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. 2006;8(2):88–97.

Managing Depression in Primary Care: Achieving Remission

PMCID: PMC1470645  PMID: 16862233

Managing Depression in Primary Care

Larry Culpepper, M.D., began his presentation by pointing out that in the United States, about 17% of the population develops major depression at some point during their lifetime1—20% to 25% of women and 7% to 12% of men.2 In a typical episode of depression, individuals sink into depression symptomatology over a period of 4 to 6 weeks, experience those symptoms for anywhere from a few months to 2 years, and then gradually improve if left untreated. A major goal of treatment is to shorten the duration of these symptomatic episodes. With each additional episode of depression, the episodes tend to become more severe and longer in duration and have a shorter interepisode interval.3

Recognizing Depression in Primary Care

Dr. Culpepper reported that, given the diverse presentations of depression in primary care, screening tools are very useful. In 2002, the United States Preventive Services Task Force4 reversed a long-standing recommendation that opposed screening for depression in primary care settings. Such screening has now been found to not only lead to improvement in the recognition of depression but also to a true improvement in patient well-being over time.4

The Preventive Services Task Force4 further found that 2 questions are useful as initial screening tools for recognizing depression: “Over the past 2 weeks, have you felt down or hopeless?” and “Over the past 2 weeks, have you felt little interest in doing things?” If patients respond “yes” to either of these questions, it is appropriate to further investigate the possibility of major depression. The 9-item Patient Health Questionnaire (PHQ-9),5 the Zung Depression Scale,6 and the Beck Depression Inventory7 are all helpful for the exploration of symptoms in patients suspected of having major depression.

A key issue in primary care is to avoid being misled by the patients' explanation of their symptoms. General practitioner researchers in United Kingdom8 identified a pattern of physician agreement with patients that led to the lack of recognition of major depression. They found that if patients attributed their symptoms to a medical explanation, the physicians frequently agreed with that attribution and failed to uncover the underlying major depression or anxiety disorder that was truly the cause. General practitioners missed the underlying diagnosis of major depression or anxiety in nearly 80% of patients who somatized or normalized their symptoms (Figure 1). Recognizing symptom attribution by the patient is a helpful step in understanding the patient, making the correct diagnosis, and then working with him or her to gain acceptance of the diagnosis of depression.

Figure 1.

Figure 1.

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Detection of Anxiety or Depression by Primary Care Physicians in Patients Who Normalized or Somatized Their Symptomsa

Depression can present in primary care in a variety of ways; understanding this fact can help the physician accurately diagnose patients. For example, somatic symptoms that are not otherwise explained by medical illness are frequent indicators that the patient may have underlying major depression. In addition, the majority of patients who are high utilizers of primary care have a lifetime history of either major depression or anxiety, and a large number have current major depression, so a pattern of high utilization also can be an indicator of underlying depression.9

Patients presenting with anxiety are often depressed as well. If the anxiety is more bothersome to them and to their families than depression, it also becomes more problematic for the physician, who then may not recognize the comorbid major depression that could be worsening the anxiety.

Comorbidity of Depression With Other Illnesses in Primary Care

According to Dr. Culpepper, comorbid anxiety tends to make major depression more severe, more prolonged, less likely to respond to treatment, and more functionally impairing in work activities, social accomplishments, and family roles. Ultimately, comorbid major depression and an anxiety disorder profoundly impair the individual's overall quality of life. More than 80% of depressed patients with comorbid anxiety will continue to be depressed at 1-year follow-up, compared with less than 60% if comorbid anxiety is not present with depression.10 Treatment outcomes are also worse in patients with comorbid anxiety disorder given pharmacotherapy or psychotherapy.11 For example, comorbid anxiety disorder has been shown to impair the ability to work (Figure 2).12 Comorbid depression and anxiety is also an indication for an evaluation of suicidality. The patient who has anxiety and major depression is likely to have a past history of suicide attempts, and such a past history is one of the best predictors of future suicidal thoughts, ideations, and suicide attempts (L.C., data on file, Brown University, Providence, R.I.).

Figure 2.

Figure 2.

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Impact of Comorbid Depression and Panic Disorder on Work Impairment During a 30-Day Perioda

Dr. Culpepper emphasized that not only is major depression comorbid with psychiatric illness, it is also comorbid with many medical illnesses. Patients with medical illnesses develop depression at a much higher rate than the general population.13 Unfortunately, major depression is less frequently recognized and appropriately diagnosed in the presence of physical symptoms than in patients who do not complain of physical symptoms.14,15 Prevalence rates of major depression in patients with cardiovascular disease,16 diabetes,17 cancer,18 or Parkinson's disease19 are between 20% and 30%.

Not only do major depression and medical illnesses occur together frequently, they also tend to make patient outcomes worse. A bidirectional interaction exists between major depression and medical illness in which both the major depression and the medical illness fare more poorly when they are comorbid than when they are separate.20 Depression and medical illnesses are associated with poorer prognoses, increased morbidity and mortality, and increased medical costs.

Dr. Culpepper noted that several specific conditions have a documented association with depression.21 The relationship between cardiovascular illness and depression has been extensively investigated.22,23 New cardiovascular disease occurs almost twice as frequently in patients with major depression compared with patients without major depression. Once patients have developed cardiovascular disease, the risk of subsequent cardiovascular morbidity and mortality is markedly elevated for at least 20 years following the patient's initial diagnosis with major depression.23 It is the major depression itself that is associated with the increase in mortality. Lesperance and colleagues24 identified that anxiety and hostility do not relate to poor prognosis in the way that major depression does; it is specifically depression that is associated with the poor prognosis.

Diabetes and cancer are similar to cardiovascular disease in their relationship with depression. Patients with diabetes have more than double the rate of depression than those without diabetes, even when controlling for all risk factors.25 The outcomes for patients with diabetes are worse if they also experience depression. Cancer develops more frequently in patients with major depression, and the prognosis for patients with cancer is worsened in the presence of major depression.18

Dr. Culpepper explained that one of the mechanisms through which depression has a negative impact on medical illnesses is its effect on compliance. Patients with depression have a 3-fold increase in the likelihood of being noncompliant with other medical treatment compared with patients without depression.26 Compliance not only includes taking medications as directed, but also adherence to diet, exercise, self-monitoring such as diabetes glucose testing, special programs such as smoking cessation, and even return visits for medical care. The successful management of major depression is an important factor in how primary care physicians can affect the outcome of not only medical illness, but the quality of life for patients.

