checklist of Clinical Situations in Which Screening for a Major Depressive Episode Should Be Considered

Treatment Tools

Checklist for When to Switch/Augment MDD Therapy
Checklist for When to Refer Patients With MDD to Specialty Care
eMPR (for drug information/dosages)
Supportive Counseling Fact Sheet for Clinicians
Tips for Improving Patient Adherence

Monitoring/Follow-up Tools

Checklist for Achieving Remission
PHQ-9 Flow Chart for Assessing Response to Treatment

Patient Education Tools

Wakefield Depression Self-Report Questionnaire
Strategies for Managing Antidepressant Side Effects
Depression Self-Care Action Plan
Quick Facts About Psychological Counseling
Patient Satisfaction Survey

Organizational Changes

Organizational Changes: Suggestions and Resources for Implementation
Strategies for Assisting Patients With Medication Management

Additional resources can be found at mycme.com/mdd_resources

First-line Treatment of MDD

Once depression has been identified, patients can be started on effective therapies. It is recommended that patients with mild-to-moderate MDD receive either antidepressant medication or psychotherapy as first-line treatment.[31] For patients with severe or chronic MDD, combined treatment with antidepressants and psychotherapy is recommended as first-line treatment.[31]

Psychological interventions, including cognitive behavior therapy and interpersonal therapy, have consistently shown comparable or superior effects compared with psychotropic medications.[32] In addition, such interventions may be more cost effective than medications.[33] Further, there are no side effects associated with psychological interventions, save for the required time commitment.

There is no evidence that there is a clearly superior pharmacologic treatment approach for patients with mild-to-moderate MDD. Should it be determined that an antidepressant trial is warranted instead of or in combination with psychological counseling, treatment decisions should be based on patient and clinician preference, potential side effects, and cost.[34]

SSRIs are now the most commonly used drugs for depression. Most of these agents can be used with no dietary restrictions. Side effects, which are generally mild but can be bothersome in some people, include nausea/stomach upset, sexual problems, fatigue, dizziness, weight change, and headaches.[34]

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer type of antidepressant. This drug class includes venlafaxine and duloxetine. Side effects associated with SNRIs include upset stomach, insomnia, sexual problems, anxiety, dizziness, and fatigue.[34]

Aminoketones such as bupropion, treat depression by an unknown mechanism. They are different than other antidepressants and only weakly affect the brain chemicals that other antidepressants influence. Their side effects include upset stomach, headache, insomnia, and anxiety.[34]

Tetracyclic antidepressants include mirtazapine. The precise effects of these drugs are unknown; they act upon both norepinephrine and serotonin. Adverse effects associated with this drug class include upset stomach, sleepiness, weight gain, and dizziness.[34]

Tricyclic antidepressants (TCAs) were among the first medications used to treat depression. Drugs in this class include amitriptyline, desipramine, imipramine, and nortriptyline. Because side effects can be severe in some people, TCAs are being used with decreasing frequency. However, they may be useful in patients who fail to respond to other medications. Regular blood tests are required to monitor the level of tricyclics in patients taking TCAs. These agents may not be safe for people with cardiovascular problems.[34]

Like TCAs, monoamine oxidase inhibitors (MAOIs) were among the earliest treatments for depression. These drugs work by blocking an enzyme, monoamine oxidase, which leads to the breakdown of neurotransmitter hormones that are thought to be responsible for mood changes, along with other physiologic functions.[34] Drugs in this class include phenelzine, tranylcypromine, and isocarboxazid. MAOIs are not prescribed very often because of their side effects. In addition, they can cause serious interactions with other medications and can cause cardiovascular problems when taken with some foods containing tyramine, a monoamine compound that is derived from the amino acid tyrosine; however, MAOIs may help people with MDD that are nonresponsive to more common drugs.[34]

It is important to note that, in addition to the general, class-wide side effects listed above, agents in each class may differ in their safety profile. For comments on safety concerns for specific agents, please see Table 1.

