- Email: [email protected]
Assessing and Treating Depression in Primary Care Medicine
The American Journal of Medicine (2007) 120, 105-108
REVIEW
Assessing and Treating Depression in Primary Care Medicine Alan J. Gelenberg, MD, Heather S. Hopkins, MA Department of Psychiatry, University of Arizona, Tucson. ABSTRACT Depression, a common and disabling condition, is often misunderstood by patients, family members, and clinicians. It is frequently underdiagnosed and untreated or inadequately treated. Criteria for major depressive disorder are listed in the DSM-IV-TR, but even less severe depression may merit intervention— especially if chronic. Our understanding of the etiology of depression is rudimentary, but it may involve multiple genes combined with negative life experiences. A variety of pharmacologic and psychosocial treatments are available for treating depression. Most patients who are well treated can be relieved of symptoms and return to full function. © 2007 Elsevier Inc. All rights reserved. KEYWORDS:
Depression; Antidepressants; Bipolar disorder; Mania; Selective serotonin reuptake inhibitors;
Psychotherapy
The word “depression” has been used so often in American English that it is frequently trivialized. Due in part to the stigma often attached to psychiatric symptoms, there is much misunderstanding about depression—as a symptom and a diagnosis. Patients and family members may mean different things when they use the word depression, and clinicians can find themselves using the same word but lacking a common understanding. Depression is a pathological and pervasive state of mood. A depressed individual sees everything—self, world, and future—through a dark prism. Feelings of helplessness, hopelessness, and worthlessness are common. Depression is not sadness. Patients who recover from depression often report being relieved to feel normal sadness again. Sadness has a cause, is finite, and does not reflect a personal lack of worth the way depression does. Many depressed patients find that their ability to feel sadness or other emotions is deadened. Grief that follows loss tends to be proportional in magnitude and duration to what was lost (eg, a loved one, a pet, a home, a dream). Grief does not usually darken one’s sense
Reprint requests should be addressed to Heather S. Hopkins, 350 N. Harrison Rd. #5205, Tucson, AZ 85748. E-mail address: [email protected]
0002-9343/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.05.059
of self, nor does it typically present with a full constellation of symptoms of depression (Table 1). The lifetime risk of developing major depressive disorder is 16.2% in the United States.1 Recurrence is the rule, and about one third of patients go on to develop chronic depression.2,3 Depression is one of the top worldwide causes of disability.4,5 It also increases mortality because it worsens many medical conditions (eg, cardiovascular disease, diabetes) and causes suicide.6,7 Depressed patients are high utilizers of health care generally and typically perform poorly in the workplace.
SYMPTOMS A number of symptom domains— emotional, somatic, and behavioral—form the constellation of depression. Not all patients experience all symptoms. The effect of depression on some domains can be either an increase or a decrease. For example, appetite (and often body weight) may be elevated or diminished, and either insomnia (of several different patterns) or hypersomnia can occur. The magnitude of symptoms also can vary from patient to patient and over time within a given case. Suffering and disability usually correlate with the severity of symptoms. Official psychiatric diagnostic terminology follows the Diagnostic and Statistical Manual of Mental Disorders
106
The American Journal of Medicine, Vol 120, No 2, February 2007
(most recently, 4th edition, text revision) of the American alcohol often cause depression, either during acute or Psychiatric Association (DSM-IV-TR).8 The major sympchronic intoxication or during withdrawal. In fact, deprestoms of depression are summarized in Table 1.9 For comsion is common in people with substance abuse and, conplete diagnostic criteria consult the DSM-IV-TR. Depression versely, people with longstanding mood disorders frethat lasts less than the threshold criterion of 2 weeks often quently abuse drugs or alcohol. will be transitory. However, if Many neurologic disorders symptoms are severe or lifecause or present as depression. threatening, clinical intervention Depression may be an early or CLINICAL SIGNIFICANCE may be required. Depression that late symptom in Alzheimer’s