Treatment of Depression in Primary Care

Dr. Culpepper pointed out that there is room for improvement in the quality of care that primary care providers give to patients with major depression. Only a small minority of patients treated for major depression in the primary care setting receive treatment that meets quality standards for adequacy of amount of treatment and adequacy of duration of treatment; in fact, in one evaluation of quality care in the United States, only 20% of patients who were treated by primary care physicians alone (that is, did not see a mental health specialist) received adequate treatment.27

Many different treatment modalities are available to primary care physicians. Psychotherapies are available, including cognitive-behavioral therapy, interpersonal therapies, and psychodynamic therapies. Pharmacologic treatment is highly valuable, either as monotherapy or as an augmentation of psychotherapy. Other treatment options such as electroconvulsive therapy and phototherapy may be useful for patients with either treatment-resistant depression or depression related to seasonal affective disorder, respectively.

Because it has been shown that patients who have residual symptoms are at high risk for relapse,28 a key in successful treatment of depression is treating patients with an intensity that achieves adequate and full control of symptomatology. In a study by Paykel et al.,28 76% of treated patients who had persistent symptoms relapsed, whereas only 25% of patients whose symptoms were fully controlled by treatment relapsed.

Continuation of functional impairment is also more likely in patients who do not achieve a full remission of symptoms.29,30 The lack of functional improvement does not just involve difficulties related to depression but any comorbid medical illness, so attaining remission is critical not only in improving outcomes for depression, but in attaining an optimal outcome for comorbid conditions.31

One strategy to improve patient outcome is the adoption of screening instruments that provide valid measures of severity and symptomatology not only at the onset of depression, but in response to treatment. The PHQ-9 is such an instrument; it has been well-validated, not only for diagnostic purposes,32 but also to measure treatment outcome.33 A copy of the PHQ-9 can be found in the MacArthur Foundation Initiative on Depression and Primary Care's Depression Management Tool Kit, which has many helpful resources for primary care physicians (www.depression-primarycare.org/clinicians/toolkits). Dr. Culpepper reiterated that other rating scales such as the Zung Depression Scale and the Beck Depression Inventory can also be used to measure progress during treatment.

In order to achieve the highest improvement in outcome of depression, primary care physicians should actively manage their depressed patients and involve the whole practice in patient care.4 Developing a practice approach that utilizes not only the physician but other resources in encouraging patient compliance can aid in improving outcomes. Having a nurse or a medical assistant in the practice call newly diagnosed patients within 1 or 2 days of their visit to assess whether they have had prescriptions filled, whether they have started the prescription, or, if psychotherapy is recommended, if they have followed through in initiating an appointment for such psychotherapy can be very helpful in improving the beginning of treatment and treatment adherence. The patient should be queried further at various points in time, particularly over the first couple of months, to ensure medication adherence and identify any new problems or adverse effects requiring tailoring of treatment.

An important part of the active management of patients is patient education. A study by Lin and coworkers34 identified several specific patient educational messages that significantly improved adherence to treatment within the first month (Table 1). In addition to relaying these messages, physicians need to educate patients about the common misperception that depression is akin to an infectious disease in which an antibiotic is continued for as long as the infection is present but then stopped once the patient is better. Instead, patients should view their depression through a chronic disease model, similar to diabetes, in which the medication must be continued long-term. Also, the physician should tell the patient that mild side effects are common and that significant side effects should be reported to the physician so that they can be actively managed. Finally, the physician should let the patient know that remission is the goal of treatment, and, most importantly, that it is achievable, even if it requires several modifications of the treatment regimen over time. When these messages are communicated to patients in primary care, there can be a marked improvement in outcome.

Table 1.

Patient Education Messages That Improve Early Adherencea

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Dr. Culpepper stated that the critical components that contribute to improved outcomes include using an evidence-based approach to diagnose and monitor treatment response, enhancing patient education systems, using active case management to support the patient in adhering to treatment, and having the backup of a mental health specialist, when required, for the patient with multiple comorbidities or the patient who does not respond to treatment.

Coordinated care models, in which a team of clinicians works together to treat the patient in the most effective way possible, have been demonstrated to lead to marked improvement in long-term outcome of patients.35 This improvement can be especially seen in the number of prescriptions filled, not only for the first or second time, but over the long-term, and in overall patient adherence.

Conclusion

Dr. Culpepper concluded his presentation by emphasizing that major depression is common in primary care settings and has a variety of presentations, including somatic presentations and high health care utilization. Major depression is highly comorbid both with anxiety disorders and medical conditions and greatly worsens patient outcomes in medical illnesses, both in the short-term and long-term. Primary care physicians have tools to increase not only the recognition, but also the effectiveness of long-term management of major depression. When these tools are used, the short-term and long-term outcome for patients can be substantially improved.

The Concept of Remission: Validity and Limitations

Remission, according to Michael E. Thase, M.D., can be defined as a level of depressive symptoms basically indistinguishable from that of someone who has never been depressed. Being in remission means that the depressed individual has been able to return to a normal level of social functioning. Remission is one of several outcomes for patients with depression (Figure 3).3 Before a patient is considered to be in remission, the patient must respond to treatment. Typically, response is defined by a 50% change in symptom intensity. Functionally, the difference between response and remission is simply the level of improvement: a patient in remission has a greater level of improvement than one who is a responder. If a patient's remission is not sustained, then the patient experiences a relapse.

Figure 3.

Figure 3.

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Distinguishing Response and Remissiona

Remission leads to recovery. Generally, a patient needs to be in remission for at least 6 to 9 months before he or she is declared to be in recovery. In practical terms, however, it is difficult to distinguish between remission and recovery.

Validating the Concept of Remission

Dr. Thase next explained that the most desired outcome of the acute phase of treatment is remission, which ideally occurs within the first 6 to 12 weeks of therapy (see Figure 3). The primary goal of the second phase, the continuation phase, is to sustain remission and prevent relapse. The third phase, maintenance, targets patients who are at high risk for recurrent depressive episodes. The maintenance phase begins at the time that the physician considers the patient to be recovered but still at a risk for recurrence, and it may last many years, perhaps even indefinitely.

