Assessing and Treating Depression in Primary Care Medicine
Article Outline
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.
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 of self, nor does it typically present with a full constellation of symptoms of depression (Table 1).
Table 1. 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. |
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 (most recently, 4th edition, text revision) of the American Psychiatric Association (DSM-IV-TR).8 The major symptoms of depression are summarized in Table 1.9 For complete diagnostic criteria consult the DSM-IV-TR. Depression that lasts less than the threshold criterion of 2 weeks often will be transitory. However, if symptoms are severe or life-threatening, clinical intervention may be required. Depression that fails to meet all the criteria of DSM-IV-TR may still be clinically significant and could require clinical intervention, particularly if it has persisted for months or years. Even low-grade chronic depression can take a substantial toll on health and functioning.10
Etiology
Psychiatry today no longer distinguishes between “endogenous” and “reactive” depression. Whether or not the patient or clinician can identify apparent precipitants does not seem to bear on the need for or probable response to treatment.
Scientists are following many different avenues to try to understand the neurobiology of depression. Still, today’s knowledge remains rudimentary. Most likely, multiple genes (and their expression) play a role in an individual’s vulnerability to become depressed. (Some fortunate people presumably have the reciprocal genetic advantage of unusual resilience under circumstances of great stress and provocation.) Negative life experiences may leave traces on the brain that adversely affect future responses to life circumstances and the probability of developing anxiety and depression. Preliminary research suggests that some genetic alleles and early life experiences might predict the likelihood of responding to antidepressant medication or specific forms of psychotherapy to treat depression.
Diagnosis
Some patients complain to their doctors that they feel depressed. In other cases, a family member will voice this concern. Some people do not like to use the word depression or any psychological terms. Instead, fatigue or other physical symptoms may be their presenting complaints.
A medical work-up for depression requires the same 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 alcohol often cause depression, either during acute or chronic intoxication or during withdrawal. In fact, depression is common in people with substance abuse and, conversely, people with longstanding mood disorders frequently abuse drugs or alcohol.
Many neurologic disorders cause or present as depression. Depression may be an early or late symptom in Alzheimer’s disease and other dementias and is a common accompaniment of stroke and many deteriorating brain conditions, including multiple sclerosis. Nutritional deficiencies sometimes present as depression.
There is no laboratory test to rule in depression, but the laboratory can rule out other causes of depressive symptoms. The choice of laboratory tests should be tailored to each individual case, based on a medical history and review of systems.
Management
With medical causes excluded, the physician must attend to several special circumstances that will affect management. Most depressed people at least consider suicide and should be specifically asked about it. If a patient has a plan and the means to carry it out, urgent and immediate referral for psychiatric assessment and probably hospitalization is required. Agitated or highly anxious patients, as well as the elderly and those lacking social support, are at higher risk to commit suicide. Ask about a history of suicide attempts. People who have made serious suicide attempts in the past are at increased risk to complete suicide.
Patients with delusions, hallucinations, or other bizarre or psychotic symptoms require different biological treatment 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 required.
Always ask a depressed patient about a past history of hypomania or mania (Table 2), as this defines bipolar disorder and requires different management. These patients should be referred to a psychiatrist. A family history of bipolar disorder should lead to consideration of this diagnosis.
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 |
Treatment
Absent one of the considerations outlined above, the next step in managing a case of uncomplicated major depression 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 3. Selective Serotonin Reuptake Inhibitors (SSRIs) Labeled for the Treatment of Major Depression
| Agent | Dosing Range |
|---|---|
| Citalopram (Celexa and others) | 20 to 40 mg/day |
| Escitalopram (Lexapro) | 10 to 20 mg/day |
| Fluoxetine (Prozac and others) | 20 to 80 mg/day |
| Paroxetine (Paxil and others) | 20 to 50 mg/day |
| Sertraline (Zoloft and others) | 50 to 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 | Dosing Range |
|---|---|
| Tricyclic antidepressants⁎ | |
 Imipramine (Tofranil) | 75 to 300 mg/day |
| Trimipramine (Surmontil) | 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. |
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 long-term 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
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- A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry. 1998;55:694–700
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- . Suicide after discharge from psychiatric hospitals in Scotland. BMJ. 1995;311:1368–1369
- . Diagnostic and Statistical Manual of Mental Disorders. 4th ed, Text Revision. Arlington, VA: American Psychiatric Association; 2000;
- 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.
- . Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am J Psychiatry. 1996;153:1411–1417
- . Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry. 2004;61:714–719
- . Medications versus cognitive behavior therapy for severely depressed outpatients: mega-analysis of four randomized comparisons. Am J Psychiatry. 1999;156:1007–1013
PII: S0002-9343(06)00699-1
doi:10.1016/j.amjmed.2006.05.059
© 2007 Elsevier Inc. All rights reserved.
