Depression is a widespread disease in our society today. Epidemiologists believe that between 8% and 19% of the general population suffers from the disorder. Indirect and direct yearly expenditures associated with depression disorders have been estimated to exceed $40 billion. It is particularly important for pharmacists involved in providing home pharmaceutical services to recognize that an estimated 6%–8% of all outpatients have symptoms of depression, leading clinicians to conclude that this is a relatively common comorbid state.

Data collected by researchers from the National Institute of Mental Health’s Epidemiologic Catchment Area Program suggest that the risk of psychiatric illness may be greater in patients who have multiple, chronic, nonpsychiatric medical conditions than in those individuals who do not have concurrent illnesses. The rate of depression coexisting with medical illnesses has been known to vary with the illness; however, this rate usually does exceed that reported for the general population.

As would be expected, patients suffering from cancer, cardiovascular disease, dementia, diabetes, Parkinson’s disease and stroke are likely candidates to exhibit depressive symptoms associated with their illness. These patients may develop somatic complaints that are typically associated with depression, such as pain, low energy and sexual dysfunctioning.

Recognizing Depression

The signs and symptoms associated with the clinical presentation of a major depressive episode are categorized by health-care pro-viders into psychological and somatic symptoms and vegetative signs. Psychological and somatic symptoms associated with depression include sadness and a sad expression, a markedly diminished interest in all aspects of life, hopelessness, low self-esteem or feelings of worthlessness, inappropriate guilt, recurrent thoughts of death (possibly including suicide with or without a specific attempt) and complaints of vague aches and pains.

Vegetative signs include changes in appetite or weight (usually loss of weight), sleep disturbances (usually early morning wakening), decreased energy and unexplained fatigue, psychomotor retardation (diminished ability to concentrate or remember, etc.) decreased sex drive, irregular menses, gastrointestinal upset (constipation, diarrhea, etc.) and biochemical abnormalities.

Particularly common symptoms of depression include a depressed mood, decreased interest or pleasure in activities, changes in appetite, weight or sleep, psychomotor agitation or retardation, loss of energy, inability to concentrate, indecisiveness and thoughts of death, dying or suicide. It is especially alarming to note that when they are left untreated, 25%–30% of adult patients with depression will commit suicide. Specific diagnostic criteria for a major depressive episode have been established and are published in the Diagnostic and Statistical Manual of Mental Disorders.

Other important depressive illnesses that should be considered include dysthymia, atypical depression and delusional depression. Individuals with dysthymia experience depressed moods most of the time for at least two years, are never without a depressed mood more than two months and have at least two vegetative symptoms. Patients with atypical depression are found to have a persistent feeling of anxiety along with symptoms of depression. These individuals often have a reversal of vegetative signs (overeating instead of losing weight, hypersomnia instead of insomnia) and also maintain some degree of enjoyment in activities. The patient with delusional depression has significant psychotic symptoms often resulting in a need for antipsychotic medication in combination with antidepressant drugs. Electroconvulsive therapy (ECT) is also an important means of treating patients with delusional depression.

Drug-Induced Depression

Pharmacists must consider the possibility of drug-induced depression in their home health care patients, most of whom are maintained on prescription or OTCmedication. Many drugs have been implicated, including anti-inflammatory agents (indomethacin, etc.), analgesics (pentazocine, etc.), antimicrobial agents (sulfonamides, ethambutol, cycloserine, etc.), cardiovascular/antihypertensive drugs (digitalis, clonidine, guanethidine, methyldopa, reserpine, hydralazine, propranolol, prazocin, etc.), medications that affect the central nervous system (amantadine, levodopa, barbiturates, chloral hydrate, carbamazepine, benzodiazepines, alcohol, etc.), hormonal agents (corticosteroids, estrogen, progesterone, etc.) and other miscellaneous drugs (disulfiram, physostigmine, antineoplastic drugs, exposure to organic pesticides, etc.).

Whenever there is suspicion that the patient’s medication regimen is responsible for causing the depression, the clinician should not only consider the drugs that the patient is taking, but also consider the temporal relationship between starting a particular drug and the occurrence of the depressive symptoms, the medical necessity for the drugs or drugs that are being used, the potential for a drug interaction to be responsible and the possibility that the patient is misusing drugs of abuse or alcohol.

