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Depression: Current Research on Body Mind Connections

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Depression: Current Research on Body Mind Connections

Julie A. Slack

Abstract:  Despite a rapid increase in research on the subject of depression in the last few decades, much remains to be discovered on the neurobiology of the disorder.  This paper will attempt to summarize what is now known about depression including definition, etiology, assessment, and treatment options. 


Benjamin Rush, considered by many to be integral to the development of mental health care in this country, wrote in a letter to President Adams the following: “I have endeavored to bring [disease of the mind] down to the level of all other disease of the human body, and to show that the mind and the body are moved by the same causes and subject to the same laws.” (Martin, 2002). He concluded his letter with the hope that “time will do my opinions justice” (Martin, 2002). 

Recently, scientists have begun to discover that the well being of the mind is intertwined intimately with the well being of the body—what effects one will frequently affect the other due to shared nervous, circulatory, immune, and endocrine systems (Lemonick, 2003). With new research indicating depression worsens health outcomes for those with co-existing disease or illness, it is imperative health care professionals become more aware of depression in order to promptly diagnose and effectively treat. 

Currently, depression is nearing an estimated 50 billion dollars annually in lost productivity and care costs (Bailey, 2002). In our fast paced, quick fix mentality, it should come as no surprise that individuals prefer to pop a pill to treat depression solely as a chemical imbalance readily corrected by medication alone, rather than investigate the root cause or pursue other methods of treatment. 

Dr Dennis Charney of the National Institute of Mental Health has stated, “There are many roads to depression, and the circuits are complex” (Moran, 2003, p.1). He continued, “Depression is a heterogenous disease.  We are identifying a circuitry that involves different brain regions that mediate different facets of depression. And we are identifying how different transmitters and neuropeptides regulate those circuits” (Moran, 2003, p.4). 

Diagnostic Criterion

Major depression is diagnosed when at least five of the following symptoms are present during the same time period (at least two weeks) and at least one of the first two symptoms is present.  These symptoms include:
•    Depressed mood most of the day, nearly every day.
•    Markedly diminished interest or pleasure in activities most of the day, nearly every
     day ( as indicated either by subjective account or observation by others of apathy
     most of the time).
•    Significant weight loss or gain.
•    Insomnia or hypersomnia.
•    Psychomotor agitation or retardation.
•    Fatigue or loss of energy.
•    Feelings of worthlessness or guilt.
•    Impaired concentration or indecisiveness.
•    Recurrent thoughts of death or suicide. (American Psychiatric Association, 2000)

Mild depression is characterized by some of the above symptoms being present and extra effort being required to accomplish activities of daily living. Moderate depression involves many of the above symptoms.  Additionally, the symptoms interfere with accomplishing activities of daily living.  Severe depression is present when nearly all of the above symptoms are present and the person experiences an inability to accomplish routine activities of daily living.


 Presenting complaints of those afflicted with depression in primary care settings frequently include:
•    Pain-including abdominal pain, headache pain, and other bodily aches.
•    Low energy – lack of energy, excessive tiredness, or a reduced capacity for
     enjoyment or pleasure.
•    A mood of irritability, anxiety, or apathy may be present, rather than or in addition to any overt sadness.
•    Sexual complaints- problems with sexual functioning or desire.  (AHCPR, p. 5)

These presenting complaints, rather than the ones noted above in the diagnostic criterion, may be due to failure to recognize depression in oneself, fear of social stigma, lack of insurance reimbursement, fear of depression as a lack of character, or some other fear rooted in misinformation.


Depression is the fourth leading cause of disability worldwide and is anticipated to become the second leading cause by the year 2020 (Thomas, Ferrier, Perry, Brown, & O’Brien, 2001).  Although depression afflicts a fair percentage of the general population, the National Institute of Mental Health estimates the disorder will be accurately diagnosed and treated in only one out of every three persons (AHCPR). In the average family practice, approximately six depression cases a week go unrecognized and therefore untreated (Nease, 2003). 

