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Article

Using Assessment Tools to Screen for, Diagnose, and Treat Major Depressive Disorder in Clinical Practice

Alan J. Gelenberg, MD

Published: March 31, 2010

Using Assessment Tools to Screen for, Diagnose, and Treat Major Depressive Disorder in Clinical Practice

Depression remains underrecognized and undertreated worldwide, although it is a leading cause of disease burden. Many instruments are available to enhance the assessment of major depressive disorder (MDD) at 3 levels: screening, diagnosing, and monitoring treatment. This article reviews a variety of tools that can be used at each level of assessment as part of a measurement-based care approach to MDD. Measurement-based care for MDD is feasible in clinical practice. Patient self-reports can be used instead of clinician-rated scales to save time, whether in paper, computerized, or interactive voice response formats. Assessment tools are available in many languages. Treatment algorithms can rationalize decision making, and collaborative care can speed and enhance treatment results.

(J Clin Psychiatry 2010;71[suppl E1]:e01)

From Healthcare Technology Systems, Inc, and the Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison. (Dr Gelenberg is now with the Department of Psychiatry, Penn State University Milton S. Hershey Medical Center, Hershey, Pennsylvania.)

This article is derived from the roundtable discussion "International Consensus Group on Depression," which was held on September 1, 2009, in Tokyo, Japan, and supported by an educational grant from GlaxoSmithKline.

Dr Gelenberg is a consultant for Eli Lilly, Pfizer, Best Practice Project Management, AstraZeneca, Wyeth, Cyberonics, Novartis, Forest, GlaxoSmithKline, ZARS, Jazz, Lundbeck, Takeda, and eResearch Technology; has received research grant funding from Eli Lilly; and is a major stock shareholder of Healthcare Technology Systems, Inc.

Corresponding author: Alan J. Gelenberg, MD, Department of Psychiatry, H073, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033. ([email protected]).

Today, depression remains underrecognized and undertreated. Routine screening, systematic diagnosis, and regular measurement of treatment response can improve outcomes for patients with major depressive disorder (MDD). Measurement scales, algorithms, and systems of collaborative care are available to help clinicians evaluate symptoms and better identify, diagnose, and treat depression in their practices.

Burden, Underrecognition, and Undertreatment of MDD

Depression ranks third among the leading causes of disease burden worldwide, but, in middle-income and high-income countries, unipolar depressive disorders rank first for disease burden.1 In low-income countries, infectious diseases and health problems related to childbirth cause greater disease burden, but depression still ranks eighth. To reduce the prevalent disability caused by MDD, better recognition and treatment are needed.

Many physicians still have difficulty recognizing and diagnosing depression. The success of general practitioners in diagnosing depression was recently examined in a meta-analysis2 of mainly urban primary care practices in more than 10 countries. The physicians identified only about half (47%) of the true cases of depression and documented about a third of cases.

For Clinical Use

  • Use screening and diagnostic tools routinely to increase detection and diagnosis of depression; save time by implementing patient-rated instruments.
  • Use treatment algorithms and collaborative care to efficiently and effectively manage depression.
  • Systematically measure depressive symptoms, side effects of treatment, and suicide risk, and treat the patient to full remission.

Few patients who do receive a diagnosis of depression receive adequate treatment. In the United States, for example, Keller and colleagues3 reported in 1982 that a small proportion of patients with depression who sought treatment in the community were adequately treated. Only one-third of patients received an antidepressant for at least 4 weeks, and the majority of those who did received a low dose. Recent reports have shown little improvement in adequate treatment rates. An analysis by Kessler and colleagues4 published in 2003 showed that, among people in the US population who had MDD in the previous 12 months, half received health care for the disorder. Treatment was adequate in only 42% of those who received treatment, meaning that, of all people with MDD, only 22% received adequate treatment. Recently, my colleagues and I5 found that, among patients with chronic MDD, only 33% of patients had ever had an adequate trial of an antidepressant. Improvement still needs to be made in the difficult tasks of recognizing, diagnosing, and adequately treating depression so that the global burden of this disease can be reduced. Implementing measurement-based care can help clinicians in these tasks.

