Primary care physicians are more likely to see patients

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1 CONCISE REVIEW FOR CLINICIANS DEPRESSION MANAGEMENT IN PRIMARY CARE USING PHQ-9 A System-Based Approach to Depression Management in Primary Care Using the Patient Health Questionnaire-9 RAMONA S. DEJESUS, MD; KRISTIN S. VICKERS, PHD, LPP; GABRIELLE J. MELIN, MD; AND MARK D. WILLIAMS, MD Primary care physicians are more likely to see patients with depression than with any other disorder except hypertension, and its management poses a challenge to busy primary care practices. The Patient Health Questionnaire-9, a simple self-administered tool of proven validity and reliability, is a commonly used screening instrument for depression in primary care practice. This review article provides a system-based approach to depression management using the Patient Health Questionnaire-9 to guide clinicians in the identification and treatment of depression and its follow-up care. Mayo Clin Proc. 2007;82(11): DSM-IV = Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition); PHQ-9 = Patient Health Questionnaire-9; STAR*D = Sequenced Treatment Alternatives to Relieve Depression Primary care physicians are more likely to see patients with depression than with any other disorder except hypertension. Depression has been ranked as the leading cause of disability and premature death among people aged 18 to 44 worldwide and is expected to be the second leading cause of disability for people of all ages by ,2 It occurs twice as frequently in women as men. Although depression can begin at any age, its average age of onset is the mid-20s. Those who experience depressed moods when younger are at risk of developing depressive disorder later in life. 3 Heritability has been estimated to range from 30% to 40%. 4 As a larger proportion of the population reaches age 65 and over, depression among the elderly is becoming a major public health problem. Primarily affecting those with chronic medical illnesses and cognitive impairment, it compounds the morbidity caused by these conditions, leading to family disruption, disability, and increased mortality. Its incidence and prevalence double in those aged 70 to 85 years. 5 Depression is becoming widely characterized as a chronic disorder, along with diabetes, hypertension, and asthma, based partly on its high recurrence rate. Approximately half of those who are diagnosed as having depression experience a recurrence within 2 years, and more than 80% within 5 to 7 years. 5-7 A crucial aspect of its epidemiology is the increased mortality associated with major depression. A recent meta-analysis of 25 studies, 8 in which more than 100,000 persons were followed up for periods ranging from 1.3 to 18.0 years, reported an overall relative risk of dying of 1.81 (95% confidence interval, ) for persons with vs those without depression. Unfortunately, depression remains an often undiagnosed and undertreated condition. Of the 12 million people in the United States with major depression, only 46% to 57% are receiving treatment and only 18% to 25% are adequately treated. 9 The US Preventive Services Task Force has therefore recommended systematic screening for depression in clinical settings with appropriate systems in place to ensure effective treatment and follow-up. 10 This concise review is meant to serve as a simple reference to assist primary care physicians in their management of depression using the Patient Health Questionnaire-9 (PHQ-9) as both a screening instrument and a means of monitoring progress towards recovery. SCREENING FOR DEPRESSION Identification of persons at risk for depression poses a challenge for a busy practice. To be useful, a screening tool must be simple to use, inexpensive, and accurate. A commonly used screening tool in primary care practice with proven validity and reliability is the PHQ-9 (Figure 1); the 9 items on this instrument are based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria. 11 The PHQ-9 has been used to screen for depression in patients with chronic illnesses such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease, as well as in ethnically diverse population groups. 12,13 Its usefulness in assessing depression severity and monitoring treatment response are well established To meet DSM-IV criteria for depression diagnosis, the patient must respond affirmatively to at least 1 of the first 2 items on the test (little interest or pleasure in doing things; feeling down, depressed, or hopeless), indicating that the symptom has been present more than half the time in the past 2 weeks, as well as score positively on some of the other 7 questions. A score of 10 or above is often used as the cutoff for a clinical diagnosis of major From the Division of Primary Care Internal Medicine (R.S.D.) and Department of Psychiatry and Psychology (K.S.V., G.J.M., M.D.W.), Mayo Clinic, Rochester, MN. Individual reprints of this article are not available. Address correspondence to Ramona S. DeJesus, MD, Division of Primary Care Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN (dejesus.ramona@mayo.edu) Mayo Foundation for Medical Education and Research Mayo Clin Proc. November 2007;82(11):

