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.

Tobacco Effects Fetal Brain

A study recently published in the Journal of Pediatrics provides more evidence of the adverse effects of tobacco use during pregnancy. There is already evidence showing that prenatal tobacco exposure is associated with neuro-cognitive effects in the first 3 years of life, including problems with attention and regulation of emotions. We also know that maternal smoking is linked with intrauterine growth restriction and decreased neonatal birth weight. Now, a study from Finland has shown a link to actual brain development.

The researchers looked at 232 infants from a single hospital from 2001-2006 who were either very low birth weight or below 32 weeks gestational age. The developing fetuses were evaluated with head ultrasounds at different points and brain magnetic resonance imaging at term. 42 of the mothers smoked during their pregnancy (18.1%) and averaged 10 cigarettes per day. This smoking rate of 18% is very similar to what is found in the United States. Mothers who smoked during pregnancy were twice as likely to drink than those who did not smoke. The findings were that infants exposed to prenatal smoking had smaller frontal lobe and cerebellar volumes. The investigators did not report on developing functioning of the children as they aged so no clear clinical implications can be drawn from lower frontal lobe and cerebellar volumes but this study is one more piece of evidence that prenatal exposure to tobacco is clearly harmful.

Thought for the day

" So come what may, I'll not upset my cheerful happiness of mind. Dejection never brings me what I want; my virtue will be warped and marred by it".

The Way of the Bodhisattva

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

Fish Oil Psychosis Prevention

There was a very interesting study published recently in the Archives of General Psychiatry looking at the possible role of fish oil in the prevention of overt psychosis in high risk individuals. Prevention of development of schizophrenic psychosis is an area of increasing interest in psychiatry due to the devastating nature of the disease. Schizophrenia is the most severe of the mental disorders which usually begins in late adolescence or early adulthood. It consists of a combination of hallucinations, delusional thinking, thought and behavior disorganization, cognitive deficits and extremely impaired interpersonal functioning. Anything that might prevent this disorder would be of very significant benefit.

Studies so far have looked at the role of antipsychotic medication given early, in high risk individuals before overt psychosis or loss of reality. But this involves using medication that can have significant adverse effects in people who don't have a mental disorder diagnosis which is very controversial. This study involved 81 patients aged 13-25 who were considered at high risk for psychosis due to intermittently hearing voices or feeling at times that someone might be trying to read their minds. Half of the study participants received a capsule containing usual doses of omega-3 polyunsaturated acids and vitamin E and the other half received capsules only containing coconut oil for a period of 12 weeks. The participants were evaluated weekly for 4 weeks, at 8 and 12 weeks and then again at 6 and 12 months. At the end of the 12 months the conversion rates to schizophrenia were 4.9% in the fish oil group and 27.5% in the placebo group.This is a very significant difference. The rate of adverse side effects was higher in the placebo group than the treatment group. of interest is that the benefits were seen at the end of 12 months although the fish oil was only given for a 3 month period.

The exact mechanism of action of the fish oil is unknown although it has been increasingly noted that dysfunctional fatty acid metabolism may play a role in the disease due to oxidative stress that may lead to neuronal cell degeneration. There is already enough evidence to suggest that adding omega-3 fatty acids in already established schizophrenia may reduce the doses of antipsychotic medication needed but to potentially prevent a problem by a readily available, low cost, natural substance with few adverse effects is amazing. I am sure that there will be follow-up studies with larger populations to see if this preventive effect can be replicated by other researchers.

Thought for the day

Prevention beats treatment.

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.

DSM-5 Diagnostic Changes Gambling - Sex

I have been discussing some proposed changes in psychiatric disorder classifications for the fifth edition of The Diagnostic and Statistical Manual of Mental Disoders (DSM-5) which were recently released in draft version by the American Psychiatric Association. The final version won't be published until 2013 and there is opportunity for anyone to make comments on the draft at www.dsm5.org until April 20 of this year. I have discussed some proposed changes in substance use diagnoses, now refereed to as Addiction and Related Disorders as well as the changes regarding autism and Asperger's syndrome. There are also proposed changes in terms of pathological gambling and a new term Hypersexual Disorder.

Pathological gambling will now be referred to as Disordered Gambling and is under the classification of Addiction and Related Disorders as the only non-substance related behavioral addiction. Consideration was given to Internet addiction but it was left out due to lack of enough research in the area. The new categorization of disordered gambling as an addiction makes sense as the dopamine reward system is "hijacked" in gambling in the same way as substance related addictions and there has been a great deal of research in this area. Those in the recovery field have long treated disordered gambling as an addiction and it is good to see some "official" support for the concept.

There was hedging in the area of compulsive like sexual problems. These are not subsumed under the addiction category but are included as a new sexual disorder category, Hypersexual Disorder.The nearest diagnostic neighbors are the paraphilic disorders which are characterized by socially anomalous or deviant sexual arousal such as exhibitionism, fetishes, and pedophilia. The new category referred to as Hypersexual Disorder refers to "normal" sexual behaviors that are repetitive, excessive, or disinhibited. The classification of such issues as a psychiatric disorders will certainly be controversial as there are significant gaps in the current scientific knowledge base regarding antecedent, concurrent, and predictive validators as well as the lack of knowledge regarding developmental risk factors, family history,cognitive markers and neurobiological substrates.In addition there is almost no knowledge regarding these issues in women. There is also no knowledge in our understanding of how excessive sexual behaviors may part of overall impulsivity and inability to delay gratification.

On Medscape, which is an Internet medical site providing medical news, continuing medical education, and physician discussion boards I was amazed by the volume of responses and the vehemence of the responders to the question of whether or not sexual behaviors could be classified as addiction. I haven't seen any other question generate more comments and more heated discussion. I am very interested to see the public comments on Hypersexual Disorder in DSM-5. I will be off blog for several days but when I return I will talk a bit on the diagnostic criteria for this disorder.

Thought for the day

May I show the same compassion for myself that I show to others.

DSM-5 Diagnostic Changes Autism Asperger's

As I mentioned yesterday the draft version of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) has been released by the American Psychiatric Association. DSM-5 will be the first changes made in diagnostic criteria for psychiatric disorders in 10 years with final publication occurring in 2013 after field trials in real world situations. The draft is available for review at www.dsm5.org with opportunity for public comment until April 20 of this year. There are several proposed diagnostic changes some of which already are controversial. I talked about the substance abuse changes yesterday and today I would like to talk about Autism and Asperger's Disorder.

DSM-5 proposes the elimination of the designation Asperger's Disorder which is to be subsumed by the new category of autistic spectrum disorders with a range of severity. There has already been complaints by those with Asperger's and those who work with patients with this disorder. Asperger's Disorder like autism is characterized by severe sustained impairment in social interaction and development of restricted patterns of behavior, interests, and activities. Unlike autism there are no delays or deviance in language acquisition nor delays in cognitive development and it is not like autism often associated with mental retardation. Characteristically patients with Asperger's appear odd to others. They frequently do not pick up on social cues, their interactions are one sided, focused entirely on their own interests with little empathy or understanding of the other as an individual. They may be intensely focused on one topic, with exclusion of all other interests. But unlike autism the desire for social interaction is present. They just don't know how to do it. Often they are loners, not always because of their own wishes but due to peer's inability to tolerate them.

Some in the field are objecting to placing Asperger's in a category of autistic spectrum disorders because of the potential for increased stigma as well as changes in research funding. I do not know the science behind the proposed change but I can understand how those with no language difficulties cognitive impairment would want to be considered in a somewhat different way than those who have these more severe impairments. I wonder what the ongoing public comments will be on this issue.

Thought for the day

May I show kindness and compassion today.