While depression was once thought to be an adult disease affecting 5-12 percent of men and 10-20 percent of women, we now recognize it can affect even the very young (Nemeroff, 1998). The leading cause of youth death is suicide, the most serious risk of depression (Navarrete, 1999). The National Institute of Mental Health now estimates as many as 3-5% of children under the age of 18 experience depression which is approximately 3.4 million children (Navarrete, 1999).

In a study of 123 students, some of whom had a learning disability, 32 responded positively to the questionnaire phrase, “I feel like hurting myself” (Navarrete, 1999). Ten of these 32 met the criteria for severe depression.   Prior to the study, none were being actively treated for depression.  This finding and the statistics above make it more imperative for clinical professionals to become proficient in rapid assessment and diagnosis of this complex disorder among increasingly younger populations. 

Depression also affects the elderly with an estimated prevalence of 2-3% for a diagnosis of major depression and 12-15% for a depressive syndrome (Thomas, Ferrier, Perry, Brown, & O’Brien, 2001). Unfortunately, geriatric psychopathology frequently develops within the context of medical and neurological disorders (Alexopoulos, 2003). “Behavioral abnormalities, cognitive deficits, and physical symptoms and signs are often contributed by more than one psychiatric, neurological, or medical condition” (Alexopoulos, 2003). When treating the elderly, the clinical picture is further complicated as symptoms change over time when co-existing disease processes progress or subside thus increasing the complexity of accurate diagnosis and treatment (Alexopoulos, 2003). 


Genetic Influences

Methodologically rigorous studies have found that major depression is a familial disorder (Sullivan, Neale, & Kendler, 2000). Indeed, the heritability of major depression has been estimated to be in the range of 31-42% (Sullivan, Neale, & Kendler, 2000). However, these family studies cannot distinguish or separate environmental risk factors from the genetic predisposition as both are familial. 

Therefore, many researchers are leaning towards the theory of a genetic defect coupled with an environmental trigger (Lemonick, 2003, Marano, 1999, & Nemeroff, 1998).  The trigger may be one of socioeconomic status, parenting style, neglect, abuse (emotional, physical, or sexual), environmental exposure or some combination of these factors. Persons who have no genetic predisposition may therefore be relatively protected from depression, while those with a genetic endowment of depression coupled with a trigger may find themselves contending with depressive symptoms throughout life (Nemeroff, 1998). 

Neurobiological Influences 

Dr. Ronald Duman of Yale University stated that “it is not possible to explain either the disease or its treatment based solely on levels of neurotransmitters” (Marano, 1999). While it was once thought that depleted serotonin levels were the cause of depression, we now know that the causes of depression and the roles of serotonin and other neurotransmitters are a “far more richly nuanced and dynamic process” (Moran, 2003, p.4). 

The most recent data indicate that depression is a neurodegenerative disorder where disruption in the structure and function of brain cells leads to destruction of nerve cell connections impairing cognitive thought processing (Marano, 1999). In depression, emotional circuits of the brain fail to generate positive feelings or to inhibit disruptive, negative, intrusive thoughts (Marano, 1999). The neurotransmitters involved in modulating those circuits and sustaining connectedness of the emotional circuitry within the brain fail to function effectively (Moran, 2003). 

Hemispheres of the brain function harmoniously in a healthy person, but in one who is suffering from depression one hemisphere may become more dominant. Scientists suspected that increasing visual stimuli to the healthier hemisphere would reduce depressive symptoms.  An experiment was conducted where both sides of the brain were visually stimulated with greater stimulation to the left side. Twenty patients felt better while fifteen felt worse (Mental Health Weekly). These results led researchers to conclude the left side was the healthier side in twenty patients while the right side was healthier in the remaining fifteen.

The prefrontal cortex, especially the left side, is crucial to emotional responses and control of those responses.  The left side has been associated with activation of positive feelings and turning off the amygdala and the negative emotions that may flow from it (Marano, 1999). Failing to activate the left prefrontal cortex may allow the amygdala to run unchecked spewing fear, dread, and other negative feelings onto the unsuspecting human (Marano, 1999).

The right prefrontal cortex is associated with negative feelings as well (Marano, 1999). Individuals may differ in their ability to activate the prefrontal cortex.  Those who experience depression may have a predisposition to right sided activation (Marano, 1999).  Richard Davidson at the University of Wisconsin states that these differences may account for personality types.  An extrovert may have more left sided activation while an introvert who feels anxious and inhibited may have increased right sided activation (Marano, 1999). 

