Practice in Clinical & Health Psychology
Mood Disorder







What is Depression?

We all feel 'blue' from time to time. Sadness is an important part of living. It helps us understand our inner world, communicate with others and gives richness and meaning to our lives. Where the 'normal' sadness that comes from the inevitable losses and frustrations of daily life, parts company with depression as an illness, is the severity, duration and the degree of disability that depression can cause.

Depression is more than a passing mood or the normal grief or bereavement most of us will feel at the loss of someone we love. Clinical or major depression is a mental disorder that occurs along a continuum from mild to life threatening. While some mild episodes of depression may resolve with time, aided by making important adjustments to daily routines and seeking out the support of others, more severe depression usually requires active treatment.

Major or clinical depression is a serious, debilitating, “whole body” illness that intensely affects how you think about things, how you feel, and ultimately how you behave. It can last for months or years and without treatment can cause permanent disability or even lead to suicide.

Depression is not a character flaw or a sign of personal weakness. It cannot be willed or wished away. People who are clinically depressed cannot simply “snap out of it” and no amount of 'pulling up your socks', true grit and determination, will lift the dark veil of depression.

Depression is a profoundly painful, distressing disorder that rarely can be overcome without external or professional help. It is an illness and it needs treatment.

Each individual experiences depression in his or her own unique manner. However, the following signs and symptoms are commonly reported and are used in making a diagnosis of depression.

  • Changes in Thinking - You may experience problems with concentration and decision making. Some people report difficulty with short term memory, forgetting things all the time. Negative thoughts and thinking are characteristic of depression. Pessimism, poor self-esteem, excessive guilt, and self-criticism are all common. Some people have self-destructive thoughts during a more serious depression.
  • Changes in Feelings - You may feel sad for no reason at all. Some people report that they no longer enjoy activities that they once found pleasurable. You might lack motivation, and become more apathetic. You might feel "slowed down" and tired all the time. Sometimes irritability is a problem, and you may have more difficulty controlling your temper. In the extreme, depression is characterized by feelings of helplessness and hopelessness.
  • Changes in Behavior - Changes in behavior during depression are reflective of the negative emotions being experienced. You might act more apathetic, because that's how you feel. Some people do not feel comfortable with other people, so social withdrawal is common. You may experience a dramatic change in appetite, either eating more or less. Because of the chronic sadness, excessive crying is common. Some people complain about everything, and act out their anger with temper outbursts. Sexual desire may disappear, resulting in lack of sexual activity and intimacy with partners. In the extreme, people may neglect their personal appearance, even neglecting basic hygiene. Needless to say, someone who is this depressed does not do very much, so work productivity and household responsibilities suffer. Some people even have trouble getting out of bed.
  • Changes in Physical Well-being - We already talked about the negative emotional feelings experienced during depression, but these are coupled with negative physical emotions as well. Chronic fatigue, despite spending more time sleeping, is common. Some people can't sleep, or don't sleep soundly. These individuals lay awake for hours, or awaken many times during the night, and stare at the ceiling. Others sleep many hours, even most of the day, although they still feel tired. Many people lose their appetite, feel slowed down by depression, and complain of many aches and pains. Others are restless, and can't sit still.

Now imagine these symptoms lasting for weeks or even months. Imagine feeling this way almost all of the time. Depression is present if you experience many of these symptoms for at least several weeks. Of course, it's not a good idea to diagnose yourself. If you think that you might be depressed, see your physician or a psychologist as soon as possible. Your primary care physician or a psychologist can assess whether you are depressed, or just under a lot of stress and feeling sad. Remember, depression is treatable. Instead of worrying about whether you are depressed, do something about it. Even if you don't feel like it right now. 

Types of Depression

Depressive disorders come in different forms. Three of the most common are Major Depression, Dysthymia, and Bipolar Disorder. Even within these types of depression there are variations in the number of symptoms, their severity, and persistence.

Major depression is manifested by a combination of symptoms (see symptom list above) that interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Some people have a single episode of depression, but many have episodes that recur.

Dysthymia is a less severe type of depression that lasts a long time but involves less severe symptoms. If you suffer from dysthymia you probalby lead a normal life, but you may not be functioning well or feeling good. People with dysthymia may also experience major depressive episodes at some time in their lives.

Bipolar Disorder (also called manic-depression) is another type of depressive disorder. Bipolar disorder is thought to be less common than other depressive disorders. If you have bipolar disorder you are troubled by cycling mood swings - usually severe highs (mania) and lows (depression). The mood swings are sometimes dramatic and rapid, but usually are more gradual. When in the depressed stage, a person can have any or all of the symptoms of a depressive disorder. When in the manic stage, the individual may be overactive, overtalkative, and have a great deal of energy. Mania affects thinking, judgment, and social behavior, sometimes in ways that cause serious problems and embarrassment. A person in a manic phase may feel elated, full of grand schemes that might range from unwise business decisions to romantic sprees. Mania, left untreated, may worsen to a psychotic state, where the person is out of touch with reality.