DSM-5 Diagnostic Changes Substance Abuse

The American Psychiatric Association has released the draft version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This is a work that has been ten years in the making and will replace DSM-IV-TR as the official diagnostic manual for mental health. The DSM-5 is still a work in progress. The draft report has been released to allow for public review and comment before 3 phases of field trials will take place in real world settings before the final version is published in 2013. Anyone can review the document at www.dsm5.org and comment before April 20th. There are a number of proposed revisions which I will discuss here over the next few days but today just want to focus on the proposed changes in substance abuse disorders.

The DSM-5 proposes the elimination of the categories of substance abuse and substance dependence replaced by the category of addictions and related disorders. There will be no differentiation between abuse and dependence. Instead all will be referred to as substance use disorders with varying levels of severity. This has been proposed to try to eliminate the confusion between physiologic dependence upon alcohol or a drug and addiction per se as well as to address the problem with our current categories in which the psychosocial consequences of abuse are given more weight than in the dependence diagnosis itself.

A Substance-Use Disorder will be defined as a clinically significant impairment or distress as manifested by 2 (or more) of the following, occurring within a 12-month period:

Failure to fulfill major role obligations at work, school, or home

Recurrent use of substances in situations in which it is physically hazardous

Continued use despite persistent social and interpersonal problems caused by the
substance

Tolerance - diminished effect with the continued use of the same amount of the substance

Withdrawal syndrome

Taken in larger amounts or over a longer period than was intended

Persistent desire or unsuccessful attempts to cut down on the substance use

A great deal of time spent in activities necessary to obtain the substance

Giving up important occupational or recreational activities

Continued use despite knowledge of having a persistent physical or psychological problem caused or exacerbated by the substance

Craving or a strong desire or urge to use a specific substance

Two to three criteria positive will be referred to as moderate severity with four or more referred to as severe. There will be a separate specifier for with or without physiological dependence.

The proposed changes are also designed to take into account that abuse and dependence are not necessarily two separate categories but represent different severity points on a continuous spectrum of problems. I think these proposed changes represents more the real world than our old categories but will lead to some disagreement about how to define the term alcoholic or addict which are not diagnostic terms per se but are commonly used in the treatment and recovery field. I invite any comments on what you think about these proposed changes.

Thought for the day

Are my actions likely to enhance or detract from an other's well being today?

30 Hour Famine World Vision

We often hear about how many problems that adolescents have in this day, problems with substance abuse, teen pregnancy,sexually transmitted diseases and educational failures so I would like to talk about something positive that many youth engaged in over the weekend. World Vision, a christian charitable organization ,sponsors each a 30 hour famine for middle school and high school age teens. Across the country young people participate in this activity which is designed to raise awareness of global poverty and provide the youth an opportunity to do something to make a difference.We had over 100 teens participate this year at our church. It is a yearly event that we have been participating in for some time now.

So what is the 30 hour famine? The youth spend the weekend together and fast for 30 hours to get some sense of what it is like for many that go hungry. During the weekend they participate in activities that both help the community as well doing awareness related activities. This year they made sandwiches for the homeless, refugee welcome baskets, worked at program that feeds the homeless and collected food for one of the local food banks. Afterwards they raise money for different projects. This year their goal was $7,500 dollars to buy insecticide treated mosquito netting for beds to give to the World Vision sponsored group End Malaria which is dedicated to the goal of eradicating malaria. The youth learned that 2,000 children die each day from malaria. The past two years they provided aid to two villages in Zambia to build wells for a clean water supply. Two years ago they had the neat experience of being able to talk with someone from the village they were working with by satellite phone.

So, kudos to all the youth across the country who participated in the 30 hour famine.

For information World Vision is accredited by the EFCA, the evangelical counsel for financial accountability which require programs to provide full financial disclosure to anyone who wants it including a financial breakdown of each project they are involved in.

Sex Education Abstinence Program

I read something encouraging in the news the other day. A study published in the February issue of the Archives of Pediatric and Adolescent Medicine reported the success of an experimental school based sexual abstinence program in Philadelphia.For reasons that have been unclear to me those who have been involved in the sex education field have been reluctant to endorse abstinence from sex as the best method of preventing unwanted teen pregnancy and sexually transmitted diseases. I understand and agree with the need to educate young people on how to avoid these complications by condom use if they engage in sex but I have never understood the black and white thinking that has resulted in hostility to the idea of abstinence.

The study reports on 662 inner city 6th and 7th graders who were assigned to one of four groups. Some were assigned to the experimental eight week hour long experimental classes only, some to traditional safe sex classes, some a combination of both and a fourth or control group taught general non sexual healthy behaviors. The program was designed not to tell the children not to have sex but to help them look at the pros and cons themselves to make their own thoughtful decisions. At the end of two years one-third of the abstinence only program participants said they had engaged in sexual activity since the classes ended vs approximately 50% in the other 3 groups.

To me this is very encouraging. Our young people need to know that everyone is not "doing it" and should receive support and encouragement to just say no. Adolescent girls especially need support in not giving in to excessive pressure as many engage in otherwise unwanted sexual behavior because they think they have to to keep their boy friends or they don't have the assertiveness and communication skills to stand up for themselves. I hope more research will be done in this area.

Thought for the day

"Destroy a single being's joy and you will work the ruin of yourself".

The Way of the Bodhisattva

Bipolar Disorder Part 7

This is the last in a series on bipolar disorder. We recently went over the medications used to treat this condition but now I would like to focus on what I call the "other two pillars" of treatment; avoidance of alcohol and substance abuse and management of stress and anxiety.

As I mentioned before the two main reasons that someone with bipolar disorder is not responding to treatment are they either are not taking their medication or there is a drug and/or alcohol problem. Over 50% of patients with bipolar disorder have some sort of a substance abuse problem and this must be dealt with for effective bipolar treatment to occur. Some people are sensitive to even small amounts of alcohol and even intermittent use can cause a problem with mood instability.

Handling stress and anxiety involves some simple things that are often overlooked. Deep breathing techniques are useful. Maintaining a regular sleep schedule and daily routines are good. Patients need to avoid periods of frenetic activity whether at work or home. Daily exercise is important as is good nutrition. Educating family members about bipolar disorder is needed. It is very useful to have a family member accompany the patient to medication follow-up appointment as they may notice early signs of mood disturbance, particularly mania which is not often recognized well by the patient. Learning to recognize early signs of mood disturbance is vital to ongoing recovery.. I always encourage my patients to learn as much as they can about the disorder. This is a lifelong disorder and there may be many different psychiatrists one could see over the course of a life. The only constant factor is the patient him/her self.

I hope this series on bipolar disorder has been helpful in some way. Again, any comments or questions are always welcomed.

Thought for the day

Compassion not judgment

Bipolar Disorder Part 6

Today I will continue to talk about medications to treat bipolar disorder. We have discussed lithium and the antiepileptic drugs and today we will review the third class of medications, the second generation antipsychotics which include some of the newer medications available to treat bipolar disorder.

The second generation antipsychotics are referred to as such in that although they initially came out to treat schizophrenia and partially work like previous antpsychotics in terms of blocking the neurotransmitter dopamine they have some different properties as well which sets them apart from the older antipsychotics or the "first generation". They have some action at serotonin type 1 and serotonin type 2 receptors as well as at dopamine receptors and they bind more at dopamine type 4 receptors and are less active at dopamine 2 receptors resulting in a much reduced tendency for neuromuscular side effects than our older drugs.

These medications include risperidone(Risperdal),quetapine(Seroquel),olanzapine(Zyprexa),ziprasidone(Geodon),Aripiprazole(Abilify), and the newest one paliperidol(Invega). They are very effective antimanic medications, we believe prevent mania and depression to some degree and unlike the other bipolar medications treat depression as well. These medications all have some different properties but tend to have the same set of side effects and risks so I will talk about them as a group.

