Article

Depression in primary care: Strategies for a psychiatry-scarce environment

The International Journal of Psychiatry in Medicine 2016, Vol. 51(2) 182–200 ß The Author(s) 2016 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0091217416636580 ijp.sagepub.com

Amy R Alson1, Diana M Robinson2, Danielle Ivanova2, John Azer2, Maria Moreno2, Marie Lyse Turk2, Abhishek Nitturkar2, and Karen S Blackman3

Abstract More than an algorithm to guide primary care providers through treatment options, integrated care, also called collaborative care, is a validated, systematic, multidisciplinary approach to depression treatment in primary care. Historically, integrated care emerged in response to a mismatch between a growing demand for mental health treatment and scarce mental healthcare resources. Working together, psychiatrists and primary care providers have demonstrated that the principles and tools of chronic disease management improve depression outcomes in primary care. Currently, most antidepressants are prescribed by primary care providers, but with disappointing rates of full, sustained remission. Primary care patients may derive the greatest benefit from existing depression treatment guidelines when they are melded with an approach informed by integrated care principles. This paper will present established guidelines for pharmacologic management of depression as part of a broader framework for depression treatment in the primary care office. Keywords depression treatment, major depressive disorder, primary care, integrated care

1

University of Virginia School of Medicine, Charlottesville, VA, USA University of Virginia Health System, VA, USA 3 Michigan State University, MI, USA 2

Corresponding Author: Amy R Alson, University of Virginia School of Medicine, PO Box 800744, Charlottesville, VA 22908-0744, USA. Email: [email protected]

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Introduction Worldwide, fewer than half of patients with depression are treated by mental health specialists. Primary care providers (PCPs) in the U.S. prescribed 62% of antidepressants in 2006–2007, compared with 21% prescribed by psychiatrists.1 In one U.S. study, fewer than half of patients referred from primary care scheduled an appointment with a mental health specialist, and fewer than half of scheduled appointments were attended.2 Psychiatric referral resources are limited,2 and psychiatrists in the U.S. are less likely to participate in private insurance than other physicians—55.3% compared to 88.7% in 2009–2010,3 further reducing access to psychiatric care. According to a 2009 meta-analysis of 41 studies involving over 50,000 patients, ‘‘motivated GPs (general practitioners)’’ correctly diagnosed 50% of depressed patients; this means that clinicians on the front line of depression care are missing half of affected patients. Explanations that have been offered for these findings include the brevity and infrequency of primary care visits, stigma interfering with symptom disclosure, and limited clinician training in mental health.4–6 Integrated care arose out of the recognition that PCPs treat depression often, and they need help to improve patient outcomes. In a formal integrated-care system, psychiatrists support stepwise treatment of depression through indirect consultation with PCPs and through direct consultation with specially trained mental-health care managers who assess patients in the primary care clinic, using validated measurements of clinical progress. Integrated care managers also act as liaisons between the busy PCPs and psychiatrists, who are in short supply. When resources for a formal integrated care system do not exist, PCPs can adopt measurement-based care, in which treatment decisions are guided by serial, systematic, standardized assessments of patient progress. Similarly, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study presented a model for prescribing antidepressants that relies on modifying treatment based on regular measurements of patient response. STAR*D and integrated care both emphasize systematic monitoring and treating to remission.7 An additional tenet of integrated care is to offer non-pharmacologic interventions for depression in primary care. While medication is recommended for moderately severe to severe depression at diagnosis, the first-line treatment for mild to moderate depression is psychotherapy.8–10 Evidence supports psychotherapy’s effectiveness11 and patient preference for it,12 and care managers embedded in primary care clinics can provide or facilitate structured psychotherapy cost-effectively.9 While the scope of this article does not permit a full explication of integrated care, the Advancing Integrated Mental Health Solutions (AIMS Center) website is a good resource for detailed information on this model of care. Primary care is already well suited to incorporate principles of integrated care when full resources for formal integrated care are not available. In fact,

