Diagnosing and Treating Depression: A Primer for Primary Care Physicians
Author: Alan J. Gelenberg, MD, Professor and Head, Department of Psychiatry, University of Arizona Health Sciences Center, Tucson, Ariz.
Peer Reviewer: Michael E. Thase, MD, Professor of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Penn.
Editor’s Note—Major depression is a common disorder, experienced by up to 19% of people at least once during their lives.1,2 Women are afflicted twice as often as men.3 The World Health Organization ranked depression fourth among worldwide illnesses in terms of disease burden in 1990, based on quality-adjusted life years, and projects that by the year 2020, it will rise to second place.4
Depression levies a heavy burden in terms of work and productivity. It impairs marriages and disrupts families. People with depression are more likely to become involved with alcohol and drugs. They have a much higher morbidity and mortality when they suffer concomitant medical disorders, including heart disease and diabetes.5,6 Without effective treatment, suicide is an eventual possibility and, among the most severely depressed, lifetime suicide rates may be as high as 15%.7
All of the above notwithstanding, depression tends to be underdiagnosed and, even when recognized, insufficiently treated.8-11 This is unfortunate, not only because of the burdens of the disease as noted above, but because depression usually is an eminently treatable disorder. This article will give a brief overview of depression and its manifestations, discuss why it frequently goes unrecognized and undertreated, examine the role of the primary care physician in managing depression, and describe principles of intervention.
Diagnosis and Differential Diagnosis
Almost everybody gets the blues—sometime. When someone experiences a disappointment or a loss, we expect them to be sad or to grieve. Whether experiencing the death of a loved one or facing an unpleasant medical diagnosis, people react with dysphoric emotions.
But grief and natural reactions to stress and loss are time-limited and "dynamic." In other words, the emotions change and evolve. The typical sufferer reaches out adaptively to others—for comfort and alternative ways to get his or her needs met. Even after a profound loss, such as the death of a spouse, the bereaved typically adjusts to the new circumstances and returns to some level of function, although experiencing a deep sense of inner loss and void. If the symptoms of depression still exist after two months, it is likely that bereavement has triggered major depression, which requires clinical attention. If the depressive symptoms associated with bereavement are particularly severe or disabling (including suicidality and psychosis), the diagnosis can be made without delay. In such circumstances, if depression is appropriately treated, the sufferer can return to the active process of grieving and moving on with his or her life.
The criteria for major depression are listed in Table 1. Clinical science has taught us that there is no magical threshold for clinically relevant depression. Any symptoms of depression that last for two weeks or longer (or even a shorter period if they are severe, dysfunctional, and/or life-threatening) are problematic and warrant clinical attention. Lower levels of depression, when ongoing, can increase mortality in the elderly6 and presumably cause loss of function and work productivity and impair family relations. In addition, patients with subthreshold depressive symptoms have a greater risk of developing a major depressive episode. Therefore, even low-grade depression should be monitored carefully.
| Table 1. Diagnostic Criteria-Major Depressive Episode40 | |
| At least five of the following symptoms have been present during the same two-week period and represent a change from previous functioning (at least 1 must be depressed mood or loss of interest or pleasure): | |
| • Depressed mood most of the day, nearly every day | |
| • Diminished interest or pleasure in activities most of the day, nearly every day | |
| • Poor appetite or weight loss or increased appetite or weight gain | |
| • Insomnia or hypersomnia | |
| • Loss of energy or fatigue | |
| • Psychomotor agitation or retardation | |
| • Feelings of worthlessness or excessive or inappropriate guilt | |
| • Diminished ability to think or concentrate, or indecisiveness | |
| • Recurrent thoughts of death or suicide | |
| The symptoms do not meet criteria for a mixed episode. | |
| The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. | |
| The symptoms are not due to the direct physiological effects of a substance or a general medical condition. | |
| The symptoms are not better accounted for by bereavement, and they persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. | |
Evaluation of depression, like the common syndromes of hypertension or arthritis, includes differential diagnostic considerations. It is unnecessary to list all possible medical, neurologic, and toxic causes of depression. Such a list would be unwieldy and doubtlessly incomplete. A clinician should consider any medical clue that might present in the course of a medical history and review of systems. If a medication was introduced (or deleted) within weeks of new-onset depressive symptoms, consider that drug a possible culprit. If there have been weight changes or altered bowel habits, consider that depression may be a symptom of cancer. If there are symptoms and signs of peripheral neuropathy, perhaps a vitamin deficiency could be a cause. Changes in skin and hair texture and temperature tolerance might indicate thyroid dysfunction. Headaches and visual changes could signal a space-occupying brain lesion. These are just examples but indicate the importance of taking a history and review of systems.