The main side effects are neuromuscular side effects and metabolic effects. Like the older antipsychotics there is a small risk for a life threatening condition, neuroleptic malignant syndrome, as well as for tardive dyskinesias which are potentially irreversible abnormal involuntary muscle movements. The other much more common and troubling side effects are metabolic. They cause weight gain, increased triglycerides and increased blood sugar leading to possible cardiovascular disease and diabetes.They are not associated with birth defects if used during pregnancy though there is a national registry to monitor this. Geodon and Abilify have much less tendency than the others to cause this metabolic triad. So why use the others? Some people will not respond to Abilify or Geodon and do respond to the others. In fact I have never seen a patient whose acute mania did not respond to Zyprexa. Because of the least amount of side effects and risks I tend to use Abilify as first line treatment because if it works there are not the problems the more severe problems we have with lithium the, aniepileptic drugs s and the other second generation antipsychotics. Geodon could also be a first line treatment for the same reasons but tens in some people to cause sedation.

So, lithium, the antiepileptic drugs and the second generation antipsychotics are what we have available to treat bipolar disorder. I hope that there will be continued development of medications with greater effectiveness and lower side effects. Tomorrow I will talk about some of the non pharmacological treatments that are helpful in bipolar disorder.

Thought for the day

"He whose heart is in the smallest degree set upon goodness will dislike no one".

Ancient Chinese

Bipolar Disorder Part 5

This is the fifth in a series about bipolar disorder. I have been talking about the dilemma of finding effective medication without undue side effects or toxicity and talked before about lithium which remains the "gold standard". Today I will discuss three more medications, carbamazepine (Tegretol), valpoate (Depakote), and lamotrigine (Lamictal). All three belong to the class of medications referred to as AED's or antiepileptic drugs. They initially were designed to stop seizures in epileptic patients before they were found to have significant mood stabilizing properties. Again, like lithium we do not know the mechanism of action in bipolar disorder.

Tegretol was the first one of these three medications found to be effective in bipolar disorder. It does a good job of treating mania and preventing further manic episodes, is not so good at preventing depression and does not at all treat depression. It generally is fairly well tolerated in terms of day to day side effects and blood levels can be monitored. There is sometimes an allergic rash,it can cause hyponatremia or low sodium levels, and is teratogenic, potentially causing congenital abnormalities if taken while pregnant. It also reduces the effectiveness of birth control pills. The most serious potential side effect though is the possibility of bone marrow suppression, impairing the ability to make white blood cells needed to fight off infections so the white blood cell count needs to be monitored on a regular basis.

Depakote was the next AED available to treat bipolar disorder. Like Tegretol it is a very effective antimanic medication, can prevent mania from recurring but does less well in preventing depression and does not at all treat depression. It is as effective as lithium in treating mania and sometimes more effective. Common side effects can be weight gain (at times quite significant) and tremor. It can cause some hair loss, alter menses, increase risk of polycystic ovary syndrome and is very teratogenic. Like Tegretol it can be monitored with blood levels. Rare but serious side effects can be drug induced hepatitis or pancreatitis or quite rare liver failure. Liver function tests need to be routinely monitored.

Lamictal is much different than any other bipolar medication. It does not treat mania nor depression but is very effective in preventing further manic episodes as well as further depressed episodes. It is extremely well tolerated day to day, is not associated with weight gain, is not teratogenic, and is not associated with the risk of bone marrow suppression or liver problems. It has a rare (but potentially fatal) risk of inducing a Stevens - Johnson reaction which is a severe rash affecting not only the skin but the mucous membranes as well. Because of it's properties of preventing mania and depression it is often used as a second medication in many cases.

As I mentioned before these medications can sound quite bad in terms of side effects and risks but in most cases the benefits of preventing the devastating consequences of untreated bipolar disorder outweigh the risks. Tomorrow I will talk about the third group of bipolar medications, the second generation antipsychotic medications.

Thought for the day

"The thought never came to mind that I too am a brief and passing thing and so, through hatred ,lust, and ignorance I have committed many sins".

The Way of the Bodhisattva

Bipolar Response

A reader posted a question on our Facebook site asking about the difference between bipolar I disorder and bipolar II disorder. I have not yet gotten to that point in the series but I will answer briefly as well as I can.

What I have been talking about so far is what we call bipolar I disorder which has previously been called manic - depressive illness. Bipolar II disorder is a cycling mood disorder in which there are episodes of depression, including chronic depression with episodes of what we refer to as hypomania or "under mania". These are periods in which there are manic like symptoms but not of the severity of full blown mania and not resulting in so many life destructive events. Most people with bipolar II disorder spend the majority of their time in depression.

I hope this helps answer the question and we will discuss this more in detail on a later post.

Bipolar Disorder Part 4

This is the fourth in a series of didactic posts on bipolar disorder. I want to talk a bit about medication treatment as it is an essential component of treatment For patients making informed decisions about these medications requires education as many of the medications that we use to treat this disorder have significant adverse side effects, can be toxic, and can have long term negative effects on different organ systems. I call it the bipolar medication dilemma as there are no easy answers, there is no one size fits all treatment, and decisions need to be made on an individual basis taking into account health risks and other health conditions that a patient may have. It is a true dilemma as these medications that I will talk about have a lot of problems and yet without medication an untreated course of bipolar disorder is a disaster. So for now we have to use them. I would like readers to keep that in mind when I discuss all the potential negative effects.

There are four goals in medication treatment of bipolar disorder. We need to treat mania without causing depression, treat depression without causing mania, prevent depression, and prevent mania. It is unusual for one medication to carry out all four of these tasks so combination medication is the rule, rather than the exception which increases the potential for medication side effects. There are three different types of medication which have clearly shown effectiveness; lithium, anti epileptic drugs used to treat seizure disorders, and the second generation anti psychotic medications. I will talk about lithium to day and cover the others later.

Lithium remains the "gold standard " for treatment of bipolar disorder. No medication has been shown to more effective than lithium which we have had available to use since the mid 70's. Lithium is not a drug. It is a basic element which binds to other molecules to become a salt just as the sodium we use for table salt does. Usually the lithium we use comes in the form of lithium carbonate. The mechanism of action is unknown. It effectively treats mania and does work to prevent mania and depression but by itself is not a good antidepressant. We have more medications available to treat mania than we do bipolar depression. There is a narrow range between therapeutic levels and toxic levels so lithium blood levels do need to be obtained. Toxic lithium levels can result in kidney failure which is not always reversible. Lithium can cause diabetes insipidus which is the inability of the distal tubules in the kidney to reabsorb fluid resulting in excessive urination. Fortunately this can be treated strangely enough by adding a diuretic. Lithium also interferes with the release of thyroid hormone leading to hypothyroidism so thyroid levels need to be monitored. The most worrisome effect though is the evidence that long term lithium use (30 years or more) results in some kidney damage and impaired kidney function. We are now beginning to see this since we have had lithium available now for 35 years. No one really knows whether or not this will result in progressive renal failure or not. Some common day to day side effects are nausea, tremor, development of acne and weight gain.

So you can see that lithium has a lot of problems but I want to state again that it is very effective. It to me is still a "miracle" in that it can stabilize a disorder that otherwise would result in chronic mental illness and difficulty or inability to live in the community. I do not like to use lithium though for milder cases of bipolar disorder but for the more serious cases with the most complications or to use lithium when other treatments are not effective. I will talk about some of the other medication treatments in my next post.

Thought for the day

"Live a life worthy of the calling to which you have been called".

St. Paul

Bipolar Disorder Part 3

I have been talking about bipolar disorder the past two days and want to look at what it takes for effective treatment. There are three main things that must be done to prevent relapses and avoid the devastating consequences of both the mania and depression. The first is adequate medication. The second is avoidance of alcohol and drugs, and the third is management of stress and anxiety. Chances of full and long lasting recovery are slim if one of these things are left out of treatment.

First is adequate medication. Unlike non bipolar depression bipolar disorder cannot be treated with cognitive behavioral and other psychosocial treatments alone. Medications are required and need to be taken lifelong. Bipolar disorder is a progressive disease with deterioration over time if left untreated. There are problems though with the medications that are available to treat bipolar disorder. Many have significant side effects and are associated with long term health risks. I will discuss the bipolar medication dilemma tomorrow.