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integrated care for depression is similar to team-based diabetes, hypertension and heart disease care, which includes non-pharmacologic interventions that are provided by a non-physician to support behavior change. Both chronic disease management and integrated care rely on standardized clinical measurements, tracked in data registries, to assess patients’ response to treatment, and to identify inadequate improvement, signaling a need to alter treatment.8,13,14

Screening The Patient Health Questionnaire-9 (PHQ-9) is favored by integrated care leaders for its ease of use by patients and because it is validated to aid in diagnosis and to monitor treatment response over time.15–17 The PHQ-9 elicits patients’ depressive symptoms and functional impairment over the previous two weeks, encompassing diagnostic criteria for Major Depressive Disorder. Higher scores are associated with more severe depression.16,18 See Table 1 for details of PHQ-9 based diagnosis. In a review of diagnostic characteristics of the PHQ-9 in 41 studies using a cut-off score of 10 to diagnose depression, the PHQ-9 had a pooled sensitivity of 92% and pooled specificity of 80%.19 The first two questions of the PHQ-9 comprise the PHQ-2, which is independently validated as a screening tool to detect risk for depression using a cut-off score of 3.20,21 The PHQ-9 is free and available on the internet in 78 international dialects.22 On average, it is completed by patients in less than 5 minutes.17 Primary care clinics can build depression screening into patient intake. Medical assistants who measure vital signs ask patients to complete the PHQ-2. Patients who score 3 or higher on the PHQ-2 are asked to complete the PHQ-9 before seeing their PCP. To avoid impeding clinic flow, it is reasonable to initiate annual depression screening for subgroups of the clinic population, such as new patients and those at elevated risk for depression. Individuals at especially high risk include veterans of combat, perinatal women, patients who are socially isolated, and those with a personality disorder, chronic pain, or other medical comorbidity.

Table 1. PHQ-9 depression scale. PHQ-9 score

Depression severity

1 to 4 5 to 9 10 to 14 15 to 19 20 to 27

None Mild Moderate Moderately severe Severe

Adapted from literature.16

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When clinic staff is familiar with the protocol, systematic screening and a system to ensure accurate diagnosis, effective treatment, and follow-up should be established for all adult and adolescent patients, as recommended by the U.S. Preventive Services Task Force.23

Assessment The PHQ-9 reveals diagnostic criteria for depression but also may reflect distress due to grief, job loss, or physical illness. Distress is a transient reaction to a disturbing environmental trigger, such as a death in the family. Asking the patient about the context of their symptoms over the prior two months may separate distress from depression; distressed patients should be reevaluated after a few weeks.8,24 Postscreening assessment focuses on symptom severity and the presence or absence of specific symptoms. For example, PHQ-9 questions about sleep, appetite, and movement require clarification: is the patient eating or sleeping too much, or not enough? During assessment, patients are asked about ongoing and past trauma, substance use, aggressive behaviors, and cultural factors that may influence adherence and health, and about past psychiatric illness, treatment, hospitalization, and suicide attempts.8,10,24 Assessment also identifies contraindications to potential treatments, such as drug interactions and active substance abuse. Before starting any antidepressant, patients should be screened for risk of bipolar disorder with a validated brief structured interview such as the Composite International Diagnostic Interview-based Bipolar Disorder Screening Scale,25,26 in addition to inquiry about psychiatric illness including bipolar disorder in family members. Depression assessment is an opportunity to build rapport, identify obstacles to treatment adherence, and to educate patients, (and family members, when appropriate), about depression and engage them in treatment and monitoring.6 Additionally, through education about how mood may affect blood pressure, pain, and diabetes control, PCPs incorporate depression treatment into primary healthcare. In integrated care clinics, care managers (e.g. psychologists, nurses, and social workers) perform psychological and risk assessments, provide psychoeducation, engage the patient in treatment and monitoring, and coordinate interim communication with PCPs. Care managers are supervised by a psychiatrist who provides indirect consultation to the care manager and PCP in most cases, and rarely assesses patients directly.9 Postscreening assessment also includes evaluation of a patient’s risk of harm to self or others. Not all suicidal thinking is associated with intent, but any patient who endorses suicidal thoughts directly, or responds >0 to PHQ-9 Question #9, must be assessed for suicidal intent, plan, and means. Unfortunately, no score-based validated tool has been validated to predict suicide risk. Existing suicide risk assessment tools are based on the presence or