Other Factors to Consider

Clinicians are often challenged when they must differentiate between depression and dementia. This problem results from the high rate of comorbidity and symptom overlap associated with these two disorders. There are some factors that can help with determining which disorder is present. Depression has a relatively rapid onset which differs from the insidious and indeterminate onset of dementia. Both types of patients have a depressed mood; however, the orientation of the depression patient is intact, while that of the dementia patient is impaired.

Another notable difference between these patients is that the patient suffering from depression has a depressed/anxious affect, unlike that of the dementia patient, which is labile and variable. The depressed patient’s ability to concentrate is inconsistent, yet patients with dementia usually have consistent recent memory potential. The disabling nature of depression is often highlighted by patients, which is quite different from dementia patients, who try to conceal their ailment. As would be expected, there is no neurologic deficit that is classically associated with depression; however, this may be present in dementia.

Patient Monitoring

The treatment options for depression include various psychotherapies, ECT, light therapy, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressant drugs (TCAs) and the newer nontricyclic antidepressant agents, such as SSRIs. The potency and complex mechanisms of action of current pharmaceutical therapies require the pharmacist to carefully monitor patients treated with such agents. Pharmacists should check for drug interactions and possible adverse drug reactions by carefully reviewing the patient’s most recent medication profile.

Counseling these patients may become particularly challenging due to the nature of their illness; therefore, it may be advisable or at times even necessary to obtain the assistance of the patient’s caregiver. Although it is beyond the scope of this article to discuss the pharmacologic management of depression in detail, the interested reader is referred to the excellent recent review articles written by Hartman and Watanabe and Jesson for additional information.

The brain’s emotional mechanism is not completely understood, but research shows that the relationship between food and mood makes up one of the brain-body links. Mood seems to be influenced by the neurotransmitter serotonin, the lack of which makes people feel depressed. Depressed people often crave carbohydrate foods foods. Eating carbohydrates increases the brain’s production of serotonin, which can lead to a heightened sense of calmness and well being. Boosting the amount of the neurotransmitter norepinephrine, that also elevates a person’s spirit, along with alertness and concentration, can be achieved by eating protein.

If you anticipate feeling anxious before a test or an interview, what could you eat to help make you feel both calm and alert? Claudia Lutz, RD, MPH, whose area of expertise is nutrition education, suggests that a good combination, eaten about an hour before the event, might be nonfat yogurt with some fruit juice and fruit. The dairy provides protein and tryptophan, the amino acid that begins the production of serotonin (5-hydroxytryptamine). You may want to give yourself a good start by getting a good night’s sleep the day before, she adds, by having no caffeine eight hours before bed time and a minimal amount earlier in the day.

Dietary choices. For examples of meals that may help you feel more alert or more relaxed, refer to CyberDiet’s article on Moods and Foods. For a “feel good” treat, eat chocolate, which contains caffeine, theobromine, and phenylethylamine, which stimulate the nervous system and produce brain endorphins (”internal morphines”).

Dietary changes, as well as nutrient and herbal supplements, can be part of an approach to relieving mild to moderate depression or anxiety. However, diagnosis of deficiencies may require a nutritionally oriented doctor, and a healthcare professional knowledgeable in the field of nutrition or medicinal plants should supervise any supplementation.

The following recommendations may be helpful.

Dietary changes. If you’re depressed, it’s advised that you avoid alcohol, as it is a powerful depressant and can make you feel worse. Additionally, alcohol depletes the body of vitamins essential to good mental health. People experiencing depression may also want to avoid sugar and caffeine to see how it affects their mood. Too much of either can lead to a crash or fatigue. Because of increased susceptibility to its stimulating effect, people experiencing anxiety should also avoid all sources of caffeine, including chocolate.

Vitamins and supplements. Iron deficiency can cause fatigue and worsen depression. Good sources of dietary iron are found in oysters, meat, poultry, fish, green leafy vegetables, wine, and acidic foods cooked in an iron pan. Iron supplements should not be taken unless a deficiency has been diagnosed, because too much can cause oxidative damage.