Second is avoidance of alcohol and drugs. Unfortunately over 50% of individuals with bipolar disorder have an alcohol or other substance abuse problem. There tends to be a continuous negative cycle in which the alcoholism worsens the disorder and the disorder reduces chances of long term abstinence. Except for non adherence to medication alcohol abuse and dependence are the number one reason for failure of adequate treatment or so called treatment resistance. I cannot overemphasize this. Bipolar disorder cannot be stabilized in the presence of an active substance abuse problem and co-occurring treatment is required.

The third main pillar of treatment is management of stress and anxiety. High levels of stress can trigger either manic or depressed episodes as well as times of interpersonal conflict. Persistent insomnia which often accompanies stress can trigger manic episodes. Regular sleep, good diet, and exercise are helpful in this regard.

Thought for the day

"God is our refuge and strength, an ever present help in times of trouble"

The Psalmist

Bipolar Disorder Part 2

This is the second part of a series on bipolar disorder which is a common mood disorder affecting about 1% of the population. I indicated that the hallmark of this disorder is episodes of mania that are not due to substance abuse or medical problems. So what exactly is mania?

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision(DSM-IV-R) defines mania as follows;

Manic episodes are characterized by at least one week of profound mood disturbance characterized by elation, irritability, or expansiveness that causes significant impairment in occupational or social functioning or represents a danger to self or others that has at least three of the following symptoms;

Grandiosity
Diminished need for sleep
Excessive talking or pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Increased level of goal directed activity at home, at work, or sexually
Excessive pleasurable activities, often with painful consequences

This definition I suppose is ok but it doesn't capture the essence of mania which includes significant impairments in appearance, mood, thought content, perceptions, self destructiveness, aggression and judgment and insight so I will try to describe common changes we see in these areas.

Appearance - we see hyperactivity, hypervigilance, restlessness, excessive energy and activity. Thinking and talking are very fast, the person will often interrupt or talk over everyone else, will have no sense of social boundaries and be behaviorally intrusive. Attire may be very disorganized or very bright, colorful, or garish and they frequently attract attention because of the way they dress. Being with a manic person makes you want to find the "off button".

Mood - we see a tendency to be inappropriate in terms of being elated, jubilant, or euphoric or a high degree of easy annoyance or irritability that seems totally out of proportion to what is actually happening.

Thought content - We see expansive and overly optimistic thinking, inappropriate self confidence or grandiosity, high distractibilty, quickly shifting from one thought to another and, can be very hard for one to follow their train of thought. Often there are thoughts that the manic person has of being special or having some sort of special knowledge and these can become very delusional. There is an apparent need to excitedly tell others about this specialness or the grandiose insights.

Perceptions - We often see overt delusions which reflect perceptions of power, prestige, self worth, or glory and will sometimes move to extreme paranoia or hallucinations.

Self destructiveness - there can be suicidality although most suicide attempts in bipolar disorder occur in the depressed phase of the illness.

Aggression - we see at times aggression and combativeness, demandingness, and acting out of the grandiose belief that others need to obey their commands or wishes with anger and irritability when someone doesn't obey.

Judgment and Insight - It is the impaired judgment that really differentiates mania from normal "highs". Patients with mania have generally no insight. They rarely see anything wrong with themselves and resist efforts at treatment not seeing any need for it. Serious mistakes are frequently made in regard to finances, marriage and relationships, and occupation, refusing to listen to any one's advice often with devastating consequences.

This is a rather long post but I wanted to describe what mania is really like and I don't think the DSM-IV-TR really describes what goes on in mania.

I will discuss tomorrow some options for treatment. Again I welcome any questions or comments.

Thought for the day

Without treatment bipolar disorder can be a devastating disease.

Bipolar Disorder

From time to time I do a series of teaching posts dealing with a particular psychiatric disorder. I encourage any readers to post any comments and questions as we go along and I hope that I can be of use to someone who is interested in knowing more about a particular topic. I have decided to focus for a short time on bipolar disorder which is a common psychiatric problem and one of the most severe, persistent, and often disabling disorders that we treat.

Bipolar disorder used to be referred to as manic depressive illness. It has been described in medical literature as far back as Hippocrates in ancient Greece. It is common, affecting approximately 1% of the population with men and women being equally affected. There have been no race or ethnicity correlations. Bipolar disorder appears to be an equal opportunity disorder. It is chronic, persistent, and associated with a variety of complications including suicide attempts and suicide, child or spousal abuse or other violent behavior, school failure, occupational failure, divorce, and alcoholism and drug addictions. Untreated it tends to worsen over a person's life. It is considered the most severe mental illness after schizophrenia and often associated with lifelong disability. Over 50% of those affected will develop alcoholism and 11% will die by suicide. It's onset is usually in late adolescence or early adulthood although it can present later in some people. It is strongly genetically linked. First degree relatives of someone with bipolar disorder are 7 times more likely than the general population to have bipolar disorder.

So what exactly is bipolar disorder and what are the features of this problem? The hallmark of bipolar disorder is episodes of mania. Bipolar disorder is diagnosed in anyone with a manic episode that is not induced by drugs or alcohol or a medical disorder, whether or not there are episodes of depression. More commonly though the person will suffer from both depressed episodes as well as mania and the majority of the time the patient will be in the depressed phase of the illness. So if mania is the hallmark what exactly is mania? It is much more than an elevated mood but affects appearance, mood, thought content, perceptions, anger or aggression, judgment, and insight Usually impairments in orientation and memory are not present.

I will discuss tomorrow what these multiple changes are.

Thought for the day

"No power of hell or scheme of man can ever pluck me from His hand".

The Newsboys

Attention Deficit Hyperactivity Disorder Girls Complications

We have known for a long time that Attention Deficit Hyperactivity Disorder (ADHD) in boys has been associated with increased risk of several psychiatric problems in young adulthood but a recent study published in the American Journal of Psychiatry shows for the first time thst the same applies to girls with ADHD.

The study was a very good one in that it that it was a prospective longitudinal study that used a full follow-up assessment after an average of 11 years after enrollment in the study. There were 96 girls with ADHD who were compared to 91 girls without ADHD. 92% of the girls with ADHD had received medication treatment sometime in the intervening 11 years with 42% receiving treatment in the year preceeding the follow-up.

The researchers found that girls with ADHD had almost a seven times higher risk for developing depression or antisocial disorders, and over twice the risk of developing substance abuse problems, anxiety disorders or eating disorders. There are probably many reasons why this is the case such as general impulsivity and risk taking behavior. The rates of depression were high. Whether this represents genetic factors or the chronic demoralization that comes from problems in school,problems with peers, and problems within the families or some combination of factors.

It is discouraging to see that girls with ADHD have as many psychiatric problems in young adulthood as do boys. Hopefully some information will become available to see if early treatment can prevent these complications but for now we don't know.

Thought for the day

"From my first cry to my final breath God holds my destiny".

The Newsboys

Post Traumatic Stress Disorder Morphine

The New York Times reported Wednesday about an article that appeared in the New England Journal of Medicine talking about post traumatic stress disorder and morphine. I do not get the New England Journal so I haven't seen the article itself yet but I want to make a few comments about what was reported.

A record review study of 696 servicemen and women who were wounded in Iraq between 2004 and 2006 noted that those who received prompt treatment with morphine had roughly half the chance of developing post traumatic stress symptoms (PTSD) within the first two years following the injury. Out of the 696 wounded 243 developed
PTSD which in itself is an alarming figure but those that received morphine within generally two hours after the injury fared better than those who did not.