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absence of known risk and protective factors. These tools require training to use in patient care and can be time-consuming. One such tool, the Columbia Suicide Severity Rating Scale, is a free online assessment available in 100 languages. Providers using the Columbia Suicide Severity Rating Scale are advised to complete a 30-min training video prior to clinical use.27 Another suicide assessment tool, the Suicide Assessment Five-step Evaluation and Triage (SAFE-T), was developed by the U.S. Substance Abuse and Mental Health Services Administration. It is available as a mobile app or printable reference card outlining suicide risk and protective factors. SAFE-T prompts clinicians to identify risk factors and document the rationale for a patient’s estimated risk level and management plan.28 Integrated care leaders recommend asking patients five questions: is life worth living, do they think about self-harm, do they intend to harm themselves or end their life, do they have a plan for ending their life, and do they have access to lethal means, such as firearms.9 If the patient has suicidal intent and means and cannot identify a safety plan, (such as removing accessible firearms and calling a suicide hotline if suicidal thoughts intensify), emergent evaluation for psychiatric hospitalization is indicated.

Treatment For all patients with a depressive disorder, the goal of treatment is full remission, or a PHQ-9 score of 14 should prompt initiation of drug therapy, with selection of initial medication class based on side effects, tolerability, safety, and cost. Medication also should be considered for patients with mild or moderate depression who are not achieving remission with psychotherapy.8,10,24,33 PCPs and patients should be aware that antidepressant side effects can occur in the first two weeks and then resolve, while full antidepressant response is typically seen between four and eight weeks. When symptom measurements, such as serial PHQ-9s, indicate incomplete remission after four to eight weeks at the maximum tolerated dose of an initial medication, treatment should be modified by switching or augmenting medications or adding psychotherapy. Improvement should occur within three to six weeks of the new intervention, and monitoring should continue to ensure achievement and maintenance of remission.8 Without adequate head-to-head trials of all antidepressants, a clear drug of first choice does not exist. Generic selective serotonin reuptake inhibitors (SSRIs) are considered first by NICE because they are generally well tolerated and inexpensive. The APA recommends starting with an SSRI, serotonin–norepinephrine reuptake inhibitors (SNRI), bupropion, or mirtazapine. The WHO starts with fluoxetine or a tricyclic antidepressant. Of note, the use of tricyclic antidepressants for initial antidepressant therapy has become less common in areas where generic SSRIs are inexpensive and widely available.

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Table 2. Psychotherapies used in integrated care.8 Therapy Cognitive behavioral therapy

Premise Negative beliefs affect behavior and emotions and modifying these beliefs can change future behavior and emotions.

Description  



Usually limited to no more than 20 structured sessions. Patients are expected to do homework assignments between sessions. Studies show CBT decreases the risk of relapse even after treatment ends.

Focuses on interpersonal crises or life-changing events and makes connections between the patient’s mood and disturbing life events.



Behavioral activation

A cognitive behavioral treatment



Uses activity scheduling to encourage patients to engage in activities they avoid, and to understand the purpose and effect of avoidance.

Problem-solving therapy

A cognitive behavioral therapy



Defines multiple solutions for specific problems then focuses on implementing the best solution. Goals include recognition and acceptance of unsolvable problems, use of planning and systematic approaches to resolving stressors, minimizing avoidance and impulsivity.

Interpersonal therapy





Supportive counseling

Provides a safe space for patient to talk about current struggles

CBT: cognitive behavioral therapy; IPT: interpersonal therapy.

 

Developed to treat depression. Studies show IPT effective in primary-care patients, pregnant and post-partum women, in developing countries, and as augmentation to medication.

Empathy is offered No solutions or new skills are developed.