Tools for Implementing Measurement-Based Care in Psychiatry

Measurement-based care is a system of patient care in which physicians use standardized scales to precisely and regularly assess patients’ symptoms.6 Measurement-based care is a familiar concept in nonpsychiatric specialties; for example, in the care of patients who may have hypertension, blood pressure measurements are the basis of diagnostic and treatment decisions. Like other specialists, psychiatrists should also continually measure what they diagnose and treat. These measurements can be used to monitor response to treatment and, along with treatment algorithms, to make treatment choices at strategic decision points. Implementing measurement-based care (some prefer the term "measurement-enhanced care") can improve depression detection, rationalize decision making, optimize treatment, and improve outcomes. To implement measurement-based care for depression, assessment should take place at the following 3 levels: screening, diagnosis, and monitoring of treatment.

Many rating scales are available for each level of assessment, and some are available in computer-based or interactive voice response (IVR) versions as well as paper versions and in languages other than English. Rush and colleagues’ handbook7 describes many scales reviewed here and includes some scales in the CD-ROM that accompanies the handbook. Suppliers of scales in various formats and languages include eResearch Technology, Inc.; Healthcare Technology Systems, Inc.; MAPI Research Trust; and Multi-Health Systems, Inc.

Screening Instruments

The first level of assessment is screening. Every patient in general practice and psychiatry offices should be screened for MDD. Screening for MDD does not have to be time-consuming for the clinician because patients can complete screening questionnaires before an appointment, and reviewing the results usually takes the physician only a few minutes. In primary care, screening can start with 2 simple questions and, when results are positive, progress to more intensive assessments. Patient self-rating scales are cost-effective because they not only save the clinician’s time but also elicit sensitive information well and collect information accurately without variations by an interviewer. Patients may be more willing to disclose certain symptoms when they are not face-to-face with the doctor. Some self-rating scales can collect information electronically.

Several patient-rated instruments are available to screen for depressive symptoms.7 These instruments include the 9-item Patient Health Questionnaire (PHQ-9),8 2-item Patient Health Questionnaire (PHQ-2),9 Zung Self-Rating Depression Scale (Zung SDS),10,11 the Hospital Anxiety and Depression Scale (HADS),12 and the Center for Epidemiologic Studies Depression scale (CES-D)13 (Table 1). All of these instruments were designed to be completed quickly by patients. They are intended as initial screening tools for depressive symptoms, but further screening is required to make a specific diagnosis. The simple 2-question PHQ-2 is a sensible first step in primary care. In cases in which a patient endorses symptoms, a longer screen may be triggered.

Table 1

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The PHQ-9 is particularly useful in clinical practice and a logical next step in cases of a positive PHQ-2. The PHQ-9 was derived from the Primary Care Evaluation of Mental Disorders (PRIME-MD) as a self-administered rating scale specifically for depression screening in primary care.14 Its 9 questions are based on the "A" criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).15 For a minimal screening tool, the PHQ-2, the first 2 questions of the PHQ-9, can be used. The 2 questions of the PHQ-2 address loss of pleasure and the basic feelings of depression, which are the core symptoms of MDD. If a patient does not have these 2 symptoms, the patient likely does not have depression and the screening is complete. If a patient has at least 1 of these 2 core symptoms, clinicians can ask him or her to complete the full PHQ-9 and then move on to a more precise diagnosis. First-line screening with the PHQ-2 and/or PHQ-9 is quick and easy.

The Zung SDS is also easy to use and widely used but lacks coverage of symptoms common in atypical depression. The HADS is designed to screen for depression and anxiety in medically ill patients. The CES-D was developed for use in community samples to measure severity of depressive symptoms and levels of distress.