Deficiencies in the B vitamins can create disturbances in mood and mental processes. Vitamin B folic acid, or folate, is needed to make SAMe (S-adenosyl-L-methionine), which appears to increase levels of dopamine, a neurotransmitter that affects mood. Folate is found in dried peas and beans, dark green leafy vegetables, citrus fruits, and wheat germ. Vitamin B12 is also needed for the production of SAMe and is found in dairy, eggs, poultry, fish, and meat. Oral contraceptives can deplete the body of Vitamin B6, which is needed to make serotonin, dopamine, and the hormone melatonin. Vitamin B6 supplementation may help alleviate depression related to premenstrual syndrome. Good sources of Vitamin B6 are found in turkey, tuna, lentils, potatoes, and bananas.

Herbal remedies. St. John’s wort extract, widely prescribed in Germany to treat mild to moderate depression, is noted in Phytomedicine 1995, to significantly relieve such symptoms as sadness, worthlessness, and fatigue. Recent research, reported in Pharmacopsychiatry 1997, suggests that St. John’s wort extract has an antidepressant action by inhibiting the reuptake of neurotransmitters serotonin, neorepinephrine, and dopamine, thereby making them more available to the brain. Ginkgo biloba, which has been shown (Am J Therapeutics, 1996) to increase concentration and memory, may also relieve depression in elderly people.

Extensively studied, the primary healing plant remedy used to treat anxiety is kava extract, which has active ingredients that may have antianxiety effects. Other botanicals, not well studied but safely used historically to treat anxiety, include passion flower and valerian.

Research on how to improve the brain’s functioning continues, with the aging generation of the baby boom eagerly awaiting identification of protective foods and plants. In the meantime, Lutz reminds us that we can make some improvements now in our mental health by assessing the soundness of our nutrition. Ask yourself the following questions. How much do you eat? When? What types of food? Are you getting enough water, adequate protein, lots of complex carbohydrates and fruits and vegetables? What nutrients are you sparing or restricting? How much caffeine and alcohol do you take? Let your answers guide you to make some corrective changes. If you need help, seek the counsel of a licensed, registered dietician.

Caveat. If you experience depression or anxiety that is severe, recurrent, or constant, it’s important that you seek expert medical care. Accurate diagnosis is critical to determining the appropriate treatment. Biochemical or physical causes need to be ruled out. For example, low thyroid function can cause depression that can be successfully treated with prescription thyroid medication. Additionally, the need for psychotherapeutic drugs and/or psychotherapy should be evaluated. For example, antidepressant medication may be required to relieve utter hopelessness or suicidal thoughts. Or cognitive behavior therapy may be necessary to relieve anxiety by teaching relaxation techniques and facilitating the development of better coping skills in stressful situations.

Many factors that put individuals at risk for stroke have been identified, including physical inactivity, high cholesterol, obesity, use of alcohol or cigarettes, diabetes and high blood pressure. For the first time, researchers have identified a psychological factor that also affects stroke risk — depression.

A study published in the July/August issue of Psychosomatic Medicine reports that increasingly, levels of depression are associated with increasing levels of risk for later stroke. This was true even for those who had only moderate symptoms of depression, and who might not actually be diagnosed with clinical depression.

“The suggestion of an increasingly strong relationship between level of depressive symptoms and stroke indicates that reducing depression may be important for everyone, not just those whose symptoms may have clinical implications,” stated Dr. Bruce S. Jonas of the National Center for Health Statistics in Hyattsville, Maryland, part of the Centers for Disease Control and Prevention (CDC).

Jonas and colleagues looked at a nationally representative sample of more than 6,000 adults, ages 25 to 74, when the National Health and Nutrition Examination Survey began in the early 1970s. The researchers surveyed participants periodically for an average of 18 years. They analyzed the information collected to see if symptoms of depression reported at the beginning of the study were related to incidence of stroke over the following decades. They discovered a strong relationship.

Scores on the depression questionnaire were sorted into high, medium and low. People who reported high levels of depressive symptoms were 73 percent more likely to have a stroke over the next two decades than those with low levels. Even those with moderate levels of symptoms had a 25 percent increase in risk.

To see if their findings were influenced by the other known risk factors for stroke, Jonas and colleagues tried several different analyses. However, even when they accounted for age and the existence of other risk factors, the results were similar. The researchers even tried excluding people who had strokes within a few years of completing the depression questionnaire, to see if changes that were already happening to their bodies might influence the relationship — but depression still predicted later stroke.