Ask about drug and alcohol abuse. Virtually all patients who abuse substances develop mood symptoms. But people with primary depression are also more likely to abuse drugs and alcohol. When in doubt which is the primary disorder, try to get a good longitudinal history from a family member. Modern antidepressant drugs are safe and will not complicate the recovery from substance abuse—even if the "chicken-and-egg dilemma" remains murky. But antidepressants alone usually will not help the substance abuser become abstinent; that requires ongoing rehabilitative treatment aimed toward achieving and maintaining abstinence.
When to Seek a Consultation or Referral
A primary care physician (PCP) should be able to diagnose and treat uncomplicated depression—major or subsyndromal ("minor"). However, consider a consultation with a psychiatrist if the diagnosis or treatment is unclear, if a patient’s comorbid conditions may be affected by antidepressant medications, or if the patient does not respond to or comply with treatment. It might be advisable to refer a patient to a psychiatrist if hallucinations or delusions accompany depression or if the patient shows signs of distorted reasoning. Similarly, when taking a psychiatric history in a patient with depression, ask about episodes of elation and overactivity in a patient’s past. These may signal the presence of a bipolar disorder that, again, is best referred to a specialist. A patient with a history of poor response to prior antidepressant treatments or serious suicidal potential or someone with severe functional impairment also might be considered for specialty referral.
Reasons for Depression Being Underdiagnosed and Undertreated
Although it is impossible to determine accurately the percentage of individuals with major depression who are undertreated, results from studies of depressed patients in the community, in primary care settings, and in the mental health care arena give an idea of the extent of the problem. Data from these studies suggest that 50-90% of individuals with major depression either do not seek help or receive inadequate treatment.12-21 The reasons for this phenomenon can be seen as originating from three sources: the patient, the physician, and the health care system.22
The Patient
There are many misconceptions about depression that may prevent a person from seeking appropriate treatment. For instance, many people believe that if there is a cause for depression (e.g., the death of a loved one), it does not need to be treated. They also may feel that depression will go away on its own eventually, so they should just get through it. There is a stigma attached to depression that anyone who cannot overcome it on their own is weak, so many people may not want to admit they need help. In addition, the symptoms of depression often leave a person lacking initiative, drive, and hope. They may not seek help because they feel nothing could help. A recent survey found that among individuals with current major depression, having health insurance and having a PCP each increased the odds of receiving antidepressant therapy fourfold.10 The next important step was the patient trusting the primary provider enough to tell him or her about depressive symptoms; this predicted a tenfold increase in treatment.
The Physician
The PCP is often the first and, in many cases, only point of contact for a person suffering from depression. In one study, 12% of patients in a primary care setting met criteria for major depression.23 Unfortunately, physicians are frequently inadequately trained to diagnose and manage this disorder. Depression can hide behind a variety of symptoms, including pain. Physicians need to have both the medical knowledge to "unmask" and treat depression and the interpersonal skills to manage a patient with disturbances in emotional, cognitive, behavioral, and somatic regulation. A physician’s lack of knowledge about antidepressant drugs could lead to a patient not receiving adequate doses or treatment for a long enough period. Physicians need to educate patients and their families about the disorder and its treatments. Too often, there is insufficient time for a PCP to attend to psychiatric conditions in a busy practice.
The Health Care System
While health care systems vary in different places around the world, many of them view depression as an acute disorder rather than the chronic, recurring disease that it is. In the United States, patients are often unreimbursed by managed care and insurance companies for their use of mental health services. Physicians are encouraged not to monitor patients frequently early in treatment, try more than one treatment approach, or refer patients to specialists. Health maintenance organizations might also limit the length of therapy.
The Costs of Undertreating Depression
The costs and consequences of inadequately treating depression are significant, both to the individual sufferer and to society. The total annual cost of depression in the United States was estimated to be $43.7 billion in 1990.24 This includes $12.4 billion in direct costs of treatment and $31.3 billion in indirect costs, such as premature death, absenteeism from work, and reduced productivity. It is estimated that adequate treatment of depression would result in indirect cost savings that would exceed direct costs of depression by $4 billion.
