CLINICAL
Depression Overview Thomas McCarter, MD, FACP
Depression is a common condition that often remains undiagnosed and untreated; however, symptoms are more likely to be recognized today than in past decades. Survey data suggest that female, nonwhite patients are more likely to report depressive symptoms, especially those who are less educated, poor, and covered by Medicaid. Depression may be a finding suggestive of dysthymic disorder, minor or major depressive disorder, seasonal affective disorder, episodic depression, or a sign of an associated mood disorder, such as bipolar disorder. Many effective treatments are available that are well tolerated. This article outlines the diagnostic approach used in primary care, as well as the different treatment options available for this condition. Depression can have serious consequences and must be treated appropriately.
A
mong adults responding to the 2006 National Health Interview Survey, 11% reported having feelings of sadness during all, most, or some of the time in the 30 days before the interview; 6% reported feeling hopeless; 5% felt worthless; and 14% felt that everything was an effort.1 Women were more likely to report such symptoms than men (13% vs 9%, respectively). Non-Hispanic black adults and Hispanic adults were more likely to report feelings of sadness or hopelessness than non-Hispanic white adults. Level of education was inversely associated with feelings of sadness, hopelessness, worthlessness, or with the feeling that everything was an effort. Adults with less than a high school diploma reported the highest levels of such feelings, and those classified as poor were twice as likely to report these feelings as those not classified as poor. Persons under age 65 who were covered by Medicaid were more likely (27%) to report depressive symptoms than those who were uninsured (14%) or those with private health insurance (7%). Among those aged 65 and older, Medicare and Medicaid “dual-eligible” patients were more likely to report feelings of sadness (28%) than those covered by Medicare alone (13%) or those with private health insurance (11%).1 Depression is a common condition that frequently remains undiagnosed and untreated. Nevertheless, depression is more likely to be diagnosed today than in past decades, because the social stigma associated with this condition has lessened; available treatments are
Dr McCarter is Chief Clinical Officer, Executive Health Resources in Newtown Square, PA.
44
AMERICAN HEALTH & DRUG BENEFITS
April 2008
effective and well tolerated; and primary care physicians, to whom most patients initially present and from whom most patients receive initial therapy, have become more willing to diagnose and treat this condition. Depression may be suggestive of dysthymic disorder, major depressive disorder (MDD), seasonal affective disorder, episodic depression, or a sign of an associated mood, bipolar, or psychotic disorder. Depression may also be episodic, in response to bereavement or a major life change. In addition, it may play a significant role in specific clinical settings, such as during pregnancy or the postpartum period,2 adolescence, or at the end of life.3 This type of depression is beyond the scope of this discussion.
Diagnosis Risk Factors Risk factors that predispose patients to depression include: • Female gender • History of anxiety • History of eating disorders • First-degree relative with a history of depression • History of or current drug or alcohol abuse • History of or current sexual abuse or domestic violence. In addition, patients with major medical conditions or with chronic medical conditions are at a greater risk of experiencing depressive symptoms. These conditions may include cardiac illnesses (ie, myocardial infarction, coronary artery atherosclerotic disease, and arrhythmias), cerebrovascular disease (after a stroke or a transient ischemic attack), diabetes, chronic lung or renal disease, cancer, and chronic pain disorders.4
CLINICAL
Table 1 DSM-IV Criteria for Major Depression A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations 1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels sad or empty) or observation made by others (eg, appears tearful) Note: In children and adolescents, can be irritable mood 2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) 3. Significant weight loss when not dieting or weight gain (eg, a change of more than 5% of body weight in a month) or decrease or increase in appetite nearly every day Note: In children, consider failure to make expected weight gains 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6. Fatigue or loss of energy nearly every day 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely selfreproach or guilt about being sick) 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms do not meet the criteria for a mixed episode (ie, no symptoms or signs of manic episode) C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hypothyroidism) E. The symptoms are not better accounted for by bereavement, that is, after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation Adapted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (Copyright 2000). American Psychiatric Association.