Dr. Thase then asked, how do we know when patients have reached a symptom level similar to that of people who have never been depressed? In one study,36 outpatients who presented with a major depressive episode had a mean score of 20 on the Hamilton Rating Scale for Depression (HAM-D). Very few patients with depression had scores below 14, and none of the patients with major depressive disorder had scores below 10. Conversely, none of the healthy control participants had HAM-D scores above 6, indicating that for a patient with depression, a score on the HAM-D of 6, 7, or 8 is the best indicator that he or she has completely moved to a level of residual symptoms that is similar to that of a never-ill person.

According to Dr. Thase, the concept of remission in depression is validated by several characteristics of the condition (Table 2).28,29,37–44 The substantial improvement in social functioning that accompanies remission is also an important validator for the concept of remission. Miller et al.29 conducted a double-blind study of patients with chronic depression (N = 635) who were randomly assigned to treatment with imipramine or sertraline. Patients who responded but did not remit were more similar in social functioning to the nonresponders than they were to the healthy community sample. By endpoint, patients who achieved remission had a level of social functioning that was almost indistinguishable from that of the community sample used in the study.

Table 2.

Risks of Incomplete Remission

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Limitations of the Concept of Remission

In depression, remission is not a pathophysiologic description, unlike in physical disorders such as cancer, in which remission means a complete absence of illness activity. Because the pathophysiologic basis of depression is not fully understood, a low level of signs and symptoms has traditionally been used as a guide for measuring remission in major depressive disorder.

Dr. Thase noted that inadequate treatment dose, insufficient duration of treatment, or, in the case of psychotherapy, inadequate frequency of sessions all could contribute to a delay in or a lack of complete remission. Individuals who have comorbidities with other psychiatric disorders or medical illnesses or who have more chronic episodes of depression may also take longer to achieve remission than someone who is less severely ill. Dr. Thase emphasized that physicians should monitor patients' symptoms and functional status at each follow-up visit and encourage patients to track their persistent symptoms so that the physician can gauge what changes in treatment might be needed. On occasion, it may be necessary to increase a dose of antidepressant medication or to prolong the course of treatment, whether it is pharmacotherapy, psychotherapy, or the combination of the two. Also, antidepressant therapy may be augmented with an additional treatment. For example, lithium, thyroid hormone, buspirone, an atypical antipsychotic, modafinil, or another agent may be added to standard antidepressant pharmacotherapy to try to alleviate the patient's last remaining symptoms. For those patients with severe and complex conditions, psychotherapy in combination with pharmacotherapy may be the best approach.

Conclusion

Dr. Thase concluded by emphasizing that remission is the optimal outcome of treatment of the acute phase of major depressive disorder. People who obtain symptomatic remission within the first 6 or 8 weeks of the acute phase of therapy have lower relapse risks than those who respond without achieving remission. Patients who achieve remission are also more likely to have longer periods of recovery and to have near-normalization of social function. Although the concept of remission in depression has some limitations, remission as the goal for treatment gives physicians a standard by which to compare treatments, and in doing so, find the best possible treatment for their patients.

Efficacy and Tolerability of Antidepressants

Maurizio Fava, M.D., began his presentation by reporting that antidepressant medications have been successfully used in the treatment of depression over the past 5 decades. Their overall efficacy, however, is not as robust as initially thought. A 1996 meta-analysis45 of the overall response rates to treatment with antidepressants showed response rates of between 50% and 70%. The rate of remission in patients given antidepressants, defined as the achievement of a state of very few or no symptoms or having a score on the 17-item HAM-D < 8, was between 30% and 40%. The rate of patients with no response to antidepressant treatment ranged between 19% and 34%, and the rate of partial responses was between 12% and 15%.

One reason for this lower-than-expected response rate may be that many patients drop out of antidepressant treatment prematurely, possibly because of the tolerability issues with antidepressants. With the newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), the most common side effects that emerge during acute treatment are nausea, agitation, anxiety, insomnia, somnolence, headache, and fatigue. Other side effects that contribute to discontinuation of treatment may emerge in the long-term phase of treatment and include anxiety, sleep disturbances, fatigue, sexual dysfunction, weight gain, apathy, and cognitive dysfunction.

Antidepressants are perceived to be well-tolerated with minimal side effects, perhaps because most clinical studies use spontaneous patient reporting to assess side effects, which underestimates their prevalence. Much greater accuracy in assessing side effects is obtained by a systematic assessment of patients, including direct questioning through a self-rated form or a clinician-rated form. Dr. Fava then went on to review the most common short-term and long-term side effects of antidepressants and common approaches to their management.

Common Side Effects of Antidepressant Treatment

Anxiety and nervousness

Dr. Fava stated that anxiety and nervousness are common side effects of antidepressant treatment. They tend to emerge early in treatment but can appear later. These side effects are especially important because they are risk factors for the emergence of suicidal ideation.

Fava and colleagues46 looked at anxiety and nervousness during double-blind acute treatment with 3 different SSRIs—fluoxetine, sertra-line, and paroxetine. In that study, a substantial proportion of patients developed anxiety and nervousness while being treated with SSRIs, but the differences in rates of anxiety and nervousness among the SSRIs studied were not statistically significant.

The most common approach to managing anxiety and nervousness is using adjunctive medications such as benzodiazepines.47 Anticonvulsants have also been used to treat anxiety and nervousness, with some success, as have buspirone and atypical antipsychotics.

Insomnia and somnolence

According to Dr. Fava, insomnia and somnolence are also common side effects of antidepressant treatment. Data from the prescribing information of most antidepressants show that somnolence and sedation are reported at rates greater than placebo with almost all antidepressant treatments with the exception of bupropion (Table 3).48–55 In the study by Fava and colleagues46 on the use of SSRIs for depression, spontaneous reports by patients showed that somnolence was reported by more than 10% of patients and insomnia was reported by more than 15% of patients.

Table 3.

Incidence of Somnolence/Sedation and Fatigue/Asthenia During Antidepressant Treatment, Active Drug Versus Placebo (%)

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Several treatments have been shown to be effective in treating insomnia associated with antidepressant treatment. In particular, benzodiazepines,56,57 nonbenzodiazepine hypnotics such as zolpidem58 and eszopiclone,59 melatonin,60 and trazodone61 have all been shown to be more effective than placebo in treating insomnia when coadministered with antidepressants. Other treatments for insomnia for which the efficacy is mostly anecdotal include mirtazapine, ramelteon, anticonvulsants, atypical antipsychotics, low-dose tricyclic antidepressants (TCAs), and antihistamines.