What Causes Depression?

What causes depression? The best answer is many things. The contributing factors vary substantially from one person to the next.

To start with, biology matters— there can be genetic and neurochemical factors that play a role in the onset and course of depression. The misconception many people have, though, is that you have a neurochemical anomaly and then depression results.

In fact, it is a two-way street: Your experience influences your neurochemistry at least as much as your neurochemistry affects your experience. These include your problem-solving capabilities, your coping style (whether you deal with problems directly and proactively or either ruminate or go into avoidance), your decision-making style (many people who are either depressed or are prone to depression make bad decisions that lead to depression and even make their depression worse), your perceptions of control (whether you see yourself as a victim of life experience or as having the power to take charge of your life), the quality of your relationships and relationship skills, and many other such personal factors.

Feeling hopeless and helpless are part of the disorder, and so depressed people are prone to believe there is nothing they can do to help themselves. That is flatly untrue. When people educate themselves and take proactive and deliberate steps to get help, including self-help, the probability of overcoming depression is high.

Ignore the disempowering interpretations people give you about the meaning of your depression. Instead focus on 1) learning what your particular risk factors and vulnerabilities are and 2) then learning the strategies you'll need for skillfully managing your mood.

Even when depression eventually lifts, you will need to manage your mood with self-awareness and skill. It's a life skill everyone needs, not just those prone to depression.

Therapy can be of great help and should feature somewhere in your plans to overcome your depression. You can't effectively treat yourself when you don't know much about what you're up against.

Is Depression Hereditary or Learned?  Genetics play a mild role in major depression (a bigger role in bipolar disorder). Genetics may serve as a predisposing factor to depression, but the evidence is growing that depression has a great deal to do with the ongoing and repetitive interactions within the family.

Just as an individual has a mood, so does a family. Is the family atmosphere a serious or playful one? Emotionally close or emotionally unexpressive? Supportive or competitive? Tolerant of individual differences or rejecting of them? Problem-solving oriented or avoidant of problems?

Growing up, you have countless interactions with parents and significant others, each of which holds the potential to teach you specific skills or perspectives. If you live with perfectionistic parents, for example, you may grow up with the idea that nothing you do is right or good enough, a belief damaging to all you may attempt to do, whether in school, the job market, or relationships. It can lead to and/or maintain depression.

Interactions within the family shape your view of yourself and the world. The feedback you get in the form of peoples' reactions lets you know what's expected of you, how others see you, what you can express, even how you should manage your own body. Your self-image is largely a product of others' feedback.

Families increase or decrease vulnerability to depression in other ways, too. For example, if parents are not good problem solvers and don't actively teach skills for managing the problems of life, you can't learn effective strategies for living. Much depression today arises when people get overwhelmed by problems they just don't know how to manage.

The values parents teach, whether through word or deed, provide either a solid or shaky foundation for making decisions in life. If you learn to value money over service to others, or competition over cooperation, many choices in your life will be affected, not all of them for the better.

The bottom line is this: Your family plays a big role in your life experience, and family members can't teach you what they don't know. Instead of either passively blaming them or suffering needlessly, you must be proactive in learning your own vulnerabilities and how to manage them skillfully.

Physical changes in the body can also trigger mental health problems such as depression. Research demonstrates that stroke, heart attack, cancer, Parkinson's disease, and hormonal disorders can cause depression. The depression can contribute to the person's medical problem, as then can become apathetic and unwilling to care for their physical needs. A severe stressor such as a serious loss, difficult relationship, financial problem can also trigger a depressive episode. A combination of genetic, psychological, and environmental factors is often involved in the onset of depression.

Depression in Women

Studies suggest that women experience depression up to twice as often as men. Hormonal factors may contribute to the increased rate of depression in women; such as menstrual cycle changes, pregnancy, miscarriage, postpartum period, pre-menopause, and menopause. Women may also face unique stressors such as responsibilities both at work and home, single parenthood, and caring for children and for aging parents.

Many women are particularly vulnerable to depression after the birth of a baby. The hormonal and physical changes, as well as the added responsibility of a new life, can be factors that lead to postpartum depression in some women. Some periods of sadness are common in new mothers; but a full depressive episode is not normal and requires intervention. Treatment by a sympathetic health care provider and emotional support from friends and family are important in helping her to recover her physical and mental well-being and her ability to care for and enjoy her baby.