Although the rates of major depression are highest among the 25- to 44-year-old age-groups, patients in older age-groups may be at increased risk, because of the loss of or separation from a spouse or peers, cognitive or physical impairments, and a higher prevalence of chronic diseases.5 This population may present specific challenges regarding the diagnosis and treatment because of a high prevalence of comorbid conditions and a higher utilization of other medications.6
Symptoms The characteristic symptoms of depression include loss of interest in activities that have historically proved to be pleasurable, sadness, irritability, feelings of worthlessness, hopelessness, guilt or anxiety, concerns over death, or suicidal ideation. Associated symptoms may include changes in appetite, weight loss or weight gain, sleep disturbances,
psychomotor activity, decreased energy, indecisiveness, or distracted attention. Patients with depression may also present with somatic complaints and may be frequent users of primary care, urgent care, and emergency or inpatient services. Patients with depression may also be those whom clinical staff identifies as “difficult” to treat. The American Psychiatric Association’s (APA) criteria for a major depression episode are listed in Table 1. Patients who are experiencing psychosocial stressors and who do not meet the criteria of major depression episode may be suffering from an adjustment disorder, or posttraumatic stress disorder. Recurrent episodes of major depression are called major depressive disorder, a condition associated with a high mortality. Patients with severe MDD have a high rate of suicide, and epidemiologic studies indicate that patients with MDD who are older than age 55 have a 4-fold increase in
www.AHDBonline.com
45
CLINICAL
Figure Assessing Depression with the PHQ-9 PATIENT HEALTH QUESTIONNAIRE (PHQ-9)
FOR DOCTOR OR HEALTHCARE PROFESSIONAL USE ONLY
English This questionnaire is an important part of providing you with the best health care possible. Your answers will help in understanding problems that you may have. Please answer every question to the best of your ability unless you are requested to skip a question. Name:________________________________________Age:________________________________________ Sex:
Female
Today’s Date:___________________________________________________
Male
Several days
0
1
More than half the days 2
Nearly every day 3
#ONSIDER -AJOR $EPRESSIVE $ISORDER
#ONSIDER /THER $EPRESSIVE $ISORDER
Over the last 2 weeks, how often have you been bothered by any of the following problems? Not at all
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
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
FOR HEALTHCARE PROFESSIONAL USE ONLY
9. Thoughts that you would be better off dead, or of hurting yourself in some way
If you checked “several days” or higher for some of the questions above, discuss your answers with a doctor. Only a doctor can make a diagnosis of depression. Also talk to your doctor if you checked “several days” or higher for (9), thinking that you would be better off dead or wanting to hurt yourself. Having repeated thoughts of death or suicide is the most serious symptom of depression. If you are thinking of harming yourself, get help immediately; make your feelings known to someone who can help you—your doctor, family members, friends. Your doctor is an excellent person to tell. KEY (for physician’s use): MDD if answer to # 1 or 2 and 5 or more of # 1-9 are at least “More than half the days” (count # 9 if present at all). All rights reserved.
6. Feeling bad about yourself, or that you are a failure, or have let yourself or your family down
© 2005 Pfizer Inc.
5. Poor appetite or overeating
ZT254386G
Printed in USA/September 2005
Copyright © Pfizer Inc. All rights reserved. Reproduced with permission of Pfizer, Inc. The PHQ-9 questionnaire can be accessed at www.phqscreeners.com.
rates of death.7 Depressive episodes associated with manic episodes are classified as bipolar disorder.
History and Physical Examination When taking the medical history, it is important to identify the severity and duration of the symptoms and any previous episodes, because depression tends to be recurrent. One should determine whether there is a family history of depression or other psychiatric illness— both major depression and bipolar disorder are heritable conditions. Recognition of manic or psychotic symptoms may identify patients who may require earlier referral to a psychiatrist. A history of suicidal thoughts, plans, or actions must be ascertained and again may identify patients who need more urgent referral. Although the physical examination is fairly insensitive for identifying depression, a thorough physical examination is important to identify contributing or causal ill-
46
AMERICAN HEALTH & DRUG BENEFITS
April 2008
nesses, such as chronic liver or renal disease, endocrine disease (hypothyroidism or adrenal insufficiency), congestive heart failure, dementia, or other conditions. In primary care settings, the point prevalence of major depression ranges from 5% to 9% among adults, and up to 50% of depressed patients are not recognized.8 The related conditions of dysthymia (a chronic low-grade depression) and minor depression are as common as major depression in primary care settings. Depressive disorders are estimated to affect from 0.8% to 2.0% of children and 4.5% of adolescents.9 Some of the barriers that may contribute to these percentages include: • Inadequate knowledge of diagnostic criteria • Competing priorities and comorbid conditions • Time limitations • Stigma associated with “labeling” a patient as depressed • Poor reimbursement mechanisms.