Adjunctive medications are also available for the treatment of hyper-somnia associated with antidepressant treatment. Somnolence can be either due to poor sleep quality at night or to a sedating effect of the antidepressant. If poor sleep quality is believed to be causing a patient's somnolence, the physician should consider adding a hypnotic such as trazodone, a benzodiazepine, or a nonbenzodiazepine.62 If the somnolence is not due to poor sleep quality, adjunctive treatments such as psychostimulants, modafinil, bupropion, nor-epinephrine uptake inhibitors, and protriptyline may be helpful.

Fatigue and asthenia

Dr. Fava continued by adding fatigue and asthenia to the list of common side effects of antidepressant treatment. As with somnolence, a greater rate of fatigue and asthenia is seen in almost all antidepressants—except bupropion—compared with placebo (see Table 3).48–55 Fatigue and asthenia associated with antidepressant treatment can be lessened with adjunctive medications such as psychostimulants, modafinil, bupropion, norepinephrine reuptake inhibitors such as reboxetine or atomoxetine, and protriptyline.63

Sexual dysfunction

Dr. Fava then advised that one of the most common side effects of antidepressant treatment is sexual dysfunction, including decreased desire (libido), arousal, orgasm, and satisfaction. In a study by Clayton et al.,64 the prevalence of sexual dysfunction in patients given one of several different antidepressants in a subpopulation without probable causes of sexual dysfunction was fairly high. In this study, almost 1 of 4 patients reported sexual dysfunction when this symptom was systematically elicited with the Changes in Sexual Functioning Questionnaire.

Several approaches are effective in the management of sexual dysfunction associated with antidepressants. Physicians may wait for tolerance to occur, reduce the dose of the medication, or switch the patient to another antidepressant that is not as likely to produce sexual side effects, all of which may affect efficacy. Cognitive-behavioral approaches have also been used to treat sexual dysfunction, but so far, the most common approach has been that of using adjunctive pharmacologic options. Pharmacologic options for treating sexual dysfunction include yohimbine, bupropion, maca root, and phosphodiesterase type 5 (PD-5) inhibitors such as sildenafil and tadalafil.

Weight gain

Dr. Fava stated that antidepressant-induced weight gain is another frequent long-term side effect of antidepressant treatment. TCAs are known to cause weight gain, and although SSRIs are generally considered to be weight-neutral, there is some evidence that they may have more of an effect on weight than is widely believed.65–67

Dr. Fava suggested that some antidepressants, such as bupropion68 and duloxetine,69 may be more weight-neutral than the SSRIs. Diet, including caloric restriction and carbohydrate restriction, and exercise are often effective options for the management of weight gain. Switching antidepressants can be helpful, but there is a risk that the patient may not respond to the new antidepressant. A number of add-on therapies are being used in clinical practice, including topiramate, bupropion, phentermine, and atomoxetine, although there is not yet any evidence for their efficacy from controlled studies.

Apathy and cognitive symptoms

Dr. Fava noted that apathy and cognitive symptoms are also side effects of long-term antidepressant treatment and can be associated with discontinuation. For example, a study by Bolling and Kohlenberg70 showed that unwanted psychological side effects, including apathy and cognitive dysfunction, were experienced by about 75% of patients and were given as the primary reason for discontinuing an antidepressant as frequently as were physical symptoms. Adjunctive medications used to treat apathy and cognitive dysfunction include psychostimulants, modafinil, bupropion, norepinephrine reuptake inhibitors such as reboxetine and atomoxetine, and dopamine agonists such as pramipexole.

Conclusion

The overall efficacy of antidepressants for the treatment of depression may not be as substantial as originally thought, perhaps due to tolerability issues that can emerge during acute and long-term treatment. Several strategies have been proposed for the management of side effects of antidepressants, including adjunctive medications and medication switching. However, most of these strategies are based on anecdotal reports; only a few have been evaluated in placebo-controlled studies. There is a clear need for new studies assessing the efficacy of these strategies.

Anxiety Disorders in Depressed Outpatients: Prevalence, Detection, and Clinical Significance

Mark Zimmerman, M.D., began by explaining that recognition of comorbid conditions such as anxiety disorders in patients seeking treatment for depression is clinically important because the presence of these disorders might influence treatment selection or predict the chronicity of the depression. Anxiety disorders, as a group, are a frequent current comorbid disorder in depressed patients. To illustrate, Dr. Zimmerman reviewed 4 studies71–74 of the comorbidity rates of all DSM-defined anxiety disorders in depressed psychiatric outpatients. Each study found that when diagnoses were based on semistructured diagnostic interviews, more than 40% of the patients had a current comorbid anxiety disorder (Table 4).

Table 4.

Prevalence (%) of Current Anxiety Disorders in Psychiatric Outpatients With a Principal Diagnosis of Major Depressive Disorder

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Are Anxiety Disorders Underrecognized in Depressed Patients?

According to Dr. Zimmerman, during the last few years, several reports have questioned the adequacy of the unstructured clinical diagnostic interview.75 Zimmerman and Mattia75 examined diagnostic frequencies in 2 separate samples of 500 patients drawn from the same outpatient practice. One group was diagnosed by raters administering the Structured Clinical Interview for DSM-IV (SCID sample), and the other was diagnosed by clinicians using an unstructured clinical evaluation (non-SCID sample). Panic disorder, social phobia, specific phobia, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) were all diagnosed significantly more frequently in the SCID sample compared with the non-SCID sample.

A subsequent report focused on the detection of anxiety disorders in depressed patients.76 As an indicator of clinical importance, the investigators asked patients whether they were interested in having treatment directed toward the comorbid anxiety disorder. Dr. Zimmerman reported that depressed patients evaluated with the SCID most often wanted treatment of comorbid GAD, panic disorder, and PTSD. These results suggest that in psychiatric outpatients with a principal diagnosis of major depressive disorder, psychiatrists underrecognized anxiety disorder comorbidity, and when an anxiety disorder was present, patients usually wanted their treatment to address the comorbid anxiety disorder.

Improving the Recognition of Anxiety Disorders in Depressed Patients

Dr. Zimmerman emphasized that the purpose of screening is to improve diagnostic recognition. In examining the performance of screening scales, a distinction should be made between principal and additional diagnoses. In mental health settings, diagnostic recognition should be adequate for the principal disorders for which patients seek treatment (i.e., the chief complaint). In contrast, the recognition of comorbid disorders that are not the principal reason for seeking treatment may be problematic. Dr. Zimmerman suggested that when evaluating a screening scale's performance in psychiatric patients, the focus should be on its diagnostic properties for disorders that are not the principal reason for seeking treatment.