2 PATIENT HEALTH QUESTIONNAIRE (PHQ-9) NAME: DATE: Over the last 2 weeks, how often have you been bothered by any of the following problems? (use to indicate your answer) Not at all Several days More than half the days Nearly every day 1. Little interest or pleasure in doing things 2. Feeling down, depressed, or hopeless 3. Trouble falling or staying asleep, or sleeping too much 4. Feeling tired or having little energy 5. Poor appetite or overeating 6. Feeling bad about yourself or that you are a failure or have let yourself or your family down 7. Trouble concentrating on things, such as reading the newspaper or watching television 8. Moving or speaking so slowly that other people could have noticed. Or the opposite being so fidgety or restless that you have been moving around a lot more than usual 9. Thoughts that you would be better off dead, or of hurting yourself in some way add columns: + + (Healthcare professional: For interpretation of TOTAL, please refer to accompanying scoring card.) TOTAL: 10. If you checked off any problems, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people? Not difficult at all Somewhat difficult Very difficult Extremely difficult FIGURE 1. Patient Health Questionnaire (PHQ-9). The PHQ-9 copyright 1999 Pfizer Inc. All rights reserved. Reproduced with permission. depression and as an indication for the initiation of therapy. At these cutoff scores, the instrument has been shown to have a sensitivity and specificity for depression of 88%. 16 As a screening instrument, however, it cannot replace sound clinical judgment. Before deciding on treatment, the clinician must carefully evaluate those with scores indicative of depression for coexisting situational issues such as suicidal thoughts; substance use; medical illnesses presenting with anergy, insomnia, or anorexia; or comorbid psychiatric condition. Furthermore, the limitations of the selfreporting of depressive symptoms should be considered when using the PHQ-9. Studies have shown that the personality traits of patients can lead to discrepancies between self-reported ratings and a more objective assessment by a clinician, ie, those obtained via a structured clinical interview. 17,18 Multimodal assessment of depressive symptoms may be more appropriate in certain settings. Although designed to be completed by the patient before or during the office visit, the PHQ-9 can also be administered by the physician or designated clinical staff member depending on practice protocols. A very flexible tool, PHQ- 9 can be used indirectly (eg, via telephone) or directly at a 1396 Mayo Clin Proc. November 2007;82(11):

3 face-to-face visit; evidence of this flexibility was provided by a large study conducted in Europe which showed a congruence between self-administered and telephoneadministered PHQ For screening alone, the first 2 items ( In the past 2 weeks, have you been down or depressed? ; Have you had little interest or pleasure in doing things you normally enjoy? ), known as the PHQ- 2, have been shown to be very useful in deciding who is at risk. 20 Some practices rely on the PHQ-2 for general screening, only using the full PHQ-9 with someone who has risk factors and/or screens positive on the PHQ-2. However, as noted by the preventive task force, screening alone is not enough. Each practice must work out the logistics of administering the tool and initiating depression management considering available resources and practice preferences. MANAGEMENT OF DEPRESSION Depression management can be usefully divided into 3 phases: initiation of treatment, continuation, and followup/maintenance. The initial goal in the first phase of depression management is to minimize depressive symptoms and achieve remission. The MacArthur Foundation and others have linked severity scores on the PHQ-9 with suggested interventions (Table 1). On the basis of the obtained score, a clinician may adopt a step-up approach to treatment selection, beginning with supportive counseling and progressing, if necessary, along the spectrum to a combination treatment with antidepressants and psychotherapy. Again, these are general guidelines developed to assist a clinician in structuring conversation with the patient about possible interventions. To facilitate the tracking of patient progress, the PHQ-9 should be entered in the medical record in a manner that allows for easy retrieval, ideally in the form of a patient registry. PHARMACOLOGICAL MANAGEMENT The decision to use antidepressant