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The diagnosis of depression and successful treatment is important, as General Practice functions as the mental health system to approximately half of the patients suffering from major depression in the United States⁶. Many new medications with less side effects are presently available enabling the primary care physician to handle most patients in an outpatient setting. However, many cases are unrecognized, and those identified are often under treated in the primary care setting^1,9. It has been proven that major depression could be effectively treated in the primary care setting, as well as by the mental health speciality in both the young and older patients¹⁶. There is insufficient evidence that minor depression and dysthymia need pharmacotherapy¹⁷. Primary care functions as the mental health system for about half of the mood disorder patients in the United States (US). The stigma of having a psychiatric illness, although still a factor for masking of emotional problems, has been less in the recent years.

Prevalence

It has been estimated that 5% to 11% of the total population suffer from major depression in the US^3,4. Annually, about 50,000 Americans die from suicide, which is the seventh leading cause of death in the US⁶. Suicide is the third leading cause of death among young adults and teenagers. Ten to 14 million people in the US are depressed in any year⁵. Many cases are unrecognized.

Diagnosis

According to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV), Major Depression is a mood disorder which could be diagnosed if five of nine specific symptoms are present, at least one of which should be depressed mood, or Anhedonia (loss of interest or pleasure), present every day for at least two weeks. The other symptoms are (1) fatigue, (2) recurrent thoughts of death or suicide, (3) indecisiveness or decreased concentration, (4) feelings of worthlessness or excessive guilt, (5) overall slowness or agitation, (6) insomnia or hypersomnia, (7) significant weight gain or loss².

It is important to appreciate that major depression is a syndrome with a cluster of symptoms and signs, consisting of fatigue, changes in mood, appetite, weight, and sleep patterns, changes in activity level, decreased sex drive, and reduced attention span and concentration. There may also be an atypical form of presentation of the syndrome with weight gain, increased appetite, increased sleep, lethargy, and agitation. This form of depression is usually seen at an earlier age of onset, while the melancholic form is seen in the late thirties and forties. Common medical conditions causing depression are, drug therapies such as for hypertension, substance abuse of alcohol, sedatives, and stimulants such as cocaine. Occult malignancies may also be another cause.

In the primary care setting it is somewhat difficult to determine accurately if a patient suffers from major depression alone or if there is a combination with a co morbid medical illness. The diagnosis is based on the medical history, physical exam and laboratory tests, to rule out other medical conditions that could cause a depressive episode. The depressive patient may present with somatic complaints, and emotional complaints such as irritability, anxiety, and apathy. The presentation may also be with memory problems.

Anhedonia has been shown to be a more sensitive marker than sadness to diagnose depression in the primary care setting. Patients may report as being "unhappy, empty, helpless, sad, or miserable." The physician may note the patient to have diminished eye contact, decreased rate and rhythm of speech, stooped posture, and irritability⁶. Psychomotor restlessness is less often seen. Once depression is diagnosed by the General Physician, it is important to distinguish if it is unipolar major depression or bipolar disorder (manic-depression). Unipolar type is the more common form of depression.

Useful laboratory tests would include urinalysis, complete blood count, thyroid, renal, and liver function tests and serology for infectious diseases. Other specific tests depend on the history and presentation of the patient.

Risk factors for depression⁷

Age - Onset is usually in the twenties or thirties, although it may begin at any age, developing over days to weeks. In the untreated patients, it has been shown by research that depressive episodes of greater than three months are unlikely to abate spontaneously⁶. In 25% of affected patients the status may become chronic.

Gender - Females are more affected than males.

Family history - Stressful events, child birth, and substance abuse.

Stressors - Loss of a child, spouse or parent, loss of job.

Older population - Symptoms may be atypical. New onset depression is unusual in the older patients, therefore a search for an underlying medical problem is important.

Suicidal risk⁶

Risk of suicide is an important part of the diagnosis. It is difficult to interpret suicidal risk. The "SAD PERSONS" scale helps with the diagnosis.

