Depression Alcohol Dependence Combination Therapy

There was an interesting stucdy in the March isssue of the American Journal of Pysychiatry that looked at combining medication treatment for those alcohol dependent patients who also suffered from co-occurring major depression. This study is important for one conclusion but as I have noted before with various studies the researchers often come to other conclusions that are not necessarily supported by their own evidence.

170 depressed alcohol dependent patients (mean 43.4 years of age) were randomly assigned to 14 weeks of the antidepressant sertraline (Zoloft) at 200 mg/day (the maximum dose), to the alcohol dependence drug naltrexone(Revia), to both drugs, or to double placebo groups and studied for a period of 14 weeks. All patients received weekly cognitive-behavioral therapy. The important finding was that at the end of 14 weeks 53% in the sertraline-naltrexone group maintained abstinence compared with an average of 23.8% for the other three treatments. This is very striking and may have significant implications for how we treat depressed alcoholics. Limitations of the study are the relatively small number of participants and the time frame of the study (3 1/2 months). But this is an important finding and one in which I hope there will be more follow-up for a longer period of time, enroll more patients, and separate out differences between men and women as well as those who received inpatient treatment compared with those were did not.

The other point they try to make in this study is that those receiving both treatments were less depressed than those with sertraline alone. They try to make the the point that there was a trend in that direction but the trend did not reach statistical significance. Reporting and highlighting trends that are not statistically significant is often a problem in that these results get reported in the media as important findings as well as the main findings and people come to conclusions that are not really supported by the evidence.

So in this case the improved abstinence rates at 3 1/2 months for the combined group is extremely important but we cannot say at this time that the combined treatment actually helps the depression.

Thought for the day

53% abstinence in a population with a co -occurring and serious psychiatric disorder is encouraging.

Depression Obesity Link

A study just published in the March issue of Archives of General Psychiatry shows a bidirectional link between depression and obesity. The study found that obese people (as defined as a body mass index of 30 or more) have a 55% increase in developing depression and those with depression have a 58% increased risk of becoming obese. I want to discuss this briefly not only because of it's clinical value in knowing this link but also to talk about how studies like this one have significant problems that affect the results and lead to greater association or causation effects than is warranted by the data.

First, the study was retrospective. It was a chart review but this was not actually undertaken by the researchers. They analyzed 15 previous studies and compiled the data. This is a common practice and does yield valuable information but the fact that different studies are conducted quite differently needs to be taken into account. Some of the studies they reviewed just looked at whether or not obesity leads to depression or the other way around. Some looked bidirectionally. There needed to have the means of assessing how depression was evaluated published but there were some diagnosed by clinical interviews and some by self report.

The second problem is that the study did not take into account several factors which can effect the results. There was no assessment of the presence or absence of substance abuse. There was no assessment of medication effect. Many medications used to treat depression induce weight gain and without knowing that it may be that the association of depression and increasing obesity risk may be entirely due to medication effect.

I don't want to put down the study though. Meta analysis for public health problems such as obesity and depression are very valuable in establishing links but that is what they establish- links, not causation which even many researchers become confused about when they try to draw the meaning and significance of their studies.

So for now, we have established a strong link between depression and obesity but don't truly know that a bidirectional causation link has been established. Only a prospective study enrolling new subjects followed for a long period of time will give us that answer.

Thought for the day

" No evil is there similar to anger. No austerity to be compared to patience".

The Way of the Bodhisattva

Antidepressant FDA Suicide Warning Prescribing Patterns

I want to take a short break from discussing the proposed changes in the new Diagnostic and Statistical Manual of Psychiatry-5to review a recently published study on what changes have been made in antidepressant prescribing patterns of physicians since the " black box warning" was issued by the US Food and Drug Administration (FDA) regarding increased risk of suicide in children and adolescents taking antidepressant medication.

In 2003 and 2004 the FDA issued 5 warnings about the increased risk of suicidality in children and adolescents taking antidepressants. This increased risk was very small and the majority of practitioners felt that not using antidepressant medication would actually increase the suicide rate among this age group. In late 2004 the FDA directed all manufacturers of antidepressants to issue a black box warning and laid out monitoring recommendations. The black box means that the first thing a physician sees when looking up a particular medication is a bold highlighted box with safety and warning information. It cannot be missed. The warning specifically called for "weekly, face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment".