Jonas and colleagues also report gender and racial differences in the association between depression and stroke. Among white men, white women, and all African-Americans (there weren’t enough to group the sexes separately), higher levels of depressive symptoms were significantly related to an increased risk of stroke, regardless of whether age and other risk factors were taken into account. No differences, however, were found between those 25 to 59 years of age and those 60 to 74.

These findings do not mean that the other risk factors aren’t important, Jonas points out. “Risk factors such as baseline age, gender, smoking status, systolic blood pressure, serum cholesterol level, history of diabetes and history of heart disease remain strong predictors of developing stroke,” he explained. “However, this study indicates that depression levels may also play an important role.”

The researchers point out that depression increased the risk of stroke about as much as would a 40-point increase in systolic blood pressure.

Overall, 9.1 percent of study participants reported high levels of depressive symptoms, and 32.7 percent reported moderate levels. Among African Americans, 15.7 percent reported high and 35.6 percent moderate, levels.

Researchers don’t fully understand the connection between depression and stroke. The changes in brain chemical activity seen in people with depression may affect the body’s ability to regulate itself and handle stress. Other research has found that depression appears to alter the hormonal and immune systems. Still other studies report increases in platelet activity among depressed people. Depression also appears to be a risk factor for high blood pressure and heart disease, both of which contribute directly to stroke risk.

Clearly, a lot more research is needed to understand how depression affects the risk for stroke. In the meantime, however, the current findings suggest that helping people with symptoms of depression may not only increase their immediate quality of life, but also decrease their risk of having a stroke further down the line.

Various studies have confirmed the prevalence of depression among chronic pain patients, with 50% to 65% of them typically being diagnosed as depressed. It has been shown that depressed chronic pain patients are less likely to respond to treatment for their pain, and that among low-back pain patients, it is the depressed ones who are most likely to avoid physical activity. It is also possible that depressed patients feel their pain more severely than others. All of this means that depression signals a worse prognosis for a chronic pain patient.

Since pain is harder to treat than depression, antidepressive therapy is often the best first step on the road to curing chronic pain. Numerous attempts have been made to produce a model capable of predicting the chances of depression in chronic pain patients, but results have generally been equivocal or contradictory. This study tried to do the same, looking at a wide range of demographic, pain-related, and work-related criteria.

The basic sample under study consisted of 254 patients who had all experienced chronic pain for at least six months. Their average age was 40, and the average duration of their pain was five years. Two-thirds were unemployed, while one-third were receiving compensation for work-related injuries. Two-thirds were married and two-thirds were white, with women comprising fractionally over half of the study population. A quarter were involved in litigation while a further third planned it.

Depression was evaluated according to the Beck Depression Inventory, a standard tool for 30 years. This questionnaire contains 21 symptoms and asks patients to rate the severity of each on a scale of one to four, by choosing the statement that best represents their experience of that symptom. It has been shown in the past to be a valid method of measuring depression in chronic pain patients. The average score of the 254 patients was 15.82 out of a possible 63, with the least depressed scoring seven and the most depressed 50.

The strongest single predictor of depression was work status. Consistent with previous findings in healthy as well as chronic pain patients, it was found that employment is important to the average adult’s self-esteem, and lack of a job made depression considerably more likely.

Among unemployed patients, the prospect of litigating over their injury was a great consolation, but the benefit wore off once the process actually had to be confronted. Among working patients, the effect was the opposite — it was those considering or pursuing litigation against their employers who were most likely to be unhappy. This may be because of the awkward position in which they found themselves as employees, or merely due, as the authors speculate, to the contradiction inherent in working while suing the company.

After work status, the factor that correlated most clearly with depression was the patient’s level of education. Those with less schooling were notably more vulnerable to depression. This may be due to the greater likelihood that their employment had been of a physical nature, and therefore was more likely to be affected by injury and subsequent pain. Many of the less well-educated patients lived in small towns where the alternatives available to them were more limited. Finally, the authors suggest that a less flexible way of thinking may cause poorly-educated people to overlook alternatives and ways of coping that others might have seen.

The unmarried were less able to cope with their suffering than those who had a partner to lean on. Again, this is a common finding in depression studies, but its validity here is somewhat weakened by the fact that the divorced, widowed and cohabiting were lumped together in the “single” group. As a rule, cohabitors are happier than other single people, while divorcees and the recently widowed tend to be the most depressed.