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Before starting any new medication, a systematic check for drug interactions is essential. Common adverse drug interactions involving antidepressants include effects on drug metabolism through CYP450 enzymes, increased risk of serotonin syndrome, and drug-induced prolongation of the corrected QT interval (QTc) on electrocardiogram. Depression increases a patient’s risk for other medical conditions,31 and many patients with depression already take multiple medications. Common medications metabolized by or affecting CYP450 enzymes include warfarin and many antimicrobials.34 Medications that increase serotonin levels include triptans, some opioid analgesics, and antiemetics like ondansetron. Whichever drug is chosen first, it should be titrated gradually to maximum tolerated dose. The choice of first antidepressant is best made with the patient, considering side effects, comorbidities, previous personal or family history of a response to an antidepressant, and potential drug–drug interactions. For example, an anxious, depressed woman of child-bearing age might start with sertraline because it is considered one of the safest antidepressants in pregnancy and lactation, and it is indicated to treat comorbid anxiety disorders. Meanwhile, a depressed university student with a PHQ-9 score of 23 who forgets to take pills might benefit from a long-acting antidepressant, such as fluoxetine. In another case, an overweight, hypersomnolent patient might best start with bupropion, an activating antidepressant with potential appetite suppression. When the initial drug does not achieve full remission, or side effects interfere, eliciting patient preference for augmentation or switching to a different antidepressant is good practice. In STAR*D augmentation trials, buspirone and sustained-release bupropion showed efficacy, and these drugs may be better tolerated than lithium8 or liothyronine, traditional augmenting agents. Several antipsychotics, such as olanzapine, quetiapine, aripiprazole, and brexiprazole are indicated for augmentation of depression treatment. However, these medications are associated with serious adverse metabolic, cardiovascular, and neurological effects, so caution is required, and monitoring is indicated for effects on lipids, glucose, waist circumference, weight, and abnormal movements. Additionally, an electrocardiogram (EKG) should be done prior to initiation for patients at high risk of QTc prolongation.35 To illustrate treatment-modification strategies, consider the university student who tried fluoxetine: he is eating and sleeping better and feels more hopeful after one month on 80 mg fluoxetine, and his PHQ-9 score dropped to 13, but he remains unmotivated and easily distracted. The PCP might want to augment fluoxetine with the stimulating antidepressant, bupropion. Meanwhile, a patient who had partial remission of depression after six weeks on mirtazapine gained significant weight; this patient prefers to take a single pill, so switching to one of the SSRIs is reasonable. Common obstacles to treatment adherence can be overcome through patient education. The most common early side effects of many antidepressants are anxiety, gastrointestinal upset, and headache. Patients should be told that

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these symptoms often resolve within weeks. Sexual dysfunction is a common later-onset adverse effect of SSRIs and SNRIs, often unreported by patients until directly asked.36 When sexual dysfunction affects depression treatment, adding sildenafil, bupropion, or buspirone may mitigate the problem, or switching to monotherapy with an antidepressant with lower associated rates of sexual dysfunction, such as bupropion or mirtazapine, also is appropriate.37,38 A detailed list of commonly prescribed psychotropic drugs and related prescribing information is available for free on the Advancing Integrated Medical Health Solutions website.9 See Table 3 for clinical differences between medications commonly used by PCPs. APA, NICE, and WHO guidelines all emphasize inexpensive medications. Newer antidepressants can cost hundreds of dollars a month in the U.S. and have not been demonstrated to be superior to older, cheaper drugs. A Canadian study of almost 16,000 patients over three years showed that higher drug costs and infrequent follow-up were associated with failure to fill a first prescription for any condition.39 In fully integrated care, care managers systematically monitor and document patients’ symptoms and treatment adherence until full remission is achieved and sustained. Failure to achieve a PHQ-9 score of 60 years) and hepatically impaired

Dosing (mg/day)

Table 3. Choosing and using antidepressants in primary care. Side Effects to Watch For

(continued)

Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y Akathisia or motor restlessness Anxiety with initiation, agitation, sleep disturbance Sexual dysfunction often a reason for discontinuation Isomer of citalopram Nausea and diarrhea common initial side Less QTc prolongation than effect; typically resolve citalopram, but more than SSRIs Apathy, weight gain may occur later in use in subset of individuals Altered platelet function may predispose to GI bleeds Most studied Hyponatremia from SIADH Rarely has withdrawal symptoms Discontinuation symptoms: due to long half-life Disequilibrium, flu-like symptoms, sleep or Most CYP450 Interactions sensory disturbances, electric shock sensaMalnutrition diminishes efficacy tions More activating than other Pediatrics: Behavioral activation - restlessSSRIs ness, hyperactivity, insomnia, internal feeling of excitation, impulsivity

Fewer Cytochrome P450 (CYP450) interactions Well studied and tolerated in post MI patients Most QTc prolongation of all SSRIs

Tips for Use in Primary Care

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Depression Generalized Anxiety Disorder Panic Disorder Social Anxiety Disorder Obsessive Compulsive Disorder Post-traumatic Stress Disorder Premenstrual Dysphoric Disorder Pediatrics: OCD

Depression Panic Disorder Social Anxiety Disorder Obsessive Compulsive Disorder Post-traumatic Stress Disorder Premenstrual Dysphoric Disorder Pediatrics: OCD

Paroxetine

Sertraline

Selective Serotonin Reuptake Inhibitors

Table 3. Continued.

(continued)

 Anticholinergic: weight gain, See above for side effects of SSRI class constipation, dry mouth, sedating  Worst discontinuation syndrome among SSRIs  Some patients benefit from lowdose fluoxetine to minimize discontinuation  Poorly tolerated in the elderly due to anticholinergic effects  Avoid in pregnancy

 Post-MI patients: studied and well Range: 50–200 mg/day tolerated Increase by 25–50 mg increments  Nearly undetectable in breast milk Max dose varies with indication:  Diarrhea more common Depression: 200 mg/day OCD: 200 mg/day Panic Disorder: 200 mg/day Social Anxiety Disorder: 200 mg/day PTSD: 200 mg/day Premenstrual Dysphoric Disorder: 150 mg/day Peds OCD: 25–200 mg/day

Range: 20–60 mg/day Increase by 10–20 mg increments ER: 25–62.5 mg/day Increase by 12.5 mg increments Max dose varies with indication: Depression: 50 mg/day GAD: 50 mg/day Panic disorder: 60 mg/day Social Anxiety: 60 mg/day OCD: 60 mg/day PTSD: 50 mg/day Peds OCD: 10–60 mg/day

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Depression

Venlafaxine

Depression Generalized Anxiety Disorder Social Anxiety Disorder Panic Disorder

Depression Diabetic Peripheral Neuropathic Pain Generalized Anxiety Disorder Fibromyalgia Chronic Musculoskeletal Pain Levomilnacipran Depression

Duloxetine

Desvenlafaxine

 May help with vasomotor symptoms in perimenopausal women  May help with symptoms of fibromyalgia  May be useful in poor metabolizers  Reports of interstitial lung disease and eosinophilic pneumonia  No generic available at this time  May start at 30 mg daily for one week if tolerability a concern  Reported to be helpful in stress urinary incontinence  Consider risk of hepatotoxicity with other hepatotoxic medications and alcohol

All SNRIs tend to have prominent discontinuation syndromes; taper to discontinue

Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y

Given in 2–3 divided doses Range: 75–375 mg/day Increase by 37.5–75 mg increments Extended release: Once daily dosing Range: 75–225 mg/day Increase by 37.5–75 mg increments

doses less than 150 mg  May be helpful for vasomotor symptoms in perimenopausal women  Should not be used in patients with uncontrolled blood pressure or uncontrolled angle closure glaucoma  Use with caution in patients with a history of seizures  Reports of interstitial lung disease and eosinophilic pneumonia

Increase by 20 mg–40 mg increments  Don’t combine with alcohol; can increase hepatic transaminases  No generic available at this time  Primarily inhibits serotonin reuptake at Immediate release:

(continued)

Headache Nausea Xerostomia Increased blood pressure Hyperhidrosis Sleep disturbance Sexual dysfunction Dizziness Anxiety with initiation  Comes in extended release capsules Range: 40–120 mg/day Initiate at 20 mg daily for 2 days, then  More noradrenergic activity than the SIADH Angle closure glaucoma increase to 40 mg/day other SNRIs

Range: 40–120 mg/day Increase by 20–30 mg increments Max dose varies with indication: Depression, GAD and DPNP: 120 mg/day Fibromyalgia and Chronic musculoskeletal pain: 60 mg/day

Range: 50–100 mg Increase by 50 mg increments

Serotonin Norepinephrine Reuptake Inhibitors

Table 3. Continued.