A study supported by the Nnational Institute of Health (NIH) and published in Psychiatric Services tried to take a look at how this monitoring recommendation was actually being carried out. To do this they looked at claims data from 2001-2005 of 22,689 episodes of major depression an a national sample of privately insured patients. They found a 19% decrease in antidepressant prescriptions after the warning. Interestingly enough the national suicide rate increased in this population during the same period although no direct cause has been confirmed. They found no evidence however for increased face-face-contact with patients after the FDA advisory recommendation coming to the conclusion that physicians either don't know or are simply ignoring the recommendations.

Why are physicians not following through with the FDA recommendation? There are probably several factor involved. One is the relative lack of accessibility of child and adolescent psychiatrists. There are simply not enough psychiatrists in this field to serve our needs. Therefore many of the prescriptions for these antidepressant medications are given from pediatricians or other primary care providers who tend to have busy overloaded practices and have either not the time or the perception of not enough time to provide weekly follow-up. Another factor is that these patients are usually brought in by the parents who both may be working full time and cannot get off work once per week. Another factor is that many families cannot afford the repeated required co-payments they need to make for weekly follow-up. The other factor that always comes in is reimbursement. Many insurance companies do not provide reimbursement for antidepressant follow-up on anything less than a monthly basis. The situation is not a good one but goes beyond the idea that this is just physicians ignoring recommendations.

Weekly follow-up after a new prescription of an antidepressant is just good clinical practice for adults as well as children. Many patients suffer from various side effects, are often under the mistaken impression that the medication should work right away, and will discontinue their medication. Regardless of the different reasons for not following the FDA recommendations they should be followed and I think it is poor clinical practice to not do so. There are always ways to work around the various obstacles.

Thought for the day

Where there is a will there is a way.

Quantitative EEG Biomarker Depression

One of the problems that we have had in the medication treatment of depression is that we don't have a way of predicting who will respond well to any given antidepressant. Because it takes up to several weeks for any antidepressant to be effective it often takes a long time to find the right medication that the patient will respond to and which has tolerable side effects. This is very frustrating both for the patient and the provider and results in long periods of suffering. What we have needed is some way, a biomarker which can predict accurately very early on whether the medication will effective or not. Aspect Medical Systems claim they have found one such biomarker.

There are two studies being published in the September issue of Psychiatric Research from what is being called the Biomarkers for Rapid Identification of Treatment Effectiveness study. The first report is of 375 patients aged 18-75 who suffered from major depression. Using the non invasive technique of quantitative electroencephalography the researchers report they determined after one week of treatment by measurements in the prefontal cortex who would respond to the antidepressant escitalopram (Lexapro). They reported that they could accurately predict what was going to happen at seven weeks with 74% accuracy.

The second study reported by the same researchers on the same group of patients showed that for those who did not show the biomarker on quantitative EEG that those switching to the antidepressant buproprion (Wellbutrin) were 1.9 times likely to respond to the new drug. It sounds very promising ..... but......

The research was highly funded by Aspect Medical Systems which makes the electrodes used in the study. Although the researchers are supposed to be independent the lead investigator disclosed that he has provided scientific consultation or served on the advisory board of Aspect Medical Systems and that he is also a minor stockholder as well.

The need for a biomarker is so great that this testing may be used on many patients before there has been any time to assess if anyone else can replicate their results. The quantitative EEG device is already in use for other conditions so already has FDA approval. The technique carries almost no risk greater than the hassle of getting the electrode goop out of your hair. So I am not concerned about any harm to patients but rather that many providers may be buying these devices, and using them prematurely before the evidence is in (and making a lot of money for the procedure charges).

Thought for the day

Sometimes only time will tell.

Serotonin Transporter Gene Depression

The Daily Musings of an Addiction Psychiatrist is back after a short hiatus. For some reason I have not been sleeping well so instead of getting up early which I enjoy and writing I have been dragging myself to work at the last possible minute. Maybe it is a guilty conscience as they say but I don't feel anxiuous at night - just awake.