Pharmacologic treatment for MDD should be discontinued only if necessary and, if so, discontinued very gradually, no matter which agent is used. Patients receiving any antidepressant should be monitored frequently to assess response.[35]

Table 1. Effectiveness and Tolerability of Antidepressants

Treating MDD to Remission: A Largely Unfulfilled Medical Need

Over the last decade, the treatment paradigm for MDD has evolved such that the goal of therapy is remission—a virtual lack of symptoms or very minimal symptoms—because it is associated with the return of normal psychosocial function, lack of disabling symptoms, and a lower risk for suicide or alcohol and drug abuse.[36] Response is defined by a 50% or better improvement in depressive symptoms. The early return of depression symptoms following a response or remission defines relapse.[2] Recovery can be declared only after at least 4 months following the onset of remission, and the early return of depressive symptoms following an apparent remission defines relapse. Recurrence refers to a new episode that occurs after recovery from a previous episode.

An adequate duration of an antidepressant trial is 6 weeks or longer.[37] Treatment response can be measured with the same tools that can be used for screening: the clinician-rated HAM-D, MADRS, or Quick Inventory of Depressive Symptomatology (QIDS); and the patient self-rated BDI, Zung Self-Rating Depression Scale, QIDS-SR, or PHQ-9.

The factors that affect the likelihood of achieving remission include the type, dose, and duration of pharmacologic treatment, symptom severity at baseline, the presence of psychiatric or medical comorbidities, the prior course of illness (eg, chronic or acute), the degree of treatment resistance, environmental supports and stressors, and the patient’s genetic vulnerability to depression.[38]

Unfortunately, up to 70% of patients fail to achieve complete remission of their symptoms. These patients have treatment-resistant or treatment-refractory depression (TRD); that is, they do not respond to at least 1 trial of 1 major class of antidepressant. Up to 15% of patients will fail multiple antidepressant trials.[39] Several clinical, biologic, and demographic factors have been attributed to nonresponse and a predisposition to TRD, including inadequate dosage and duration of the regimen or compliance to it, depression subtype, extremes of age at diagnosis, and psychiatric or medical comorbidities.[40]

Anxiety, alcohol or substance abuse, and personality disorders often are present in patients with TRD and should be treated simultaneously. Finally, many patients labeled with TRD have an underlying physical cause; while endocrine disorders, such as hypothyroidism, Cushing’s disease, and Addison’s disease, have received the most attention, other conditions, including diabetes, coronary artery disease, connective tissue disorders,[41] cancer, and HIV infection, may play a role in TRD, if they are not identified or adequately managed.[42,43]

Another important reason for treatment is lack of patient adherence to the treatment regimen. For patients with MDD whose symptoms fail to remit after first-line treatment, adherence to the initial treatment regimen must be assessed. If adherence is not determined to be a contributing factor, the clinician must determine how to safely and effectively advance therapy.

Treatment Strategies for Achieving Remission in MDD

A number of treatment strategies are available for patients who fail to respond to initial MDD therapy; these include dose increase, augmentation or combination therapy, and switching.[44,45]

Dose increase of the original antidepressant is often the first-line treatment approach (tolerability permitting), as clinicians strive to ensure that they deliver a therapy that is optimized both in terms of dose as well as duration.

In augmentation or combination therapy, a second agent is added to enhance the efficacy of the partially effective or completely ineffective original antidepressant. Augmentation therapy involves the addition of an agent that is not considered to be an antidepressant when administered as monotherapy. For combination therapy, the additional agent is another antidepressant.

Switching involves discontinuing an ineffective antidepressant and initiating treatment with an alternative agent.

Achieving remission via any of these strategies can largely be a matter of trial and error. Below are data from clinical trials on augmentation/combination and switching therapy for patients failing to respond to initial therapy.

Augmentation/Combination Therapy

Augmentation and combination treatment strategies have several potential advantages over switching for patients who have not responded to antidepressant therapy. First, withdrawing a partially effective therapy and substituting it with a second one (ie, switching) may result in a loss of the partial therapeutic benefit that is not subsequently “gained back” during the second trial. This may be avoided by choosing an augmentation/ combination strategy instead. In addition, the dosage of the first antidepressant may need to be tapered before switching to another antidepressant, or a “washout” period may be required before initiation of the alternative agent. Furthermore, switching may result in patients experiencing antidepressant-associated withdrawal symptoms, the risk of which is minimized with augmentation/combination (unless the adjunctive agent chosen significantly reduces the blood levels of the first agent).