Depression in Men

Men are less likely to suffer from depression than women, but as many as half a million men in Canada are affected by depression. Men are less likely to admit to depression, and doctors are less likely to suspect it. More women attempt suicide, but more men actually commit suicide. After age 70, the rate of men's suicide rises, peaking after age 85.

Depression can also affect the physical health in men differently from women. One study showed that men suffer a high death rate from coronary heart disease following depression. Men's depression may be masked by alcohol or drugs, or by working excessively long hours. Rather than feeling hopeless and helpless, men may feel irritable, angry, and discouraged.

Even if a man realizes that he is depressed, he may be less willing than a woman to seek help. In the workplace, employee assistance professionals or worksite mental health programs can help men understand and accept depression as a mental health disorder that needs treatment.

Depression in the Elderly

It's not normal for elderly people to feel depressed. Most older people feel satisfied with their lives. Depression in the elderly is sometimes dismissed as a normal part of aging; causing needless suffering for the family and for the individual. Depressed elderly persons usually tell their doctor about their physical symptoms; and may be hesitant to bring up their emotions.

Some symptoms of depression in the elderly may be side effects of medication the person is taking for a physical problem, or they may be caused by a co-occurring illness. If a diagnosis of depression is made, treatment with medication and/or psychotherapy will help the depressed person return to a happier, more fulfilling life. Recent research suggests that brief psychotherapy is effective in reducing symptoms in short-term depression in older persons who are medically ill. Psychotherapy is also useful in older patients who cannot or will not take medication.

Source: Information from the National Institute of Mental Health and from professional experience in practice as a psychologist treating depressed people.


Spotting the Signs of Depression
By Chris Iliades, MD
Common symptoms of depression include guilt, irritability, and having a feeling of sadness that won't go away.
Being in a "blue mood" sometimes is a normal part of life. If you lose a loved one or are laid off from your job, it is natural to be sad. When you have depression symptoms because of a stress that has occurred in your life, it is called "situational depression." Most people recover from situational depression over time, although it may take days or weeks.
However, when depression symptoms just won't go away and the depression starts to interfere with your ability to function, normally it is called "clinical depression" or “major depression.” Major depression is a serious illness that may last for weeks, months, or years. If you have major depression, you need to get help, so it is important to know which symptoms of depression might indicate it.
The symptoms of depression are overwhelming. People may describe major depression as a "black hole" that they just can't get out of. A sense of impending doom is also common in this type of depression. You may feel lifeless, limp, and apathetic.
Symptoms of Depression: 10 Warning Signs
People with serious depression do not all have the same symptoms, but they may include:
·         Sadness. When feeling sad is a symptom of depression, it may include feeling hopeless and empty. You may find that no matter how hard you try, you just can't control your negative thoughts. You may find yourself crying for no obvious reason.
·         Guilt. People with severe depression may feel that they are worthless and helpless. They may even experience their depression as a sign of weakness, and can be overly self-critical.
·         Irritability. This depression symptom may cause you to feel angry, anxious, or restless. Men who are seriously depressed often express their depression through aggression or reckless behavior.
·         Mental symptoms. If you have trouble concentrating, making decisions, or remembering details, these could be symptoms of depression. People with depression may feel that their thought processes have slowed down.
·         Physical symptoms. People with depression often have aches and pains, headaches, or digestive problems that do not seem to have any other medical cause and do not respond to treatment.
·         Loss of energy. If you have depression, you may feel tired all the time. People with depression may feel that their physical abilities are slowed down.
·         Loss of interest. A common depression symptom is loss of interest in pleasurable activities like sex, hobbies, or social interactions. This may also show up as neglecting your responsibilities and your physical grooming.
·         Sleep changes. Waking up too early in the morning, not being able to fall asleep, or sleeping too much can all be symptoms of depression.
·         Appetite changes. Changes in eating habits due to depression can result in eating too much or too little. A weight gain or loss of more than 5 percent of your body weight in one month is one of the warning signs of depression. Some people experience a loss of interest in food, while for others food becomes a way of compensating for feelings of depression.
·         Suicidal thoughts. Having thoughts of harming yourself is a serious symptom of depression and always needs to be taken seriously. If you’re thinking about suicide, you need to get help immediately.
To see a brief YouTube video describing clinical depression in some detail, GOTO:  

Psychotherapy as a Treatment for Depression

Psychological treatment of depression (psychotherapy) can assist the depressed individual in several ways. First, supportive counseling helps ease the pain of depression, and addresses the feelings of hopelessness that accompany depression.  Second, cognitive therapy changes the pessimistic ideas, unrealistic expectations, and overly critical self-evaluations that create depression and sustain it. Cognitive therapy helps the depressed person recognize which life problems are critical, and which are minor. It also helps him/her to develop positive life goals, and a more positive self-assessment. Third, problem solving therapy changes the areas of the person's life that are creating significant stress, and contributing to the depression. This may require behavioral therapy to develop better coping skills, or Interpersonal therapy, to assist in solving relationship problems.