A recent study has once again caused dissapointment in those of us who are continuing to hope that we will learn more about the genetic links that predispose us to depression. It had recently been thought that mutations in the gene coding for the serotonin transporter protein might be one of those factors. This seemed to make sense as we have known that the neurotrasmitter serotonin is associated with depression and that many of our antidepressant medications have an effect on serotonin. A large scale study though has shown that this gene is not a factor. Instead what is more associated with depression are the number of stressful life events.

This once again show that enviromental factors strongly influence the occurence of depression but leaves us wondering what the genetic differences are that would make one person respond to life stressful events with depression and another doesn't. What are the genetic differences that either protect us from or make us more vulnerable to depreesion? We still don't know.

Thought for the day

"In all things give thanks".

St. Paul

Depression, Recovery, part6

This post is the last in a series on depression. I want briefly to discuss bipolar disorder and how it differs from non bipolar depression. Bipolar disorder used to be called manic depressive illness. It is a modd disorder that affects 1-2% of the population and equally affects both men and women. It is a highly genetically influenced disorder and tends to run in families as well as sharing some links with migraine with aura. It is characterized by episodes of "highs" as well as depressed periods.

The bipolar highs can be euphoric but usually are not pleasant for the person with bioplar disorder but are characterized by frantic activity, racing thoughts, dosorganized behavior, loud, intrusive and at times obnoxious behavior, unrealistic highly inflated sense of one's abilities talents and greatness accompanied by rapid mood shifts with prominent agitation, irritability and at times hostile or aggressive behavior. The person in a manic state usually has remarably impaired judgment and is unable to see the behavior as abnormal or problematic and often will engage in reckless behavior or make very poor decisions. At times in severe cases there can be a loss of reality testing and the appearance of hallucinations or frank delusions.

Manic episodes can be dramatic but are treatable and the long term disability from this disorder is predominately due to the depressed periods which can become chronic and unremitting. Bipolar depression does not respond well to typical antidepressant medications and antidepressants can induce an episode of mania as well as lead to increased mood cycling. There are a number of mood stabilizing medications which are helpful but most of these are more effective for the manic phases of the illness Usually it requires a combination of medications to acheive longterm stability and medications are required life long.

A good resource for more information about depression and bipolar disorder an be found at www.dbsalliance.org which is the we site for the Depressiona and Bipolar Support Alliance.

Thought for the day

"A power greater than ourselves can restore us to sanity"

AA

Depression, Recovery, part 5

This is part 5 on my series on depression. Today I want to cover the question How is depression treated?

There are four aspects to the treatment of depression. The first is removing or modifying contributing factors. An example of this would be to stop alcohol use. A second step is cognitive-behavioral therapy which focuses on unhealthy thought patterns that contribute to the depressed state. A third aspect is the use of antidepressant medications. These are not needed in every case of depression but can be very useful, particularly in those forms of more severe depression. Fourthly we need lifestyle maintenance which includes adequate sleep, stress reduction, exercise, good diet, smoking cessation, support group, and spirituality.

What are antidepressant medications and how do they work? Antidepressant medication can be an important part of the treatment of depression just as blood pressure lowering and cholesterol lowering medications are important in the treatment of heart disease. Antidepressants are not "happy pills". They are not addicting. They work by affecting the way brain cells communicate by affecting certain chemical transmitter systems such as serotonin, norepinephrine, and dopamine which in turn changes the production of various proteins in the emotional regions of the brain. These changes take place over several weeks and usually the depression does not improve until the antidepressant medication has been taken for 2-3 weeks, though some people begin to respond more quickly.

I will finish up this series on depression next week discussing bipolar depression. Please comment if you find these rather didactic posts useful or not so I will know if I should do more in the future. Thanks!

Thought for the day

I really would like your comments.

Depression, Recovery part 4

I will continue this series on depression moving on to a few common questions.

Is there any test for depression? There is no medical test currently available to assist in the diagnosis of depression. Laboratory blood work is usually obtained to help assess for other medical conditions that may be contributing to depression or that may affect treatment.

What causes depression? There have been a variety of possible explanations that have been examined over the years. Ancient Greek physicians believed that depression was caused by abnormalities in what they called 'black bile". Although our understanding of physiology has advanced the idea that depression involves some abnormality in the body is an old idea. One psychological explanation has been that depression is anger that is "turned inward" and directed against the self. Another is the idea of learned helplessness. This is the recognition that we like all mammals will respond to stress which we are unable to change with a tendency to become helpless and give up. There is also the chemical idea that there is an imbalance of neurotransmitters which need to be corrected.