Untreated episodes of major depression can last six months or longer.25 During an untreated episode, depression can significantly interfere with recovery from comorbid conditions like cancer, diabetes, stroke, and myocardial infarction. Depression similarly can complicate pregnancy, childbirth, and the postpartum. In general, patients with unrecognized or undertreated depression tend to be higher users of medical services than patients without depression; major depression not only causes unexplained physical symptoms but also amplifies the symptoms of other medical illnesses.26 Untreated depression may get worse (and lead to suicide) or become chronic. The longer the first episode lasts, the greater likelihood of recurrence. In addition, rates of relapse and recurrence increase with each subsequent episode.27
Treatment
In the treatment of major depression, the goals are to eliminate all signs and symptoms of depression, restore the patient’s ability to function in work and social settings, and, finally, to reduce the likelihood of a relapse or recurrence. When a patient has uncomplicated depression of mild to moderate severity, the first step in the treatment algorithm is to decide between psychotherapy or antidepressant medications. Often, the choice can be made by the patient: some would rather talk, others prefer to take medication. Even though both methods take a number of weeks to achieve full benefit, antidepressant drugs tend to work faster than psychotherapy. Some symptoms, such as insomnia, may respond to medicine even more quickly.
Psychotherapy
Several forms of psychotherapy, such as cognitive behavioral therapy and interpersonal psychotherapy, have been shown in scientific controlled studies to be equal in efficacy to antidepressant medications in mild to moderate depression.28-30 In some locales, there may not be psychotherapists trained in these techniques. In the absence of professionals with such qualifications, try to find therapists with good professional reputations. If the patient is taking an antidepressant, choose a therapist with a positive attitude about medication. Encourage patients to use their own judgment and not feel obligated to stay with a psychotherapist if the "chemistry" is not right. Moreover, a depressed patient should not stay with the same treatment approach if there has not been at least a moderate degree of benefit after 2-3 months. In such cases, the possibility of adding a medication trial should be seriously considered. Some studies show combined psychotherapy and antidepressant medication to be more effective than either treatment alone.28
Medications
For patients with moderate to severe depression, antidepressant medications are considered first-line treatment.31 Pharmacologic treatment is also recommended for depression with psychotic, melancholic, or atypical symptoms and for patients who:
• do not have access to adequate psychotherapy;
• have responded to medication in the past;
• will need maintenance treatment;
• have had symptoms for more than two years that have not responded to psychosocial intervention; or
• are experiencing significant impairment of work or social functioning.
There are currently available a wide range of antidepressant medicines from different classes (see Table 2). The majority of U.S. physicians now turns first to selective serotonin reuptake inhibitors (SSRIs) for most depressed patients.31 These are fluoxetine, sertraline, paroxetine, and citalopram. Other antidepressants sometimes considered for first-line use are nefazodone and venlafaxine. Bupropion is usually reserved for a second- or third-line treatment, and, although mirtazapine has been available in the United States for more than three years, it still is not widely used by PCPs. The most sedating of the newer antidepressants, mirtazapine shares with bupropion and nefazodone a low incidence of sexual dysfunction. Tricyclic antidepressants, such as amitriptyline and clomipramine, are generally second- or third-line options. The monoamine oxidase inhibitor (MAOI) antidepressants, such as phenelzine, tranylcypromine, and isocarboxazid, are invaluable but usually far down the list of choices due to their side effects and need for dietary and medication restrictions. MAOIs are most commonly prescribed by psychiatrists. St. John’s wort is now widely used as an over-the-counter remedy for depression, but its efficacy has yet to be established by rigorous, controlled trials.