Until recently, few randomized, double-blind, placebo-controlled clinical trials had been conducted to provide data supporting the effectiveness and safety of augmentation therapy.[45] Early studies of augmentation of standard antidepressant therapies (TCAs or SSRIs) with lithium*, triiodothyronine (T3)*, pindolol*, methylphenidate*, and modafinil* provided preliminary data with inconclusive, inconsistent, or negative results.[46-54] Additional trials provided considerable data to show that augmentation with mianserin* or mirtazapine* was more effective than SSRI monotherapy[55-57] and that the addition of omega-3 fatty acid* to standard antidepressant therapies improved symptoms of MDD compared with placebo.[58,59] These drugs are, of course, not without risk. Though shown to be generally safe in the aforementioned trials, side effects include tremor, thirst, and nausea for lithium[46-48]; insomnia, tremor, and weight loss for T3[49]; headache for modafinil[50,51]; dizziness, fatigue, and joint pain for pindolol[52]; insomnia, nausea, and nervousness for methylphenidate[53,54]; drowsiness and blurred vision for mianserin[55,56]; and abnormal dreams/thinking and constipation for mirtazapine.[57]
*(Not an FDA-approved treatment)

During the course of the past 8 years, atypical antipsychotic agents have been extensively studied as adjunctive therapy for nonpsychotic MDD (in nonelderly adults only). The studies have suggested a potential role for these agents in improving remission rates in nonresponders to traditional antidepressants. Limitations of the studies included the fact that they only involved some of the drugs in the atypical class, pooling clinical trials that had various patient and study inclusion/exclusion criteria, variability of effect across different response measures, lack of randomization during prospective treatment, relatively small sample sizes, and specific patient criteria (eg, exclusion of patient who failed >3 antidepressant treatment trials).[45,60-62]

In addition, the utility of the atypical antipsychotics as add-on therapy is limited greatly by their side-effect profiles. These agents are associated with a number of potentially serious adverse events, including metabolic effects (weight gain, dyslipidemia, glucose dysregulation), endocrine effects (hyperprolactinemia), extrapyramidal symptoms (akathisia, Parkinsonism, dystonic reactions, tardive dyskinesia, neuroleptic malignant syndrome), and cardiovascular effects (QTc interval prolongation).[45,63] In 1 meta-analysis of 10 clinical trials in 1500 outpatients with TRD on an antidepressant whose therapy was augmented with olanzapine, risperidone, or quetiapine, although patients in the augmentation group were more likely to achieve remission (P<.0001) or clinical response (P<.0001), they were also more likely to discontinue treatment because of intolerance (P<.0001)[61] (Figure 1).

Figure 1. Atypical Antipsychotic Augmentation in TRD: Meta-analysis of 10 RCTs With Olanzapine, Risperidone, or Quetiapine

Results from one section of the STAR*D trial indicated that augmentation of antidepressants with bupropion (sustained-release) or buspirone may improve remission rates in patients not responding to a traditional antidepressant (Figure 2). Bupropion augmentation resulted in a significantly lower QIDS-SR-16 score at the end of treatment (8.0 vs 9.1, P<.02) and a significantly lower discontinuation rate owing to intolerance (12.5% vs 20.6%). Study limitations included the open treatment design and lack of placebo control. The authors added that nonspecific treatment effects undoubtedly accounted for some proportion of the acute response or remission rates observed in this study.[64]

Figure 2. Effectiveness and Tolerability of Level 2 or Level 3 Augmentation Therapy in the STAR*D Trial

Cognitive behavioral therapy (CBT) may also be useful as augmentation therapy in patients who are not responding to standard therapy with an antidepressant. In one study, patients who did not achieve remission after 12 weeks of citalopram treatment were randomized to either switch therapy with CBT or another antidepressant (sertraline, bupropion, or venlafaxine), or to augmentation of citalopram with CBT or medication (bupropion or buspirone). Based on a definition of remission as HAM-D score of 7 or less, CBT and medication achieved similar remission rates whether administered as a switch strategy (25.0% and 27.9%, respectively) or an augmentation strategy (23.1% and 33.3%, respectively). Patients who switched to another antidepressant reported more adverse events and were more likely to discontinue due to intolerance than were those who switched to CBT. Limitations of the study included study design (may have inadvertently biased patients against receiving CBT versus a second pharmacologic therapy); cost of CBT (pharmacologic therapy was provided to patients who received it); and patients who received CBT had to travel to a different site, which, the authors speculated, could be a real-life limitation as well.[65]