agents should be made jointly by the clinician and the patient. Some factors to consider in drug selection include patient preferences, potential drug-drug interactions, insurance limitations, and adverse effects. Patients with major depression should remain on a successful medication regimen for at least 6 months for the first episode and longer for subsequent episodes; it is therefore critical that they are able to tolerate and afford that period of treatment. Patient involvement and education are key factors in treatment adherence. A step-up dosing schedule can be helpful in minimizing adverse effects; initial doses should also be lower for elderly patients and those with hepatic or renal impairment. Tables 2 and 3 list the commonly prescribed antidepressants and TABLE 1. Applying Patient Health Questionnaire-9 (PHQ-9) Scores to Practice PHQ-9 Severity/provisional Treatment score diagnosis recommendations <5 Community norm No action recommended 5-9 Mild symptoms Watchful waiting, selfmanagement education, periodic rescreening Major depression, Pharmacotherapy or mild psychotherapy, creation of a treatment and follow-up plan, education, reevaluation Major depression, Immediate institution of moderately severe treatment (pharmacotherapy and/or psychotherapy) 20 Major depression, Pharmacotherapy AND severe psychotherapy, referral Adapted from MacArthur Initiative on Depression and Primary Care, 15 with permission. their dosages as well as adverse effects and options for addressing them. 21 Currently, patients have many effective treatment options, including more than 20 antidepressant medications approved by the Food and Drug Administration and several scientifically tested psychotherapies. Clinicians should recognize that no one treatment is universally effective and that many depressed patients do not experience satisfactory clinical benefit from initial treatment. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, sponsored by the National Institute of Mental Health, confirmed that several sequential treatment steps are often needed to obtain remission. However, when more treatment steps are required, short-term remission rates decline and relapse rates increase during the follow-up phase. 22 Those who do not respond to the first step of a step-up treatment approach can be more easily identified when patient responses can be documented within 4 to 6 weeks of initiating medications or 8 to 12 weeks of initiating psychotherapy. These patients can then be moved to the next step, which may involve a simple change of medication or the referral to a mental health professional. PSYCHOTHERAPY Psychotherapy can reduce depressive symptoms, improve function, and prevent relapse in patients with major depression. 23,24 Access to a psychotherapist, however, can pose a challenge in many health care systems. Two proposed solutions are the administration of cognitive-behavioral therapy by telephone and the training of nurses to act as care managers, providing focused care using concepts of behavioral activation. 25 Combined treatment with pharmacological agents is recommended for those with partial or no response to 12 weeks of psychological counseling, those with severe depression, or those with a prior chronic course Mayo Clin Proc. November 2007;82(11):

4 TABLE 2. Commonly Used Antidepressant Medications Starting dose Usual dose Antidepressant medication (mg/d)* (mg/d) Generic drug Tricyclics Tertiary amine Amitriptyline Yes Clomipramine Yes Doxepin Yes Imipramine Yes Trimipramine Yes Secondary amine Desipramine Yes Nortriptyline Yes Protriptyline Yes Selective serotonin reuptake inhibitors Escitalopram No Citalopram Yes Fluoxetine Yes Fluvoxamine Yes Sertraline Yes Paroxetine Yes Norepinephrine-dopamine reuptake inhibitors Bupropion Yes Bupropion, sustained release Yes Bupropion, extended release Yes Serotonin-norepinephrine reuptake inhibitors Venlafaxine No Venlafaxine, extended release No Duloxetine No Serotonin modulators Nefazodone No Trazodone Yes Norepinephrine-serotonin modulators Mirtazapine No Monamine oxidase inhibitors Irreversible, nonselective Phenelzine Yes Tranylcypromine Yes Reversible Moclobemide Yes *Lower starting doses are recommended for elderly patients. Monitor liver function tests periodically; if 3 times or more are greater than normal, then discontinue. Adapted from American Psychiatric Association, 21 with permission. of illness. Patient preferences (specific gender, specific therapist in mind), health plan restrictions, and out-ofpocket costs should be considered in the selection of a psychotherapist. CLINICAL GUIDELINES Guidelines have been developed to facilitate the incorporation of the principles of evidence-based medicine into depression identification and management. Prominent examples that target the primary care population are the MacArthur Foundation