Diagnostic Instruments

The second level of assessment is diagnosis. A more precise diagnosis is necessary after initial screening, and both clinician-rated and self-rated instruments are available for systematic diagnosis (Table 2).

Table 2

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Clinician-rated diagnostic instruments include the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)16 and the Mini-International Neuropsychiatric Interview (MINI).17 The SCID-I has 9 diagnostic modules. Several versions of the SCID-I exist, including electronic versions and translations. A clinician-rated version (SCID-CV)18 was designed for use in clinical practice and is available in a computer-assisted form. The SCID-CV covers diagnoses most commonly seen in clinical practice. Required probe questions and suggested follow-up questions are provided and directions to skip subsequent questions are given when subjects fail to meet a critical criterion. Information about all versions is available on the SCID Web site. The MINI17 was designed to be a short interview carried out by a clinician to diagnose disorders based on DSM-IV and International Statistical Classification of Diseases, 10th Revision (ICD-10) criteria. Nineteen modules evaluate 16 Axis I disorders and the MINI Plus includes 8 additional disorders. Computer-based and Spanish versions are obtainable.

Patient-rated tools to diagnose MDD are also available. The PHQ-98 can be used for diagnosing as well as screening for MDD. The PRIME-MD19 (also known as the Mental Health Screener) has a quick patient-rated evaluation for anxiety, depressive, and alcohol-related symptoms, and a longer clinician evaluation guide for follow-up. The PRIME-MD is available in a paper format and an IVR format.20 The Psychiatric Diagnostic Screening Questionnaire (PDSQ)21 is a self-report that screens for 13 DSM-IV Axis I disorders commonly found in mental health outpatients and enables secondary disorders to be easily identified. The best choice is whatever is practical, simple, and cost-effective for a health care system. Electronic patient-administered instruments are likely to become the standard.

During the differential diagnosis, doctors should rule out disorders with depressive symptoms that require different treatment than MDD. These disorders include bipolar disorder, MDD with psychotic features, covert substance abuse, and depression due to a medical condition such as neurologic or endocrine disorders.

Monitoring Instruments

Once the patient has been diagnosed with MDD, the third level of assessment begins, which is monitoring response to treatment. Clinician-rated and self-rated scales are available to measure symptom severity, adverse effects, and suicidality (Table 3).

Table 3

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Symptom severity. Among clinician-rated scales to monitor depressive symptoms, the Hamilton Depression Rating Scale (HDRS)22 is the gold standard and evaluates severity of most DSM-IV depressive symptoms and comorbid anxiety. The Early Clinical Drug Evaluation Unit (ECDEU) version11 is most commonly used. The paper version of the scale is in the public domain, but the HDRS is also available in computerized and telephone versions. The HDRS may be most reliable when structured interview formats are used by trained interviewers.23 It may be less reliable in elderly patients, those with general medical illness, people with atypical features of depression, and those with anxiety symptoms.7

Other available scales to measure the severity of depressive symptoms include the Montgomery-Šsberg Depression Rating Scale (MADRS),24 which was designed to be sensitive to antidepressant treatment effects and is often used in clinical trials. The 30-item Inventory of Depressive Symptomatology (IDS)25 and the shorter 16-item Quick Inventory of Depressive Symptomatology (QIDS)26 are both available in clinician- and patient-rated versions, and both have acceptable psychometric properties.27 The IDS and QIDS are in the public domain, available in paper or electronic versions, and are frequently used to monitor depressive symptoms. The IDS assesses all 9 DSM-IV criteria symptom domains of MDD, melancholic and atypical features, irritability, and anxiety. The 16 items of the QIDS-16, like the PHQ-9, mirror the DSM-IV MDD "A" criteria. The clinician-rated and self-rated versions, including the IVR format, of the QIDS-16 are as effective for assessing depression severity as the clinician-rated version of the more time-consuming 17-item HDRS in outpatients with nonpsychotic MDD.28