At first glance, this may seem like several different therapies being used to treat depression. However, all of these interventions are used as part of a cognitive treatment approach. Some psychologists use the phrase, cognitive-behavioral therapy and others simply call this approach, cognitive therapy. In practice, both cognitive and behavioral techniques are used together. 

Once upon a time, behavior therapy did not pay any attention to cognitions, such as perceptions, evaluations or expectations. Behavior therapy only studied behavior that could be observed and measured. But, psychology is a science, studying human thoughts, emotions and behavior. Scientific research has found that perceptions, expectations, values, attitudes, personal evaluations of self and others, fears, desires, etc. are all human experiences that affect behavior. Also, our behavior, and the behavior of others, affects all of those cognitive experiences as well. Thus, cognitive and behavioral experiences are intertwined, and must be studied, changed or eliminated, as an interactive pair.

List of Cognitive Factors in Depression

Self-evaluation is a process that is ongoing. We evaluate how we are managing life tasks, and we evaluate whether we are doing what we should, saying what we should, or acting the way we should. In depression, self-evaluation is generally negative and critical. When a mistake occurs, we think, "I messed up. I'm no good at anything. It's my fault things went wrong." When someone is depressed, he/she tends to take responsibility for everything that goes wrong, and tends to give others credit for things that turn out fine. Psychologists assume that self-evaluation, in depressed individuals, is too critical, and feeds low self-esteem and a sense of failure.

Identification of Skill Deficits. Sometimes a depressed person may accurately identify a skill deficit. "I'm not good at telling people what I want from them." This is usually coupled with negative self-evaluation, "therefore, it's my fault that I didn't get what I want."  However, in depression, the person assumes that he/she cannot learn how to do what is necessary to achieve a better outcome. The depressed person believes that he/she cannot learn how to act differently. Accurate identification of social skill deficits complicates depression, because it provides a reality base for the other irrational and exaggerated negative perceptions of the depressed person.  If the skill deficit is real, then the depressed person assumes that all of the other negative self-assessments must be real too. Further, when depressed, a person is more likely to identify negative characteristics of self, and less likely to see the positive. The result is a long list of the "things I cannot do," or "tasks I'm no good at," or "mistakes I've made." Psychologists help depressed persons identify their social skill deficits, and also help them develop a plan to improve those skills. This part of cognitive therapy is more behavioral, as the psychologist teaches the depressed person how to manage their life problems better.

Evaluation of Life Experiences. When depressed, a person will focus on minor negative aspects of what was otherwise a positive life experience. For example, after a vacation at the beach, the depressed person will remember the one day it rained, rather than the six days of sunshine. If anything goes wrong, the depressed person evaluates the entire experience as a failure, or as a negative life experience. As a result, memories are almost always negative. This is reflective of unrealistic expectations.  Nothing in life ever works out just as you want. If we expect perfection, we will always be disappointed. Psychologists help you to develop realistic expectations about life, and help you determine what you need versus what you want. After all, most of the things that don't work out are little things. And even when important problems develop, we can either resolve the problem, or regroup, recover, and start again, with hope for a better future. In depression, the hope is missing.

Self-talk is a way of describing all the things we say to ourselves all day long as we confront obstacles, make decisions, and resolve problems. Self-talk is not "talking to yourself" in a literal sense, although it sometimes does involve talking out loud (depending on the person). There is a myth, that when you talk to yourself, it is a sign of "craziness" or mental illness. That idea stems from the "voices" or auditory hallucinations experienced in severe forms of mental illness, such as schizophrenia. When a person hears voices, he/she thinks it is someone else talking to them. The self-talk we are describing here is not like that at all. We all engage in self-talk. Usually, it is part of our thinking process, or what we call "stream of consciousness." As we are presented with problems, or decisions, we might think, "Okay, how do I handle this?' or "This looks like it is difficult, I better ask for help." or "I know how to fix this!"

Self-talk is not bad, or wrong, or a sign of psychological problems. It is normal. But, negative self-talk prevents us from solving problems, and can contribute to a variety of psychological problems, including depression. When faced with a problem, if our self-talk is negative, it can immobilize us. "I can't do this, I'm just going to foul it up again" or "I'll probably get fired after they see how incompetent I am." Psychologists help depressed individuals identify negative self-talk, and also teach them how to challenge these negative statements, and how to replace them with positive self-talk.