Interestingly enough, a hormone known as cortisol may also be linked to this process.  When the left pre-frontal cortex is active, levels of cortisol (a stress hormone) are low.  However, during periods of stress, the hypothalamus releases additional corticotrophin releasing factor (CRF)which stimulates the pituitary to release adrenocorticotropic hormone (ACTH) which stimulates the adrenals to release more cortisol (Susman, Schmeelk, & Worrall, 1999). Chronic activation of the hypothalamus-pituitary-adrenal (HPA) system may create a predisposition for future medical illness as well as depression (Nemeroff, 1998). 

Anatomically, autopsy research has found that the subgenual prefrontal cortex which sits beneath the corpus collosum and is connected to the hypothalamus is as much as 40% smaller in depressed persons than in non-depressed persons (Marano, 1999).

Perhaps the immune system is implicated as well, although research has yet to prove the connection. Schleifer (2002) reports in a study of 331 adolescents that those with major depression had higher circulating levels of lymphocytes including T, B, CD4+, and CD29+ cells (Schleifer, Bartlett, & Keller, 2002). They also found lower levels of HLA-DR+ lymphocytes and possibly lower percentages of the natural killer cells known as CD56+ (Schleifer, Bartlett, & Keller, 2002). These findings bear further investigation as to whether they are associated with adolescence itself or if they in some way may trigger an adult immune dysfunction related to early onset of an episode of major depression during adolescence.

Another area of research is focusing on the role of norepinephrine.  Apparently, a depletion can lead to depression, while an excess can lead to a manic episode (Nemeroff, 1998).  Norepinephrine is a critical neurotransmitter from the brain stem throughout the limbic system and may be proven to play a significant role in regulating emotions (Nemeroff, 1998). Among those committing suicide, autopsy studies have revealed increased norepinephrine receptor sites (Nemeroff, 1998).  This phenomena is known as “up-regulation” and results when there is a low supply and therefore more receptors are created to demand and accept whatever norepinephrine is available in the synapse (Nemeroff, 1998). 

Neurobiologists are now leaning towards a theory of a certain level of plasticity within the human brain. According to this theory, effective antidepressant treatments exert their effect by creating /stimulating nerve development and new neurocircuitry within the brain which creates new ways of being in response to life’s challenges, a type of behavioral flexibility (Marano, 1999). 

Dr. Bruce McEwen stated, “We thought that after birth, the brain is a stable organ like a computer that just works away, and no more new nerve cells are produced.  The emphasis was on chemical imbalances, as if the circuitry itself was fairly stable…[now]…the idea that there are long lasting, even permanent, changes in structure and function that can affect the way brains process information is the most important part of what we are doing in the lab” (Marano, 1999). 

A specific nerve growth factor known as brain-derived neutrophic factor (BDNF) has recently been discovered (Marano, 1999).  This substance strengthens synaptic connections in the hippocampus where learning and memory are concentrated (Marano, 1999).  This substance is also associated with growth of neurons that are serotonin responsive (Marano, 1999). 

Environmental Influences

Early life experiences may shape the wiring within the brain and create a predisposition to neuroimpairments in the future. Indeed, research in animals supports this theory and indicates that stress early in life does create disruption of nerve circuits creating predisposition for depression later in life (Marano, 1999).
Stress appears to exert an effect on the hippocampus by changing the shape, size, and number of neurons present within this important brain center (Marano, 1999).  Brain-derived neutrophic factor (BDNF) levels are also adversely affected by stress either social or environmental (Marano, 1999). 

Vitamin B12 and folate are intrinsically involved in the one-carbon metabolism essential for producing monamine neurotransmitters (Tiemeier, Tuijl, et al, 2002). Folate deficiency is related to decreased or loss of appetite and may also be a contributing trigger in the development of depression (Tiemeier, Tuijl, et al, 2002). 