S - Sex. More than three males for one female tend to kill themselves⁸.
A - Age. Older persons kill themselves more than younger Caucasian males.
D - Depression. Suicide is preceded by depression in up to 70% of cases.
P - Previous attempts. Greater than four attempts increase the risk.
E - Ethanol use. Recent use of ethanol and sedative hypnotic drugs.
R - Rational thinking loss. Cognitive function is slowed, or may present with psychotic depression.
S - Social support deficit.
O - Organized plan. Physician should inquire as to the presence of a plan.
N - No spouse. Absence of a spouse or significant other increases the risk.
S - Sickness. Medical illness coexisting with depression. A positive family history of suicide is an important factor.

Management of Major Depression

After establishment of the diagnosis it is important that a patient oriented approach⁶ be instituted. This approach is found to enhance patient compliance by improving the patient's self-esteem. Patient education regarding the disease and medications is a major step toward compliance with the treatment plan.

The drug treatment plan may be divided into three phases⁷. An acute phase, continuation phase, and a maintenance phase.

Acute phase - Usually lasts from six to 12 weeks, patient needs to be evaluated every two to three weeks to determine the response, adjustment of the dosage, monitor side effects and provide emotional support. It should be stressed to the patient that improvement in symptoms may not be apparent for two to four weeks after initation of drug therapy. About 70% of patients usually respond within this period. In case of no response by 12 weeks, the medication will need to be changed, or the patient referred to a psychiatrist.

Continuation phase - The goal of this phase is to prevent relapse, medication is continued for six to nine months after symptoms have resolved. Visits every two to three months would be satisfactory unless there are problems or concerns.

The maintenance phase - May last from several months to a life time. This is recommended for 6 to 9 months, if a first relapse occours after remission of the initial episode¹⁵. For the third relapse, maintenance is recommended for an indefinite period of time. This phase is considered for high risk patients with three or more major depressive episodes, or those with a family history of depression, or bipolar disorder and having had two or more episodes. It is also for patients whose initial episode was before age 20, presenting with severe depressive symptoms. Patients who need maintenance therapy will need to be evaluated by a psychiatrist.

Antidepressant therapy

Choosing the appropriate antidepressant for a particular patient needs consideration of many factors. One factor is the positive past response to a particular medication¹⁰. Similarly, a past history of negative response contraindicates the medication. Further, past side effects eliminate certain choices of medications. Other significant factors are family history of response to a medication, drug interactions on patients who are on other medications (such as for medical problems).

It has been found that all antidepressants are equally effective¹¹. The newer antidepressants produce less side effects and less consequences in case of an overdose.

Antidepressants generally used in a primary care setting, as the first line of treatment are the Selective Serotonin Re uptake Inhibitors (SSRI's). They are namely Citalopram (Celexa), Fluoxetine (Prozac), Fluvoxamine (Luvox), Paroxetine (Paxil), and Sertraline (Zoloft). They are well tolerated and have simpler dosing schedules. They are convenient to use, safe and usually prescribed in the morning to prevent sleep disturbances. Side effects include weight changes, and sexual dysfunction seen in both men and women. There may be orgasmic dysfunction anorgasmia, and delayed ejaculation in men¹³. Some SSRI's, namely Fluoxetine (Prozac) and Sertraline (Zoloft) cause more stimulation than Citalopram (Celexa) and Paroxetine (Paxil). Therefore Fluoxetine and Sertraline could be used as the initial choice for the hyper somnolent depressed patient, while Paroxetine or Citalopram for the depressed patient with anxiety.

Mirtrazapine (Remeron) in a newer drug which is a Serotonin and Alpha Two Norepinephrine Receptor Blocker. Nefadazone (Serzone) is a Serotonin 2 A Receptor Blocker and a weak Serotonin Uptake inhibitor. Both these drugs cause sedation rather than over stimulation. Venalafaxine (Effexor) is a Serotonin Norepinephrine reuptake inhibitor (SNRI) while Bupropion (Wellbutrin) is a Dopamine Norepinephrine Reuptake Inhibitor.

Some patients may need a dosage greater than the minimum therapeutic level. In those with a poor response, the appropriate time for a dosage increase is in about the fifth week. It is reported that most elderly patients require dosages comparative to younger adults¹².

Fluoxetine (Prozac). The initial dosage is 10-20 mg per day. Elderly and those with liver and kidney dysfunction should be started at 10 mg per day. The half life of the drug is about two weeks, thus eliminating a risk of a discontinuation syndrome, but one should be cautious of starting a new drug soon after the discontinuation of Fluoxetine due to effect of drug interactions.