Automatic thoughts are repetitive, automatic self-statements that we always say to ourselves in certain situations. They can be positive or negative. Psychological problems develop when our automatic thoughts are consistently negative. They are automatic, because they are not the result of an analysis of the problem, they are a "knee-jerk" reaction to specific situations. For example, in social situations, do you always presume the other person dislikes you, or thinks you are stupid? When automatic thoughts control our emotional response to people, problems, and events, we ignore evidence that contradicts the automatic thought. If we cannot ignore it, we explain the evidence in terms of the automatic thought.

For example, if we talk to someone and they smile, they are really laughing at us, rather than being pleased to see us. The automatic thoughts create an expectancy of something negative. Since many things in life are vague, and can be interpreted in many ways, we learn how to negatively evaluate the world, so it agrees with our negative automatic thoughts. Psychologists help you to identify your negative automatic thoughts, and how to develop positive challenges to those negative ideas.

Irrational Ideas and Beliefs. Albert Ellis first presented the idea that irrational beliefs are at the core of most psychological problems. We could also call these beliefs unrealistic, incorrect, or maladaptive. Psychologists have also suggested that these ideas are irrational because they are not logical, or are based on false assumptions. Some examples of irrational beliefs:

     I cannot be happy unless everyone likes me.
     If I do what is expected of me, my life will be wonderful.
     Bad things don't happen to good people.
     Good things don't happen to bad people.
     In the end, bad people will always get punished.
     If I am intelligent (or work hard), I will be successful.

What makes these ideas irrational, or maladaptive, is the belief that they are always correct. Sure, working hard will increase your chances for success, but success is not guaranteed. But, there are times when we do everything right, and we still don't get what we want. For some people, this leads to the conclusion that they are lazy, no good, incompetent, or weak. The result is a loss of self-esteem, and sometimes, depression. Psychologists help you to identify your irrational ideas, and also how to evaluate which ideas are irrational and which are not. Finally, the ideas need to be changed to reflect the real world.

Overgeneralizing or Catastrophizing. Catastrophizing is a negative overgeneralization. It is "making a mountain out of a mole hill!" For example:

  • One person at work does not like you, and tells you, so you know it's not mistaken judgment. You then assume no one at work likes you, or you assume that you must be a terrible person if he/she does not like you.
  • You make a small mistake on a project, and assume that you will be fired when the boss finds out.
  • You try your hand at a new hobby, and it does not turn out well. You conclude, "I'm  no good at anything."

We all make mistakes. If you overgeneralize one, or even a few mistakes, to the conclusion that you are bad, incompetent, or useless, you might become depressed. Psychologists help you identify and change negative overgeneralizations.

Cognitive distortions are another way of describing the irrational ideas, overgeneralizing of simple mistakes, or developing false assumptions about what other people think about us, or expect from us. We are distorting reality by the way we are evaluating a situation. The concept of cognitive distortion highlights the importance of perceptions, assumptions and judgments in coping with the world.  Psychologists help us determine what evaluations are distortions by providing objective feedback about our evaluations of the world, and by teaching us how to change the way we are perceiving problems.

Pessimistic thinking does not cause depression, but it appears to be easier to become depressed if you tend to view the world with considerable pessimism. After all, pessimism is a tendency to think that things won't work out as you wish, that you won't get what you want. Pessimism feeds the negative cognitive distortions and self-talk. On the other hand, optimism appears to create some protection from depression.

Hopelessness is a central feature of depression, along with helplessness. If you view your world as bad, filled with problems, and don't think you can do anything about the problems, you will feel helpless. If you don't believe your life will improve, if you think the future is bleak, then you will begin to feel hopeless. Pessimism encourages these negative assessments of your life.  Optimism prevents you from reaching those conclusions. In fact, psychologists have researched ways to learn how to be more optimistic, as a way of fighting depression. 

Summary of Cognitive Psychotherapy Approach

First, remember that we cannot present cognitive psychotherapy in one web page, or in a few paragraphs.  But, the essence of cognitive therapy is the assumption that irrational thoughts and beliefs, overgeneralization of negative events, a pessimistic outlook on life, a tendency to focus on problems and failures, and negative self assessment, as well as other cognitive distortions, promote the development of psychological problems, especially depression.  Psychologists use cognitive therapy to help you identify and understand how these cognitive distortions affect your life. Cognitive therapy helps you to change, so that these issues will not rule your life.  If you are feeling overburdened, that life is not working for you, and you don't know what to do next, talk to someone who can help, consult a psychologist.