CLINICAL
Because of these barriers, a number of case-finding instruments have been developed and validated, including the Beck Depression Inventory, the Center for Epidemiological Studies-Depression Scale, the Zung Self-Assessment Depression Scale, the General Health Questionnaire, and the Hopkins Symptom Checklist, among others.9 Recently, 2 related tools are increasingly being used to screen and diagnose depression. The Patient Health Questionnaire (PHQ)-2 is an abbreviated version, consisting of the anhedonia and mood items of the PHQ-9. The PHQ2 can be used as a very brief and quick depression-screening tool in primary care. In primary care patients, a PHQ2 score of 3 or more has 83% sensitivity and 92% specificity for identifying patients with major depression.10 If the PHQ-2 is positive, screening may be confirmed by completing all the questions on the PHQ-9 (Figure). The PHQ-9 can be used as a screening tool, with summed score ranging from 0 (no depressive symptoms) to 27 (all symptoms occurring daily). A PHQ-9 score of 10 or more has been found to have 88% sensitivity and 88% specificity for a diagnosis of major depression.10 The PHQ-9 can also be used as a diagnostic assessment; with major depression diagnosed if 5 or more of the 9 symptoms have been present at least more than half the days of the past 2 weeks and 1 of these symptoms is either depressed mood or anhedonia.
Drug Therapy Untreated depression is associated with increased deaths, adverse outcomes, deficits in function, increased use of health services, poor on-the-job performance, and increased absenteeism. Treatments most frequently used by primary care physicians are (1) medications and (2) psychotherapy in cooperation with a psychologist, psychiatrist, or therapist. More than half of depressed patients respond to initial treatment with medications. Medication options are numerous (Table 2), and treatment recommendations should be tailored to the individual patient on the basis of the symptom profile, side effects of the drugs, comorbid conditions, and previous responses to treatment if available. Most drugs focus on serotonin and norepinephrine levels in the brain, supported by the major theory of depression known as the monoamine-deficiency hypothesis. The biochemical basis for this hypothesis and numerous other theories have been recently reviewed elsewhere.11 Several classes of drugs have been found effective in treating depression, through increasing the concentrations of the neurotransmitters serotonin and norepinephrine in the postsynaptic cleft of neurons in the cen-
tral nervous system. These agents include selective serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors (NRIs), and dual-action agents that inhibit the reuptake of serotonin and norepinephrine. Monoamine oxidase inhibitors (MAOIs) increase concentrations of neurotransmitters by inhibiting their degradation. Other agents increase the availability of neurotransmitters by blocking alpha-adrenergic autoreceptors, as well as serotonin (5-HT)2a reuptake and 5HT3 receptors, and histamine H1 receptors. Mood stabilizers, such as lithium, and anticonvulsants, such as lamotrigine, valproic acid, divalproex, or carbamazepine, may play an adjunctive role to antidepressants in the treatment of bipolar disorder. Antipsychotics and atypical antipsychotics may play a role in treating depression with psychotic features, as well as resistant major depression and bipolar depression.12 However, patients with these conditions may be more appropriately managed in conjunction with a psychiatrist. There are 3 phases in the treatment of depression— the acute phase, the continuation phase, and the maintenance phase. During the acute phase, treatment should be initiated and follow-up scheduled at 1- to 2week intervals to ensure a response. If a certain medication has worked previously for a patient or a family member, this may be an appropriate first choice. Antidepressants are started at low doses and titrated upward at appropriate time intervals based on response and side effects. If a patient’s response to a drug is inadequate at appropriate treatment doses, a change to a medication in the same or another class may be appropriate (patients who do not respond to one SSRI may respond to another agent within the class). Once an adequate response has been achieved in the acute phase, the continuation phase begins and can last as long as 9 months from remission. During this phase, treatment goals are to eliminate residual symptoms, to restore previous level of functioning, and to prevent recurrence or relapse. If there is no recurrence of symptoms during the first 6 months of treatment, a consideration to wean the medication and assess for the possibility of “early discontinuation” may be reasonable. If symptoms return, the medication should be re-titrated upwards to an effective dose and maintained for an additional 3 to 6 months. Early discontinuation does have a higher rate of relapse.12 Discontinuation in itself may produce symptoms (“discontinuation syndrome”), including balance problems, gastrointestinal upset, myalgias, weakness, sensory and sleep disturbances, anxiety, agitation, and emotional volatility. A maintenance phase treatment for 12 to 36 months may be indicated for patients with recurrent episodes of