Another STAR*D trial report described the results of treatment in 142 patients who had not achieved remission with initial therapy with citalopram and a second trial of switch therapy with bupropion, sertraline, or venlafaxine, or an augmentation trial with buspirone or bupropion. Patients were randomized to augmentation therapy with lithium* or T3* for up to 14 weeks. Remission rates were 13.2% and 24.7% with lithium* and T3* augmentation, respectively, but were not significantly different; however, lithium as a Level 3 augmentation was associated with a significantly higher incidence of adverse effects (23.2% vs 9.6%, P=.027). The study had several limitations: among them were lack of statistical power to reliably detect small differences in remission rates between the augmentation therapies; laboratory indices, including pretreatment assessment of thyroid function and serial monitoring of lithium levels, were not assessed; augmentation therapies were administered in an open-label manner; and lack of a control group. In addition, participants in the lithium augmentation group took relatively low doses because of side effects, leaving open the question of whether the effectiveness of the drug as augmentation therapy is limited if it is given in small doses.[66]
*(Not an FDA-approved treatment)

Switching Antidepressant Therapy

Some disadvantages of switching versus augmentation/combination were discussed in the above section. However, switching may also have certain advantages over augmentation/combination strategies. For example, patients experiencing side effects from an ineffective agent may opt to switch to an agent that potentially could be better tolerated. In addition, the use of a single agent may enhance compliance as well as reduce the risk for drug-drug interactions.

One recent meta-analysis of 4 clinical trials in patients with SSRI-resistant MDD found that patients switched to a non-SSRI antidepressant (bupropion, mirtazapine, or venlafaxine) were more likely to achieve response than were those switched to another SSRI (paroxetine, citalopram, or sertraline) (P=.007). Several study limitations were identified; among them were the use of HAM-D rating scale to assess response; the studies only focused on 3 SSRI agents, thus, results may not be applicable to other SSRIs; and the studies utilized only 1 outcome measure. The heterogeneous nature of meta-analyses was mentioned as a final limitation.[67]

The benefit of switching patients with treatment-resistant MDD to another class of antidepressant was seen again in 2 small crossover studies (N=108), in which patients unresponsive in double-blind trials to a TCA or an MAOI were switched to treatment with the other agent (Figure 3). Based on Clinical Global Impressions scale scores, up to 67% of patients previously unresponsive to imipramine responded to phenelzine (P<.05). Of those previously unresponsive to phenelzine, up to 41% responded to phenelzine (P<.05). These findings suggest that patients who do not respond to a TCA trial may benefit from an MAOI trial, even though it is common practice to switch TCA-resistant patients to another heterocyclic antidepressant (eg, fluoxetine or bupropion). Study limitations included the small sample sizes and the absence of an adequate control for time or the possible effects of continued treatment with the initial agent.[68,69]

Figure 3. Results of Crossover Switch Therapy With a TCA or an MAOI in Patients With Treatment-Resistant Depression

While all of the preceding data provide insight that effective treatment strategies to achieve remission in MDD exist and others are continuously being researched, being able to implement these strategies requires more than knowledge of the published data. In particular, barriers to achieving remission in practice must first be identified and addressed before such treatment strategies can be implemented.

Thus, the remainder of this article will focus on how primary clinicians can implement small but effective interventions into their practice to facilitate the achievement of symptomatic remission in patients with MDD.

Addressing Barriers to MDD Management

As mentioned previously, many patients with depression do not achieve adequate remission of symptoms. While effective pharmacologic and behavioral strategies, such as those presented above, are available and are appropriate for use in primary care,[70] a host of practice-, clinician-, and patient-related factors, as well as capitation and cost issues, all can affect the delivery of care and reduce its effectiveness.