To see a brief YouTube video on cognitive-behavioral therapy for depression, GOTO: 


Efficacy of Cognitive-Behavioral Therapy
as a Treatment for Depression

Several meta-analyses have been conducted over the years to determine the clinical efficacy of cognitive-behavioral therapy in the treatment of depression as compared to no treatment, pharmacotherapy, and other forms of psychotherapies as well as the relative efficacy of the pure cognitive and behavioral components individually.

All meta-analyses found evidence of a clear superiority of cognitive behavioral therapy over “no treatment” or “wait-list” control conditions. Six of nine studies found significantly greater treatment effects for cognitive therapy as compared to other forms of psychotherapy. Of the six studies directly comparing cognitive therapies to behavioral therapies, cognitive therapy outperformed behavioral therapy in three studies and was comparable to behavior therapy in three studies. Finally, cognitive therapy outperformed medication in all five meta-analyses comparing the two.

Taken as a whole these meta-analyses provide substantial evidence that cognitive-behavioral therapy is an effective treatment for depression; at least as effective as medication.  

The high degree of relapse (i.e., a continuation of the index episode of depression before recovery) or recurrence (i.e., a new episode of depression after recovery) in depression has made the issue of maintenance of treatment success a critical one for both psychotherapy and pharmacotherapy. Without additional treatment, the range of relapse appears to vary between 50% and 80% within the first year of recovery from depression. Medication studies estimate that symptom relapse or recurrence tends to occur within 6-24 months after treatment is discontinued.

Cognitive-behavioral therapy has generally been associated with a lower rate of relapse than patients treated with medications alone. Although the methodology of studies varies, meta-analysis of cognitive-behavioral treatment studies has generally reported 0%-50% relapse rates within 1-2 years after treatment ends.

Source: Weissman, M.M. (Ed.) (1999). Treatment of Depression: Bridging the 21st Century. (pp.264-274). New York, NY: APA Press.    



What neuroimaging research has shown us.

Major depression is a disorder of the brain’s affective system. Major depression is characterized by a triad of symptoms: (1) low or depressed mood; (2) loss of interest or pleasure in almost all activities (anhedonia); and (3) low mental and physical energy or fatigue. Other symptoms such as sleep and psychomotor disturbances, pessimism, guilty feelings, low self-esteem, suicidal tendencies, and food-intake and body weight dysregulation, are also frequently present but not essential to making the diagnosis.

Findings from Brain Imaging Studies

Early studies using Positron Emission Tomography (PET) to examine resting cerebral glucose metabolism and Functional Magnetic Resonance Imaging (fMRI) to examine regional cerebral blood flow in depressed versus normal subjects have generally found decreased activity in the prefrontal cortex of depressed individuals. This decreased metabolic activity is correlated with severity of depression and has been found to reverse with recovery from depression.

A more recent PET study of treatment-resistant patients with depression found, in addition to the usual decreased prefrontal metabolism, an increase of metabolic activity in the subgenual cingulate gyrus (a part of the limbic system). This is the same area that demonstrates increased blood flow in normal subjects when sadness is induced. This area of the brain also responds to treatment with antidepressant drugs.

Numerous brain imaging studies over the last few decades have been broadly consistent in showing sadness and depressed mood to be associated with abnormal neuronal activation in the medial prefrontal cortex (mPFC), including the anterior cingulated gyrus (ACC) and orbito-frontal cortex (OFC). These areas in the cortex receive input through the anterior nucleus of the thalamus from the hippocampus (HC), amygdala (Am), and mammilary bodies of the hypothalamus (MB).

Figure A.  Areas of the brain involved in depression.

Electroencephalographic (EEG) studies have largely confirmed these findings by demonstrating increased alpha (8-12 Hz) EEG power in the left frontal regions of the brains of depressed individuals. Since alpha is generally viewed as a cortical idling rhythm and is inversely related to neuronal activity, increased left frontal alpha results in deactivation of the left prefrontal cortex and a relative overactivation of the right prefrontal cortex. Indeed, a number of brain researchers have suggested a laterality of the brain’s affective system; with negative emotions having a bias in activating the right hemisphere and positive emotions activating the left hemisphere. The left frontal lobes may be considered to include an “approach behavior” circuit whereas the right frontal lobes may include an “avoidance-behavior” circuit. As the left becomes more active, we tend to see things as generally more interesting, more rewarding, more approachable. In contrast, activation of the right circuit causes us to see things as potentially more dangerous and less rewarding. Brain research suggests that a person's mood may largely depend on which side of the prefrontal cortex is more active.