fails to meet all the criteria of disease and other dementias and ● Depression is one of the top worldwide DSM-IV-TR may still be clinically is a common accompaniment of causes of disability. significant and could require clinstroke and many deteriorating ● Depressed patients are high utilizers of ical intervention, particularly if it brain conditions, including mulhealth care generally and typically perhas persisted for months or years. tiple sclerosis. Nutritional defiEven low-grade chronic depresciencies sometimes present as form poorly in the workplace. sion can take a substantial toll on depression. ● The lifetime risk of developing major dehealth and functioning.10 There is no laboratory test to pressive disorder is 16.2% in the United rule in depression, but the laboStates. ratory can rule out other causes ETIOLOGY of depressive symptoms. The ● About one-third of patients go on to Psychiatry today no longer distinchoice of laboratory tests should develop chronic depression, but a majorguishes between “endogenous” and be tailored to each individual ity of depressed patients improve “reactive” depression. Whether or case, based on a medical history not the patient or clinician can identhrough the selective use of medication and review of systems. tify apparent precipitants does not and psychotherapy. Optimal relief of seem to bear on the need for or symptoms can allow return to full funcMANAGEMENT probable response to treatment. tion. The risk of relapse, however, reScientists are following many With medical causes excluded, the mains high. different avenues to try to underphysician must attend to several ● Most cases of depression can be treated stand the neurobiology of depresspecial circumstances that will afsion. Still, today’s knowledge refect management. Most depressed successfully by primary care physicians. mains rudimentary. Most likely, people at least consider suicide multiple genes (and their expresand should be specifically asked sion) play a role in an individual’s about it. If a patient has a plan and vulnerability to become depressed. (Some fortunate people the means to carry it out, urgent and immediate referral for presumably have the reciprocal genetic advantage of unpsychiatric assessment and probably hospitalization is reusual resilience under circumstances of great stress and quired. Agitated or highly anxious patients, as well as the provocation.) Negative life experiences may leave traces on elderly and those lacking social support, are at higher risk to the brain that adversely affect future responses to life circommit suicide. Ask about a history of suicide attempts. cumstances and the probability of developing anxiety and People who have made serious suicide attempts in the past depression. Preliminary research suggests that some genetic are at increased risk to complete suicide. alleles and early life experiences might predict the likeliPatients with delusions, hallucinations, or other bizarre hood of responding to antidepressant medication or specific or psychotic symptoms require different biological treatforms of psychotherapy to treat depression. ment and should be referred to a psychiatrist. Psychotic patients are more likely to harm themselves. Rarely, they can place others at risk. Immediate hospitalization is usually DIAGNOSIS required. Some patients complain to their doctors that they feel deAlways ask a depressed patient about a past history of pressed. In other cases, a family member will voice this hypomania or mania (Table 2), as this defines bipolar disconcern. Some people do not like to use the word depression order and requires different management. These patients or any psychological terms. Instead, fatigue or other physshould be referred to a psychiatrist. A family history of ical symptoms may be their presenting complaints. bipolar disorder should lead to consideration of this A medical work-up for depression requires the same diagnosis. differential diagnosis of any nonspecific symptom. Many toxic, metabolic, and neurologic abnormalities can present as depression. For example, thyroid dysfunction and other hormonal abnormalities commonly affect mood. A number of toxic substances can lead to depression. Drug abuse and
TREATMENT Absent one of the considerations outlined above, the next step in managing a case of uncomplicated major depression
Gelenberg and Hopkins Table 1
Assessing and Treating Depression
Symptoms of Depression
