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