In the Rotterdam Study, researchers found after adjusting for age, gender, alcohol consumption, smoking, education, and cognitive functioning that those who had a vitamin B12 deficiency were 70% more likely to have a depressive disorder (Tiemeier, Tuijl, et al, 2002). However, it is difficult to ascertain if the depression precedes the B12 deficiency or if the deficiency is the cause of the depression. 



Depression screening instruments need to be easy to administer and interpret as most patients are initially seen in a family practice clinic and may be complaining of something other than depression. Vital signs are routinely addressed at each office visit.  Now the Joint Commission on the Accreditation of Health Care Organizations has listed pain as the fifth vital sign in addition to the commonly accepted temperature, pulse, blood pressure and respiratory rate.  Perhaps, depression score needs to be added as the sixth vital sign. 

Many review studies have been completed examining the currently available depression scales and scoring tools.  Clinicians should avail themselves of this information and make an informed choice as to which of the tools will work best in their practice. A comparison table of common assessment tools may be accessed at (Sharp, 2002). 

Neurological Testing

Neuroimaging techniques experienced a surge of development late in the last century.  Now, the range of techniques available are anticipated to vastly increase understanding of brain function. These techniques include regional cerebral blood flow studies (rCBF), positron emission tomography (PET or PET scan), single photon emission computed tomography (SPECT), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)(Hendren, DeBacker, & Pandina, 2000).

Bower (1999) reports on a positron emission tomography study where women were asked to recall a sad experience.  The PET scan revealed images of increased blood flow to the emotional areas of the brain with decreased blood flow to the parts of the brain related to attention and executive functioning. This finding supports the wandering thoughts and indecisiveness that frequently affects those suffering from depression (Bower, 1999). 

In a similar study which focused on men who had been treated and recovered from depression, the researchers found that men had an increase in blood flow to the attention centers of the brain and a decreased blood flow to the emotional centers of the brain. One might conclude from this research that antidepressants function by decreasing emotion and increasing one’s ability to pay attention and problem solve. 

In an outpatient study of 24 depressed adults and 16 control adults, PET scans noted increased activity in three brain areas—the caudate, the thalamus, and the prefrontal cortex (Bower, 2001). The depressed persons were allowed to choose either psychotherapy or antidepressant medication. Fourteen chose the former and ten chose the latter.  At the next scan, those who had participated in psychotherapy had increased activity on the left side of the insula which is an area of the brain that regulates sad feelings and may reduce symptoms of depression (Bower, 2001). Caudate activity was equally affected by psychotherapy and antidepressant therapy.  An overall reduction in activity was noted in the motor center of the caudate (Bower, 2001).  However, the reason for the reduction of activity is not clear.  This appears to be in contradiction as one would think that an increase in motor activity associated with increased control would result rather than a lessening of activity. 

Generally, depression is associated with slowed motor activity, which causes one to question why there would be increased activity in the motor center of the caudate during depression and a decrease as the depression lifts?  Definitely more study is indicated of this phenomena.

In an MRI study of 65 subjects hospitalized with depression and 18 controls, a significantly smaller ratio of frontal lobe to total cerebral volume was noted among depressed subjects (Hendren, DeBacker, & Pandina, 2000). The depressed subjects also had a significantly larger ratio of lateral ventricles to total cerebral volume compared to controls (Hendren, DeBacker, & Pandina, 2000). 

These findings support the body-mind theory of interconnectedness.  Unfortunately, we cannot yet differentiate between observed effects and causation.  As non-invasive imaging techniques become more affordable, we may be able to perform baseline routine scans and observe change over time in response to life events and biochemical changes.



In treating depression, medication therapy is individualized in order to optimize the treatment benefits and reduce side effects and/or risks. Considerations when prescribing medication include the age of the patient, presence of co-morbid disease, allergies, potential for drug interactions, anticipated therapeutic benefit, potential short and/or long term side effects, previous response or lack of response to medication. Generally, geriatric and pediatric patients are started at lower doses.