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47
CLINICAL
Table 2 Antidepressants: Dosing, Indications, and Off-Label Use Maintenance dosage
Indications
Off-label use
Side effects (>10%)
Contraindications
Y
40 mg/d
MDD
Somnolence, insomnia, nausea, xerostomia, diaphoresis
Lexapro (escitalopram) Luvox (fluvoxamine) Luvox CR
N
10 mg/d
MDD, GAD
Y
100 mg bid
OCD
Alcoholism, coronary arteriosclerotic depression, OCD, panic disorder, PMDD, tension-type headache Mixed anxiety and depressive disorder, panic disorder Autism, depression, eating disorder, panic disorder
Y
100 mg/d
Paxil (paroxetine)
Y
20 mg/d
Paxil CR
N
25 mg/d
Pexeva (paroxetine) Prozac (fluoxetine)
N
30 mg/d
Y
20 mg/d
Prozac Weekly
N
90 mg/wk
OCD, Social anxiety disorder GAD, MDD, OCD, panic disorder, PTSD, social anxiety disorder MDD, panic disorder, PMDD, social anxiety disorder MDD, OCD, panic disorder, GAD Bulimia nervosa, MDD, OCD, panic disorder MDD
Headache, somnolence, insomnia, nausea, ejaculation disorder Headache, somnolence, insomnia, nausea, nervousness, dizziness, diarrhea, xerostomia, weakness
Sarafem (fluoxetine) Zoloft (sertraline)
N
20 mg/d
PMDD
Y
50 mg/d
MDD, OCD, panic disorder, PTSD, PMDD, social phobia
Alzheimer's depression, post-MI depression, dysthymia, night-eating syndrome
Dizziness, fatigue, headache, insomnia, somnolence, decreased libido, anorexia, diarrhea, nausea, xerostomia, ejaculatory disturbances, tremors, diaphoresis
N
60 mg/d
Diabetic neuropathy, GAD, MDD
Fibromyalgia, urinary incontinence
Y
37.5 mg bid
MDD
Hot sweats, OCD, PMDD
N
75 mg/d
N
50 mg/d
MDD, GAD, social anxiety disorder, panic disorder MDD
Y
100 mg 3 times daily 150 mg bid 300 mg/d
MDD
Y
25 mg 3 times daily
OCD
Asendin (amoxapine)
Y
150 mg/d
Elavil (amitriptyline)
Y
50 mg/d
MDD, endogenous depression, severe major depression with psychosis MDD
Norpramin (desipramine)
Y
100 mg/d
MDD
Pamelor (nortriptyline)
Y
25 mg 3 times daily
MDD
Class/Drug brand name (nonproprietary name) Selective Serotonin Reuptake Inhibitors Celexa (citalopram)
Mixed/Dual Cymbalta (duloxetine) Effexor (venlafaxine) Effexor XR
Pristiq (desvenlafaxine) Wellbutrin (bupropion) Wellbutrin SR Wellbutrin XL Tricyclics Anafranil (clomipramine)
48
Generic available?
Y Y*
Compulsive gambling, drug-induced depression, hot sweats, premature ejaculation
Body dysmorphic disorder, cancerdepression, DM-depression, dysthymia, fibromyalgia, hot sweats, PTSD, Raynaud's
Chronic pain, delusional disorder, MDD, ejaculatory disorder, panic disorder, pervasive development disorder
Headache (treatment/prophylaxis), pain, polyneuropathy, postherpetic neuralgia ADHD, diabetic neuropathy
ADHD, neurogenic bladder, nicotine dependence, nocturnal enuresis, postherpetic neuralgia
AMERICAN HEALTH & DRUG BENEFITS
April 2008
Somnolence, insomnia, headache, dizziness, decreased libido, nausea, xerostomia, constipation, diarrhea, weakness, ejaculatory disturbances, diaphoresis
Insomnia, headache, anxiety, nervousness, somnolence, decreased libido, nausea, diarrhea, anorexia, xerostomia, weakness, tremor, pharyngitis, yawning
Market share, %
Cost of 30-day supply
Concomitant use of MAOI + pimozide
8.29
$$
Concomitant use of MAOI + pimozide Concomitant use w/ alosetron, pimozide, thioridazine, tizanidine, MAOI Concomitant use of linezolid, MAOI, pimozide, thioridazine
13.78
($$$) $$$$
Depression Overview Thomas McCarter, MD, FACP
Depression is a common condition that often remains undiagnosed and untreated; however, symptoms are more likely to be recognized today than in past decades. Survey data suggest that female, nonwhite patients are more likely to report depressive symptoms, especially those who are less educated, poor, and covered by Medicaid. Depression may be a finding suggestive of dysthymic disorder, minor or major depressive disorder, seasonal affective disorder, episodic depression, or a sign of an associated mood disorder, such as bipolar disorder. Many effective treatments are available that are well tolerated. This article outlines the diagnostic approach used in primary care, as well as the different treatment options available for this condition. Depression can have serious consequences and must be treated appropriately.