Why does morphine help? My guess is that it works by inhibiting the excessive firing of the amygdala under stress. The amygdala is a group of cells in the front portion of both temporal lobes and as far as we know is responsible for the overall emotional tone we associate with events. It is also known as the "fear center" of the brain. The amygdala is next to and highly linked with the hippocampus which is responsible for encoding memories. Our current understanding then is that an event that gets encoded as a memory by the hippocampus will be encoded with a greater strength as well as with a connection to fear if the amygdala is highly active during the event.

There are some problems with this study though that need to be sorted out with further work before we can recommend morphine for non combat traumas. It has been noted that the same benefit of morphine has been seen in children at burn centers. The problems with this post traumatic stress disorder morphine study first of all is that it is a record review, a retrospective study which is never as beneficial as a prospective study. Secondly we may be confusing association with causation. These were men and women injured in combat. It may be that quick and adequate pain control is responsible for the effect on trauma. This makes sense with burned children as well. The trauma could be the pain itself especially as many of the wounded here did not get adequate morphine pain relief until well after two hours of the injury. It was also noted that many of the wounded received anti-anxiety medication as well so it may be length of time to receive help after a combat wound is the determining factor rather that the morphine itself.

I hope to be able to read the New England Journal article itself soon. Some of these issues may be addressed there. It is important that further work be carried out in this area as the symptoms of post traumatic stress disorder can be devastating and disabling and there are many more sorts of trauma than combat injuries and burn injuries.

Thought for the day

Every day is new with possibility.

Cocaine Sudden Death

We have known that cocaine is sometimes associated with sudden cardiac death and occasionally hear about someone in the news who has died that way. We haven't known particulars though such as prevalence, doses of cocaine used, age ranges and other concomitant drug or alcohol use. A recent study from Spain published in the European Heart Journal has provided us with some of this information.

The study from the Institute of Legal Medicine in Seville, Spain is the first study to look at cocaine-related deaths in a systematic way with autopsies and toxicology screens in a series of 600 consecutive sudden death victims. The study showed that 3% of these sudden deaths were cocaine-related with the majority due to cardiac causes.

All the cocaine deaths were males. Myocardial infarction (heart attack) was the most common cause of death although there were strokes as well. Interestingly the serum cocaine concentrations varied widely so any amount of cocaine can be deadly. The demographic findings were that most of the victims were working and died at home on the weekends suggesting that they were "recreational " users rather than chronic cocaine addicts. 81% smoked and 76% had used alcohol along with the cocaine both which decrease coronary arterial blood flow. The most important take home message from this study is that no amount of cocaine is "safe".

In the United States there are approximately 500,000 emergency room visits per year for cocaine related events. We have no idea of the figures of sudden death because we have no way at present of reporting cocaine related sudden death and also because autopsies with toxicology screens are not usually performed but left to the discretion of the pathologist. It would be a good idea for us to develop some standard reporting procedures.

Thought for the day

No amount of cocaine use is safe.

American Academy Addiction Psychiatry 2009 part 2

I want to continue to update you on some of the studies recently presented at the annual meeting of Addiction Psychiatry held earlier this month. As I said before I did not attend the conference. I received my information from medical sites on the web. There was an interesting presentation The study was conducted by a professor of psychiatry at the University of Colorado School of medicine funded by National Institute on Drug Abuse and involved Concerta ( a slow release version of methylphenidate) which is used to treat attention deficit hyperactivity disorder.

The findings from 303 adolescents ranged in age from 13-18 from 11 community based treatment programs who had both ADHD and substance abuse showed that Concerta after a 16 weeks was no more effective in the treatment group than the placebo group. The drugs that were used were marijuana (91%) alcohol (56%) hallucinogens (12%) cocaine 10%) and smaller numbers for opioid and amphetamine abuse. One confounding factor which needs to be investigated further is that both the treatment and placebo groups received cognitive behavioral therapy. Both groups showed improvement but there is always improvement in placebo groups so we don't know whether the cognitive behavioral therapy had any effect or not. The study was not designed to address that question. But it is clear that Concerta is generally of no value in treating adolescents with ADHD who are abusing alcohol and drugs. It will be interesting to see if similar studies will show the same lack of effectiveness. I don't think any of the pharmaceutical companies will funding or helping fund such research.


Thought for the day


If you are abusing alcohol and drugs you might as well quit taking your medication as it won't work unless you quit.

American Academy Addiction Psychiatry 2009

For the next several days I will be presenting some highlights from the 2009 annual meeting of the American Academy of Addiction Psychiatry recently held in Los Angeles December 3-6. I did not attend the meeting. I don't usually attend this meeting as it is always in December and I am already taking some time off for the holidays. I also don't like going out of town in December. I did attend the meeting several years ago when it was held in Phoenix, Arizona and it was interesting and worthwhile.

A study conducted at the University of California is interesting as it looked at a group of methamphetamine addicts that were "pure". That is they had no other substance abuse except for nicotine and had no co-occurring psychiatric disorder. This is not a patient population we normally see in the "real world" but it did give a chance to look at the effects of methamphetamine itself uncomplicated by other factors.

They recruited 56 volunteers who stayed at an inpatient clinical research center for 5 weeks. Generally at time of admission they had high levels depressive, mood, and psychotic symptoms which resolved in 2-3 days. The withdrawal was mild, consisting of red and itchy eyes, poor memory, lack of energy, lack of motivation and irritability and lasted from 2-6 days. The most important finding though was that at the end of 5 weeks 30% of the patients had drug cravings as intense as they were when they came in to treatment. This magnitude of continued intense cravings has not been found for other drugs except for possibly nicotine. It is also probable that in the average methamphetamine dependent population in which there are high levels of co-occurring psychiatric problems and other substance abuse problems this percentage of continued intense cravings may be more than 30%.

At the moment there are no medications available to treat methamphetamine cravings. Cognitive behavioral therapy has been shown to have some efficacy in other studies but it is not always easy to obtain and the results take time. We don't know how long the cravings persist after 5 weeks but it does remind us that methamphetamine addicts in particular need very close follow-up after inpatient treatment, active psychotherapy, and strong early participation in Narcotics Anonymous or other support groups.

Thought for the day

Methamphetamine use is increasing.

Breast Cancer Screening USPSTF

As many of you know the United States Preventive Services Task Force (USPSTF) recently came out with new recommendations for mammogram screening for breast cancer that included the recommendation that women 40-49 not be screened routinely despite approximately 35,000 breast cancers are detected in this age group each year and that each year there are over 4,000 deaths in women in their 40's. USPSTF is not a government agency but it is funded by the federal government so although the recommendations are not official US policy they are pretty close to being so in actual practice. The American Cancer Society has been very active in refuting this recommendation.

I indicated before that I thought this recommendation was entirely based upon desire for cost control with the sense that women in their 40's could go ahead and die with breast cancer as the number of cases detected by mammograms each year was not enough to justify routine screening according to USPSTF. We were assured that this was not primarily a cost saving recommendation but already USPSTF recommendations are being used to deny screening to poor women. Most states have been providing free mammogram and Pap smear screenings for the uninsured poor. But already less than a month after the USPSTF recommendations the state of New York has changed it's policy. Women less than 50 are no longer eligible for free screening unless they have a "serious" family cancer history. We will have to see how soon other states follow New York's lead.

Thought for the day

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

OTC Drug Abuse Dextromethorphan

It is nice to be writing again. I have been on a very pleasant at home vacation but am now back at work. It is good to get back in the swing of things including this blog.


I have discussed several times the problem of the increasing abuse of prescription pain pills (the opioids) among adolescents and the potential dangers of that abuse but I would like to talk about another aspect of teen drug use and that is misuse of over the counter medications, in particular dextromethorphan, The federal Substance Abuse and Mental Health Services Administration (SAMHSA) has indicated that there are currently approximately 3 million teens who are abusing dextromethorphan which is found in cough medicines. There has been a 7 fold increase since 1999. It is likely that the use is increasing because like the pain pills they are easily accessible and perceived as harmless by many young people.