Other self-rated scales for monitoring depression symptoms are the PHQ-9,8 Beck Depression Inventory (BDI),29 Clinically Useful Depression Outcome Scale (CUDOS),30 and HADS.12 The PHQ-9 can be used for monitoring depressive symptoms as well as screening and diagnosis. The latest version of the BDI, the BDI-II, is the closest version to DSM-IV.31 The CUDOS is useful to identify remission and assesses DSM-IV inclusion criteria for MDD, dysthymic disorder, psychosocial impairment, and quality of life. The HADS can be used for monitoring change in depressed mood and anxiety

In clinical practice, patient reporting of symptoms can be useful not only for screening but also for serial monitoring of outcomes. The physician’s knowledge of symptoms could be enhanced because patients may be more willing to disclose sensitive information via self-report questionnaires than in person, and the process of completing self-reports may also help patients remember problems as they monitor their own symptoms.32 Multidisciplinary team communication could be enhanced through sharing the information provided by the patient. Patient-reported outcome data could be linked via computer technology to practice guidelines and clinical pathways, thus improving care.

Adverse effects. A useful rating scale to monitor side effects is the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale (formerly known as the Frequency and Intensity of Side Effects Rating and Global Rating of Side Effects Burden [FISER/GRSEB] scales).33 This self-report instrument was designed for patients who are being treated for nonpsychotic depression, and an IVR version is available. The questions cover the frequency and intensity of the side effects of depression treatment, as well as their interference with functioning, but do not address specific side effects. Clinicians need to follow up by asking patients which particular side effects are troublesome. Routine laboratory tests are not available for depression, but, for safety monitoring, electrocardiograms and specific blood tests based on clinical criteria may be useful.

Suicidality. Suicide in patients treated for depression and the possibility that antidepressant medications might increase suicidal thoughts and behaviors are worldwide concerns. Scales are available to monitor suicidality. The Columbia Suicide Severity Rating Scale (C-SSRS)34 and Columbia Classification Algorithm of Suicide Assessment (C-CASA)35 provide definitions of terms and interview tips. The C-SSRS is clinician rated but an electronic version in IVR format exists, which is patient rated. The C-SSRS is obtainable in more than 90 languages. Currently, however, data are not available to assess whether suicidal ideation is predictive of self-harm or suicide. The C-CASA is only used by researchers to retroactively examine clinical trial databases.

Using Measurement-Based Care in Clinical Practice

Feasibility

Using measurement-based care has been found to be feasible even in practices with limited resources. A 1-year study36 assessed how helpful the PHQ-9 was to clinicians when managing patients with depression (N = 1,763) in 19 diverse psychiatric practices. Two practices withdrew from the study before completion. Clinical decisions were influenced by PHQ-9 scores in 93% of patient visits; the benefits of treatment were confirmed in 60% of patient visits, and treatment was changed in 1 way in 40% of the visits. The types of treatment change made are shown in Table 4.

Table 4

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Figure 1

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Monitoring Response and Remission

The goal of depression treatment is to help patients achieve full remission of symptoms, not simply to achieve response to treatment. Using measurement-based care in clinical practice helps indicate response and remission during depression treatment. Scales such as the HDRS and PHQ-9 numerically define mild, moderate, and severe MDD. Response and remission during treatment can be observed objectively via score improvements.

Patients who improve, but who still have residual symptoms, have a higher rate of relapse compared with patients who achieve full remission. In a 15-month follow-up study,37 after 15 months of antidepressant treatment, 76% of patients whose HDRS scores indicated that they had residual symptoms relapsed versus 25% of those without residual symptoms. In a prospective naturalistic study38 of 356 outpatients treated for MDD, those who had partial remission were significantly more likely to relapse than those who achieved complete remission (P < .0001; Figure 1).