Persistent sad, anxious, or “empty” mood Feelings of hopelessness, pessimism Feelings of guilt, worthlessness, helplessness Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex Decreased energy, fatigue, being “slowed down” Difficulty concentrating, remembering, making decisions Insomnia, early-morning awakening, or oversleeping Appetite and/or weight loss or overeating and weight gain Thoughts of death or suicide; suicide attempts Restlessness, irritability Persisent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain. Source: National Institutes of Mental Health, http://www.nimh. nih.gov/publicat/depression.cfm#ptdep1
is treatment. For nonpsychotic depression of mild to moderate severity, either psychotherapy or antidepressant medication is a reasonable option. Patient preference, availability of psychotherapy, and cost will usually drive the decision. The combination of psychotherapy and an antidepressant may be superior in outcome than either alone, but this is obviously more costly and time consuming.11 Several forms of psychotherapy (most notably cognitive behavioral therapy and interpersonal psychotherapy) have been demonstrated efficacious in randomized clinical trials.12 In many geographical areas, there is a dearth of therapists skilled in these approaches. If a patient prefers psychotherapy but the physician does not have access to a psychotherapist skilled in one of these techniques, the patient may be referred to any psychotherapist with a good background, credentials, and references. When a patient is referred for psychotherapy, marked clinical improvement should be expected within 2 to 3 months. Failing that, an alternate approach, such as pharmacotherapy, should be entertained. It is reasonable for a primary care internist to prescribe an antidepressant for a patient with uncomplicated nonpsychotic major depression of mild to moderate severity. The most widely prescribed first-line antidepressants are the selective serotonin reuptake inhibitors (SSRIs; see Table 3). Table 2
Symptoms of Mania Abnormal or excessive elation Unusual irritability Decreased need for sleep Grandiose notions Increased talking Racing thoughts Increased sexual desire Markedly increased energy Poor judgement Inappropriate social behavior
Source: National Institutes of Mental Health, http://www.nimh. nih.gov/publicat/depression.cfm#ptdep1
107 Table 3 Selective Serotonin Reuptake Inhibitors (SSRIs) Labeled for the Treatment of Major Depression Agent
Dosing Range
Citalopram (Celexa and others) Escitalopram (Lexapro) Fluoxetine (Prozac and others) Paroxetine (Paxil and others) Sertraline (Zoloft and others)
20 10 20 20 50
to to to to to
40 mg/day 20 mg/day 80 mg/day 50 mg/day 200 mg/day
When an antidepressant is prescribed, the patient needs to learn in advance about the most common side effects and that these medicines typically take several weeks to begin working. Someone should be available to answer questions within the first few days a patient is taking medication (usually about side effects), and the patient should be seen in follow-up by the physician or an extender within 1 to 2 weeks. Failure to provide information and follow-up may result in early discontinuation of the medicine. Based on a patient’s tolerance and clinical response over the early weeks of treatment, dose adjustment may be required. Expect to see at least the beginnings of clinical improvement by 2 weeks of treatment at a therapeutic dose. Often a family member may spot improvement before the patient becomes aware of it. There is roughly a 60% to 70% chance of a good response to a first antidepressant. The goal of treatment is remission, which is the virtual reversal of all symptoms of depression. Once a patient is in remission, continuation therapy after a single episode of depression is recommended for 6 to 12 months. After 2 or 3 episodes of depression, lifelong maintenance treatment is in order. If a patient fails to respond satisfactorily to a first antidepressant, the likelihood of response to a second is about 50%. Most experts recommend choosing an antidepressant from a different category (Table 4).
Table 4
Non-SSRI Antidepressants
Agent Tricyclic antidepressants* Imipramine (Tofranil) Trimipramine (Surmontil)
Dosing Range 75 to 300 mg/day 50 to 150 mg/day for outpatients 100 to 300 mg/day for inpatients
Monoamine oxidase inhibitors (MAOIs) Isocarboxazid (Marplan) 20 to 30 mg/day Phenelzine (Nardil) 45 to 90 mg/day Tranylcypromine (Parnate) 30 to 60 mg/day Other Bupropion (Wellbutrin and others) 200 to 450 mg/day Mirtazapine (Remeron) 7.5 to 45 mg/day Nefazodone 50 to 400 mg/day Venlafaxine (Effexor) 75 to 375 mg/day *These are examples. There are at least 6 tricyclic antidepressants currently available.