Zimmerman and Chelminski77 examined the ability of the Psychiatric Diagnostic Screening Questionnaire (PDSQ) to screen for anxiety disorders in depressed patients. The PDSQ is a self-report questionnaire that consists of 126 questions assessing the symptoms of 13 DSM-IV disorders in 5 areas: eating, mood, anxiety, substance use, and somatoform disorders.78 The PDSQ assesses 6 specific DSM-IV anxiety disorders: panic disorder, agoraphobia, PTSD, OCD, GAD, and social phobia.

Dr. Zimmerman explained that the PDSQ was intended as a diagnostic aid to be used in clinical practice to facilitate the efficiency of conducting the initial diagnostic evaluation. From a clinical perspective, it is most important that the diagnostic aid have good sensitivity and corresponding high negative predictive value. With high negative predictive value, the clinician can be confident that when the test indicates that the disorder is not present, there is little need to inquire about that disorder's symptoms. Because the PDSQ's anxiety disorder subscales have been shown to have high sensitivity and negative predictive value,77 they could function well as a screening instrument in depressed patients.

Clinical Significance of Anxiety Disorders in Depressed Patients

Dr. Zimmerman stressed that the underrecognition of comorbid anxiety disorders is not simply of academic interest—it has important potential clinical significance. Epidemiologic studies such as the National Comorbidity Study79,80 have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from depression. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients81 and primary care patients as well.82

The clinical implications of under-diagnosing comorbid anxiety disorders in depressed patients, Dr. Zimmerman explained, depend on 2 factors: (1) whether or not anxiety disorders have an impact on the longitudinal course of depression, and (2) the availability of effective treatment that is specific for anxiety disorders. The literature79–82 suggests that the presence of a comorbid anxiety disorder is associated with a poorer outcome. One might speculate that improved diagnostic practice, resulting in improved detection of anxiety disorders and treatment directed to the additional concerns related to anxiety disorders, will result in improved treatment outcome. However, it is also possible that the presence of a comorbid anxiety disorder will be associated with poorer outcome even when the diagnosis is known. In studies81,82 finding that the presence of a comorbid anxiety disorder was associated with a greater likelihood of depression chronicity, it is not clear whether the health care providers were aware of the researchers' anxiety disorder diagnoses. It is, therefore, unknown if the greater chronicity of depression in patients with high levels of anxiety was due to the failure of appropriate treatment or the failure to provide appropriate treatment.

Influence of Comorbid Anxiety Disorders on Antidepressant Selection

No studies have examined the important question of whether the treatment of depressed patients with and without comorbid anxiety disorders should differ. Few scientific data demonstrate that treatment outcome can be enhanced or optimized by selecting an antidepressant based on a patient's clinical profile (with the exception of monoamine oxidase inhibitors for atypical symptoms). Zimmerman and colleagues83 hypothesized that clinicians nonetheless base their selection of antidepressants on patients' clinical characteristics. The study found that the presence of comorbid anxiety disorders, particularly panic disorder and generalized anxiety disorder, most frequently influenced antidepressant selection (Table 5). Thus, although few empirical data are available to guide clinicians in selecting an antidepressant based on patients' clinical characteristics, these factors are often used as the basis for antidepressant choice.

Table 5.

Comorbid Conditions Influencing Antidepressant Choice in 1137 Depressed Outpatientsa

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Conclusion

Dr. Zimmerman reiterated that the literature is consistent concerning the prevalence and impact of anxiety disorder comorbidity in depressed patients. Substantial rates of comorbid disorders have been found in epidemiologic and clinical populations using structured research diagnostic interviews. However, much lower comorbidity rates have been found in clinical populations using unstructured clinical interviews. Given that the structured interview is considered the diagnostic gold standard, this finding suggests that comorbidity is underdiagnosed in routine clinical settings.

Structured interviews such as the SCID are too long and unwieldy for routine use. It is more likely that clinicians would use an inexpensive screening instrument that does not intrude on the clinician's usual practice but provides clinically relevant diagnostic information. A reliable and valid self-report screening questionnaire, such as the PDSQ, would potentially enhance, not obstruct, usual clinical practice.

Drug names: atomoxetine (Strattera), bupropion (Wellbutrin and others), buspirone (BuSpar and others), citalopram (Celexa and others), duloxetine (Cymbalta), eszopiclone (Lunesta), fluoxetine (Prozac and others), imipramine (Tofranil and others), lithium (Eskalith, Lithobid, and others), mirtazapine (Remeron and others), modafinil (Provigil), paroxetine (Paxil, Pexeva, and others), phentermine (Adipex-P and others), pramipexole (Mirapex), protriptyline (Vivactil), ramelteon (Rozerem), sertraline (Zoloft), sildenafil (Viagra), tadalafil (Cialis), topiramate (Topamax), trazodone (Desyrel and others), venlafaxine (Effexor), zolpidem (Ambien).

Disclosure of off-label usage: The chair has determined that, to the best of his knowledge, atomoxetine, buspirone, lithium, and modafinil are not approved by the U.S. Food and Drug Administration for the augmentation of antidepressants; pramipexole is not approved for the treatment of depression; topiramate is not approved for use for weight loss; reboxetine is not approved in the United States as an antidepressant; and bupropion and yohimbine are not approved for the treatment of sexual dysfunction. If you have questions, contact the medical affairs department of the manufacturer for the most recent prescribing information.

Footnotes

This ACADEMIC HIGHLIGHTS section of The Primary Care Companion to The Journal of Clinical Psychiatry presents the highlights of the teleconferences “Review of the Pharmacologic Management of Depression,” which were held in December 2005. This report was prepared by the CME Institute of Physicians Postgraduate Press, Inc. and was supported by an educational grant from GlaxoSmithKline.

The teleconferences were chaired by Michael E. Thase, M.D., Department of Psychiatry, University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic, Pittsburgh, Pa. The faculty were Maurizio Fava, M.D., Depression Clinical and Research Program, Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston; Mark Zimmerman, M.D., Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence; and Larry Culpepper, M.D., M.P.H., Department of Family Medicine, Boston University, Boston, Mass.