toolkit (available at -primarycare.org), the Guideline for Major Depression in Adults in Primary Care of the Institute for Clinical Systems Improvement (revised 2006; available at and the Guideline for Depression of the National Institute for Health and Clinical Excellence, which has been implemented throughout Britain ( In choosing a guideline, the primary care practitioner should assess the quality and currency of the guideline and its relevance to the practice. Once a guideline is chosen, the next challenge is to ensure that practitioners remember to use it. Those practices with electronic medical records have the opportunity to embed flags or reminders about steps in a guideline into their daily practice. Implementation in practices without electronic records will be more challenging. FOLLOW-UP FREQUENCY The aims of treatment in the continuation and maintenance treatment phases are to prevent relapse in the short-term and the return of any new episodes in the long-term. Nearly half of patients who receive an initial prescription for an antidepressant discontinue treatment during the first month; few receive the recommended levels of follow-up care. 7,26 Frequent contacts during follow-up have been as Mayo Clin Proc. November 2007;82(11):

5 TABLE 3. Characteristics of Commonly Used Antidepressant Medications* Antidepressant medication Adverse effects Treatment of adverse effects Tricyclics Cardiovascular Advantages Orthostatic hypotension Lower dose; discontinue medication; prescribe fludrocortisone; Inexpensive add salt to diet Useful for chronic pain and migraines Reduced cardiac output Discontinue medication Disadvantages Arrythmias Discontinue medication Adverse effects including weight gain Anticholinergic Risk of death in overdose Dry mouth Prescribe pilocarpine oral rinse; suggest gum or candy Risk of serious adverse effects and mortality in Constipation Hydrate; prescribe bulk laxatives patients with ischemic heart disease Urinary hesitancy Prescribe bethanechol Visual changes Prescribe pilocarpine eye drops Delirium Discontinue medication; prescribe antipsychotic medication Sedation Adopt bedtime dosing Weight gain Lower dose; change to secondary amine (if tricyclic antidepressant required); discontinue medication Neurologic Myoclonus Lower dose; discontinue medication; prescribe clonazepam Adverse sexual effects Arousal, erectile dysfunction Lower dose; discontinue medication; prescribe sildenafil Orgasm dysfunction Lower dose; discontinue medication; prescribe sildenafil Selective serotonin reuptake inhibitors Nausea, vomiting Lower dose; discontinue mediation Advantages Activation Lower dose; discontinue mediation Fewer adverse effects than tricyclics Insomnia Lower dose; discontinue mediation; adopt morning dosing; Few drug-drug interactions in patients taking prescribe trazodone at bedtime multiple medications Neurologic Disadvantages Extrapyramidal symptoms; Lower dose; discontinue medication Reported increased risk of suicide among tardive dyskinesia children and adolescents. FDA extended black Headaches Lower dose; discontinue medication box warning in young adults aged y Adverse sexual effects Arousal, erectile dysfunction Lower dose; discontinue medication; prescribe sildenafil Norepinephrine-dopamine reuptake inhibitors Nausea, vomiting Lower dose; discontinue medication Advantages Insomnia Lower dose; discontinue mediation; adopt morning dosing; Low incidence of weight gain prescribe trazodone at bedtime Low incidence of adverse sexual effects Neurologic Used for concomitant smoking cessation Seizures Lower dose; discontinue medication; prescribe antiepileptic medication Disadvantages Headaches Lower dose; discontinue medication May worsen concomitant anxiety in patients Serotonin-norepinephrine reuptake inhibitors Cardiovascular Advantage Hypertension Lower dose; discontinue medication Duloxetine has indication for chronic pain Activation Lower dose; discontinue medication Nausea, vomiting Lower dose; discontinue medication Adverse sexual effects Arousal, erectile dysfunction Lower dose; discontinue medication; prescribe sildenafil Orgasm dysfunction Lower dose; discontinue medication; prescribe sildenafil Serotonin syndrome Discontinue medication Serotonin modulators Sedation Adopt bedtime dosing Advantage Adverse sexual effects Helpful for insomnia Priapism (trazodone) Discontinue medication; consider surgical correction Norepinephrine-serotonin modulators Cardiovascular Advantages Increase in cholesterol Lower dose; discontinue medication Useful for symptoms of insomnia accompanying Sedation Adopt bedtime dosing depression Weight gain Lower dose; change to secondary amine (if tricyclic antidepressant Useful for poor appetite and weight loss required); discontinue medication accompanying depression Agranulocytosis Discontinue medication; monitor white blood