108
The American Journal of Medicine, Vol 120, No 2, February 2007
SSRIs tend to be remarkably well tolerated. Nausea and headache are usually mild and transitory, and can be managed by a temporary dose reduction or taking the medicine with food. Sexual dysfunction (most commonly, decreased libido and difficulty achieving orgasm) is unfortunately common and tends to persist. Some patients experience weight gain over time. SSRIs have a benign cardiac profile and may actually improve longterm outcome following a myocardial infarction. They do increase the risk of bleeding and in elderly patients can cause the syndrome of inappropriate antidiuretic hormone and hyponatremia. Many different agents are recommended and prescribed as adjuncts to antidepressants. It is probably best to refer treatment-resistant depressed patients to psychiatrists. Patients with severe, psychotic, or treatment-refractory depression are often candidates for electroconvulsive therapy (ECT). Vagus nerve stimulation, which requires surgical implantation of an electrical stimulator, was recently approved for the treatment of refractory depression. Patients to be considered for either of these approaches should be referred for psychiatric evaluation. Depression is common, disabling, costly, and often deadly. Treating it, on the other hand, can be most gratifying. A majority of depressed patients recover through the selective use of medication and psychotherapy, and can be relieved of symptoms and return to full function. Most cases of depression can be treated successfully by primary care physicians. The most important guidelines are attention to differential diagnosis, knowledgeable use of medications, and active communication with patients and family members.
References 1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105. 2. Judd LL, Akiskal HS, Maser JD, et al. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998;55:694-700. 3. Keller MB, Lavori PW, Rice J, Coryell W, Hirschfeld RM. The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up. Am J Psychiatry. 1986; 143:24-28. ¨ stün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. 4. U Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184:386-392. 5. Bloom BS. Prevalence and economic effects of depression. Manag Care. 2004;(6 suppl Depression)13:9-16. 6. Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002; 68:167-181. 7. Stark C, Hall D, O’Brien F, Smith H. Suicide after discharge from psychiatric hospitals in Scotland. BMJ. 1995;311:1368-1369. 8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. Arlington, VA: American Psychiatric Association; 2000. 9. National Institute of Mental Health. Depression: Symptoms of Depression and Mania. Bethesda (MD): National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services; 2000. Available at http://www.nimh.nih.gov/publicat/ depression.cfm#ptdep1. Accessed January 8, 2007. 10. Judd LL, Paulus MP, Wells KB, Rapaport MH. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996;153:1411-1417. 11. Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C. Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry. 2004;61:714-719. 12. DeRubeis RJ, Gelfand LA, Tang TZ, Simons AD. Medications versus cognitive behavior therapy for severely depressed outpatients: megaanalysis of four randomized comparisons. Am J Psychiatry. 1999;156: 1007-1013.
REVIEW
Assessing and Treating Depression in Primary Care Medicine Alan J. Gelenberg, MD, Heather S. Hopkins, MA Department of Psychiatry, University of Arizona, Tucson. ABSTRACT Depression, a common and disabling condition, is often misunderstood by patients, family members, and clinicians. It is frequently underdiagnosed and untreated or inadequately treated. Criteria for major depressive disorder are listed in the DSM-IV-TR, but even less severe depression may merit intervention— especially if chronic. Our understanding of the etiology of depression is rudimentary, but it may involve multiple genes combined with negative life experiences. A variety of pharmacologic and psychosocial treatments are available for treating depression. Most patients who are well treated can be relieved of symptoms and return to full function. © 2007 Elsevier Inc. All rights reserved. KEYWORDS:
Depression; Antidepressants; Bipolar disorder; Mania; Selective serotonin reuptake inhibitors;
Psychotherapy
The word “depression” has been used so often in American English that it is frequently trivialized. Due in part to the stigma often attached to psychiatric symptoms, there is much misunderstanding about depression—as a symptom and a diagnosis. Patients and family members may mean different things when they use the word depression, and clinicians can find themselves using the same word but lacking a common understanding. Depression is a pathological and pervasive state of mood. A depressed individual sees everything—self, world, and future—through a dark prism. Feelings of helplessness, hopelessness, and worthlessness are common. Depression is not sadness. Patients who recover from depression often report being relieved to feel normal sadness again. Sadness has a cause, is finite, and does not reflect a personal lack of worth the way depression does. Many depressed patients find that their ability to feel sadness or other emotions is deadened. Grief that follows loss tends to be proportional in magnitude and duration to what was lost (eg, a loved one, a pet, a home, a dream). Grief does not usually darken one’s sense
Reprint requests should be addressed to Heather S. Hopkins, 350 N. Harrison Rd. #5205, Tucson, AZ 85748. E-mail address: [email protected]
0002-9343/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.05.059
of self, nor does it typically present with a full constellation of symptoms of depression (Table 1). The lifetime risk of developing major depressive disorder is 16.2% in the United States.1 Recurrence is the rule, and about one third of patients go on to develop chronic depression.2,3 Depression is one of the top worldwide causes of disability.4,5 It also increases mortality because it worsens many medical conditions (eg, cardiovascular disease, diabetes) and causes suicide.6,7 Depressed patients are high utilizers of health care generally and typically perform poorly in the workplace.