Lack of time is the key barrier to the diagnosis of depression in the primary care setting. The time allotted to a typical office visit is 10 to 15 minutes—barely sufficient to address the medical needs of the patient and certainly not adequate for a definitive diagnosis of depression, discussion of the disorder, and explanation of treatment options. In addition, few primary care practices have additional staff to assist with the administration and interpretation of depression screening tools and to counsel patients on using these tools. For those practitioners who are less comfortable dealing with, or who have less interest in, mental health disorders than medical illnesses, the availability of psychiatric referral resources may be limited. Lastly, primary care clinicians often lack the time required for frequent follow-up visits to monitor symptoms, treatment compliance, and medication side effects, and may not feel completely confident in their ability to treat these conditions.[71,72]

Patient-related factors may also contribute to a delay in diagnosis and treatment. Many patients, for example, may not recognize the signs of depression and may instead complain of somatic symptoms. Some patients may regard depression as a personal weakness, or refuse to accept the diagnosis or treatment because of the stigma surrounding mental illness. Others may be reluctant to discuss their mental health problems with their provider. Even if treatment is initiated, lack of compliance may result from difficult socioeconomic or personal circumstances, or strong feelings about the type of treatment prescribed. Patients may not be able to return for follow-up appointments for a number of reasons, including social or economic factors.[71,72]

Current trends in managed healthcare can negatively influence the effective treatment of depression. With cost concerns and capitation schemes, some managed care plans may not reimburse primary care providers for multiple follow-up visits for MDD or favor referral to a mental health specialist. Furthermore, medications in managed care formularies may be limited to exclude newer and more costly treatments, even though their effectiveness may reduce overall outpatient costs and the need for medication changes.[71,72]

Interventions to Improve Long-term Management of MDD in the Primary Care Setting

How can these barriers to the diagnosis and treatment of depression be addressed? Although depression screening has been incorporated into practice by many primary care providers, it remains underutilized. In general, primary care providers recognize, treat, and monitor depressive symptoms in their patients in the short term; their challenge is long-term management of those patients unresponsive to initial therapy. A number of practical interventions, such as those recommended by the Agency for Healthcare Research and Quality (AHRQ), can improve the quality of treatment of MDD in the primary care setting over the long term.[73]

The AHRQ-based interventions include the following:
Provider reminder systems are means of maintaining patient- or encounter-specific information to help clinicians standardize care of patients with MDD, such as symptom checklists, questions, orders, and management schedules.

Audit and feedback include patient satisfaction surveys as well as summaries of performance for providers by outside auditors.

Provider education can be obtained through educational workshops, meetings, lectures, outreach visits by trained representatives, clinical guidelines, and audiovisual materials.

Patient education utilizes print or audiovisual materials to provide patients with information.

Promotion of self-management may include distribution of materials or access to a resource that enhances the patient’s ability to manage his or her condition, the communication of useful clinical data to the patient, or follow-up calls from the provider to the patient with recommended adjustments to care.

Patient reminder systems are provider-driven efforts to encourage patients to keep appointments or adhere to other aspects of the self-management of their condition.

Organizational changes within the practice should include at least 1 of the following: disease or case management by an individual or multidisciplinary team in collaboration with the primary care provider; team or personnel changes involving the addition of new members to the treatment team, creation of a multidisciplinary team, or re-evaluation of the roles of existing team members; communications, case discussions, and the exchange of treatment information between distant health professionals; and, implementation of total quality management or continuous quality improvement techniques. Table 2 lists specific practice changes that incorporate the AHRQ tenets and that may assist primary care providers in treating patients with MDD to remission.

Table 2. Possible Interventions in Clinical Practice in the Primary Care Setting to Assist in Treating MDD to Remission

It would be impossible for busy primary care clinicians to implement all or most of these interventions; selecting just 1 intervention that would be most beneficial to a provider’s individual practice is much more feasible and can still positively impact patient care. For example, to implement use of PHQ-9 scores to assess treatment response, a note could be placed in the chart of a patient initially diagnosed with depression via this scale, reminding the clinician to repeat the questionnaire on follow-up visits. Use of patient feedback forms can be implemented by placing the form in the patient’s chart upon diagnosis, as a reminder to ask a patient to complete it at a future visit. Integration of follow-up visits or telephone calls 3 to 4 weeks after diagnosis or treatment change can be accomplished by designating a staff member to make phone calls to patients and scheduling the calls immediately following diagnosis or treatment changes, or by scheduling follow-up visits at that time.