cell count; prescribe Disadvantage granulocyte colony stimulating factor Weight gain Monoamine oxidase inhibitors Weight gain Lower dose; change to secondary amine (if tricyclic antidepressant Disadvantages required); discontinue medication Potential for serious adverse effects Cardiovascular Necessity for dietary restrictions Hypertensive crisis Discontinue medication; prescribe intravenous α blocker Neurologic Myoclonus Lower dose; discontinue medication; prescribe clonazepam Sexual dysfunction Orgasm dysfunction Lower dose; discontinue medication Serotonin syndrome Discontinue medication *FDA = Food and Drug Administration. Generally reserved for patients who do not respond to other treatments. Adapted from American Psychiatric Association, 21 with permission. Mayo Clin Proc. November 2007;82(11):

6 TABLE 4. Using the Patient Health Questionnaire-9 (PHQ-9) to Assess Initial Treatment Response* After 4 to 6 Weeks of Adequate Pharmacotherapy PHQ-9 score Treatment response Recommended action Decrease of 5 points Adequate or complete Do not change treatment; conduct periodic follow-up or more from baseline Decrease of 2 to 4 points Partial Reconfirm diagnosis; consider comorbid conditions; from baseline increase dose of same agent or add second agent Decrease of 1 point or Poor or none Reconfirm diagnosis; consider comorbid conditions; no change/increase in score augment medication; switch medication; obtain psychiatric consultation; add psychological counseling *Goal of the initial phase of treatment is remission, defined as a PHQ-9 score of less than 5. Adapted from MacArthur Initiative on Depression and Primary Care, 15 with permission. sociated with better outcome. Patients should be seen 2 to 4 weeks after starting therapy to assess medication acceptance and response, reinforce educational messages, and address adverse effects and suicide risk. After the initial identification of a depressed patient, 3 contacts within 12 weeks are considered ideal. The PHQ-9 should be administered during these follow-up visits to monitor patient progress. Studies that investigated the sensitivity of the PHQ-9 to change have shown that the measure is responsive to pharmacological and psychosocial interventions. 27,28 Changes in the PHQ-9 scores after treatment with antidepressant agents correspond with clinician ratings of patient responses to treatment. 28 Practice models will dictate who will see the patient on follow-up and whether follow-up can be conducted through nonvisit care. For instance, under the collaborative care model described below, follow-ups are performed by the care manager with case supervision by a psychiatrist and/or primary care physician. Using the PHQ-9 to assess treatment response (Table 4), clinicians can classify and manage patients as follows: complete response/remission, in which case therapy should be continued for at least 6 months; partial response, in which case a higher dose of the same agent should be used or a second agent or psychotherapy added; and no response, in which case a switch should be made to a different category of drug or to psychotherapy. Indefinite antidepressant therapy should be discussed with patients who have additional risk factors such as 2 or more prior episodes of depression in 5 years, an initial episode after age 50, and difficult-to-treat episodes. The collaborative care model, a structured approach to care based on chronic disease management principles, involves allied specialists, such as registered nurses, who act as care managers and work in conjunction with the primary care physician and mental health specialist. This model uses a care manager and creates a collaborative relationship between a primary care practice and a psychiatrist; other critical components include the use of a screening instrument, the establishment of a registry where results can be entered and patients followed, and the use of evidencebased guidelines. Substantial evidence has shown this model to be more effective than standard care in improving short-term and long-term depression outcomes. 6,29,30 The system of care included in a collaborative model addresses weaknesses in systems that only screen for depression and do not follow up on those who have been identified or who have dropped out of care. A more detailed discussion of the model is beyond the scope of this paper. REFERRALS FOR PSYCHIATRIC EVALUATION Although primary care clinicians capably manage more than 75% of patients with depression, 31 referral for psychiatric evaluation is recommended in the following patients: those with a history of psychosis or who are suspected of having a primary psychotic disorder, those with a history of bipolar disorder or with symptoms of mania, those who have substantial trouble tolerating medication adverse effects, those whose depression has not responded to 2 adequate