Faculty disclosure: In the spirit of full disclosure and in compliance with all ACCME Essential Areas and Policies, the faculty for this CME article were asked to complete a statement regarding all relevant financial relationships between themselves or their spouse/partner and any commercial interest (i.e., a proprietary entity producing health care goods or services) occurring within the 12 months prior to joining this activity. The CME Institute has resolved any conflicts of interest that were identified. The disclosures are as follows: Dr. Thase is a consultant for AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Novartis, Organon, Pfizer, and Wyeth, and is a member of the speakers/advisory boards for AstraZeneca, Eli Lilly, GlaxoSmithKline, Organon, and Wyeth. Dr. Culpepper is consultant for and is on the advisory boards of Eli Lilly, Forest, Pfizer, and Wyeth. Dr. Fava has received research support from Abbott, Lichtwer Pharma GmbH, and Lorex; has received honoraria from EPIX, Bayer AG, Compellis, Janssen, Knoll, Lundbeck, Dov, Biovail, BrainCells, Cypress, Fabre-Kramer, Grunenthal GmbH, MedAvante, Inc., Sepracor, and Somerset; has received both research support and honoraria from Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Novartis, Organon, Pfizer, Pharmavite, Roche, Sanofi-Synthelabo, Solvay, and Wyeth; and his spouse/partner has received research support from Parke-Davis and Pfizer. Dr. Zimmerman has received grant/research support from UCB Pharma and is a member of the speakers/advisory boards for Bristol-Myers Squibb, Forest, GlaxoSmithKline, Pfizer, Sepracor, and Takeda.

The opinions expressed herein are those of the faculty and do not necessarily reflect the views of the CME provider and publisher or the commercial supporter.