In this vein, Henriques & Davidson (1990, 1991) examined frontal EEG asymmetry in currently depressed versus never depressed individuals and found elevated left frontal alpha power in the depressed individuals. Other researchers have confirmed these findings as well as observing that individual differences in frontal asymmetry emerge early in life and are associated with individual differences in “approach-withdrawal” behavior and the “introversion-extroversion” personality dimension. Taken together, these findings suggest that EEG asymmetry marked by relative left frontal hypoactivation may be a biological marker of familial and, possibly genetic risk for mood disorders.

Figure B.  Nx-Link QEEG brain maps of an elderly male suffering from severe depression.
Note the excessive relative power in alpha band in the left temporo-frontal region.

Neurological patterns found associated with depression are asymmetry of frontal lobe activity, deficiency of slow-wave (theta) activity or excessive fast wave (beta) activity in the occipital or posterior region of the brain, as well as deficiency in 13-15 Hz activity over the sensorimotor cortex.

These findings with respect to depression are quite consistent with the more general notion that abnormal activity in the EEG reflects psychopathology and, conversely, normalizing the EEG can improve brain function and reduce psychopathology.


Neurotherapy Approaches to the Treatment
of Depression: A Viable Alternative to Drugs

More recent research suggests that medication is most effective in the treatment of severe depression and may be only mildly more effective than placebo in the treatment of mild to moderate depression. Moreover, it commonly requires trying more than two antidepressant drugs over periods of as long as three months before finding the particular drug that will work best for any given patient with depression.

EEG neurofeedback (EEG biofeedback) may offer an effective alternative to invasive treatments such as medication, electroconvulsive therapy (ECT), and intense transcranial magnetic stimulation (TMS).

The treatment of depression with EEG neurofeedback generally involves increasing the activation of the left prefrontal cortex relative to the right prefrontal cortex. This may be accomplished by decreasing left prefrontal alpha (8-12 Hz) activity and/or increasing left prefrontal low beta (13-18 Hz) activity and/or increasing right prefrontal alpha activity.

Other forms of neurotherapy that have demonstrated clinical effectiveness in the treatment of depression are: Audio-Visual Entrainment (AVE), Hemoencephalographic (HEG) Biofeedback, Cranial Electrostimulation (CES), and Transcranial Direct-Current Stimulation (tDCS).

For more information on these various neurotherapy techniques, GOTO: EEG Neurotherapies

Suggested Readings:

Davidson, R. & Hugdahl, K. (eds) (1995). Brain Asymmetry. Cambridge, MA: MIT Press.

Hammond, C. (2005). Neurofeedback treatment of depression and anxiety. Journal of Adult Development, 12(2-3): 131-137.

Rosenfeld, J.P. (2000). An EEG biofeedback protocol for affective disorders. Clinical Electroencephalography, 31(1): 7-12.

Walker, J., Lawson, R., Kozlowski, G. (2007). Current status of QEEG and neurofeedback in the treatment of depression. (pp.341-351).  In J. Evans (Ed.)(2007), Handbook of Neurofeedback. Binghampton, NY: Haworth Medical Press.


Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo

Source: MedScape  By: Deborah Brauser

August 24, 2010 — A new review of 4 meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only "marginally efficacious" compared with placebo and "document profound publication bias that inflates their apparent efficacy."

In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.

"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.

Sustained Benefit "Jaw Dropping"

"In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number," added Dr. Pigott.

Overall, "the reviewed findings argue for a reappraisal of the current recommended standard of care of depression," write the study authors.

"I believe there are likely some people where [antidepressants] are truly beneficial beyond placebo. The problem right now is that we simply have no way of knowing who those people are," noted Dr. Pigott. "My hope is that this kind of analysis creates 'more oxygen' for looking at other kinds of approaches to treatment."

The study was published in the August issue of Psychotherapy and Psychosomatics.

When registering new drug application trials with the FDA, drug companies must prespecify the primary and secondary outcome measures, the investigators report. "Prespecification is essential to ensure the integrity of a trial and enables the discovery of when investigators selectively publish the measures that show the outcome the sponsors prefer following data collection and analysis, a form of researcher bias known as HARKing or 'hypothesizing after the results are known'," they write.

For this article, Dr. Pigott and his team reviewed the following meta-analyses:

  • 1. Rising and colleagues (reviewed all efficacy trials for new drugs between 2001 and 2002)
  • 2. Turner and colleagues (reviewed 74 past trials of 12 antidepressants)
  • 3. Kirsch and colleagues, 2002 (reviewed 47 trials of 6 FDA-approved antidepressants)
  • 4. Kirsch and colleagues, 2008 (reviewed depression severity and efficacy in 35 trials)

The researchers also sought to reevaluate the methods and findings of STAR*D, a randomized, controlled trial of patients with depression. Its prespecified primary outcome measure was the Hamilton Rating Scale for Depression (HRSD), whereas the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) was secondary for identifying remitted and responder patients.