A
mong adults responding to the 2006 National Health Interview Survey, 11% reported having feelings of sadness during all, most, or some of the time in the 30 days before the interview; 6% reported feeling hopeless; 5% felt worthless; and 14% felt that everything was an effort.1 Women were more likely to report such symptoms than men (13% vs 9%, respectively). Non-Hispanic black adults and Hispanic adults were more likely to report feelings of sadness or hopelessness than non-Hispanic white adults. Level of education was inversely associated with feelings of sadness, hopelessness, worthlessness, or with the feeling that everything was an effort. Adults with less than a high school diploma reported the highest levels of such feelings, and those classified as poor were twice as likely to report these feelings as those not classified as poor. Persons under age 65 who were covered by Medicaid were more likely (27%) to report depressive symptoms than those who were uninsured (14%) or those with private health insurance (7%). Among those aged 65 and older, Medicare and Medicaid “dual-eligible” patients were more likely to report feelings of sadness (28%) than those covered by Medicare alone (13%) or those with private health insurance (11%).1 Depression is a common condition that frequently remains undiagnosed and untreated. Nevertheless, depression is more likely to be diagnosed today than in past decades, because the social stigma associated with this condition has lessened; available treatments are
Dr McCarter is Chief Clinical Officer, Executive Health Resources in Newtown Square, PA.
44
AMERICAN HEALTH & DRUG BENEFITS
April 2008
effective and well tolerated; and primary care physicians, to whom most patients initially present and from whom most patients receive initial therapy, have become more willing to diagnose and treat this condition. Depression may be suggestive of dysthymic disorder, major depressive disorder (MDD), seasonal affective disorder, episodic depression, or a sign of an associated mood, bipolar, or psychotic disorder. Depression may also be episodic, in response to bereavement or a major life change. In addition, it may play a significant role in specific clinical settings, such as during pregnancy or the postpartum period,2 adolescence, or at the end of life.3 This type of depression is beyond the scope of this discussion.
Diagnosis Risk Factors Risk factors that predispose patients to depression include: • Female gender • History of anxiety • History of eating disorders • First-degree relative with a history of depression • History of or current drug or alcohol abuse • History of or current sexual abuse or domestic violence. In addition, patients with major medical conditions or with chronic medical conditions are at a greater risk of experiencing depressive symptoms. These conditions may include cardiac illnesses (ie, myocardial infarction, coronary artery atherosclerotic disease, and arrhythmias), cerebrovascular disease (after a stroke or a transient ischemic attack), diabetes, chronic lung or renal disease, cancer, and chronic pain disorders.4
CLINICAL
Table 1 DSM-IV Criteria for Major Depression A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations 1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels sad or empty) or observation made by others (eg, appears tearful) Note: In children and adolescents, can be irritable mood 2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) 3. Significant weight loss when not dieting or weight gain (eg, a change of more than 5% of body weight in a month) or decrease or increase in appetite nearly every day Note: In children, consider failure to make expected weight gains 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6. Fatigue or loss of energy nearly every day 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely selfreproach or guilt about being sick) 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms do not meet the criteria for a mixed episode (ie, no symptoms or signs of manic episode) C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hypothyroidism) E. The symptoms are not better accounted for by bereavement, that is, after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation Adapted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (Copyright 2000). American Psychiatric Association.