| Table 2. Commonly Used Antidepressant Drugs | ||
| Generic name (Trade name) | Starting Dose (mg/d)* | Usual Dose (mg/d) |
| Tricyclics and tetracyclics | ||
| Tertiary amine tricyclics | ||
| 25-50 | 100-300 | |
| Clomipramine (Anafranil) | 25 | 100-250 |
| Doxepin (Sinequan) | 25-50 | 100-300 |
| Imipramine (Tofranil) | 25-50 | 100-300 |
| Trimipramine (Surmontil) | 25-50 | 100-300 |
| Secondary amine tricyclics | ||
| Desipramine (Norpramin) | 25-50 | 100-300 |
| Nortriptyline (Pamelor) | 25 | 50-200 |
| Protriptyline (Vivactil) | 10 | 15-60 |
| Tetracyclics | ||
| Amoxapine (Ascendin) | 50 | 100-400 |
| Maprotiline (Ludiomil) | 50 | 100-225 |
| Selective serotonin reuptake inhibitors (SSRIs) | ||
| Citalopram (Celexa) | 20 | 20-60 |
| Fluoxetine (Prozac) | 20 | 20-60 |
| Fluvoxamine (Luvox) | 50 | 50-300 |
| Paroxetine (Paxil) | 20 | 20-60 |
| Sertraline (Zoloft) | 50 | 50-200 |
| Dopamine-norepinephrine reuptake inhibitors | ||
| Bupropion (Wellbutrin) | 150 | 300 |
| Serotonin-norepinephrine reuptake inhibitors | ||
| Venlafaxine (Effexor) | 37.5 | 75-225 |
| Serotonin modulators | ||
| Nefazodone (Serzone) | 50 | 150-300 |
| Trazodone (Desyrel) | 50 | 75-300 |
| Norepinephrine-serotonin modulator | ||
| Mirtazapine (Remeron) | 15 | 15-45 |
| Monoamine oxidase inhibitors (MAOIs) | ||
| Irreversible, nonselective | ||
| Isocarboxazid (Marplan) | 10 | 20-30 |
| Phenelzine (Nardil) | 15 | 15-90 |
| Tranylcypromine (Parnate) | 10 | 30-60 |
| Reversible MAOI-A (RIMA) | ||
| Moclobemide (Manerix) | 150 | 300-600 |
| Adapted from: The American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depressive Disorder. Am J Psychiatry 2000;157:1-45. | ||
| * Lower starting dosages are recommended for elderly patients and for those with panic disorder, significant anxiety or hepatic disease, and general comorbidity. | ||
| Dosage varies with diagnosis. | ||
| Not available in the United States. | ||
There are few differences in comparisons of grouped data. There are dramatic differences in the effectiveness of antidepressants for particular patients.31 The choice of agent usually is based on the following seven factors:32
• side effects (see Table 3);
• safety in overdose;
• the ease with which a therapeutic dose can be achieved;
• the patient’s (or family’s) history of response;
• cost;
• half-life; and
• the effect of the medication (or its side effects) on underlying medical conditions.
| Table 3. Potential Treatments for Side Effects from Antidepressant Drugs31 | ||
| Side Effect | Antidepressant(s) Associated With | Treatment |
| Cardiovascular | ||
| Orthostatic hypotension | TCAs, trazodone, nefazodone, MAOIs | Lower dose, discontinue medication, fludrocortisone, add salt to diet |
| Reduced cardiac output | TCAs | Discontinue medication |
| Arrhythmias | TCAs | Discontinue medication |
| Hypertension | Venlafaxine | Lower dose, discontinue medication |
| Hypertensive crisis | MAOIs | Discontinue medication, intravenous phentolamine |
| Increase in cholesterol | Mirtazapine | Lower dose, discontinue medication |
| Anticholinergic | ||
| Dry mouth | TCAs Pilocarpine oral rinse, gum, candy | |
| Constipation | TCAs | Hydration, bulk laxatives |
| Urinary hesitancy | TCAs | Bethanechol |
| Visual changes | TCAs | Pilocarpine eye drops |
| Delirium | TCAs | Discontinue medication, antipsychotic medication |
| Sedation | TCAs, trazodone, nefazodone, mirtazapine | Bedtime dosing |
| Weight gain | TCAs, mirtazapine, MAOIs | Lower dose, change to secondary amine (if TCA required), discontinue medication |
| Nausea, vomiting | SSRIs, bupropion (SR), venlafaxine (R) | Lower dose, discontinue medication |
| Insomnia | SSRIs, bupropion | Lower dose, discontinue medication, morning dosing, trazodone at bedtime |
| Activation | SSRIs, venlafaxine | Lower dose, discontinue medication |
| Neurologic | ||
| Myoclonus | TCAs, MAOIs | Lower dose, discontinue medication, clonazepam |
| Extrapyramidal symptoms | Amoxapine, SSRIs | Lower dose, discontinue medication tardive dyskinesia |
| Seizures | Bupropion, amoxapine | Lower dose, discontinue medication, antiepileptic medication |
| Headaches | SSRIs, bupropion | Lower dose, discontinue medication |
| Sexual side effects | ||
| Arousal, erectile dysfunction | Paroxetine, venlafaxine | Lower dose, discontinue medication, sildenafil, yohimbine, ginkgo, methylphenidate, dextroamphetamine, pemoline |
| TCAs, SSRIs | Lower dose, discontinue medication, sildenafil, yohimbine, ginkgo, bethanechol, neostigmine | |