REFERENCES

  1. Kessler RC, McGonagle KA, and Swartz M. et al. Sex and depression in the National Comorbidity Survey, I: lifetime prevalence, chronicity, and recurrence. J Affect Disord. 1993 29:85–96. [DOI] [PubMed] [Google Scholar]
  2. Clinical Practice Guideline Number 5: Depression in Primary Care, vol 1. Detection and Diagnosis. Rockville, Md: US Dept Health Human Services, Agency for Health Care Policy and Research. 1993  [PubMed] [Google Scholar]
  3. Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry. 1991;52(5, suppl):28–34. [PubMed] [Google Scholar]
  4. Pignone MP, Gaynes BN, and Rushton JL. et al. Screening for depression in adults: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2002 136:765–766. [DOI] [PubMed] [Google Scholar]
  5. Pfizer Incorporated. Patient Health Questionnaire (PHQ-9). Available at: http://www.pfizer.com/pfizer/phq-9/index.jsp. Accessed Jan 26, 2006. [Google Scholar]
  6. Zung WWK. A self-rating depression scale. Arch Gen Psychiatry. 1965;12:63–70. doi: 10.1001/archpsyc.1965.01720310065008. [DOI] [PubMed] [Google Scholar]
  7. Beck AT, Ward CH, and Mendelson M. et al. An inventory for measuring depression. Arch Gen Psychiatry. 1961 4:561–571. [DOI] [PubMed] [Google Scholar]
  8. Kessler D, Lloyd K, and Lewis G. et al. Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ. 1999 318:436–439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Katon W, Von Korff M, and Lin E. et al. Distressed high utilizers of medical care: DSM-III-R diagnoses and treatment needs. Gen Hosp Psychiatry. 1990 12:355–362. [DOI] [PubMed] [Google Scholar]
  10. Gaynes BN, Magruder KM, and Burns BJ. et al. Does a coexisting anxiety disorder predict persistence of depressive illness in primary care patients with major depression? Gen Hosp Psychiatry. 1999 21:158–167. [DOI] [PubMed] [Google Scholar]
  11. Brown C, Schulberg HC, and Madonia MJ. et al. Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Am J Psychiatry. 1996 153:1293–1300. [DOI] [PubMed] [Google Scholar]
  12. Roy-Byrne PP, Stang P, and Wittchen HU. et al. Lifetime panic-depression comorbidity in the National Comorbidity Survey: association with symptoms, impairment, course and help-seeking. Br J Psychiatry. 2000 176:229–235. [DOI] [PubMed] [Google Scholar]
  13. Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol Psychiatry. 2003;54:216–226. doi: 10.1016/s0006-3223(03)00273-7. [DOI] [PubMed] [Google Scholar]
  14. Dantz B, Ashton AK, and D'Mello DA. et al. The scope of the problem: physical symptoms of depression. J Fam Pract. 2003 Dec. suppl:S6–S8. [PubMed] [Google Scholar]
  15. Tylee AT, Freeling P, Kerry S. Why do general practitioners recognize major depression in one woman patient yet miss it in another? Br J Gen Pract. 1993;43:327–330. [PMC free article] [PubMed] [Google Scholar]
  16. Musselman DL, Evans DL, Nemeroff CB. The relationship to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry. 1998;55:580–592. doi: 10.1001/archpsyc.55.7.580. [DOI] [PubMed] [Google Scholar]
  17. Musselman DL, Betan E, and Larsen H. et al. Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment. Biol Psychiatry. 2003 54:317–329. [DOI] [PubMed] [Google Scholar]
  18. Spiegel D, Giese-Davis J. Depression and cancer: mechanics and disease progression. Biol Psychiatry. 2003;54:269–282. doi: 10.1016/s0006-3223(03)00566-3. [DOI] [PubMed] [Google Scholar]
  19. Lieberman A. Depression in Parkinson's disease: a review. Acta Neurol Scand. 2006;113:1–8. doi: 10.1111/j.1600-0404.2006.00536.x. [DOI] [PubMed] [Google Scholar]
  20. Evans DL, Charney DS. Mood disorders and medical illness: a major public health problem. Biol Psychiatry. 2003;54:177–180. doi: 10.1016/s0006-3223(03)00639-5. [DOI] [PubMed] [Google Scholar]
  21. Evans DL, Staab JP, and Petitto JM. et al. Depression in the medical setting: biopsychological interactions and treatment considerations. J Clin Psychiatry. 1999 60(suppl 4):40–55. [PubMed] [Google Scholar]
  22. Glassman AH, O'Connor CM, and Califf RM. et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002 288:701–709. [DOI] [PubMed] [Google Scholar]
  23. Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary artery disease and depression. Biol Psychiatry. 2003;54:227–240. doi: 10.1016/s0006-3223(03)00587-0. [DOI] [PubMed] [Google Scholar]
  24. Lesperance F, Frasure-Smith N, and Talajic M. et al. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation. 2002 105:1049–1053. [DOI] [PubMed] [Google Scholar]
  25. Anderson RJ, Freedland KE, and Clouse RE. et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001 24:1069–1078. [DOI] [PubMed] [Google Scholar]
  26. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101–2107. doi: 10.1001/archinte.160.14.2101. [DOI] [PubMed] [Google Scholar]
  27. Young AS, Klap R, and Sherbourne CD. et al. The quality of care for depressive and anxiety disorders in the United States. Arch Gen Psychiatry. 2001 58:55–61. [DOI] [PubMed] [Google Scholar]
  28. Paykel ES, Ramana R, and Cooper Z. et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995 25:1171–1180. [DOI] [PubMed] [Google Scholar]
  29. Miller IW, Keitner GI, and Schatzberg AF. et al. The treatment of chronic depression, pt 3: psychosocial functioning before and after treatment with sertraline or imipramine. J Clin Psychiatry. 1998 59:608–619. [DOI] [PubMed] [Google Scholar]
  30. Druss BG, Schlesinger M, Allen HJM Jr. Depressive symptoms, satisfaction with health care, and 2-year work outcomes in an employed population. Am J Psychiatry. 2001;158:731–734. doi: 10.1176/appi.ajp.158.5.731. [DOI] [PubMed] [Google Scholar]
  31. Simon GE, Revicki D, and Heiligenstein J. et al. Recovery from depression, work productivity, and health care costs among primary care patients. Gen Hosp Psychiatry. 2000 22:153–162. [DOI] [PubMed] [Google Scholar]
  32. Martin A, Rief W, and Klaiberg A. et al. Validity of the brief Patient Health Questionnaire Mood Scale (PHQ-9) in the general population. Gen Hosp Psychiatry. 2006 28:71–77. [DOI] [PubMed] [Google Scholar]
  33. Lowe B, Unutzer J, and Callahan CM. et al. Monitoring depression treatment outcomes with the patient health questionnaire-9. Med Care. 2004 42:1194–1201. [DOI] [PubMed] [Google Scholar]
  34. Lin EH, Von Korff M, and Lin E. et al. The role of the primary care physician in patient's adherence to antidepressant therapy. Med Care. 1995 33:67–74. [DOI] [PubMed] [Google Scholar]
  35. Von Korff M, Goldberg D. Improving outcomes in depression. BMJ. 2001;323:948–949. doi: 10.1136/bmj.323.7319.948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Thase ME. Comparing the methods used to compare antidepressants. Psychopharmacol Bull. 2002;36(suppl 1):1–17. [PubMed] [Google Scholar]
  37. Judd LL, Paulus MJ, and Schettler PJ. et al. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry. 2000 157:1501–1504. [DOI] [PubMed] [Google Scholar]
  38. Thase ME, Simons AD, and McGeary J. et al. Relapse after cognitive behavioral therapy of depression: potential implications for longer courses of treatment. Am J Psychiatry. 1992 149:1046–1052. [DOI] [PubMed] [Google Scholar]
  39. Lustman PJ, Anderson RJ, and Freedland KE. et al. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care. 2000 23:934–942. [DOI] [PubMed] [Google Scholar]
  40. de Groot M, Anderson R, and Freedland KE. et al. Association of depression and diabetes complications: a meta-analysis. Psychosom Med. 2001 63:619–630. [DOI] [PubMed] [Google Scholar]
  41. Frasure-Smith N, Lesperance R, Talajic M. Depression following myocardial infarction: impact on 6-months survival. JAMA. 1993;270:1819–1825. [PubMed] [Google Scholar]
  42. Penninx BW, Beekman AT, and Honig AT. et al. Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry. 2001 58:221–227. [DOI] [PubMed] [Google Scholar]