Seventy percent of those prescribed antidepressants will obtain significant short term relief (Carlin, 1997). Thirty percent will find drugs ineffective (Carlin, 1997). Ideally, medication therapy will be continued through an acute phase, a stabilization or continuation phase, and then a maintenance phase prior to discontinuing it (AHCPR, p. 16) 

Each year nearly 35,000 Americans commit suicide (Carlin, 1997). Antidepressants work by eliminating symptoms and enhancing one’s motivation and energy (Marano, 1999). Seventy percent of those prescribed antidepressant medication find relief in 6-10 weeks (Marano, 2003).  Although researchers are unsure of the exact functioning of antidepressants, it appears they chemically interact and tweak levels of neurotransmitters to improve chemical signals within the brain (Lemonick, 2003). Most appear to work on more than one neurotransmitter and by both direct and indirect actions (Surgeon General). Medication may be the first line of treatment to facilitate a decrease in the rate of suicide.

The most commonly prescribed classification of medication to treat depression are the selective serotonin reuptake inhibitors (SSRIs). There is no real advantage to prescribing one SSRI over another as they are more similar than different (Surgeon General). Seventy percent of those who use SSRIs are affected by sexual side effects (Marano, 1999). 

To increase medication adherence, some physicians may be comfortable having a patient periodically skip a couple of days of dosing to restore sexual desire and function. Others may add Wellbutrin to an SSRI dosing regimen.  Unfortunately, some may even feel that sexual side effects are just the price one has to pay to relieve the depression. Or, patients may be hesitant to describe the sexual side effects and instead stop taking medication altogether. 

Prozac, a popular SSRI,  has been used successfully to treat depression for more than a decade.  A recent PET scan study noted that Prozac boosts the activity and metabolism in the brain stem and the hippocampus (Science News).

A potential side effect of the SSRIs is undesired weight gain. Some physicians may prefer to prescribe non-SSRIs, such as Serzone or bupropion, to reduce the risk of unnecessary weight gain (Marano, 2003). Buproprion appears to have a “novel neurochemical profile in terms of dopamine and norepinephrine” which helps to decrease anxiety as well as lift depression (Surgeon General). 

In the elderly, medications such as a dopamine D3 agonist which enhance the functioning of the frontostriatal circuitry neurotransmitters may have a positive effect and lessen symptoms of depression as well as improving cognition (Alexopoulos, 2003). It may be necessary or even advantageous to augment antidepressant medication with a medication that increases alertness such as modafinil (Alexopoulos, 2003).

It is important for persons taking prescription antidepressants to reduce dosages and wean from medication rather than discontinue abruptly. Abrupt cessation can lead to a withdrawal syndrome with presenting symptoms of gastrointestinal or somatic complaints, sleep disruption, mood fluctuations, and movement disorders (Ackerman & Williams, 2002). Limiting dosages to lowest therapeutic dose will minimize risk of withdrawal syndrome as well as minimize adverse risks to medication therapy. 

Substance P antagonists (SPA) are a new class of medications which may be effective in treating anxiety and depression (Manisses Communication Group, April 2003). Aprepitant, an SPA, was used in a clinical trial compared to paroxetine and placebo.  In 213 patients (including controls), the aprepitant was significantly better in reducing depressive symptoms than the placebo but similar to the paroxetine (Manisses Communication Group, April 2003).  In addition to reducing depressive symptoms, the aprepitant was also effective in reducing anxiety symptoms in this study. 


Psychotherapy is generally recognized as taking longer to exert its effect, but the effects are longer lasting and extend well beyond the initial treatment period (Bailey, 2002). Some therapists are concerned that by prescribing medication, we are allowing patients to mask symptoms and “feel happy” while not addressing the issues that caused the depression in the first place. Psychotherapy promotes adaptation and growth in an individual with increased/renewed coping skills to manage the complexities of life more competently.

Cognitive behavioral therapy (CBT) “involves identification and confrontation of thoughts that perpetuate depression [cognitive] and a conscious effort to decrease behaviors that reinforce depression while engaging in more positive and productive activities [behavioral]” (Ackerman & Williams, 2002).  Problem solving therapy involves “training patients to approach tasks that feel insurmountable by conceptualizing and approaching them as smaller, more manageable problems” (Ackerman & Williams, 2002). 

Combination Treatment

The best treatment plan usually involves medication commonly with an SSRI and a form of psychotherapy.  Usually behavioral and/or cognitive techniques are recognized as most successful (Marano, 1999). 