While all of these probably have some truth to them they are over simplistic and do not take into account that there are a variety of factors that may contribute to depression. One way to see depression is as a stress-vulnerability condition. This means that there are varying degrees of vulnerability to depression that each one of us has and that many different stresses may contribute to the development of depression. These factors include genetic predisposition, ongoing abuse of alcohol or drugs, history of early life trauma, chronic relationship stress, chronic pain, hormonal influences, medical illnesses, diet and exercise, and negative thinking patterns. Recognizing this is important for treatment as we want to address as many of these factors as possible and treat not just symptoms but also raise one's resiliency to development of depression in the future.

I will address treatment in my next post.

Thought for the day

Nothing is psychiatry is simple. All is multifactorial.

Depression, Diagnosis, Recovery part 3

In my last two posts I talked about some aspects of psychiatric diagnosis but today I want to get into the issue of depression which exists on a continuum of mild to severe. What is depression? Depression is a normal mood state that comes and goes but clinical depression is different. I wish we had a better name for it. Clinical depression is not just a transient mood state. It is a disorder that affects mood, thinking, and behavior in fairly characteristic patterns and which impairs the ability to function in areas of work, school, personal and other social relationships, and other activities. It involves not only emotions but also involves the body as a whole and is associated with a variety of changes in how the brain processes information and interacts with the body's stress response system and immune function.

Depression is fairly common and results in significant disability. The World Health Organization has determined that depression is the second leading cause of chronic disability world wide. In the United States depression affects anywhere from 8-11% of the population at any one time with a lifetime risk of developing a depressive episode requiring treatment to just over 20%. Woman are affected at greater than twice the rate of men.

How do I know if I have depression? DSM-IV-TR refers to clinical depression as Major Depressive Episode defined by at least two weeks of persistent daily depressed mood or significant loss of pleasure in activities associated with at least five of the following symptoms; depressed mood and/or loss of pleasure, significant changes in appetite or weight, persistent insomnia or hypersomnia, agitation or severe psychomotor slowing, profound fatigue and loss of energy, decreased ability to think and concentrate as well as severe indecisiveness, feelings of worthlessness or excessive guilt and recurrent thoughts of death or suicide. Another cardinal feature not listed is the sense that everything is overwhelming and that even simple tasks of daily living can be seen as insurmountable obstacles. There are often associated physical symptoms such as headaches, nausea, irritable bowel or constipation, increased muscle tension.

I will talk more on this tomorrow. I hope that even though these posts are somewhat didactic that they are still useful and of some interest.

Thought for the day

Run after mature righteousness- faith, love and peace.

St. Paul

Depression, Diagnosis, Addiction, Recovery part 2

I am doing a series on depression and discussed how psychiatric diagnoses are phenomenological ( based upon clinical signs and symptoms) and how this is similar to other conditions such a migraine and Parkinson's. But phenomenological diagnoses are simply approximations and may include different "entities" within the same diagnosis. These approximations are useful though as they give us a common language, help make predictions regarding prognosis and types of treatment and provide diagnostic criteria for research purposes so that groups of people and treatment responses can be studied. In psychiatry these diagnoses are listed in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision, or DSM-IV-TR. One of the limitations of DSM-IV-TR is that diagnoses are categorical, that is listed as discrete and separate problems while in reality there are many overlaps. What is missing is the dimensional character of many problems, that is symptom problems that may be associated with many categorical diagnoses that are measured on a spectrum from mild to severe. Despite these limitations DSM-IV-TR is quite helpful.

One of the main things to understand about categorical diagnoses is that all of the diagnoses do not carry the same "weight". That is some diagnoses are much more reliable than others and probably do represent discrete "entities" and some do not. A characteristic of this type of diagnosis is that the greater the severity of the problem the more stereotyped it is in presentation and more likely does represent a certain entity. For example binge drinking in college may turn out to be a number of things from a transient problem to the beginnings of a more severe problem. There is no way to predict who may go on to develop alcoholism. So binge drinking is not a reliable diagnosis or a single entity. End stage alcoholism is different. It looks the same in most people. The same signs and symptoms are present, the same health problems are experienced and it is very predictable that death will ensue if the person does not stop drinking. The same goes for eating disorders Many people with a variety of problems may engage in the purging behavior of bulimia but severe malnourished life threatening anorexia nervosa is different. It does appear to be an entity all of it's own whose signs and symptoms are the same from person to person.