SYMPTOMS A number of symptom domains— emotional, somatic, and behavioral—form the constellation of depression. Not all patients experience all symptoms. The effect of depression on some domains can be either an increase or a decrease. For example, appetite (and often body weight) may be elevated or diminished, and either insomnia (of several different patterns) or hypersomnia can occur. The magnitude of symptoms also can vary from patient to patient and over time within a given case. Suffering and disability usually correlate with the severity of symptoms. Official psychiatric diagnostic terminology follows the Diagnostic and Statistical Manual of Mental Disorders
106
The American Journal of Medicine, Vol 120, No 2, February 2007
(most recently, 4th edition, text revision) of the American alcohol often cause depression, either during acute or Psychiatric Association (DSM-IV-TR).8 The major sympchronic intoxication or during withdrawal. In fact, deprestoms of depression are summarized in Table 1.9 For comsion is common in people with substance abuse and, conplete diagnostic criteria consult the DSM-IV-TR. Depression versely, people with longstanding mood disorders frethat lasts less than the threshold criterion of 2 weeks often quently abuse drugs or alcohol. will be transitory. However, if Many neurologic disorders symptoms are severe or lifecause or present as depression. threatening, clinical intervention Depression may be an early or CLINICAL SIGNIFICANCE may be required. Depression that late symptom in Alzheimer’s fails to meet all the criteria of disease and other dementias and ● Depression is one of the top worldwide DSM-IV-TR may still be clinically is a common accompaniment of causes of disability. significant and could require clinstroke and many deteriorating ● Depressed patients are high utilizers of ical intervention, particularly if it brain conditions, including mulhealth care generally and typically perhas persisted for months or years. tiple sclerosis. Nutritional defiEven low-grade chronic depresciencies sometimes present as form poorly in the workplace. sion can take a substantial toll on depression. ● The lifetime risk of developing major dehealth and functioning.10 There is no laboratory test to pressive disorder is 16.2% in the United rule in depression, but the laboStates. ratory can rule out other causes ETIOLOGY of depressive symptoms. The ● About one-third of patients go on to Psychiatry today no longer distinchoice of laboratory tests should develop chronic depression, but a majorguishes between “endogenous” and be tailored to each individual ity of depressed patients improve “reactive” depression. Whether or case, based on a medical history not the patient or clinician can identhrough the selective use of medication and review of systems. tify apparent precipitants does not and psychotherapy. Optimal relief of seem to bear on the need for or symptoms can allow return to full funcMANAGEMENT probable response to treatment. tion. The risk of relapse, however, reScientists are following many With medical causes excluded, the mains high. different avenues to try to underphysician must attend to several ● Most cases of depression can be treated stand the neurobiology of depresspecial circumstances that will afsion. Still, today’s knowledge refect management. Most depressed successfully by primary care physicians. mains rudimentary. Most likely, people at least consider suicide multiple genes (and their expresand should be specifically asked sion) play a role in an individual’s about it. If a patient has a plan and vulnerability to become depressed. (Some fortunate people the means to carry it out, urgent and immediate referral for presumably have the reciprocal genetic advantage of unpsychiatric assessment and probably hospitalization is reusual resilience under circumstances of great stress and quired. Agitated or highly anxious patients, as well as the provocation.) Negative life experiences may leave traces on elderly and those lacking social support, are at higher risk to the brain that adversely affect future responses to life circommit suicide. Ask about a history of suicide attempts. cumstances and the probability of developing anxiety and People who have made serious suicide attempts in the past depression. Preliminary research suggests that some genetic are at increased risk to complete suicide. alleles and early life experiences might predict the likeliPatients with delusions, hallucinations, or other bizarre hood of responding to antidepressant medication or specific or psychotic symptoms require different biological treatforms of psychotherapy to treat depression. ment and should be referred to a psychiatrist. Psychotic patients are more likely to harm themselves. Rarely, they can place others at risk. Immediate hospitalization is usually DIAGNOSIS required. Some patients complain to their doctors that they feel deAlways ask a depressed patient about a past history of pressed. In other cases, a family member will voice this hypomania or mania (Table 2), as this defines bipolar disconcern. Some people do not like to use the word depression order and requires different management. These patients or any psychological terms. Instead, fatigue or other physshould be referred to a psychiatrist. A family history of ical symptoms may be their presenting complaints. bipolar disorder should lead to consideration of this A medical work-up for depression requires the same diagnosis. differential diagnosis of any nonspecific symptom. Many toxic, metabolic, and neurologic abnormalities can present as depression. For example, thyroid dysfunction and other hormonal abnormalities commonly affect mood. A number of toxic substances can lead to depression. Drug abuse and