Although the rates of major depression are highest among the 25- to 44-year-old age-groups, patients in older age-groups may be at increased risk, because of the loss of or separation from a spouse or peers, cognitive or physical impairments, and a higher prevalence of chronic diseases.5 This population may present specific challenges regarding the diagnosis and treatment because of a high prevalence of comorbid conditions and a higher utilization of other medications.6
Symptoms The characteristic symptoms of depression include loss of interest in activities that have historically proved to be pleasurable, sadness, irritability, feelings of worthlessness, hopelessness, guilt or anxiety, concerns over death, or suicidal ideation. Associated symptoms may include changes in appetite, weight loss or weight gain, sleep disturbances,
psychomotor activity, decreased energy, indecisiveness, or distracted attention. Patients with depression may also present with somatic complaints and may be frequent users of primary care, urgent care, and emergency or inpatient services. Patients with depression may also be those whom clinical staff identifies as “difficult” to treat. The American Psychiatric Association’s (APA) criteria for a major depression episode are listed in Table 1. Patients who are experiencing psychosocial stressors and who do not meet the criteria of major depression episode may be suffering from an adjustment disorder, or posttraumatic stress disorder. Recurrent episodes of major depression are called major depressive disorder, a condition associated with a high mortality. Patients with severe MDD have a high rate of suicide, and epidemiologic studies indicate that patients with MDD who are older than age 55 have a 4-fold increase in
www.AHDBonline.com
45
CLINICAL
Figure Assessing Depression with the PHQ-9 PATIENT HEALTH QUESTIONNAIRE (PHQ-9)
FOR DOCTOR OR HEALTHCARE PROFESSIONAL USE ONLY
English This questionnaire is an important part of providing you with the best health care possible. Your answers will help in understanding problems that you may have. Please answer every question to the best of your ability unless you are requested to skip a question. Name:________________________________________Age:________________________________________ Sex:
Female
Today’s Date:___________________________________________________
Male
Several days
0
1
More than half the days 2
Nearly every day 3
#ONSIDER -AJOR $EPRESSIVE $ISORDER
#ONSIDER /THER $EPRESSIVE $ISORDER
Over the last 2 weeks, how often have you been bothered by any of the following problems? Not at all
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
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
FOR HEALTHCARE PROFESSIONAL USE ONLY
9. Thoughts that you would be better off dead, or of hurting yourself in some way
If you checked “several days” or higher for some of the questions above, discuss your answers with a doctor. Only a doctor can make a diagnosis of depression. Also talk to your doctor if you checked “several days” or higher for (9), thinking that you would be better off dead or wanting to hurt yourself. Having repeated thoughts of death or suicide is the most serious symptom of depression. If you are thinking of harming yourself, get help immediately; make your feelings known to someone who can help you—your doctor, family members, friends. Your doctor is an excellent person to tell. KEY (for physician’s use): MDD if answer to # 1 or 2 and 5 or more of # 1-9 are at least “More than half the days” (count # 9 if present at all). All rights reserved.
6. Feeling bad about yourself, or that you are a failure, or have let yourself or your family down
© 2005 Pfizer Inc.
5. Poor appetite or overeating
ZT254386G
Printed in USA/September 2005
Copyright © Pfizer Inc. All rights reserved. Reproduced with permission of Pfizer, Inc. The PHQ-9 questionnaire can be accessed at www.phqscreeners.com.
rates of death.7 Depressive episodes associated with manic episodes are classified as bipolar disorder.
History and Physical Examination When taking the medical history, it is important to identify the severity and duration of the symptoms and any previous episodes, because depression tends to be recurrent. One should determine whether there is a family history of depression or other psychiatric illness— both major depression and bipolar disorder are heritable conditions. Recognition of manic or psychotic symptoms may identify patients who may require earlier referral to a psychiatrist. A history of suicidal thoughts, plans, or actions must be ascertained and again may identify patients who need more urgent referral. Although the physical examination is fairly insensitive for identifying depression, a thorough physical examination is important to identify contributing or causal ill-
46
AMERICAN HEALTH & DRUG BENEFITS
April 2008
nesses, such as chronic liver or renal disease, endocrine disease (hypothyroidism or adrenal insufficiency), congestive heart failure, dementia, or other conditions. In primary care settings, the point prevalence of major depression ranges from 5% to 9% among adults, and up to 50% of depressed patients are not recognized.8 The related conditions of dysthymia (a chronic low-grade depression) and minor depression are as common as major depression in primary care settings. Depressive disorders are estimated to affect from 0.8% to 2.0% of children and 4.5% of adolescents.9 Some of the barriers that may contribute to these percentages include: • Inadequate knowledge of diagnostic criteria • Competing priorities and comorbid conditions • Time limitations • Stigma associated with “labeling” a patient as depressed • Poor reimbursement mechanisms.