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Depression Seasonal affective disorder Smoking cessation

Depression

Bupropion (norepinephrine dopamine reuptake inhibitor)

Mirtazapine (dual serotonin and norepinephrine agent)

Novel Mechanism of Action

Table 3. Continued.

Range: 15–45 mg/day Increase by 15 mg increments

Immediate release: Range: 200–450 mg/day in 2–3 divided doses Start at 100 mg twice daily for 3 days Max single dose 150 mg 12-hour extended release: Range: 200–400 mg/day in 1–2 divided doses Start at 150 mg ER daily for 3 days Max single dose 200 mg 24-hour extended release: Range: 150–450 mg/day as one daily dose Start at 150 mg ER daily for 4 days Increase by 150 mg increments Max single dose 450 mg









tion Relative lack of significant drugdrug interactions Can be helpful for insomnia and poor appetite Below 30 mg/day, sedative effects more prominent Alpha 2 antagonist

 More stimulating than other antidepressants  Lower rate of sexual dysfunction  Not associated with weight gain  Contraindicated in past and current diagnosis of Anorexia or Bulimia Nervosa  Avoid in patients at higher risk of seizure, such as heavy alcohol users  Contraindicated in Seizure Disorder; do not use if patient is abruptly discontinuing alcohol or sedative use  Avoid immediate release formulation as higher risk of seizures  Lower incidence of sexual dysfunc-

(continued)

Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y Sedation Weight gain Increased serum cholesterol Xerostomia Agranulocytosis (rare) Neutropenia (rare)

Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y Agitation Insomnia Anxiety Weight loss Seizure Constipation Xerostomia Tremor Elevated blood pressure

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Range: 20–40 mg daily Start with 10 mg daily for 7 days, then 20 mg daily for 7 days Increase by 10 mg increments

Depression

Depression

Vilazodone (dual acting serotonin reuptake inhibitor plus 5HT1A partial agonist)

Vortioxetine (multimodal agent)

Range 5–20 mg daily Start with 10 mg daily Can decrease to 5 mg daily if not tolerated Increase (or decrease) in 5–10 mg increments

Range: 150–600 mg Increase by 50 mg increments Extended release: 150–375 mg/day

Depression

Trazodone (non-selective serotonin reuptake inhibitor)

Novel Mechanism of Action

Table 3. Continued.

Suicidal ideation: black box warning for children, adolescents, young adults 18-24 y Nausea Vomiting Diarrhea Insomnia Sexual dysfunction Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y Nausea Vomiting Diarrhea Headache Dizziness

 Give with food  Taper to discontinue  No generic available at this time

 Will need 50% dose reduction if given with strong cytochrome P2D6 inhibitors like bupropion, fluoxetine, paroxetine  Taper to discontinue  No generic available at this time

(continued)

Suicidal ideation: black box warning for children, adolescents, young adults 18–24 y Priapism Drowsiness Dry mouth Lightheadedness Headache Fatigue Blurred vision Nausea Vomiting Vivid dreams and nightmares

 Generally too sedating for full dose antidepressant use  Often used at low dose (50– 100 mg at bedtime) in combination with SSRIs or bupropion to promote sleep

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ER: Extended release; OCD: Obsessive compulsive disorder; QTc: corrected QT interval; PTSD: Post-traumatic stress disorder; GAD: Generalized anxiety disorder; MI: myocardial infarction; SSRI: selective serotonin reuptake inhibitor; SIADH: syndrome of inappropriate antidiuretic hormone; SNRI: serotonin-norepinephrine reuptake inhibitor; Peds: Pediatric.