TREATMENT Absent one of the considerations outlined above, the next step in managing a case of uncomplicated major depression
Gelenberg and Hopkins Table 1
Assessing and Treating Depression
Symptoms of Depression
Persistent sad, anxious, or “empty” mood Feelings of hopelessness, pessimism Feelings of guilt, worthlessness, helplessness Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex Decreased energy, fatigue, being “slowed down” Difficulty concentrating, remembering, making decisions Insomnia, early-morning awakening, or oversleeping Appetite and/or weight loss or overeating and weight gain Thoughts of death or suicide; suicide attempts Restlessness, irritability Persisent physical symptoms that do not respond to treatment, such as headaches, digestive disorders, and chronic pain. Source: National Institutes of Mental Health, http://www.nimh. nih.gov/publicat/depression.cfm#ptdep1
is treatment. For nonpsychotic depression of mild to moderate severity, either psychotherapy or antidepressant medication is a reasonable option. Patient preference, availability of psychotherapy, and cost will usually drive the decision. The combination of psychotherapy and an antidepressant may be superior in outcome than either alone, but this is obviously more costly and time consuming.11 Several forms of psychotherapy (most notably cognitive behavioral therapy and interpersonal psychotherapy) have been demonstrated efficacious in randomized clinical trials.12 In many geographical areas, there is a dearth of therapists skilled in these approaches. If a patient prefers psychotherapy but the physician does not have access to a psychotherapist skilled in one of these techniques, the patient may be referred to any psychotherapist with a good background, credentials, and references. When a patient is referred for psychotherapy, marked clinical improvement should be expected within 2 to 3 months. Failing that, an alternate approach, such as pharmacotherapy, should be entertained. It is reasonable for a primary care internist to prescribe an antidepressant for a patient with uncomplicated nonpsychotic major depression of mild to moderate severity. The most widely prescribed first-line antidepressants are the selective serotonin reuptake inhibitors (SSRIs; see Table 3). Table 2
Symptoms of Mania Abnormal or excessive elation Unusual irritability Decreased need for sleep Grandiose notions Increased talking Racing thoughts Increased sexual desire Markedly increased energy Poor judgement Inappropriate social behavior
Source: National Institutes of Mental Health, http://www.nimh. nih.gov/publicat/depression.cfm#ptdep1
107 Table 3 Selective Serotonin Reuptake Inhibitors (SSRIs) Labeled for the Treatment of Major Depression Agent
Dosing Range
Citalopram (Celexa and others) Escitalopram (Lexapro) Fluoxetine (Prozac and others) Paroxetine (Paxil and others) Sertraline (Zoloft and others)
20 10 20 20 50
to to to to to
40 mg/day 20 mg/day 80 mg/day 50 mg/day 200 mg/day
When an antidepressant is prescribed, the patient needs to learn in advance about the most common side effects and that these medicines typically take several weeks to begin working. Someone should be available to answer questions within the first few days a patient is taking medication (usually about side effects), and the patient should be seen in follow-up by the physician or an extender within 1 to 2 weeks. Failure to provide information and follow-up may result in early discontinuation of the medicine. Based on a patient’s tolerance and clinical response over the early weeks of treatment, dose adjustment may be required. Expect to see at least the beginnings of clinical improvement by 2 weeks of treatment at a therapeutic dose. Often a family member may spot improvement before the patient becomes aware of it. There is roughly a 60% to 70% chance of a good response to a first antidepressant. The goal of treatment is remission, which is the virtual reversal of all symptoms of depression. Once a patient is in remission, continuation therapy after a single episode of depression is recommended for 6 to 12 months. After 2 or 3 episodes of depression, lifelong maintenance treatment is in order. If a patient fails to respond satisfactorily to a first antidepressant, the likelihood of response to a second is about 50%. Most experts recommend choosing an antidepressant from a different category (Table 4).
