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.

Chantix FDA Warning

The Food and Drug Administration has recommended a safety labeling change for varenicline( Chantix) which is manufactured by Pfizer and is used as an aid to nicotine cessation. This seems to me to be a good idea as it has been known to have psychiatric side effects in some people.

My experience with Chantix has been mixed. It clearly is effective and has worked for a number of my patients who were motivated to quit smoking. But I had a few experiences that have taught me a few lessons and made me more cautious about prescribing this medication. One case is that of Mrs.G, a 45 year old woman who was at Cottonwood for treatment of alcoholism. She had a history of depression and was on antidepressant medication although she was not depressed at the time of admission. She was doing quite well in treatment and understanding the link between tobacco use and alcoholism decided to quit smoking while she was here. She had tried quitting before with the help of the nicotine patch but was unsuccessful so I prescribed Chantix. About one week later she went into a profound depression which was worse than she had ever had before. There had been no apparent psychological trigger so we discontinued the Chantix and about 5-6 days later the depression had resolved completely. Fortunately she was able to quit smoking, used the nicotine patch again and was successful this time.

Not that long afterwards I had a similar experience with Mr. S., a 38 year old man who was at Cottonwood for treatment of polysucbstance dependence. He had a concurrent anxiety disorder which we treated along with his substance abuse problem. He did not want to attempt to quit smoking here but was doing well at the time of discharge so he decided it might be a good time to quit. I prescribed Chantix for him at the time of his going home and did warn him about the possibility of return of anxiety or depressive symptoms while taking Chantix. He called me in a frantic state about 10 days later saying he had a severe exacerbation of his anxiety disorder. I recommended he stop taking the Chantix and several days later his anxiety resolved. Interestingly enough to me he had not recalled our previous conversation about Chantix side effects. This taught me two lessons, first to not prescribe any new medication as the patient is leaving, and secondly a reminder that many patients have too much to remember and may not remember verbal instructions.

It has been known since February of 2008 that some people on Chantix develop behavior changes, depression, or suicidal thoughts. The manufacturer Pfizer did not attempt to hide this data but immediately made changes in the product labeling to include these side effects. What is new in the FDA recommendation is that Chantix carry a "black box " warning in the prescribing instructions. The black box warning means that this information is highlighted in bold letters in a black box which is the first thing a prescriber will see when looking up the medication.

Does this mean Chantix should not be used? This information about Chantix needs to be taken to account in the context that tobacco related illnesses are by far the greatest cause of death in the United States. The people that I see at Cottonwood though may represent a high risk group for psychiatric side effects so will continue to use Chantix only when other smoking cessation efforts fail.

Thought for the day

I will say it once more. All medical treatments carry some risk as well as their benefits.

FDA, Opioids, and Risk Evaluation and Mitigation Strategies

I noticed in the news today that the Food and Drug Administration (FDA) has plans to increase regulation of certain narcotic prescription pain medications, including OxyContin and morphine and Fentanyl patches. The FDA already regulates these medications as Schedule II narcotics but has not had the ability or authority to do more than make recommendations and monitor prescribing patterns. In 2007 a law was passed, the Risk Evaluation and Mitigation Strategies (REMS), that allows the FDA greater authority in it's ability to require both manufacturers of these drugs and prescribing physicians to follow certain guidelines.

The FDA is responding to a significant problem in that these medications, while successfully treating pain in cancer patients and chronic pain patients, are increasingly becoming drugs of misuse, abuse, diversion, and addiction. Prescription pain medications are now the number one abused substance after nicotine and alcohol. Pain medications have overtaken marijuana as the most commonly used drug in teenagers and their use is increasing. Here at Cottonwood abuse of these medications are the most commonly presenting addiction after alcoholism. Again, after alcoholism the addiction and misprescribing of these medications are the second most common reason for disciplinary actions of state boards of medicine. In addition to the addiction potential these medications are dangerous in overdoses and have been responsible for many deaths. These drugs can be lethal when mixed with certain sedatives and are believed to have been responsible for the tragic death of actor Heath Ledger last year.

Something clearly needs to be done about this problem. I support the FDA in taking a stronger stance on this issue. It is unclear what the new regulations will be but I am sure will include required additional training for physicians who wish to prescribe certain opioid pain medications. My support comes with some trepidation however. This will be the first regulatory action that will affect physician autonomy in prescribing. While necessary in this case I do have some concerns that REMS can be used in the future to limit physician autonomy in other areas of prescribing such as use of psychophamacologic medications in which proposed restrictions are motivated more by an ideological and political agenda rather than based upon science. We will have to wait and see.

Thought for the day

Change brings both opportunity and risk.