Dextromethorphan( DXM) is found primarily in OTC cough syrups and the pill form Coricidin. It's chemical structure is very close to that of codeine, an opioid with abuse potential. The first use of a similar medication came out in 1958 as Remilor which was subsequently removed from the market due to extensive misuse. The most popular form used by teens today is Coricidin which are little red tablets each containing 30 mg of dextromethorphan. Because of their appearance they are known a skittles or red hots by many teens. Cough syrup was previously the main formulation use and still is but a whole bottle must be taken to get the euphoric effect so the tablets are easier.

Use of high amounts of DXM has a simlar effect to the use of ketamine and PCP, both of which are referred to as dissociative drugs. DXM provides euphoria, a sense of unreality, and a stimulant effect. It does not show up on urine drug screens. Referred to as "robo tripping'"it is seen as a "safe" drug but results in 6,000 emergency department visits per year. It is often mixed with alcohol which intensifies it's effects and can lead to respiratory depression and even death. If used by a person taking antidepressants it can cause the serotonin syndrome, a triad of mental changes, autonomic nervous system abnormalities and muscle twitching and tremor. The serotonin syndrome is seen as a medical emergency and can be life threatening. DXM is often found in preparations that contain antihistamines such as chlorpheneramine which can cause seizures in high doses or acetaminophen which can cause liver toxicity.

I believe that the best way to combat the increasing use of DXM is education both for physicians, teens, and the general public. We need to be aware that it is important to ask about this specific drug use in the same way that we do with alcohol and marijuana.

Thought for the day

There is no such thing as a "safe drug".

Dementia Worldwide Disability

The Center for Public Mental Health in London reported recently on a research study looking at various diseases which are contributors to chronic disability in the elderly. The research was sponsored in part by the World Health Organization and the study looked at more than 15,000 people in China, India, Dominican Republic, Venezuela, Mexico, and Peru. It had previously been thought that blindness, deafness, and heart disease were the major contributors to disability but this study found that dementia is "overwhelmingly and consistently the largest contributor to disability". Stroke and arthritis were the next other high ranking contributors.

The disability was determined using the 12 item World Health Organization disability assessment schedule. I have not seen that so am not really sure what that entails. Dementia, depression, hypertension, and chronic obstructive pulmonary disease were measured by clinical assessment but other diseases were determined by self report which the investigators acknowledge is a limitation of their study. The findings do remind us though of a significant impending problem as the incidence of dementia in the United States alone is estimated to triple by mid century.

I hope that we will have found ways by then to prevent dementia as enormous financial resources are required to care for individuals with dementia that as of now is not reversible.

Thought for the day

Show kindness to all as everyone you meet is fighting a battle of some kind.

USPSTF Breast Cancer Epidemiology Nonsense, Part 3

Yesterday Health and Human Services Director, Kathleen Sebelius, tried to do some damage control in regard to the the public response to the new United States Preventive Services Task Force guidelines regarding screening mammography. She said to women "keep doing what you've been doing for years" and indicated that the task force " does not set federal policy and they don't determine what services are covered by the federal government".

One of the task force members, Dr. Timothy Wilt, indicated that he stuck by the new recommendations.

I don't have anything new to say about this. I am just providing updates for those who are following this issue.

Thought for the day

Keep it simple.

USPSTF Breast Cancer Epidemiology Nonsense Part 2

Yesterday I briefly discussed the new breast cancer screening guidelines published by the United States Preventive Services Task Force (USPSTF). The USPSTF is not a government agency but is funded by the federal government and operates under a congressional mandate. The highlights and controversial aspects of the recommendations are:

Against self breast examination

Uncertainty about whether a doctor's clinical breast exam does more harm than good

and the main one- recommendations against routine mammography screening for women age 39-49

Both the American Cancer Society and the American College of Obstetrics and Gynecology have written responses challenging these new guidelines. Why the challenge? The USPSTF report indicates that screening mammography for women in their forties does more harm than good. The report indicates that 1339 women in their 50's need to be screened to save one life and that 1904 women in their 40's need to be screened to save one life. With 22,327,592 women age 40-49 in the United States as of July 1, 2008 the difference between 1339 and 1904 seems pretty small to me. 17% of all breast cancer deaths each year are in women diagnosed in their 40's. Over 45,000 deaths from breast cancer occur in women age 40-49 over a 10 year time span.

The USPSTF report acknowledges that the benefits of screening mammography for women in their forties are the same as for those in their 50's with a mortality risk of 0.85 from 39-49 and 0.86 for women in their 50's. But because of the total smaller number of diagnoses in the 40-49 age range and more false positives the USPSTF believes that due to "anxiety, distress and other psychosocial effects" the risks outweigh the benefits. I believe that the anxiety and distress caused by learning of a breast cancer that could have been diagnosed earlier far outweighs the anxiety of a false positive mammogram. The only psychosocial benefit in not screening women in their 40's is cost reduction.

I would welcome any thoughts or comments on this issue.

Thought for the day

One day at a time.

USPSTF Breast Cancer Epidemiology Nonsense

The United States Preventive Services Task Force (UPSTF) has published new breast cancer screening guidelines in the Annals of Internal Medicine. The USPSTF is not a government agency. It is an independent body financially supported by the Agency for Healthcare Research and Quality which is a federal agency. The new guidelines are a bit surprising and I am sure will generate a lot of controversy.

The new guideline recommendations are:

Against teaching breast self examination.

Against routine mammography screening for women age 40-49.

Women age 50-75 years old should have biannual rather than annual screening mammography.

Insufficient evidence to determine the benefits and harms for clinical breast exams

Insufficient evidence to determine the benefits and harms of screening mammography after age 75.

Insufficient evidence to determine the benefits and harms of digital mammography or MRI vs film mammography screening

How did they come up with this? This was determined after a meta analysis of all studies that were identified through the Cochrane Register of Controlled Trials, the Cochrane Database of Systematic Reviews, a MEDLINE search from January 2001 to December 2008, Web of Science searches, and the Breast Cancer Surveillance Consortium for screening mammography. The problem with such meta analysis studies is that they often miss the trees for the forests. They compile statistical data but do not take into account the great individual and even group differences that can be widely different and need different recommendations. The guidelines are made for everyone and that is how we end up with what I call epidemiological nonsense.

Women -don't do self breast examinations? Doctors - don't do clinical breast exams? It may do more harm than good? Don't do mammography screening for women ages 39-49 even though this analysis even shows that mammography screening in this age range results in a 15 % decrease in breast cancer mortality rates? This is nonsense . Our faith in and dependence upon large scale meta analyses has led to absurdities such as these USPSTF guidelines. These guidelines are not just absurd, they are dangerous. Women will be confused about what they should do and because of this confusion women will die who would not otherwise. These guidelines will encourage insurance companies to deny payment for mammograms until age 50. At least women can appeal these denials. Under a government run health care system there would be no recourse.

I am interested to see what other health organizations including the American Cancer Society will have to say.

Thought for the day

" Cast your anxieties upon the Lord as He cares for you"

St. Peter

.

Prenatal Tobacco Exposure Neurodevelopmental

We have known for some time that tobacco use during pregnancy is not a good idea. One of the consistent findings has been the association with tobacco use and low birth weights. Low birth weights are a nonspecific factor that correlates with fetal growth retardation which can occur from a variety of different factors. Tobacco use is one of those. Three studies recently presented at the 56th annual meeting of the American Academy of Child and Adolescent Psychiatry suggest longer term neurodevelopmental problems.

These three studies are all prospective studies. These were not chart reviews looking for correlating factors but involved looking directly at children and their behavior. The first study enrolled 304 women before their fourth month of pregnancy. Self reports were used to assess smoking during pregnancy. The investigators examined the newborn children 1-3 days after birth and at weeks 2 and 4 looking at reflex assessments, orientation to audio and visual stimuli and response to stressors. The infants of mother's who smoked were less attentive and exhibited consistently more irritability. This is consistent with previous findings that suggest some tobacco withdrawal symptoms do occur.