When making any improvements to a practice, clinicians should remember that improvement occurs in small steps over time and that implementing new ideas may require repeated attempts. Practitioners should strive to involve the entire medical team in the process. Patients should be assessed regularly to determine whether an intervention is having a positive impact on outcomes.

Factors to Consider for Referral to a Mental Health Specialist or Inpatient Treatment

Primary care clinicians can provide adequate supportive counseling and recommend coping strategies for their patients with MDD, and patients also can benefit from psychological counseling by a mental health specialist.[74] There are instances in which a primary care provider may choose to refer a patient with MDD. The provider may lack the skills or confidence to diagnose and treat the disorder, or may be unfamiliar with antidepressant drug pharmacology and have concerns about potential drug interactions or appropriate dosing regimens or drug combinations. It is also appropriate to refer patients with psychiatric comorbidities and those who fail to respond to 1 or more adequate antidepressant trials or several pharmacologic strategies. Primary care providers also may consider referring patients who report aggressive or homicidal impulses, self-destructive behavior, or suicidal ideation, and those who show signs of a personality disorder. Lastly, some patients may request a referral for psychological counseling or a specific therapist.

For outpatients who fail to respond to adequate antidepressant trials, have a minimal capacity to collaborate with their providers and optimize treatment, or those with an inadequate social support system, inpatient treatment may be worthy of consideration in an effort to achieve remission of depressive symptoms. Inpatient treatment also may be preferable for patients with substance abuse issues or serious psychiatric or medical conditions that complicate the treatment course.

Summary

The recognition of, and response to, depressive symptoms in the primary care setting has improved in recent years, yet depression remains a significant healthcare burden in the United States. A number of validated screening and assessment tools are available and should be incorporated into routine primary care in order to identify patients with depression and initiate pharmacologic treatment with the goal of complete remission of depressive symptoms. Unfortunately, many patients do not achieve remission even after multiple adequate trials of antidepressants, and TRD remains a clinical challenge to the primary care provider.

Augmentation with an atypical antipsychotic agent has been the best studied therapeutic strategy for the treatment of TRD, although neither long-term efficacy nor efficacy as a second-line treatment has been established. However, a serious limitation of this class of agents is a tolerability and safety profile that may limit their use in many patients. Alternatively, therapy may be switched within the same class of antidepressant or to a different class. There is considerable trial data to demonstrate the efficacy of switching to an SNRI, SSRI, NDRI (norepinephrine and dopamine reuptake inhibitor), or SNRA in SSRI-resistant patients, while only inconsistent or weak data exist for switching to a TCA or an MAOI.

While a number of provider-, patient-, and practice-related factors present challenges to the optimal management of depression in the primary care setting, improved screening for depression and implementation of practice changes and interventions will create a milieu for improved outcomes for patients with MDD.

Case Study

Mrs. K is a white 48-year-old married mother of 2 teenagers. She works as a middle school secretary and is involved in a number of school- and church-related activities. Her husband is a management consultant and often travels on business. Mrs. K has been in your primary care practice for the 3 years she has lived in the area and takes an interest in maintaining good health. She has no significant health problems other than mild hypertension, diagnosed about 1 year ago, and is compliant with her calcium-channel blocker regimen. She does not use oral contraceptives. During a recent office visit for blood pressure monitoring, Mrs. K complained of intermittent headaches and lower back pain that are relieved by nonsteroidal anti-inflammatory agents or acetaminophen, irritability, and lack of energy. In the past, she exercised on a regular basis but admits to losing interest in it recently. Her physical examination is unremarkable, including normal blood pressure. She denies dietary changes or use of supplements that could exacerbate headaches and cannot recall any recent physical activity or changes in work environment that may have caused lower back pain. When you inquire about her mood, Mrs. K admits to episodes of feeling down over the past few weeks and to having little interest or pleasure in doing things in the last 2 weeks. You order laboratory tests to check her thyroid function and ask Mrs. K to return for a follow-up visit in 2 weeks.