Using Algorithms to Improve Treatment Response

Patient-reported outcomes data can be used with treatment algorithms. Algorithms provide a systematic step-by-step guide to treatment choices. In a German study39 of 148 inpatients with depression, algorithm-guided treatment improved response and reduced medication changes compared with treatment as usual. Median time to remission was 7.0 weeks for those who received algorithm-guided treatments versus 12.3 weeks for patients who received treatment as usual. However, more patients dropped out of algorithm-guided treatment than treatment as usual (33 versus 12). In the Texas Medication Algorithm Project (TMAP) in the United States,40 patients with MDD treated according to an algorithm had substantially greater mean reductions in IDS symptom scores than patients who received treatment as usual. The use of depression treatment guidelines and algorithms is discussed in more detail in the article by Jonathan R. T. Davidson, MD, "Major Depressive Disorder Treatment Guidelines in America and Europe,"41 in this supplement.

Using Collaborative Care to Ensure Adequate Treatment

Collaborative care is an approach to enhance depression treatment in which care managers, who have master’s level education and specialized training, advise the patient’s primary physician about the patient’s status based on the use of an algorithm. A full psychiatric consultation by the physician is replaced with algorithm-driven care provided by the care manager, making adequate treatment more likely. Computerized algorithm systems may ultimately obviate the need for care managers.

The use of collaborative care was recently studied in a 2-year study42 of 599 patients over 60 years of age in 20 primary care practices in the United States. Social workers, nurses, and psychologists trained to use algorithm procedures helped physicians recognize depression, made recommendations based on an algorithm, monitored depressive symptoms and medication side effects, and, if patients declined medication, offered interpersonal psychotherapy. These care managers also addressed patients’ concerns about treatment adherence and could make house calls to patients unable to visit practice offices. At endpoint, the reduction in suicidal ideation was 2.2 times greater in the collaborative care group than in the usual care group. More patients in the collaborative care group received antidepressants and/or psychotherapy (85%-89%) than in the usual care group (49%-62%). The collaborative care group also experienced earlier treatment response and significantly greater reduction in severity of major depression as measured by HDRS score from baseline than the usual care group (P < .001). At 24 months, 1.4 times more patients in the intervention group had achieved remission than in the usual care group. Under this collaborative care system, therefore, patients were more likely to receive treatment, less likely to experience suicidal ideation, and more likely to achieve remission.

Summary

Because underrecognition and undertreatment of MDD are so prevalent worldwide, strategies such as using rating instruments for assessment and implementing collaborative care procedures to follow treatment algorithms are needed. Outcomes can be improved by using accepted assessment tools within a system of measurement-based care. Many instruments are available for performing systematic and objective screening, diagnosis, and monitoring of treatment response. Patient self-rating versions of these instruments are available in many instances and make these tools quick and easy to use in practice, and computer or telephone formats may further speed their use. Language and literacy difficulties can be overcome because many translations and IVR versions are available. Algorithms help physicians rationalize treatment by emphasizing strategic decision points, and care managers may aid physicians in the use of algorithms.

Discussion

Professor Nutt: Traditionally, clinicians thought that patient self-reporting was completed by patients in the waiting room before an appointment, but can this be done at home now?

Dr Gelenberg: Yes, self-reporting can be highly flexible and easily individualized. Self-reporting can still be done on paper, but it can also be done electronically using a telephone or a laptop with a Web-based or a local application. Self-reports can be completed at home, in the waiting room, or wherever is easy and convenient for the patient. Patient self-reports can be used at first visits and at follow-up visits.

When the self-report is completed on paper, clinicians have to spend a few seconds looking through the report to see the results. The ease of electronic reports is that they can present the clinician with the information instantly. For example, in primary care, if a review of systems found that only urinary frequency was problematic, that is the only information that would appear on the screen because everything else was negative. Similarly, depression or suicidal ideation would appear for a patient with these symptoms, but no other information would have to be reviewed.

Professor Nutt: So, are systems now available that link the patient’s self-report to the doctor’s computer?