Sertraline (Zoloft). Starting dose is 25-50 mg a day and increased in increments of 25-50 mg up to 100 to 200 mg a day.

Citalopram (Celexa). This is the most selective of the SSRI's. This drug was approved recently in the United States for the treatment of major depression. Initial dosage is 20 mg a day. The dosage is titrated up to 40-60 mg a day over a period of about four weeks. The recommended dosage for the elderly and those with impaired hepatic and renal function is up to half the above dosage. The adverse effects commonly reported are dry mouth, nausea, insomnia, increased sweating and somnolence is some patients. Sexual side effects are less than with the other SSRI's.

Paroxetine (Paxil). It is usually started at a dosage of 10 mg a day, gradually increased up to 20-30 mg a day. Maximum dosage for the treatment of depression is 50 mg a day. Due to the sedating effect of Paroxetine, it would be beneficial to use it at bedtime.

Other classes of antidepressants

Bupropion (Wellbutrin). This offers equivalent efficacy to other antidepressants. It may be used for patients who are unable to use SSRI's due to adverse effects. It has an effect of activation making it useful for patients with excessive somnolence and fatigue. It has been reported to have an increased incidence of seizures. Patients on Zyban (used for smoking cessation) should not be prescribed Wellbutrin due to similar action of both drugs. Starting dose is 100 mg increased to a usual effective dose of 300 mg given in three divided doses. Maximum dosage is 450 mg a day.

Venalafaxine (Effexor) It is useful in treating patients who are refractory to other antidepressants, or are unable to use SSRI's due to adverse effects. Hypertension has been reported with the use of Venalafaxine.

Nefadazone (Serzone). It could be used in patients with depression and anxiety. It may cause dry mouth, nausea, and dizziness. Sedation is the most prominent side effect, making it useful for those experiencing insomnia. Sexual side effects are rarely seen. Initial dose is 50 mg b.i.d. increased gradually to a dosage of about 150-300 mg b.i.d.

Mirtazapine (Remeron). This drug is useful for patients with anxiety and depression, and seldom associated with sexual dysfunction. Side effects reported are drowsiness, dizziness, and weight gain. Recommended initial dose is 15 mg a day, may be increased up to 30 mg a day. It is usually prescribed as a night dose.

Tricyclic Antidepressants. These are not recommended in the outpatient treatment of depression due to high incidence of systemic side effects. They are mixed reuptake and neuroreceptor antagonists. Examples: Amitriptyline (Elavil), Amoxapine (Ascendin), Clomipramine (Anafranil), Doxepin (Sinequan), Imipramine (Tofranil), and Trimipramine (Surmontil).

Monoamine Oxidase Inhibitors - They are not recommended for use in the primary care setting without psychiatric consultation.

Antidepressant discontinuation syndrome

Abrupt withdrawal of any class of antidepressant may be followed by manifestation of a syndrome showing anxiety, dizziness, parasthesiae, insomnia, lethargy, and nightmares. Patients receiving antidepressants with a short half life such as Paroxetine is more prone to this syndrome than antidepressants with a long half life. Such cases may be treated by re instituting the medication, or by switching to an agent which has a longer half life, e.g., Prozac (with a half life of about two weeks).

Supportive therapy - psychotherapy and medication when used concurrently have been shown to have better effects than when either is used by itself.

Follow up in the outpatient setting

A recent study has shown that a program of systematic follow up and case management by telephone, of patients treated for depression with antidepressants significantly improved the outcomes¹⁴.

Psychiatric consultation

Patients with suicidal tendencies, psychotic symptoms, extremely severe depression, and a history of bipolar disorder should be referred to a psychiatrist. Failure of two medication trials is also an indication¹¹ for referral.

Conclusion

Successful treatment of depression by the primary care physician requires evaluation of the history, previous successful treatment of depression, responses to treatment with antidepressants, and current medication status before initiation of an antidepressant. Appropriate antidepressant dosage and duration of treatment is important. Primary care physicians should be comfortable in managing the side effects of the medications and decide when to change the medication, and refer to a psychiatrist.

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About the Author

Wineetha S. Fernando is an Associate Professor of the American College of General Physicians. She is a general physician practicing in the State of Kansas.

This article represents soley the opinion of the author and does not reflect the official policy of the American Academy of General Physicians nor the institutions with which the author is affiliated.

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