CLINICAL
Because of these barriers, a number of case-finding instruments have been developed and validated, including the Beck Depression Inventory, the Center for Epidemiological Studies-Depression Scale, the Zung Self-Assessment Depression Scale, the General Health Questionnaire, and the Hopkins Symptom Checklist, among others.9 Recently, 2 related tools are increasingly being used to screen and diagnose depression. The Patient Health Questionnaire (PHQ)-2 is an abbreviated version, consisting of the anhedonia and mood items of the PHQ-9. The PHQ2 can be used as a very brief and quick depression-screening tool in primary care. In primary care patients, a PHQ2 score of 3 or more has 83% sensitivity and 92% specificity for identifying patients with major depression.10 If the PHQ-2 is positive, screening may be confirmed by completing all the questions on the PHQ-9 (Figure). The PHQ-9 can be used as a screening tool, with summed score ranging from 0 (no depressive symptoms) to 27 (all symptoms occurring daily). A PHQ-9 score of 10 or more has been found to have 88% sensitivity and 88% specificity for a diagnosis of major depression.10 The PHQ-9 can also be used as a diagnostic assessment; with major depression diagnosed if 5 or more of the 9 symptoms have been present at least more than half the days of the past 2 weeks and 1 of these symptoms is either depressed mood or anhedonia.
Drug Therapy Untreated depression is associated with increased deaths, adverse outcomes, deficits in function, increased use of health services, poor on-the-job performance, and increased absenteeism. Treatments most frequently used by primary care physicians are (1) medications and (2) psychotherapy in cooperation with a psychologist, psychiatrist, or therapist. More than half of depressed patients respond to initial treatment with medications. Medication options are numerous (Table 2), and treatment recommendations should be tailored to the individual patient on the basis of the symptom profile, side effects of the drugs, comorbid conditions, and previous responses to treatment if available. Most drugs focus on serotonin and norepinephrine levels in the brain, supported by the major theory of depression known as the monoamine-deficiency hypothesis. The biochemical basis for this hypothesis and numerous other theories have been recently reviewed elsewhere.11 Several classes of drugs have been found effective in treating depression, through increasing the concentrations of the neurotransmitters serotonin and norepinephrine in the postsynaptic cleft of neurons in the cen-
tral nervous system. These agents include selective serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors (NRIs), and dual-action agents that inhibit the reuptake of serotonin and norepinephrine. Monoamine oxidase inhibitors (MAOIs) increase concentrations of neurotransmitters by inhibiting their degradation. Other agents increase the availability of neurotransmitters by blocking alpha-adrenergic autoreceptors, as well as serotonin (5-HT)2a reuptake and 5HT3 receptors, and histamine H1 receptors. Mood stabilizers, such as lithium, and anticonvulsants, such as lamotrigine, valproic acid, divalproex, or carbamazepine, may play an adjunctive role to antidepressants in the treatment of bipolar disorder. Antipsychotics and atypical antipsychotics may play a role in treating depression with psychotic features, as well as resistant major depression and bipolar depression.12 However, patients with these conditions may be more appropriately managed in conjunction with a psychiatrist. There are 3 phases in the treatment of depression— the acute phase, the continuation phase, and the maintenance phase. During the acute phase, treatment should be initiated and follow-up scheduled at 1- to 2week intervals to ensure a response. If a certain medication has worked previously for a patient or a family member, this may be an appropriate first choice. Antidepressants are started at low doses and titrated upward at appropriate time intervals based on response and side effects. If a patient’s response to a drug is inadequate at appropriate treatment doses, a change to a medication in the same or another class may be appropriate (patients who do not respond to one SSRI may respond to another agent within the class). Once an adequate