Dr Gelenberg: Technology is being used differently in different places. The United States does not have an organized and integrated system. As a patient, I have used an electronic health record. As a physician, I have never used one. As a patient, I interact with my doctor and my doctor’s nurse through a Web site that is protected to safeguard confidentiality. I report symptoms, ask for visits, and ask for prescription renewals via the Web site.

Dr Davidson: Dr Gelenberg, do you think the measurement tools that you highlighted are transculturally valid? For example, in societies that may have some inclination to deny psychological symptoms, but more readiness to endorse somatic symptoms, could cultural differences impact the way a patient would complete the PHQ-9 or other instruments?

Dr Gelenberg: In theory, yes. In practice, I do not have an empirical answer for every scale. Most of the scales have been used in clinical trials throughout the world, and many of these instruments have been translated into other languages. I assume sufficient validity has been established for the different cultures. Most of the scales I have been involved in using are translated into the language of every country represented at this conference. Many languages have subvariants, and there are accepted means of translation and cross-translation. For example, a study43 in Boston among recent immigrants from China validated the Chinese version of the PHQ-9 as a depression screening tool; 4 common dialects of Chinese were used, including Cantonese and Mandarin. Of the patients who screened positive for depression on the PHQ-9, 92% were diagnosed with MDD by the SCID-I.

I do not know to what extent instruments have been cross-validated. The HDRS is used throughout the world, and, because it has more of a somatic emphasis than other scales, it may be useful in cultures likely to endorse somatic symptoms.

Professor Nutt: Drs Higuchi and Zhang, have any scales been developed in Japan or China, or do you rely on translations of European or American scales?

Dr Higuchi: Usually, in Japan we use the PHQ-9 and have no scales developed originally in Japanese.

Dr Zhang: In China, we use the PHQ for depression in elderly patients only. We do not use the PHQ for the general population, and we have not developed any depression scales specifically for Chinese people.

Dr Davidson: One scale that is probably worth mentioning is the General Health Questionnaire (GHQ).44,45 This scale is not just for depression. It has been widely used and validated and can help identify either anxiety or depression.

Dr Higuchi: In Japan, most patients with depression first visit a primary care physician, but most primary care physicians do not have any training in depression. Because they are unfamiliar with the disorder, they are often unwilling to use scales like the PHQ. Primary care physicians probably successfully diagnose a minority of cases of depression. How do you get the primary care physicians in your country to use this scale?

Dr Gelenberg: The PHQ, of course, is self-administered, and the primary care doctor does not have to ask the questions or complete the questionnaire. The primary care doctor should simply look at the results and then should act on them. The issue is how to motivate primary care doctors and change their behavior.

Currently, health care provision in the United States is variable, and motivation differs from one provider to another. For example, in the Veterans Health Administration (VHA) system for US military veterans, doctors who do not follow the VHA treatment guidelines cannot continue to work there. That is a strong motivator.

In other parts of the US health care system in which clinicians have greater autonomy, the individual clinic or hospital is overseen by an accrediting body that sets standards for how patients with certain kinds of symptoms should be treated. The motivation is that, if the clinic or hospital does not meet the standards, then a poor grade may be awarded by the accrediting body, leading to stricter oversight, reduced reimbursement, or possibly even closure of the facility.

We have to find various ways within different health care systems to motivate the individual practitioner to change behavior. Setting, maintaining, and improving standards of care is a continuous process. The challenge is how to educate doctors about scientific findings, thus narrowing the gap between knowledge and its application.

Dr Sakamoto: In Japan, a primary care doctor could diagnose MDD, but if the primary care doctor were to refer such a patient to a specialist, the wait for an appointment may be several weeks or, in extreme cases, a few years because specialists are so busy. What are your thoughts about that situation?

Dr Gelenberg: Perhaps fewer referrals to specialists can be made if we provide the primary care physicians with the tools to do an efficient, effective job in a cost-effective, rapid way. Most depressed patients can successfully be treated in primary care with the help of an algorithm. I would argue that depression is an inexpensive disorder to treat, in that society gets back more than it spends through the benefits of the patient’s enhanced performance at work and at home.