Alternative Treatments

Why would someone consider alternative treatments?  Well, for many, the answer lies in the adverse effects experienced with antidepressant medication.  Side effects commonly complained of include sexual dysfunction, nausea, drowsiness, diarrhea, restlessness or agitation, weight gain, and sleep disturbances.

Alternative Medicine

Dr. William Walsh (2002) gathered biochemical data on 3000 persons diagnosed with clinical depression.  He discovered that depression is “not a single condition”, but rather “an umbrella term covering several completely different conditions” (Walsh, 2002). His biochemical classifications include: High histamine, low histamine, pyroluria, hypercupremia (high copper), and toxic overload.

The high histamine diagnosis is associated with low levels of dopamine, serotonin, and norepinephrine (Walsh, 2002). The optimal range of histamine is between 40 and 70 mcg/dl (Walsh, 2002). Treatment for this condition includes calcium, methionine, SAM-e, magnesium, zinc, omega-3 fatty acids, B6, inositol, and vitamins A, C, and E (Walsh, 2002).

The low histamine patient tends to be nervous, anxious, and prone to despair and paranoia (Walsh, 2002). Treatment extends for 2-4 months and includes vitamins B3, C, and B12 as well as other nutritional supplements including omega 3 fatty acids, manganese, zinc, and choline.

The biochemical signature of pyroluria is one of low levels of arachidonic acid, a double deficiency of B6 and zinc, and elevated urine kryptopyrroles (Walsh, 2002). Symptoms include frequent infections, temper outbursts, anxious depression, mood swings, inability to eat breakfast, and absence of dream recall (Walsh, 2002). Persons with this disorder readily respond to treatment with B6, zinc, omega-3 fatty acids, and nutrient supplementation (Walsh, 2002). A positive response is generally achieved within seven days and the imbalance is corrected within 1-2 months (Walsh, 2002).

High copper is a strictly female disorder and the most common of these five biochemical signatures of depression for women to experience (Walsh, 2002). Serum copper levels may be above 140 mcg/dl (Walsh, 2002). Treatment includes zinc in increasing doses and avoidance of copper containing foods, supplements, and environments (Walsh, 2002). 

Toxic overload can occur as a response to lead, cadmium, mercury, and/or a variety of inorganic and organic chemicals (Walsh, 2002). Treatment involves recognition of the type of toxicity and use of appropriate detoxification treatment to avoid kidney damage while restoring health (Walsh, 2002). 

When treating depression with alternative methods, the clinician is encouraged to obtain up-to-date research based information from reliable sources. Additionally, it is important to recognize that depression affects individuals in vastly different ways.  A particular treatment methodology may result in a worsening of symptoms before a gradual improvement occurs or may actually be worsening the condition even though improvement appears to be occurring (Walsh, 2002).  Caution and careful record keeping is indicated by both patient and clinician to track an individual’s response over time. 

Homeopathic Remedies

Homeopathic remedies purportedly do result in a cure for responsive patients, which may make them a more attractive option than medication or psychotherapy. In a recent study of 12 patients with depression or social phobia, homeopathic remedies were prescribed with a 58 percent favorable response (Ullman, 2002). Homeopathic remedies for depression include natrum muriaticum, aurum metallicum, staphysagria, phosphoricum acidum,  pulsatilla, calcarea carbonica, sepia, and ignatia.  As with any medication, each has its indications.

A dose of a single preparation of 30X or 30C potency is taken every six to twelve hours up to four doses until depression lifts (Ullman, 2002). If depression does not lift, waiting 72 hours and then using either an alternative remedy or seeing a homeopath is recommended (Ullman, 2002). 

Homeopathic remedies sometimes produce side effects including rash, cough, nasal discharge, onset of menses, and other symptoms (Ullman, 2002). These side effects generally resolve within a few hours to a few days and are usually well tolerated if the depression has lifted (Ullman, 2002). 

Herbal Supplements

St. John’s Wort worked in a German study against moderate depression as effectively as synthetic drugs with fewer side effects (Carlin, 1997). However, in a multisite placebo controlled trial examining St. John’s Wort in 200 patients who met inclusion criteria for severe depression, those who were randomized to the placebo experienced similar effects as those randomized to the active St. John’s Wort (Tatum, 2001).  These researchers recommended that given the seriousness of major depression and the recognized effectiveness of antidepressant medication, that St. John’s Wort should not be a first line treatment for major depression (Tatum, 2001). 