trials of antidepressants, those with complex comorbid medical conditions that complicate a choice of antidepressant, and those with complex comorbid mental conditions and/or a substance abuse problem. Patients with positive scores on the 9th item of PHQ-9 should be assessed further by their primary care team for suicidal risk. Immediate psychiatric evaluation or emergency referral for hospitalization is necessary whenever there is imminent danger that patients will harm themselves. Clarifying which patients are in imminent danger of suicide is a clinical decision best made by the practitioner directly involved with the patient. In making that determination, the practitioner should consider whether patients are preoccupied with or have thoughts about suicide, have stated their intent to act on those thoughts, have access to lethal means, and have a history of suicide attempts. Patients who are deemed to be imminently at risk should be moved to a safe environment. A collaborative relationship between the mental health specialist and the primary 1400 Mayo Clin Proc. November 2007;82(11):

7 care physician will help facilitate prompt intervention and ensure patient safety, particularly around this issue. An additional resource for patients and their families is the National Suicide Prevention Lifeline ( TALK or PATIENT EDUCATION Success in depression management largely depends on enabling patients to be active participants in their care process. Clinicians can help by providing educational materials or directing patients to available resources. They can also remind patients that depression, like asthma or diabetes, is a chronic and recurring disorder, the management of which requires their participation. They can educate patients regarding their medication, letting them know that 2 to 4 weeks of drug therapy may be needed before symptoms improve and alerting them to any potential adverse effects. They can remind them of the importance of taking their medication daily, continuing their medication for at least 6 months after they are feeling better, and consulting their physician if adverse effects or other problems with medication occur or before changing the dosage of or discontinuing medication. Finally, patients should be advised of the importance of eating a healthy diet, avoiding alcohol, and obtaining enough sleep. CONCLUSIONS Depression is the second most common reason for consultation in primary care practice but still remains frequently undiagnosed and undertreated. The PHQ-9 is a validated and reliable tool that the primary care physician can use to diagnose and treat depression and to monitor progress. A score of 10 or higher is used as the cutoff for a clinical diagnosis of depression and as an indication of the need to begin therapy. However, the PHQ-9 is intended only as a tool to facilitate clinical decision making and does not replace sound medical judgment. The goal of the initial treatment phase is to achieve remission either by pharmacotherapy, psychotherapy, or a combination of modalities. Clinical guidelines have been developed to provide clinicians with management algorithms. Continuation and maintenance phases aim at preventing relapse and lifelong recurrence; the PHQ-9 score can guide clinicians on treatment modifications and the need for referrals for psychiatric evaluation. Frequent follow-ups have been associated with better outcomes; 3 contacts within the 12 weeks after initial diagnosis are considered ideal. Decisions regarding screening and follow-up ie, where, how, and by whom the follow-up will be conducted will be made by practices on the basis of their individual needs. The collaborative care model appears to be the most effective for depression management in primary care and addresses system weaknesses, particularly those associated with follow-up care. In screening for depression, clinicians should particularly assess for suicidal risk; certain factors can help identify those at imminent risk of suicide. Ultimately, success in depression management largely depends on patient participation and self-activation. We wish to thank Sara Huntley for assistance in manuscript preparation. REFERENCES 1. Murray CJL, Lopez AD, eds. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability From Diseases, Injuries, and Risk Factors in 1990 and Projected to Cambridge, MA: Harvard University Press; Murphy JM, Laird NM, Monson RR, Sobol AM, Leighton AH. A 40- year perspective on the prevalence of depression: the Stirling County Study. Arch Gen Psychiatry. 2000; 57(3): Hankin BL. Adolescent depression: description, causes, and interventions. Epilepsy Behav Feb;8(1): Epub 2005 Dec Ebmeier KP, Donaghey C, Steele JD. Recent developments and current controversies in depression. Lancet. 2006;367(9505): Alexopoulos GS. 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