Ethnicity was found to bear no relation to stress, although, again, the findings might have been different if the study had distinguished between different categories of nonwhite. Small sample size, however, precluded this refinement.

Comparisons of age and gender led to what are probably the most interesting results to come out of this survey. It was found that among women, depression declined with age, while among men it worsened. Thus, among those under 40, women were most affected, but among those older than this it was men who had the highest Beck scores. This is not at all a common finding in depression studies not looking at chronic pain sufferers. No obvious reason for this trend presents itself.

As for the degree and duration of the pain itself, this had remarkably little effect on the patients’ mental state. The number of surgical interventions undergone, the number of drugs being taken for pain, and the subjective assessment of suffering on a one-to-10 point scale were all found to bear no significant correlation to patient depression. Only the overall duration of the chronic pain was found to have an effect, with long-term patients the most depressed. This effect, too, was less pronounced than many demographic factors.

At the end of the day, this survey provides a rough guide to the sort of patients most likely to be emotionally laid low by injury, but the small size of the sample and the difficulty in separating various risk factors means there is still more research needed in this area, particularly as some of these findings contradict previous studies in the same area. The authors are at pains to acknowledge that there is nothing in this study which removes the need to make assessments of depression, in chronic pain patients as in anybody else, on a firmly individual basis.

Depression is an illness that affects many older people. Depression in older people is often triggered by losses that accompany aging, such as loss of a job, good health, and the loss of a spouse or any other significant person or relationship. In some cases, however, it occurs “out of the blue,” for no obvious reason. While depression is considered a mental disorder, its effects on physical health are also well known. In fact, a recent study found that depression may lower the odds of survival among sick older adults.

Previous research had shown that depression is more common among hospitalized older patients. Now, researchers from the San Francisco Veterans Affairs Medical Center in San Francisco, California, have found that depression can interact with medical illnesses, leading to poorer outcomes. In a sample of nearly 600 hospitalized elderly patients, the rate of death was 56 percent higher in patients with six or more depressive symptoms, than in patients with fewer depressive symptoms. Notably, when potentially confounding factors such as disability, physical illness, and mental impairment were eliminated, patients with six or more depressive symptoms continued to have a 34 percent higher mortality rate than other elderly patients.

The researchers speculate that depressive symptoms may contribute to lowered survival rates through various mechanisms, including the inability to seek expert advice or adhere to necessary treatment regimens, the inability to recruit assistance from family and friends, or diminished physical functioning due to lack of activity and exercise.

Fortunately, depression is a highly treatable illness, and complete or partial recovery may be achieved in 80 to 90 percent of cases. Medical professionals, family and friends can all play a vital role in recognizing the symptoms of depression, and helping vulnerable older persons obtain the help they need.

Coronary heart disease (CHD), chest pain, heart attack – they all occur in your chest, right? Well, according to recent research, various forms of heart disease may actually start in your head.

Medical research linking these two topics clearly depicts a bi-directional path of symptom development and disease progression. For instance, previous research has shown that depression is a common problem in patients with coronary heart disease. Major depression is found in nearly 20 percent of patients who have recently had a heart attack. Minor depression is found in more than 25 percent of them. It is also estimated that within one year of a heart attack, one out of three patients will experience major depression.

A study from the University of Munich recently reported that a depressive mood paired with heart disease can intensify perceived chest pain. Patients diagnosed with high levels of depression in the period immediately after a heart attack were three times more likely to experience anginal pain six months later. The authors suggest that their findings point to a pain trigger that may be unrelated to the usual (i.e., nervous) sources. They recommend more broad-based therapeutic interventions following a heart attack, rather than solely conventional anti-anginal treatments.

Depression has also been related to an increased risk for coronary death. These results, uncovered by researchers at the Duke University Medical Center, link depression with impaired baroreflex sensitivity (BRS). BRS refers to the ability of the circulatory system to manage changes in blood pressure. In the Duke study, patients who were severely depressed had a 30 percent reduction in BRS function compared with patients with little or no depressive symptoms. Although based on a small sample, these results suggest that the inability of depressed patients to respond appropriately to blood pressure changes may render them more vulnerable to adverse cardiac events such as heart attack.