One week later, Mrs. K calls to come in to the office, reporting no improvement in her earlier complaints and adds that it takes her about an hour to fall asleep most nights; she wakes up during the night and does not feel rested in the morning. In addition, she has little interest in her church activities and feels less able to cope with her family responsibilities, particularly when her husband is away. You have received the results of her laboratory tests, which indicate normal thyroid function.

Given that there is no apparent reason for her somatic complaints, the positive screen for depression at her initial visit, and a worsening of her mood, you suspect that Mrs. K’s complaints may be symptoms of depression rather than a medical illness. When you ask if she has experienced similar physical and emotional symptoms in the past, she reports having low back pain, “feeling tired a lot,” and being somewhat overwhelmed and anxious for about 6 weeks after the relocation 3 years ago, but that the symptoms improved after she found employment and became involved in the community. With further questioning, Mrs. K admits that she has been concerned about her 77-year-old mother’s recent bouts of ill health and the fact that her home and work responsibilities prevent her from making frequent trips out of state to visit or oversee her mother’s healthcare. In addition, Mrs. K notes feelings of hopelessness and helplessness on most days; although she sometimes feels that life is not worth living, she also indicates she would not harm herself.

You ask Mrs. K to take the PHQ-9 and her score is 15. You tell her the results indicate she is moderately depressed. She indicates surprise at the diagnosis but also relief that there is an explanation for her symptoms. You tell her that depression is a treatable disorder, discuss therapeutic options, and let her know that she may not experience noticeable improvement for 3 to 4 weeks. You recommend an SSRI, escitalopram 10 mg, as initial therapy and explain to Mrs. K that some side effects may occur in the first weeks of treatment (eg, nausea, gastrointestinal distress, sexual dysfunction) but tell her that these can be managed and usually resolve with continued treatment. Mrs. K is willing to take educational materials home and to consider psychotherapy, as well as pharmacologic treatment.

Mrs. K returns in 4 weeks and completes another PHQ-9 for monitoring of her symptoms. This time, her score is only 3 points lower than at diagnosis; while she notes some improvement in her sleep habits, she reports still having little interest or taking pleasure in doing things she previously enjoyed, despite taking the medication as prescribed. She also has had 2 sessions with a psychotherapist since you last saw her.

You increase Mrs. K’s escitalopram therapy to 20 mg and encourage her to continue with her cognitive behavioral therapy and return in another 4 weeks.

At the second follow-up visit after 8 weeks of SSRI treatment, Mrs. K’s PHQ-9 score is 7—another 5-point reduction. Although she seems to be responding to treatment, she has not achieved remission. She has regained some interest in her church activities and reports having somewhat more energy; however, her self-reproach over not being a support for her mother and inability to cope with work and family responsibilities persist. Her blood pressure has been normal at each of her follow-up visits. At this point, the treatment options for Mrs. K are to switch her medication to another SSRI, to a NDRI, or to an SNRI. Alternatively, her SSRI treatment can be augmented with an adjunctive pharmacotherapeutic agent or combined with another antidepressant.

Mrs. K agrees with the addition of another medication to try to achieve full remission of her symptoms. Since the SSRI induced a partial response and was well tolerated, and Mrs. K has complied with the treatment regimen, you decide to start the patient on bupropion 150 mg once a day in addition to the escitalopram and CBT. You ask Mrs. K to return in 4 weeks.

At the next visit, Mrs. K’s PHQ-9 score is 3, showing she has improved significantly with augmentation therapy. She reports feeling “back to normal,” less stressed, and has resumed participation in most of her church activities. Mrs. K is also coping more easily with her caretaker concerns and other family responsibilities. To ensure Mrs. K achieves remission with continuation of this augmentation regimen, you schedule a 3-month follow-up visit.

 

George I. Papakostas, MD; Catherine R. Judd, MS, PA-C; Mary D. Moller, DNP, ARNP, APRN; Radu V. Saveanu, MD
Published on April 13, 2010


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