Many other published studies of St. John’s Wort have had similar results with some proving efficacy and some indicating ineffectiveness. Unfortunately, this phenomena may be more due to study design than actual variances in effectiveness. Therefore, clinicians should conduct further investigation and encourage patients through education to make an informed choice.

Nutritional Supplements

Omega-3 fatty acids, and S-adenosyl-L-methionine (SAM-e) are being investigated as alternative therapies. In a study of SAM-e compared to imipramine, researchers found efficacy did not differ statistically.  However, adverse effects were fewer with SAM-e than with the imipramine (Chiaie, 2003).

SAM-e is a methyl-donor molecule that appears to be involved in numerous metabolic pathways.  Its usage in depression may be effective because methylation may be involved in the symptoms of the disorder. 

Since the 1980s more than 40 studies regarding SAM-e and its use in treating depression have been published (Walsh-D’Epiro, 2000). In a meta-analysis of 6 studies comparing SAM-e with placebo and 7 studies comparing it with typical antidepressants, SAM-e was found to be superior to placebo and comparable to the antidepressant (Walsh-D’Epiro, 2000). SAM-e and other supplements which have yet to be discovered may be a viable alternative for those who prefer not to take a prescription medication. 


Exercise on a regular basis reduces anxiety and lessens negative thoughts (Carlin, 1997). However, most exercise studies used groups or supervised exercise.  This makes it difficult to determine if the exercise was the effective tool in reducing depression or if the increased socialization was partly responsible (Lawlor, 2001).  More trials need to be conducted on this to determine overall effects and benefits. 

In a study of 156 persons with depression randomized to either exercise, antidepressant therapy, or a combination of exercise and antidepressant therapy, researchers found that exercise was as effective as sertraline in treating major depressive disorder (Miser, 2000). The sertraline worked faster and more patients continued with the antidepressant therapy than the exercise program (Miser, 2000).  The researchers recommended that for those whom exercise might be contraindicated that antidepressant therapy should be prescribed (Miser, 2000). For those who might be reluctant to take a daily medication or who might want to try an alternative approach, group aerobic exercise may be very effective (Miser, 2000). 


Acupuncture may work by enhancing higher levels of serotonin and endorphins within the brain (Carlin, 1997). In a study of 38 clinically depressed women, researchers found that those treated with acupuncture experienced significant relief.  Once the trial was over, all participants were given acupuncture resulting in 70% experiencing a drop in depressive symptoms, which is comparable to antidepressant therapy (Sussex Publishers, 1999). 

Adjunct medication therapy

Psychostimulants including Adderall, Dexedrine, and Ritalin have all been prescribed as adjuncts to antidepressant therapy (Marano, 2003).  These medications are generally used to treat attention deficit disorder or narcolepsy.  Their value to depressed patients appears to be one of boosting the efficacy of the antidepressant or in reducing drowsiness and improving executive functioning.


 If depression is the result of a combination of factors, then the best chance for a cure is to investigate and explore every recognized health promoting tool in order to correct the underlying emotional cause, right the brain chemistry, and enhance functioning. These tools may include drug therapy, psychotherapy, nutrition, exercise, meditation, acupuncture, and social engagement. (Carlin, 1997).

Nesse states it best when he says, “Patients who believe that depression is normal may refuse drug treatment for fear of covering up the real problem, while those who believe depression is purely a product of brain pathology may be reluctant to examine how their relationships may contribute to their symptoms” (Bailey, 2002). Bailey (2002) concludes, “Like every discovery since fire, medication can be helpful or hurtful. It’s all in how you use it”.

As clinicians, we must be aware of the changing face of depression and prepare ourselves to accurately diagnose and effectively treat this disorder with an individualized plan of care which may or may not include medication. Ideally, we must also work to reduce social stigma and facilitate insurance reimbursement.  Depression needs to be recognized as a disorder affecting mind and body requiring treatment much as insulin is required by diabetics. 


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