The second study involved 207 infants from the first study evaluated at 6 months of age. The infants exposed to tobacco prenatally showed lower attention spans than non exposed infants.

A third study evaluated self regulation and executive control in a different population of 237 otherwise normally developing three year olds. Those exposed to tobacco prenatally showed poorer ability to wait for a reward and to regulate motor behavior. While Attention Deficit Hyperactivity Disorder (ADHD) is not diagnosed in preschoolers these findings are similar to the problems that do show up in children with ADHD. The study is ongoing and will follow these children on an ongoing basis.

These three studies suggest that smoking during pregnancy is related to attention and self regulatory problems at multiple points of development. Given that about 20% of expectant mothers smoke a large number of children are affected. Tobacco cessation is difficult but perhaps these findings may increase the motivation to quit in women who smoke during pregnancy.

Thought for the day

Tobacco use during pregnancy is simply not a good idea.

Pregnancy Anxiety Depression SSRI's

There has been a great deal of uncertainty in the last several years about the risks of the selective serotonin reuptake inhibitors (SSRI's) in pregnancy. These medications which include Prozac, Zoloft, Paxil, Celexa, Luvox, and Lexapro are used to treat both depression and anxiety disorders. All of them are considered Category C medications which mean there are not adequate well controlled studies in women to answer the question of safety to the developing child, that caution is advised, and that the benefits of the medication may outweigh the potential risks of not using the medication. As you can see this guideline is extremely vague and doesn't really help the clinician in knowing what to do with a pregnant woman with depression or an anxiety disorder.

There are several areas of concerns for a pregnant woman. First, does the medication cause any congenital malformations? Secondly does the medication increase the risks of low birth weight or preterm delivery? Are there ill effects on the newborn such as lower Apgar scores, withdrawal symptoms, or increased need for Neonatal Intensive Care (NICU) services and finally what is the effect on the developing brain of the fetus when medications are used during pregnancy and how might that affect the cognitive and emotional development of the child? These are a lot of questions and we don't have clear answers. I will leave aide the issue of nursing for now.

What is known at this time is that SSRI's put infants at risk of low preterm birth, lower 5 minute Apgar scores and increased risk of admission to the NICU. Paxil has been associated with a slightly higher risk of congenital abnormalities than in the general population. A number of infants will develop some withdrawal symptoms of increased irritability and poor muscle tone, seizures and respiratory problems. On the other hand untreated depression is linked to preterm birth, lower birth weights, and lower Apgar scores indicating that untreated depression has an adverse effect on the developing fetus as well. Pregnant women with untreated depression ate also at significantly higher risk of alcohol use and abuse (which clearly causes fetal problems) and failure to receive adequate prenatal care. In all the studies it has also been unclear whether the adverse effects are due to the SSRI's themselves or that the SSRI use is not simply linked to women who experience significant depression who develop more problems.

A recent study published in the November issue of Paeditaric and Perinatal Epidemiology does give us some new information about untreated anxiety in pregnancy. 763 women were assessed and followed during the course of pregnancy which indicated that mild or moderate anxiety is not associated with any adverse fetal effects but that high levels of anxiety were associated with smaller birth weights and risk of preterm delivery. This does not necessarily help us with the medication issue though. It does tell us that anxiety needs to be assessed and addressed in pregnancy but there are non medication means of reducing anxiety.

So, little by little we are gaining more knowledge but for now the clinician and soon to be mother have to decide in each individual case whether it is better to continue ore use antidepressant medication during pregnancy.

Thought for the day

There are not always easy answers in medicine.

Health Care Reform HR 3962

The views expressed in this blog are my own personal opinions and do not represent the views of Cottonwood nor it's administration.

As everyone knows by now HR 3962, the health care reform bill, passed in the House of Representatives by a vote of 220-215. Our own representative in Congress, Gabrielle Giffords, voted in favor of the bill. I have previously outlined my concerns about this version of health care reform, indicating that it goes beyond health care reform and is essentially a government takeover of the entire health care system. I don't have anything new to say except that while the initial version HR 3200 was 1300 pages long HR 3962 is 1900. I will next comment on this issue after the final version is complete after coordination and merger with the Senate version which we have yet to see.

There is a lot that will be said by many on this bill that is based upon rumor.. I won't comment on it until I have read the final version in it's entirety just as I did HR 3200 so it will be awhile. I read the previous version while my wife was out of town and I had plenty of time on my hands!

Thought for the day

Give thanks to the Lord for He is good. His mercy endures forever.

Human Genome Project NIH Watson

I left out this post by mistake and it should have come before today's,

The Human Genome Project is the most important scientific advancement that we have made in this century. It was a huge undertaking sponsored by the US Department of Energy, the National Institute of Health(NIH) with involvement of a number of other countries as well Incredibly by 2003 all the genes in human DNA were identified as well as the sequence of the 3 billion chemical base pairs that make up human DNA.This has enormous implications in a wide variety of areas but in medicine it has allowed examination of specific genes that may be involved in a number of diseases, including psychiatric disorders. One of the goals of the project was to address the ethical, legal, and social issues that arise from this project. It didn't tale long for controversy to emerge


J.Venter, a biologist at NIH, began the process of requesting patents. He had not sequenced whole genes but rather fragments of DNA referred to as EST (Expressed Sequence Tags). I have tried to understand what exactly is an EST but it is way over my head. By the early 90's he had requested over 7,000 patents for different EST's. In effect he was trying with NIH to basically patent the human gene which would be a disaster for science. James Watson opposed this policy and had to resign as Director of the project as NIH was planning on continuing the patenting process. The controversy eventually was resolved when the US Patent Office rejected all the applications.


So as much as there is present controversy regarding James Watson he did lose the chance to complete The Human Genome Project by standing up for scientific principles over profit.



Thought for the day

Sometimes it is hard to do the right thing.

James Watson Eugenics Cold Spring Harbor Lab

This is the last of a series of postings in regard to James Watson who along with Francis Crick and Maurice Wilkins won a Nobel prize in 1962 for their work in 1953 in determining the chemical structure of DNA. Watson has been a controversial figure because of statements he has made over the years that seem to indicate his continuing interest in eugenics. Eugenics is the attempt to improve mankind and enhance human development by weeding out problematic genes and enhancing those that are associated with better physical and mental health. Eugenics is nothing new but the ethical dilemmas are much increased now that the entire human genome has been sequenced.

Eugenics was the movement in the early 1900's that increased in influence until 1940 when it essentially went underground. The idea of a "master race" did not originate with Adolf Hitler. He used already prevalent eugenics ideas to justify his extermination of the Jews. The heart of the eugenics movement was not Nazi Germany however. It was the United States and it's intellectual center was Cold Spring Harbor Laboratory in New York. It was there that eugenics "research " was begun and it was there where there was a eugenics register kept. The ideas of those believing in eugenics were widely adopted here in the 1930's and resulted in the mass involuntary sterilization of thousands of the mentally ill and developmentally disabled.

Although the Cold Spring Harbor Laboratory changed it's major focus to cancer research, for years it was headed by James Watson who was the Director, later the President, and then the Chancellor of the research center.. Watson has made no secret about his eugenics ideas and leanings and the fact that he directed Cold Spring Harbor Laboratory for many years is disturbing. He was only forced into retirement in 2007 when a statement he made to the effect that Africans were not as intelligent as whites became widely publicized.

Watson is not alone among genetic researchers in thinking that the new genetic knowledge we have can be put to use to improve the human race. While hopefully there will be many positive benefits to us all from the new genetics I want to say that the eugenics movement is not dead and we must all keep vigilance to make sure that the ideas of weeding out the weak or ethnic groups is not repeated.

Thought for the day

One mark of a society is how it treats it's weakest members.