MAOIs are not recommended for use in primary care without psychiatric consultation: Washout required.

Tricyclic Antidepressants: Cost-effective in most countries, dangerous in overdose  More sedating than others in class Suicidal ideation: black box Amitriptyline Depression Range: 25–300 mg/day  Often used for insomnia or head- warning for children, adolesIncrease by 50–75 mg increments ache - caution required (drug/drug cents, young adults 18–24 y Constipation interaction)  Least sedating in class Xerostomia Desipramine Depression Range: 25–300 mg/day  Least associated with weight gain Urinary intentioin Increase by 50–75 mg increments Blurred vision  Extremely sedating Doxepin Depression Range: 25–300 mg/day Increased heart rate  Good antipruritic Anxiety Increase by 50–75 mg increments Confusion Anxiety: Drowsiness Range: 25–300 mg/daily Dizziness Increase by 50–75 mg increments Nausea Weight gain  Extremely constipating Imipramine Depression Range: 25–200 mg/day Conduction disturbances  Often used for diarrhea-predomi- Orthostatic hypotension Enuresis Increase by 50–75 mg increments nant IBS caution required (drug/ Decreased libido drug interaction) SIADH  Less sedating than amitriptyline Tinnitus Nortriptyline Depression Range: 25–150 mg/day  Often used for headache - caution Increase by 25 mg increments required (drug/drug interaction) CYP450 interactions with SSRIs and other CYP450 inhibitors may increase adverse effects

Table 3. Continued.

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For those not yet practicing in an integrated model, it is possible to borrow from its principles, which echo the principles of chronic disease management: screen, assess, treat to target, monitor, and quantify treatment response. When measurement-based treatment is implemented, serial assessment scores can document that PCPs are providing high quality and effective depression treatment. Studies of depression treatment over the past two decades have revealed problems that a systematic approach helps solve, such as failure to identify depression and its severity in patients not yet receiving any mental healthcare, and insufficient follow-up to ensure treatment tolerability and adherence. Integrated care promotes screening and standardized reassessment to ensure remission is achieved, while evidence-based prescribing algorithms reiterate the value of using validated ratings to guide timely treatment changes when remission is not occurring. Current evidence supports initial use of generic medications with sensitivity to common side effects and patient preference. PCPs can reduce the risks inherent in treating people with many medical conditions when multiple specialists are involved by coordinating treatment and monitoring for drug interactions. Integrated care incorporates non-pharmacologic interventions into primary care depression treatment, particularly for mild to moderate depression or as augmentation in treatment of more severe disease. The value of behavioral care managers, who bring mental healthcare knowledge and psychotherapy skills to primary care, is reflected in reduced healthcare utilization by patients whose depression remits.13,14 When care managers are not available, PCPs should: 1) use validated questionnaires to streamline the assessment of patients from diagnosis to sustained remission, 2) consider increasing the frequency of betweenvisit contact to improve adherence and identify obstacles to achieving clear treatment goals, and 3) optimize the use of psychotherapy referrals for patients who are open to this treatment.

Conclusion In a world of limited access to and follow-through with psychiatric referral, and with increased demand for mental health treatment, the initial detection and treatment of depression has become part of primary care medicine. Integrated care is an effective, evidence-based system for measurement-based treatment of depression by PCPs. PCPs who do not work within integrated care can become better at identifying and treating depressed patients by following established guidelines for screening, assessment, and treatment and can improve outcomes by monitoring patients until remission of depression is complete and sustained. PCPs already are familiar with a systematic approach to chronic disease management. By embracing the opportunity to identify and treat depression in a similar manner to other chronic illnesses, PCPs can free up limited psychiatric access for the most challenging depressed patients, who do not respond to treatment despite initial adequate, evidence-based care. Integrated care researchers

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and the PCPs who have adopted these principles have shown that this approach improves quantifiable mental and physical health outcomes in people with depression and can lead to reduced healthcare utilization overall.13,14,41 Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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