| Orgasm dysfunction | SSRIs, venlafaxine | Lower dose, discontinue medication, granisetron, amantadine, cyproheptadine, sildenafil |
| MAOIs, TCAs | Lower dose, discontinue medication, cyproheptadine, amantadine | |
| Priapism | Trazodone | Discontinue medication, surgical correction |
| Serotonin syndrome | SSRIs, MAOIs, venlafaxine | Discontinue medication |
| Agranulocytosis | Mirtazapine | Discontinue medication, monitor white blood cell count and granulocyte colony-stimulating factor |
| TCA = tricyclic antidepressant; SSRI = selective serotonin reuptake inhibitor; MAOI = monoamine oxidase inhibitor | ||
When a patient taking an antidepressant takes other medications concomitantly, potential interactions must also be considered. Pharmacodynamic interactions involve additive effects, such as cardiac conduction effects or sedation. We now know more about pharmacokinetic interactions, as pharmacology studies have demonstrated which among the drug-metabolizing enzymes of the cytochrome P450 system are influenced by different medications (see Table 4).
| Table 4. P450 Isoenzymes—Potential Antidepressant Drug Interactions | ||
| Isoenzyme | Metabolizes | Inhibited by |
| 2D6 | SSRIs: | Fluoxetine |
| Fluoxetine | Paroxetine | |
| N-desmethylcitalopram | Sertraline | |
| Norfluoxetine | Clomipramine | |
| Paroxetine | ||
| Tricyclic antidepressants | ||
| Amitriptyline | ||
| Clomipramine | ||
| Desipramine | ||
| Imipramine | ||
| N-desmethylclomipramine | ||
| Nortriptyline | ||
| Trimipramine | ||
| Other: | ||
| Venlafaxine | ||
| 1A2 | Amitriptyline | Fluvoxamine |
| Clomipramine | ||
| Imipramine | ||
| 3A4 | Nefazodone | Fluoxetine |
| Sertraline | Fluvoxamine | |
| Venlafaxine | Nefazodone | |
| Some tricyclics | Sertraline | |
| Trazodone | ||
| 2C19 | Amitriptyline | Fluoxetine |
| Clomipramine | Fluvoxamine | |
| Imipramine | Sertraline | |
Treatment Failure
Approximately 50% of patients fail to respond adequately to initial treatment with an antidepressant medication.31 Some improvement should be observable (by family members if not by the patient) within about two weeks. If benefit is not apparent within 2-3 weeks, the dose should be raised. If a patient is beginning to achieve benefits, on the other hand, it is best to let the dose stay where it is. Full accrual of benefits from an antidepressant may take 8-12 weeks.33 If the patient does not respond within this time frame, it may be due to an inappropriate diagnosis; coexisting general medical conditions; psychiatric disorders or complicating psychosocial factors that are impeding recovery; or noncompliance with treatment. These factors should be reviewed and addressed. If the patient’s lack of response is not due to any of these factors, another (preferably non-MAOI) antidepressant should be tried. The primary care doctor should become familiar with the dosing and side effects of a few antidepressants and know them well. If a patient fails to improve after two or three trials of different antidepressants, it may be worthwhile to refer the patient to a psychiatrist.
Continuation and Maintenance Treatment
If a patient has responded favorably to an antidepressant, continue that drug at the therapeutic dose for at least six months. If the patient then has been entirely free of symptoms for at least two months, gradually taper and discontinue the medication. Educate the patient and family members to be on the alert for a future episode and to bring it immediately to clinical attention. Stay in contact with the patient to assess potential recurrences.
Tricyclic antidepressants are associated with a group of common symptoms upon discontinuation, including gastrointestinal or general medical symptoms such as vomiting, nausea, diarrhea, headache, fatigue, and malaise; sleep abnormalities; akathisia and parkinsonism; and paradoxical behavioral activation resulting in hypomanic or manic symptoms.34 These symptoms usually begin 24-48 hours after the last dose and may last as long as one month. A withdrawal syndrome has also been reported in association with some of the serotonin reuptake inhibitor antidepressants.35 It generally begins 2-3 days after the last dose, although sometimes it starts during the taper (indicating that the taper is too rapid). The symptoms—which are often described as "flu-like" and include dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood—generally abate within three weeks.