Experts have long recognized that many adults with depression had traumatic experiences as children. For example, loss of a parent to death or divorce is a risk factor for adult depression, as is child abuse. Recent research has gone beyond these observed associations to reveal their biological basis.

"There is now ironclad evidence to support the preeminent role of early trauma in the development of adult psychiatric disorders," Emory University professor Charles B. Nemeroff, M.D., told a group of physicians this week at the annual meeting of the American College of Physicians/American Society for Internal Medicine, in Philadelphia.

Nemeroff specializes in clinical neuroscience — the study of the role of the nervous system in clinical conditions such as depression, anxiety, schizophrenia, and so on. He explained that one of the most important findings so far in this area of research is the discovery that compared to non-depressed folks, patients with depression secrete significantly more of the hormone cortisol.

In non-depressed people, levels of cortisol rise and fall in a circadian rhythm — a pattern that repeats every 24 hours. In depressed patients, cortisol levels are higher, and remain elevated throughout a 24-hour period, without the normal rising and falling. According to Nemeroff, these changes in hormone patterns are caused by higher levels of a brain chemical called corticotropin-releasing factor, which is released by the hypothalamus. corticotropin-releasing factor causes the pituitary gland to release another substance called adrenocorticotrophic hormone, known as ACTH, which in turn leads to the secretion of cortisol.

The hypothalmus and pituitary gland are located at the base of the brain, and control the production of many hormones.

corticotropin-releasing factor is also found in other areas of the brain, particularly those that regulate mood and cognition. Increased levels of this chemical cause some symptoms of depression, such as decreases in appetite, sexual interest, and sleep. When researchers began to look at the spinal fluid of depressed patients, says Nemeroff, they discovered high levels of corticotropin-releasing factor. They also discovered that after successful treatment of depression, these high corticotropin-releasing factor levels returned to normal.

Nemeroff knew that child abuse is associated with an increased risk of depression, substance abuse, anxiety disorders, and suicide. He wanted to see if early experiences caused actual brain changes. He used the cortisol findings to study the long-term effect of early experiences in rats. The basic question, he says, is "whether a deprived or uncertain or frankly abusive relationship could have long-term consequences on neurobiology. Does early experience contribute to the development and vulnerability to various psychopathologies?"

In rats, the answer was a definite yes. Nemeroff and his colleagues removed baby rats from their mothers for three hours every day while they were still nursing, leaving them alone in a separate cage for that period. When the pups were grown, he tested them to see if they behaved differently from their littermates.

Not only did the rats that had been isolated from their mothers as pups have higher levels of corticotropin-releasing factor in their spinal fluid as adults, but they also showed a rat version of depression. For example, when offered sugar water in addition to regular water, the test rats weren’t interested. They also responded differently to stressful situations compared to their littermates, and secreted higher levels of cortisol under stress.

"This was the first demonstration that early trauma (being taken from the mom) causes a life-long, persistent super-sensitive stress response," explained Nemeroff. He noted that once the researchers began removing the pups from their mothers, "the moms never treated the pups that are taken from them the same way they do their litter mates." For example, the mother rats were slower to retrieve these pups when they wandered out of the nest, and spent less time nursing them.

"Now for those of you who are beginning to feel a little bit of guilt about child care, let me assure you that you don’t have to," Nemeroff reassured his audience. He explained that when he took pups from their mothers as before, but instead of isolating them put them with "foster mothers," the pups developed normally and were no different from their former littermates as adults.

But what about humans? Nemeroff also described a clinical study with women that will soon be published in the Journal of the American Medical Association. He looked at four groups of women: those who’d been physically or sexually abused as children and were depressed as adults, those who’d been abused but had no history of psychiatric illness, those who were depressed and were not abused as kids, and those who had no history of either abuse or depression.

The women’s levels of cortisol and ACTH were monitored during tasks that caused moderate stress. Those who’d been abused as children showed significantly higher levels of these chemicals than those who hadn’t, and depressed women who’d been abused had the highest levels of all.

"There is no doubt that there is both a genetic and an experiential component to vulnerability to depression," Nemeroff concluded. His research shows that experience actually changes the way the brain works. On the positive side, he reported, his research also shows that these biological changes can be modified with antidepressants. In both rats and humans, medication restores normal levels of these brain chemicals.