"STAR*D was designed to identify the best next-step treatment for the many patients who fail to get adequate relief from their initial SSRI trial," the study authors write.

"When I first read about STAR*D's step 1 phase, it just seemed biased to me," explained Dr. Pigott. "I thought of it as the 'tag, you're healed' research design. Patients who were scored as having a remission during the first 4 to 6 weeks of up to 14 weeks of acute care treatment were counted as remitted, taken out of the subject pool, and put into the follow-up care phase. In other words, they didn't have the ability to have a relapse. But as most people know, depression ebbs and flows.

"So what made me want to continue to follow this study was that it became clear that the only way that people were really going to be able to evaluate the antidepressants' effectiveness was to wait for the publication of the follow-up findings," he added. "After their major final summary study was published, I felt as though the results weren't really being portrayed in a manner that was consistent with the study's prespecified criteria."

High Dropout, Low Remission Rates

In addition to reporting on low efficacy of antidepressants compared with placebo, the 4 meta-analyses "also document a second form of bias in which researchers fail to report the negative results for the prespecified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure, as though it was their primary measure of interest," the investigators write.

For example, they note, the meta-analysis from Rising and colleagues found that studies with favorable outcomes were almost 5 times more likely to be published and that over 26% of primary outcome measures were left out of journal articles. Turner and colleagues found that antidepressant studies were 16 times more likely to be published if favorable compared with those with unfavorable outcomes.

In reanalyzing the STAR*D methods, the researchers found that the high dropout rate resulted in frequently missed exit HRSD and IDS-C30 interviews. So the revised statistical analytical plan dropped the IDS-30 for the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), which was given at each visit.

"Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1 [and] the dropout rate was slightly larger than the success rate," the study authors write. Steps 2 through 4 also each showed increasingly fewer success rates and larger dropout rates.

Of the 4041 patients at the study's initiation, 370 (9.2%) dropped out within 2 weeks, and only 1854 patients (45.9%) obtained remission "using the lenient QIDS-SR criteria." Of these, 670 dropped out within a month of their remission, and only 108 "survived continuing care" and underwent the final assessment.

Dr. Pigott described reanalyzing STAR*D as being "a bit like an onion. Each time we thought we understood the results, we found another layer. It wasn't until about a year and a half ago that we discovered that the secondary outcome measure, the QIDS-SR, was not originally supposed to be used as a research measure. What was particularly disconcerting to me was that in their summary article, they basically used the QIDS-SR to report all of the results, which clearly had an inflationary effect on the outcome."

He also noted that STAR*D did not have a placebo design. "Because the patients knew they were receiving the active medication, I would have expected a higher remission rate than what you'd find normally in a placebo-controlled study.

"The inescapable conclusion from the STAR*D results is that we need to explore more seriously other forms of treatment (and combination thereof) that may be more effective. This effort will require developing new service delivery models to ensure that as treatments are identified, they are widely implemented," the investigators conclude.

Need for Biomarkers

"For STAR*D, we wanted to do a study that other people could then reanalyze and look at. So I'm very glad that these authors reexamined it and saw it slightly differently, which came mainly from ways of analyzing data," Maurizio Fava, MD, STAR*D trial investigator and executive vice chair of the Department of Psychiatry at Massachusetts General Hospital in Boston, told Medscape Medical News.

"I think their analysis is reasonable and not incompatible with what we had reported," added Dr. Fava, who was not involved with this review.

He noted that the review's message for clinicians is that "there's been a failure of the field to demonstrate robust advantages of antidepressants over placebo. It's doesn't mean that clinicians shouldn't use antidepressants, but they should recognize that there's a limitation. On the other hand, we have very plausible, reasonable explanations for such failure, including the fact that patients who don't actually have the disease have often been enrolled in the studies. Therefore, this failure may have to do with imperfect clinical trial design and conduct."

In addition, Dr. Fava said that the review points to a lack of long-term efficacy for antidepressants, although "this may be due to things such as inadequate management of patients without dose adjustments and other things that can increase the likelihood of remaining well.

"Regardless of how you look at it, this study suggests the importance of developing biomarkers to identify patients who really need these antidepressants both in the short and the long term," concluded Dr. Fava. "I'd say there's a real opportunity here for that."

Dr. Pigott reports consulting in the past 3 years for CNS Response, Midwest Center for Stress and Anxiety, and SmartBrain Technologies. Dr. Fava reports several disclosures, which are listed in the original STAR*D papers.

Original article was published in: Psychotherapy & Psychosomatics, 2010;79:267-279.