Table 4
Non-SSRI Antidepressants
Agent Tricyclic antidepressants* Imipramine (Tofranil) Trimipramine (Surmontil)
Dosing Range 75 to 300 mg/day 50 to 150 mg/day for outpatients 100 to 300 mg/day for inpatients
Monoamine oxidase inhibitors (MAOIs) Isocarboxazid (Marplan) 20 to 30 mg/day Phenelzine (Nardil) 45 to 90 mg/day Tranylcypromine (Parnate) 30 to 60 mg/day Other Bupropion (Wellbutrin and others) 200 to 450 mg/day Mirtazapine (Remeron) 7.5 to 45 mg/day Nefazodone 50 to 400 mg/day Venlafaxine (Effexor) 75 to 375 mg/day *These are examples. There are at least 6 tricyclic antidepressants currently available.
108
The American Journal of Medicine, Vol 120, No 2, February 2007
SSRIs tend to be remarkably well tolerated. Nausea and headache are usually mild and transitory, and can be managed by a temporary dose reduction or taking the medicine with food. Sexual dysfunction (most commonly, decreased libido and difficulty achieving orgasm) is unfortunately common and tends to persist. Some patients experience weight gain over time. SSRIs have a benign cardiac profile and may actually improve longterm outcome following a myocardial infarction. They do increase the risk of bleeding and in elderly patients can cause the syndrome of inappropriate antidiuretic hormone and hyponatremia. Many different agents are recommended and prescribed as adjuncts to antidepressants. It is probably best to refer treatment-resistant depressed patients to psychiatrists. Patients with severe, psychotic, or treatment-refractory depression are often candidates for electroconvulsive therapy (ECT). Vagus nerve stimulation, which requires surgical implantation of an electrical stimulator, was recently approved for the treatment of refractory depression. Patients to be considered for either of these approaches should be referred for psychiatric evaluation. Depression is common, disabling, costly, and often deadly. Treating it, on the other hand, can be most gratifying. A majority of depressed patients recover through the selective use of medication and psychotherapy, and can be relieved of symptoms and return to full function. Most cases of depression can be treated successfully by primary care physicians. The most important guidelines are attention to differential diagnosis, knowledgeable use of medications, and active communication with patients and family members.
References 1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105. 2. Judd LL, Akiskal HS, Maser JD, et al. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998;55:694-700. 3. Keller MB, Lavori PW, Rice J, Coryell W, Hirschfeld RM. The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up. Am J Psychiatry. 1986; 143:24-28. ¨ stün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. 4. U Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184:386-392. 5. Bloom BS. Prevalence and economic effects of depression. Manag Care. 2004;(6 suppl Depression)13:9-16. 6. Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002; 68:167-181. 7. Stark C, Hall D, O’Brien F, Smith H. Suicide after discharge from psychiatric hospitals in Scotland. BMJ. 1995;311:1368-1369. 8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. Arlington, VA: American Psychiatric Association; 2000. 9. National Institute of Mental Health. Depression: Symptoms of Depression and Mania. Bethesda (MD): National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services; 2000. Available at http://www.nimh.nih.gov/publicat/ depression.cfm#ptdep1. Accessed January 8, 2007. 10. Judd LL, Paulus MP, Wells KB, Rapaport MH. Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996;153:1411-1417. 11. Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C. Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry. 2004;61:714-719. 12. DeRubeis RJ, Gelfand LA, Tang TZ, Simons AD. Medications versus cognitive behavior therapy for severely depressed outpatients: megaanalysis of four randomized comparisons. Am J Psychiatry. 1999;156: 1007-1013.