There is a role for maintenance therapy in depression. It is rarely appropriate after a single episode of depression but might be considered in very severe cases or when there is a heavy family history, particularly for patients who have attempted suicide.36 After two closely spaced or severe episodes of depression, maintenance therapy should be considered. Patients with three or more lifetime episodes of depression should take antidepressant medication (or be in some form of effective psychotherapy) indefinitely. Prophylactic treatment should also be considered for patients who are older than 50 years when they have their first episode. Maintenance treatment should use the same dosage of the same drug that was used in the acute and continuation phases.37
Relapse and Recurrence
Symptom breakthroughs occur in 10-20% of patients during continuation or maintenance treatment.32 When symptoms return before full recovery, they are considered to be part of the previous episode of depression (i.e., a relapse). If symptoms occur following recovery, they are considered the start of a new episode (i.e., a recurrence). Symptoms must be absent for six months or longer for the patient to be considered completely recovered.38 Symptom breakthroughs may result from intermittent adherence to treatment, the addition of alcohol, a concurrent illness, increased stress, or possibly the beginning of a bipolar disorder. Support, close observation, and possibly an increase in dose are necessary.
Compliance
Many individuals who make the effort to get treatment for depression do not stick with it. Reasons for noncompliance include the delay in the onset of effects from antidepressant medications or psychotherapy, the need to continue taking medication after symptoms have remitted, and the adverse effects of medications (see Table 5). The following six messages, delivered to the patient by the primary care provider, can help patients adhere to antidepressant therapy:39
| Table 5. Obstacles and Solutions to Adherence Problems | ||
| Obstacle | Solution | |
| Attitudes/misconceptions | Patient/family education | |
| Side effects | Side effect monitoring,dose adjustment, adjunctive agents, medication switch | |
| Euthymia leading to treatment discontinuation | Patient/family education | |
| Symptom worsening | Symptom monitoring, psychotherapy, medication changes | |
| Suboptimal functioning or psychosocial problems | Support, formal therapy, rehabilitative efforts | |
| Discouragement | Patient/family groups (e.g., Depressive and Manic Depressive Association, National Alliance for the Mentally Ill, Mental Health Association) | |
| Adapted from: Rush AJ. J Clin Psychiatry 1999;60:21-26. | ||
• Take medication daily.
• Antidepressants must be taken for at least 2-4 weeks for a noticeable effect.
• Continue medication even when feeling better.
• Do not stop medication without checking with physician.
• Call with any questions.
• Mild side effects are common and often improve after 7-10 days.
These messages take less than one minute to be delivered slowly and clearly to the patient. Patients should be given this advice at the start of treatment and at every follow-up visit.
Summary and Conclusions
Major depression is a serious medical illness that often goes unrecognized and, even when diagnosed, inadequately treated. This article has reviewed the burden of depression on individuals and on the community, the diagnosis and treatment of this disorder, and reasons why many patients do not get the help they need. To ensure that depressed patients receive optimal therapy and adhere to their treatment regimen, PCPs must learn about antidepressant medications and take the time to educate patients and their families about the illness and its treatments.
Psychiatric neuroscience is pushing knowledge and treatment potential forward in the field of depression. New pharmacotherapies as well as new magnetic, electrical, and neurosurgical interventions are being studied. In the meantime, the treatment of depression can be gratifying to clinicians, patients, and family members alike. It is extremely rewarding to see a smile reemerge on a face that has been furrowed with worry lines and pessimism.
References
1. Weissman MM, et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276:293-299.
2. Blazer DG, et al. The prevalence and distribution of major depression in a national community sample: The National Comorbidity Survey. Am J Psychiatry 1994;151:979-986.
3. Gelenberg AJ, Delgado PL. Depression. In: Gelenberg AJ and Bassuk EL, eds. The Practitioner’s Guide to Psychoactive Drugs. 4th ed. New York: Plenum; 1997:19-97.
4. Murray CJL, Lopez AD (eds.) The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020: Summary. Cambridge, MA: The Harvard School of Public Health on behalf of The World Health Organization and The World Bank; Distributed by Harvard University Press; 1996.
5. Gelenberg AJ. Morbidity, mortality, and mood. Biol Ther Psychiatry Newsletter 1994;17:9-11.
6. Whooley MA, et al. Association between depressive symptoms and mortality in older women. Arch Intern Med 1998;158:2129-2135.