response has been achieved in the acute phase, the continuation phase begins and can last as long as 9 months from remission. During this phase, treatment goals are to eliminate residual symptoms, to restore previous level of functioning, and to prevent recurrence or relapse. If there is no recurrence of symptoms during the first 6 months of treatment, a consideration to wean the medication and assess for the possibility of “early discontinuation” may be reasonable. If symptoms return, the medication should be re-titrated upwards to an effective dose and maintained for an additional 3 to 6 months. Early discontinuation does have a higher rate of relapse.12 Discontinuation in itself may produce symptoms (“discontinuation syndrome”), including balance problems, gastrointestinal upset, myalgias, weakness, sensory and sleep disturbances, anxiety, agitation, and emotional volatility. A maintenance phase treatment for 12 to 36 months may be indicated for patients with recurrent episodes of
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47
CLINICAL
Table 2 Antidepressants: Dosing, Indications, and Off-Label Use Maintenance dosage
Indications
Off-label use
Side effects (>10%)
Contraindications
Y
40 mg/d
MDD
Somnolence, insomnia, nausea, xerostomia, diaphoresis
Lexapro (escitalopram) Luvox (fluvoxamine) Luvox CR
N
10 mg/d
MDD, GAD
Y
100 mg bid
OCD
Alcoholism, coronary arteriosclerotic depression, OCD, panic disorder, PMDD, tension-type headache Mixed anxiety and depressive disorder, panic disorder Autism, depression, eating disorder, panic disorder
Y
100 mg/d
Paxil (paroxetine)
Y
20 mg/d
Paxil CR
N
25 mg/d
Pexeva (paroxetine) Prozac (fluoxetine)
N
30 mg/d
Y
20 mg/d
Prozac Weekly
N
90 mg/wk
OCD, Social anxiety disorder GAD, MDD, OCD, panic disorder, PTSD, social anxiety disorder MDD, panic disorder, PMDD, social anxiety disorder MDD, OCD, panic disorder, GAD Bulimia nervosa, MDD, OCD, panic disorder MDD
Headache, somnolence, insomnia, nausea, ejaculation disorder Headache, somnolence, insomnia, nausea, nervousness, dizziness, diarrhea, xerostomia, weakness
Sarafem (fluoxetine) Zoloft (sertraline)
N
20 mg/d
PMDD
Y
50 mg/d
MDD, OCD, panic disorder, PTSD, PMDD, social phobia
Alzheimer's depression, post-MI depression, dysthymia, night-eating syndrome
Dizziness, fatigue, headache, insomnia, somnolence, decreased libido, anorexia, diarrhea, nausea, xerostomia, ejaculatory disturbances, tremors, diaphoresis
N
60 mg/d
Diabetic neuropathy, GAD, MDD
Fibromyalgia, urinary incontinence
Y
37.5 mg bid
MDD
Hot sweats, OCD, PMDD
N
75 mg/d
N
50 mg/d
MDD, GAD, social anxiety disorder, panic disorder MDD
Y
100 mg 3 times daily 150 mg bid 300 mg/d
MDD
Y
25 mg 3 times daily
OCD
Asendin (amoxapine)
Y
150 mg/d
Elavil (amitriptyline)
Y
50 mg/d
MDD, endogenous depression, severe major depression with psychosis MDD
Norpramin (desipramine)
Y
100 mg/d
MDD
Pamelor (nortriptyline)
Y
25 mg 3 times daily
MDD
Class/Drug brand name (nonproprietary name) Selective Serotonin Reuptake Inhibitors Celexa (citalopram)
Mixed/Dual Cymbalta (duloxetine) Effexor (venlafaxine) Effexor XR
Pristiq (desvenlafaxine) Wellbutrin (bupropion) Wellbutrin SR Wellbutrin XL Tricyclics Anafranil (clomipramine)
48
Generic available?
Y Y*
Compulsive gambling, drug-induced depression, hot sweats, premature ejaculation
Body dysmorphic disorder, cancerdepression, DM-depression, dysthymia, fibromyalgia, hot sweats, PTSD, Raynaud's
Chronic pain, delusional disorder, MDD, ejaculatory disorder, panic disorder, pervasive development disorder
Headache (treatment/prophylaxis), pain, polyneuropathy, postherpetic neuralgia ADHD, diabetic neuropathy
ADHD, neurogenic bladder, nicotine dependence, nocturnal enuresis, postherpetic neuralgia
AMERICAN HEALTH & DRUG BENEFITS
April 2008
Somnolence, insomnia, headache, dizziness, decreased libido, nausea, xerostomia, constipation, diarrhea, weakness, ejaculatory disturbances, diaphoresis
Insomnia, headache, anxiety, nervousness, somnolence, decreased libido, nausea, diarrhea, anorexia, xerostomia, weakness, tremor, pharyngitis, yawning
Market share, %
Cost of 30-day supply
Concomitant use of MAOI + pimozide
8.29
$$
Concomitant use of MAOI + pimozide Concomitant use w/ alosetron, pimozide, thioridazine, tizanidine, MAOI Concomitant use of linezolid, MAOI, pimozide, thioridazine
13.78
($$$) $$$$