  43. Vaccarino V, Kasl SV, and Abramson J. et al. Depressive symptoms and risk of functional decline and death in patients with heart failure. J Am Coll Cardiol. 2001 38:199–205. [DOI] [PubMed] [Google Scholar]
  44. Judd LL, Akiskal HS, Paulus MP. The role and clinical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder. J Affect Disord. 1997;45:5–18. doi: 10.1016/s0165-0327(97)00055-4. [DOI] [PubMed] [Google Scholar]
  45. Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996;19:179–200. doi: 10.1016/s0193-953x(05)70283-5. [DOI] [PubMed] [Google Scholar]
  46. Fava M, Hoog SL, and Judge RA. et al. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. J Clin Psychopharmacol. 2002 22:137–147. [DOI] [PubMed] [Google Scholar]
  47. Londborg PD, Smith WT, and Glaudin V. et al. Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance, and core symptoms of depression. J Affect Disord. 2000 61:73–79. [DOI] [PubMed] [Google Scholar]
  48. Wellbutrin (bupropion). Physician's Desk Reference. Montvale, NJ: Medical Economics. 2006 1579–1583. [Google Scholar]
  49. Celexa (citalopram) [package insert]. St. Louis, Mo: Forest Laboratories, Inc. 2005. Available at http://www.fda.gov/cder/foi/label/2005/020822s29lbl.pdf. Accessed Jan 30, 2006. [Google Scholar]
  50. Prozac (fluoxetine) [package insert]. Indianapolis, Ind: Eli Lilly and Company. 2005 Available at: http://pi.lilly.com/prozac.pdf. Accessed Jan 30, 2006. [Google Scholar]
  51. Remeron (mirtazapine). Physician's Desk Reference. Montvale, NJ: Medical Economics. 2002 2483–2486. [Google Scholar]
  52. Serzone (nefazodone). Physician's Desk Reference. Montvale, NJ: Medical Economics. 2002 1104–1108. [Google Scholar]
  53. Paxil (paroxetine) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. 2005. Available at: http://us.gsk.com/products/assets/us_paxil.pdf. Accessed Jan 30, 2006. [Google Scholar]
  54. Zoloft (sertraline) [package insert]. New York, NY: Pfizer Inc. 2004. Available at http://www.fda.gov/cder/foi/label/2005/019839s053S054lbl.pdf. Accessed Jan 30, 2006. [Google Scholar]
  55. Effexor (venlafaxine) [package insert]. Philadelphia, Pa: Wyeth Pharmaceuticals. 2004 Available at http://www.fda.gov/cder/foi/label/2004/2015slr028,030,032,20699slr041,048,052_effexor_lbl.pdf. Accessed Jan 30, 2006. [Google Scholar]
  56. Nolen WA, Haffmans PM, and Bouvy PF. et al. Hypnotics as current medication in depression: a placebo-controlled, double-blind comparison of flunitrazepam and lorme-tazepam in patients with major depression, treated with a (tri)cyclic antidepressant. J Affect Disord. 1993 28:179–188. [DOI] [PubMed] [Google Scholar]
  57. Cohn JB. Triazolam treatment of insomnia in depressed patients taking tricyclics. J Clin Psychiatry. 1983;44:401–406. [PubMed] [Google Scholar]
  58. Asnis GM, Chakraburtty A, and DuBoff EA. et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry. 1999 60:668–676. [DOI] [PubMed] [Google Scholar]
  59. Fava MF, Buysse DJ, and Rubens R. et al. Eszopiclone co-adminstered with fluoxetine or insomnia associated with major depressive disorder (MDD): effects on sleep and depression. Presented at the 45th annual meeting of the New Clinical Drug Evaluation Unit (NCDEU). 6–9June2005 Boca Raton, Fla. Session II-92. [Google Scholar]
  60. Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry. 1998;155:1119–1121. doi: 10.1176/ajp.155.8.1119. [DOI] [PubMed] [Google Scholar]
  61. Nierenberg AA, Adler LA, and Peselow E. et al. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994 151:1069–1072. [DOI] [PubMed] [Google Scholar]
  62. Fava M. Daytime sleepiness and insomnia as correlates of depression. J Clin Psychiatry. 2004;65(suppl 16):27–32. [PubMed] [Google Scholar]
  63. Fava M. Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment. J Clin Psychiatry. 2003;64(suppl 14):30–34. [PubMed] [Google Scholar]
  64. Clayton AH, Pradko JF, and Croft HA. et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002 63:357–366. [DOI] [PubMed] [Google Scholar]
  65. Michelson D, Amsterdam JD, and Quitkin FM. et al. Changes in weight during a 1-year trial of fluoxetine. Am J Psychiatry. 1999 156:1170–1176. [DOI] [PubMed] [Google Scholar]
  66. Sussman N, Ginsberg DL, and Bikoff J. et al. Effects of nefazodone on body weight: a pooled analysis of selective serotonin reup-take inhibitor- and imipramine-controlled trials. J Clin Psychiatry. 2001 62:256–260. [PubMed] [Google Scholar]
  67. Fava M, Judge R, and Hoog S. et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000 61:863–867. [DOI] [PubMed] [Google Scholar]
  68. Weihs KL, Houser TL, and Batey SR. et al. Continuation phase treatment with bupropion SR effectively decreases the risk of relapse for depression. Biol Psychiatry. 2002 51:753–761. [DOI] [PubMed] [Google Scholar]
  69. Mallinckrodt C, Tran PV, and Detke MJ. et al. Minimal effect of the antidepressant duloxetine on body weight. In: New Research Abstracts of the 155th Annual Meeting of the American Psychiatric Association. 22May2005 Philadelphia, Pa. Abstract NR441:119. [Google Scholar]
  70. Bolling MY, Kohlenberg RJ. Reasons for quitting serotonin reuptake inhibitor therapy: paradoxical psychological side effects and patient satisfaction. Psychother Psychosom. 2004;73:380–385. doi: 10.1159/000080392. [DOI] [PubMed] [Google Scholar]
  71. Fava M, Rankin MA, and Wright EC. et al. Anxiety disorders in major depression. Compr Psychiatry. 2000 41:97–102. [DOI] [PubMed] [Google Scholar]
  72. Melartin TK, Rytsala HJ, and Keskela US. et al. Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study. J Clin Psychiatry. 2002 63:126–134. [PubMed] [Google Scholar]
  73. Sanderson WC, Beck AT, Beck J. Syndrome comorbidity in patients with major depression or dysthymia: prevalence and temporal relationships. Am J Psychiatry. 1990;147:1025–1028. doi: 10.1176/ajp.147.8.1025. [DOI] [PubMed] [Google Scholar]
  74. Zimmerman M, McDermut W, Mattia JI. Frequency of anxiety disorders in psychiatric outpatients with major depressive disorder. Am J Psychiatry. 2000;157:1337–1340. doi: 10.1176/appi.ajp.157.8.1337. [DOI] [PubMed] [Google Scholar]
  75. Zimmerman M, Mattia JI. Psychiatric diagnosis in clinical practice: is comorbidity being missed? Compr Psychiatry. 1999;40:182–191. doi: 10.1016/s0010-440x(99)90001-9. [DOI] [PubMed] [Google Scholar]
  76. Zimmerman M, Chelminski I. Clinician recognition of anxiety disorders in depressed outpatients. J Psychiatr Res. 2003;37:325–333. doi: 10.1016/s0022-3956(03)00020-7. [DOI] [PubMed] [Google Scholar]
  77. Zimmerman M, Chelminski I. Screening for anxiety disorders in depressed patients. J Psychiatr Res. 2006;40:267–272. doi: 10.1016/j.jpsychires.2005.03.001. [DOI] [PubMed] [Google Scholar]
  78. Zimmerman M, Mattia JI. The Psychiatric Diagnostic Screening Questionnaire: development, reliability and validity. Compr Psychiatry. 2001;42:175–189. doi: 10.1053/comp.2001.23126. [DOI] [PubMed] [Google Scholar]
  79. Kessler RC, Nelson CB, and McGonagle KA. et al. Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. Br J Psychiatry. 1996 168(suppl 30):17–30. [PubMed] [Google Scholar]
  80. Kessler RC, McGonagle KA, and Zhao S. et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 51:8–19. [DOI] [PubMed] [Google Scholar]
  81. Coryell W, Endicott J, and Andreasen NC. et al. Depression and panic attacks: the significance of overlap as reflected in follow-up and family study data. Am J Psychiatry. 1988 145:292–300. [DOI] [PubMed] [Google Scholar]
  82. Brown C, Schulberg HC, Pigerson HG. Factors associated with symptomatic improvement and recovery from major depression in primary care patients. Gen Hosp Psychiatry. 2000;22:242–250. doi: 10.1016/s0163-8343(00)00086-4. [DOI] [PubMed] [Google Scholar]
  83. Zimmerman M, Posternak M, and Friedman M. et al. Which factors influence psychiatrists' selection of antidepressants? Am J Psychiatry. 2004 161:1285–1289. [DOI] [PubMed] [Google Scholar]

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