The Double Helix Watson DNA Part 3

Since I have already recommended The Double Helix by James Watson I will not discuss anymore the bock except for a few brief points. I then want to move into two different scientific controversies in which Watson has subsequently been involved.

Watson and Crick received a Nobel prize in 1962 for their work on DNA. What I did not know was that another researcher, Maurice Wilkins, at a different laboratory shared the Nobel prize along with Watson and Crick as they used a lot of his data on X ray crystallography in their own work. The interesting thing to me was that Rosalind Franklin who worked with Wilkins and did much of the crystallography work herself and whose x ray picture of DNA was used (some say stolen) as the final piece of evidence that Watson and Crick needed to develop their model did not share the Nobel. Four researchers and three prizes. The woman was left out. I hope we have come along way since 1962. Watson did in his book credit her. She died before the Nobels were awarded so never knew she was excluded.

In 1988 Watson became Director of the National Institute of Health (NIH) project on the human genome, an ambitious project to sequence the entire human genome. NIH had several goals. They wanted to identify all the approimately 20,00-25,000 genes in DNA, determine the sequencing of the 3 billion base pairs that make up human DNA, store the information in data bases, improve tools for data analyses, transfer technologies to the private sector and address the ethical, legal, and social issues that could arise from such a project. Amazingly the identification of all the human genes and determination of all the base pairs crompising DNA was accoilplished in 2003. Watson resigned in 1992, howsever and was not there to see the project to completion. I will discuss that in another post.

Thought for the day

"Utter not a word by which anyone could be wounded"

Ancient Hindu saying

The Double Helix DNA Watson Part 2

Yesterday I recommended the book The Double Helix by James Watson, his own first person account of the events leading up to the determination of the chemical structure of DNA. It is a short fascinating and actually suspenseful read that I thin anyone interested in science would enjoy. As I mentioned before I am extremely awed by all the orchestrations that must take place at the biochemical and molecular levels to sustain life and for some reason more awed than by contemplating the stars.

I have never been proficient in biochemistry. I love to read about it and have learned a lot but never was very good at it. I failed to pass biochemistry in two different attempts as an undergraduate. I dropped the courses before the drop deadlines so my grades were not affected but I know I would not have done well if I continued. In medical school I had to take it again and it was the only course that I came near to failing. At that time we had a large class at the University of Tennessee and no one would be allowed to continue to progress if one did not get at least a C grade in the course. If I failed this time I would have had to wait to join the next year class of medical students and take biochemistry again. Needless to say I sweated this one out and barely received my C grade, the only one I had in school.

What is comforting for me to know and is well described in The Double Helix is that James Watson though having a Ph.D in biology never was able to pass organic chemistry. He was co-discoverer of what may be the most important organic chemical molecular structure undelrying all of life but he couldn't pass his course. The difference is that he was a genius and having initially no interest in chemistry taught himself by reading The Nature of the Chemical Bond by Linus Pauling. I don't think it spoils the book (since we know the outcome) but Linus Pauling was studying DNA at the same time as Watson and Crick!

The only negative thing about The Double Helix is the intial descriptions of another DNA reasercher Rosalind Franklin who died before this book was written.

Thought for the day

It is never too late to teach an old dog new tricks.

The Double Helix DNA Watson

I finished rereading The Double Helix by James Watson this weekend. Watson along with Francis Crick first determined the chemical structure of DNA which has revolutionized the field of biology. While many people are awed by looking at the stars and contemplating the size of the universe I seem to be awed more by contemplating the very small but extremely complicated molecular interactions that sustain life. To me this area is very fascinating and strengthens my belief in a creator the same way that many find in astronomy.

I had just read The Astonishing Hypotheses: The Scientific Search for the Soul by Francis Crick. Crick was a reductionist and saw ourselves as just molecular interactions and nothing more. The book is from the 90's and since that time there has been a great deal more work on trying to understand awareness and consciousness. The subtitle is rather misleading as most of the book demonstrates the extensive knowledge that Crick had developed regarding the visual system and computer neural network models but it is a good read nonetheless. From there I was wanting to know more about the work that he and Watson did regarding DNA so I googled and found a copy of their original paper that was published in the journal Nature in 1953. It is amazing that this paper is only one page long. I never would have imagined this. They did follow-up with the implications of their findings in the very next issue of Nature but again this was a very short article.

There have been other books written on the early work on DNA but The Double Helix is particularly interesting as it is a first person account. This of course leads to potential for significant bias about these events but it is well written and actually quite suspenseful. It is a short book and I highly recommend it. I will discuss this further tomorrow.

Thought for the day.

It just seems incredible to me that the most far reaching discovery in biology and biochemistry was initially described in just one page.

Heroin Dependence Implant

The October issue of the Archives of General Psychiatry contained a report about the potential usefulness of an implant containing sustained release naltrexone for the treatment of heroin dependence. Heroin dependence is very difficult to treat with relatively few users who are able to maintain abstinence. The standard treatments now include both methadone and buprenorphine which are heroin substitution therapies that greatly reduce the risk of complications such as HIV, hepatitis C, unemployment, criminality and prostitution. There are limitations to both of these treatments however and many patients continue to use heroin despite taking these medications so anything new that shows promise is very encouraging.

Since 1984 an oral form of naltrexone has been available to treat heroin dependence but has essentially been useless. Naltrexone is an opioid antagonist. It sits on the opioid receptors and blocks the ability of heroin and other opioids to bind to these receptors. As a result, using heroin has no effect. The problem is though that all one has to do is stop taking the naltrexone and the ability to get high returns quickly. So oral naltrexone has been of very limited usefulness. What has been developed is a sustained release version of naltrexone which can be implanted under the skin and which can have an effect for up to 6 months providing a long period in which the user can move away from the heroin lifestyle.

The study included 70 adult patients who were randomly assigned to receive oral naltrexone plus a placebo implant or daily placebo tablets with a naltrexone implant. During the 6 month period 63% of patients receiving the implant reported complete abstinence with 17% returning to daily heroin use and the rest reporting heroin use a few times per month. In contrast the patients taking only oral naltrexone had 62% returning to regular heroin use, 26% reporting abstinence and the others heroin use several times per week. Although not looked at in this study about 20% of heroin addicts remain abstinent in this time period with psychosocial treatments only.

63% 6 month abstinence is amazing in heroin addiction and I hope that these findings can be replicated by others in follow-up studies.

Thought for the day

Most heroin users hate their lifestyle. They just feel trapped.

Neuroenhancement American Academy of Neurology 2

Yesterday I talked about the guidance document for physicians that came from the American Academy of Neurology dealing with the issue of neuroenhancement, which is the prescription of psychotropic medication to healthy individuals who want to enhance their cognitive performance. They concluded that it is ethical for physicians to prescribe medication for these purposes. It is interesting to see their argument and justification for their conclusion.

The argument that they make is that they divide the practice of medicine into three domains, a core domain, a middle domain, and an outer domain. The core domain are those actions consistent with the traditional goals of medicine: to prevent, diagnose, and treat disease or injury, reduce suffering and to help patients die in peace. The outer domain are those actions that are ethically prohibited such as participating in the torture of prisoners and the like. They describe the middle domain as those actions that are not prohibited but fall outside the traditional role of physicians. They use cosmetic surgery as an example of a middle domain action and liken this to cognitive enhancement.


Right now we have three types of medications used for cognitive enhancement; stimulants, the wakefulness agent modafanil, and the anticholinesterase inhibitors used to slow down memory loss in dementia. There will be more to come in the near future so this is an issue that will stay with us.


I do not think that I will participate in the use of medications for cognitive enhancement in healthy individuals. Medications can result in great benefits but have side effects and risks as well. The physician must always balance potential benefit vs. potential risk. For example I would find it hard to justify myself prescribing Adderall to healthy individuals and putting them at risk of addiction or cardiac difficulties.


I would love to get comments or questions on this issue.


Thought for the day


This is the day that the Lord has made. Let us rejoice and be glad in it.