7. Keller MB. The difficult depressed patient in perspective. J Clin Psychiatry 1993;54(Suppl 2):4-8.
8. Gelenberg A. Depression is still underrecognized and undertreated. Arch Int Med 1999;159:1657-1658.
9. Davidson JRT, Meltzer-Brody SE. The underrecognition and undertreatment of depression: What is the breadth and depth of the problem? J Clin Psychiatry 1999;60(Suppl 7):4-11.
10. Druss BG, et al. Underuse of antidepressants in major depression: Prevalence and correlates in a national sample of young adults. J Clin Psychiatry 2000;61:234-237.
11. Dunner DL, et al. Depression and the introduction of SSRIs. J Clin Psychiatry 1999;17(Monograph 3):4-15.
12. Robins LN, et al. An overview of psychiatric disorders in America. In: Robins LN and Regier DA (eds.) Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York: Free Press;1991:328-366.
13. Keller MB, et al. Treatment received by depressed patients. JAMA 1982;248:1848-1855.
14. Kessler RC, et al. Prevalence, correlates, and course of minor depression and major depression in the National Comorbidity Survey. J Affect Disord 1997;45:19-30.
15. Keller MB, et al. Treatment for chronic depression with sertraline and imipramine: Preliminary blinded response rate and high rates of undertreatment in the community. Psychopharmacol Bull 1995;31:205-212.
16. Shelton RC, et al. The undertreatment of dysthymia. J Clin Psychiatry 1997;58:59-65.
17. Katon W, et al. Adequacy and duration of antidepressant treatment in primary care. Med Care 1992;30:67-76.
18. Simon GE, von Korff M. Recognition, management, and outcomes of depression in primary care. Arch Fam Med 1995;4:99-105.
19. Wells KB, et al. Use of minor tranquilizers and antidepressant medications by depressed outpatients: Results from the Medical Outcomes Study. Am J Psychiatry 1994;151:694-700.
20. Goethe JW, et al. A comparison of adequately vs inadequately treated depressed inpatients. J Nerv Ment Dis 1988;24:75-80.
21. Keller MB, et al. Long-term outcome of episodes of major depression: Clinical and public health significance. JAMA 1984;252:788-792.
22. Hirschfeld RM, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997;277:333-340.
23. Spitzer RL, et al. Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. JAMA 1994;272:1749-1756.
24. Greenberg PE, et al. The economic burden of depression in 1990. J Clin Psychiatry 1993;54:405-418.
25. Judd LL. The clinical course of unipolar major depressive disorders. Arch Gen Psychiatry 1997;54:989-991.
26. Von Korff M, et al. Disability and depression among high utilizers of health care. A longitudinal analysis. Arch Gen Psychiatry 1992;49:91-100.
27. Keller MB, Boland RJ. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biol Psychiatry 1998;44:348-360.
28. Weissman MM, Markowitz JC. Interpersonal psychotherapy: Current status. Arch Gen Psychiatry 1994;51:599-606.
29. Gloaguen V, et al. A meta-analysis of the effects of cognitive therapy in depressed patients. J Affect Disorder 1998;49:59-72.
30. Scott J. Cognitive therapy of affective disorders: A review. J Affect Disord 1996;37:1-11.
31. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000;157(Suppl 4):1-45.
32. Depression Guideline Panel. Clinical Practice Guideline: Depression in Primary Care: Treatment of Major Depression. Rockville, MD: US Dept of Health and Human Services, Agency for Health Care Policy and Research. 1993;2. AHCPR publication 93-0551.
33. Thase ME. Long-term nature of depression. J Clin Psychiatry 1999;60(Suppl 14):3-9.
34. Zajecka J, et al. Discontinuation symptoms after treatment with serotonin reuptake inhibitors: A literature review. J Clin Psychiatry 1997;58:291-297.
35. Coupland NJ, et al. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996;16:356-362.
36. Greden JF. Antidepressant maintenance medications: When to discontinue and how to stop. J Clin Psychiatry 1993;54(Suppl 8):39-45.
37. Rush AJ. Strategies and tactics in the management of maintenance treatment for depressed patients. J Clin Psychiatry 1999;60(Suppl 14):21-26.
38. Frank E, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48:51-855.
39. Lin EH, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care 1995;33:67-74.
40. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington DC: American Psychiatric Association; 1994.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content