Dr Kanba: I have a question about suicidal ideation. When a patient checks the item for suicidal ideation on the PHQ-9, what should we recommend to a primary care physician or our colleagues as the next steps? As you said, no validated scale is available to help predict suicidal activity based on suicidal ideation.

Dr Gelenberg: A psychiatrist, or at least a mental health specialist, should be involved when suicide is considered a serious risk. However, there are many false negatives and many false positives, and even highly skilled specialists have limited ability to predict suicide. Depressed patients can convincingly assure clinicians that they are not suicidal but then commit suicide. To answer your question, I would say to a primary care doctor, "Refer the patient to a specialist if there is worry about suicide."

Dr Karamustafalıoğlu: When we implemented screening tools in primary care practices in Turkey, we found out that some people were not fluent in reading and writing Turkish. This was a problem because some patients came to the office with a relative and they did not want to try to complete the screening report in front of the relatives.

Dr Gelenberg: Did these patients use other languages, or were they illiterate?

Dr Karamustafalıoğlu: Some of them used other languages and some of them were illiterate. So, we encouraged the primary care physicians to ask 2 questions to all patients related to their sleep and their sexual symptoms. If needed, they then screen for depression using the DSM items in person rather than having patients complete written self-reports.

Dr Gelenberg: Several instruments are available in many languages; you may be able to find some instruments in the patient’s first or second language. For example, the PHQ-9 is available in Arabic, Greek, Hungarian, and others. For patients who are illiterate, in the United States we often use IVR because most people can speak on the telephone and have access to telephones even if they do not have access to a computer.

Dr Terao: Referring back to Dr Kanba’s question about primary care physicians seeking referral to a psychiatrist for a suicidal patient, do you think it is necessary to teach primary care physicians to differentiate suicidality in depression from suicidality in borderline personality disorder? I think it is difficult to differentiate between the two, but patients with borderline personality disorder have an impulsivity or aggression that is somewhat different from those with depression, and I think it is necessary to teach this in regard to suicidal ideation. What do you do?

Dr Gelenberg: I do not have a good answer, Dr Terao. I fully agree with you. Patients with borderline personality disorder who are threatening to hurt themselves, or actually do hurt themselves, have different motivation and experience than depressed people. But how we screen and how we manage this problem is unclear. Patients with borderline personality disorder have a great likelihood of self-injury and also a real likelihood of suicide. The borderline patient who is always saying, "I’ m going to hurt myself. I’ m going to hurt myself," is a problem for clinicians in practice. If the clinician stops listening, then the patient may actually commit suicide.

What you are identifying is a gap in knowledge. To understand the nature of the self-harm impulse, to distinguish borderline personality disorder from depression and then, most importantly for us, to predict suicide risk are areas where the knowledge level is far from ideal.

Professor Nutt: In the United Kingdom, a barrier to investing effort in diagnosing depression in primary care practices is the fear that if the physicians uncover any hint of suicidal ideation, they will have to follow up with assessments and documentation. Do any data indicate threshold scores for referral due to suicidality on any of these scales?

Dr Gelenberg: Prospective assessment of suicidality via systematic scales is being implemented in clinical research and in pharmaceutical trials but may not happen in clinical practice. In the trials, different sponsors can adopt different thresholds at which to do something about suicidality. At what level do you raise an alarm and say the patient is at risk for suicide? Until data from these trials are captured, all that physicians can use is clinical intuition.

I probably would err on the conservative side and say that a simple "yes" answer on the screen should at least provoke the use of a more elaborate scale. Perhaps someone less expensive than a psychiatrist could assess the patient based on those results to make a decision whether psychiatric referral is necessary. With full humility, all that I can say is that we are doing the best we can, and we will see many false negatives and false positives.

Professor Nutt: Thank you, Dr Gelenberg.

Disclosure of off-label usage: The author has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration−approved labeling has been presented in this article.

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