For patients with a single episode of mild to moderate major depression, treatment with medication seems to be about as effective as treatment with psychotherapy. In patients with severe episodes, medication is usually recommended. But in patients with chronic depression, the best treatment hasn’t been established, partly because up to one-third of these patients don’t respond well to either treatment.

Now a new study shows that combining medication and psychotherapy for patients with chronic major depression may produce significantly better results than using either of the treatments alone. Furthermore, the study reports a much higher response rate than is usually seen in non-chronic depression.

In a study of more than 500 patients who’d been continuously depressed for at least two years, those who received both treatments for 12 weeks had an overall response rate of 85 percent compared to just over 50 percent for each of the single-treatment groups. Response was defined as either “remission” — achieving a normal score on a commonly used depression measure — or “satisfactory” — reducing one’s score by at least half.

“This is the first time that combination therapy has been proven to be so much more effective than either medication or psychotherapy alone,” stated lead investigator Dr. Martin B. Keller from Brown University in Providence, Rhode Island. “For some of the study patients who underwent combination therapy, it was the first time in more than 20 years that they could sustain pleasure and function fully at work and with family and friends”.

The patients were randomly assigned to receive one of three regimens: the antidepressant nefazodone (Serzone), a form of cognitive-behavior therapy specially designed for patients with chronic depression, or both treatments. Those taking the drug were started at 100 mg twice a day, with the dose increased gradually to between 300 and 620 mg daily. Patients receiving psychotherapy began with two sessions a week, switching to one session a week after four weeks.

The researchers explain that in the specific psychotherapy used, called the “cognitive behavioral-analysis system of psychotherapy,” or CBASP, “patients learn how their cognitive and behavioral patterns produce and perpetuate their interpersonal problems and learn how to remedy maladaptive patterns of interpersonal behavior”. This approach has met with success in some smaller studies, and is based on the well-established system of cognitive therapy.

The researchers, located at 12 centers around the United States, also looked at response rates for all the patients who actually started the study, regardless of whether they completed it. This is important because people who drop out may do so because the treatment isn’t working or because they can’t tolerate its side effects. About one-quarter of each treatment group dropped out. Among those taking nefazodone alone, 14 percent dropped out because of side effects, compared to seven percent of those getting combination therapy. Only about one percent of each group said they quit because their treatment wasn’t effective.

Among these larger groups, combination therapy still produced significantly greater improvements. Just under half of each of the single-treatment groups responded to treatment compared to almost three-quarters of those getting both treatments.

“These findings on the dual treatment approach for the treatment of chronic depression are incredibly exciting,” stated Dr. Madhukar Trivedi of the University of Texas Southwestern Medical Center in Dallas. “The large difference in response rates after only three months of treatment is truly astonishing.”

Despite their enthusiasm, however, the researchers do point out that their findings can’t be generalized to all patients with chronic depression. Writing in the May 18th issue of The New England Journal of Medicine, they note that their study has limitations. The most important of these, writes Dr. Jan Scott of Gartnavel Hospital in Glasgow, Scotland, is the narrow range of patients allowed into the study. In an editorial in the same issue, Dr. Scott points out that because the study excluded patients who had a history of other psychiatric conditions, these results may be of limited help to physicians.

The conditions that were excluded include schizophrenia, psychosis, bipolar disorder, obsessive-compulsive disorder, panic and anxiety disorders, post-traumatic stress syndrome, certain kinds of personality disorders and substance abuse. All of these conditions frequently occur along with depression. But for a study’s results to be clear, patients with more than just depression are usually excluded.

“Concentrating on short-term outcomes creates a snapshot of depression and its treatment that is not easy to reconcile with the realities of clinical practice,” notes Dr. Scott, citing another reason that more research will be needed. For example, long-term follow-up might reveal that the single-treatment groups eventually “catch up” to the combination group. If so, researchers would need to figure out who would benefit most from the early effectiveness of dual treatment.

Overall, however, both Scott and the original researchers agree that these findings are very promising. Both groups call for more research to verify and expand these results to make them as useful as possible for practicing physicians.

Editorial Commentary: Chronic depression is generally considered more difficult to treat than shorter duration depressions. While though an 85 percent response rate is considered excellent for even mild or moderate depressions. Therefore, there is great interest in seeing if this response is sustained, and if so, what about the study explains its high rate of success –the type of psychotherapy, the drug, or the way the study was conducted.