Depression is also one of those diagnoses that occur on a spectrum. I will talk more about that tomorrow.

Thought for the day

Happy Monday!

Depression, Diagnosis, Addiction, Recovery

I thought I would take some time over the next days to review depression, a common problem we see here at Cottonwood as we are a dual diagnosis treatment facility specializing in the treatment of addictions complicated by other psychiatric disorders. I will talk a bit about diagnosis in general, then about depression itself, what it is etc., and then how we appraoch the treatment of depresion here at Cottonwood. This will be a somewhat lengthy series which I will break up from time to time as other thoughts and other subjects come to me. I hope that it will be useful and not too boring as it will be a bit didactic and I welcome comments and questions as we go along.

Before we talk about depression itself though I want to talk a bit about psychiatric diagnosis in general, particularly the concern that some have that our diagnoses are too subjective since we don't have objective signs such as lab tests etc. There are four types of diagnoses made in medicine and the diagnosis by signs and symptoms is a legitimate diagnostic strategy that also has it's place in other branches of medicine. The first kind of disgnosis is that based upon tissue pathology. This is what we do in cancer. A biopsy of certain tissue is made and then there is a determination of whether or not there are cancer cells. The second kind of diagnosis is made by defining a deviation from the standard norm. This is how we define such conditions as hypertension, diabetes, and obesity. The third type of diagnosis is based upon the identification of the etiologic or causative agent. This is common in infectious diseases such as streptococcal pharyngitis,urinary infections, HIV, and hepatitis.

The fourth kind of diagnosis is phenomenological or based upon a common set of signs and symptoms This type of diagnosis is used in psychiatry but also includes such conditions such as migraine, Parkinson's disease, Alzheimer's disease, and suspicion of an acute abdominal condition such as appendicitis. So phenomenologic diagnoses can be quite specific and objective as well. I will speak further on this on Monday, how psychiatric diagnoses are made.

Thought for the day

"Let justice roll down like waters and righteousness like an ever flowing stream".

The Hebrew prophet Amos

Depression, Heart Disease, Nurse's Study, Risk Factor

Two recent reports from studies on depression remind us once again of the mind-body connection. It has been known for quite some time that depression is common in those patients who have suffered a heart attack or stroke and that those who have depression tend to have a worse survival outcome. The American Heart Association recommends that everyone with heart disease be regularly screened for depression. It also has been shown that those with diabetes have an increased risk of depression but also that depression is an independent risk factor for the development of diabetes. Now the same link has been shown with depression and heart disease. Depression is an independent risk factor for the development of heart disease similar to high cholesterol and hypertension.

The American Journal of Cardiology reported findings from The Nurse's Study which involved 63,000 women who were followed from 1992-2004. None of the women(mostly white) had heart disease but 8% had depression. Those with depression were found to have twice the risk of dying from sudden cardiac death than those without and to a lesser degree other forms of heart disease. Sudden cardiac death usually results from an abnormal heart rhythm. An additional interesting finding was that the use of antidepressants was linked to the increase in sudden cardiac death although the newer antidepressant medications have not been associated with heart rhythm abnormalities. It is thought that the use of antidepressants is more common in those with severe depression and that might account for the findings but further research needs to be done.

A recent paper presented at the American Psychosomatic Society showed a similar depression- heart disease link. The Washington University of St. Louis along with the Veteran's Administration studied twins from 1992-2005. Twin studies are often used to help determine the degree of genetic influence in a disease. They found that in those with a genetic risk of both heart disease and depression those who had depression at the onset of the study developed heart disease while those at genetic risk who did not have depression did not develop heart disease.

Both these studies show once again the potential devastating effects of depression and support the idea that there needs to be adequate insurance benefits for evaluation and treatment of depression which will reduce overall disease burden as well as decrease total health care costs.

Thought for the day

The mind and body are inseparable.