I am trying to be open-minded about this study that investigated inserting genes into the brains of mice that were genetically altered to be “depressed”. First we have to talk about “depressed” mice. One model of depression in mice is to measure how vigorously the mouse struggles to get out of a beaker of water. “Depressed” mice do not try very hard. We imagine the mouse thinking “What’s the use?” We presume that this is because it lacks enthusiasm, motivation and will to survive. You can begin to see that the study basis leaves much to be desired. To be fair, researchers have to start somewhere in looking for treatments for depression because they cannot run around treating depressed people with any old idea that popped into their creative scientist brains. You cannot engineer mutant humans and getting your hands on their brain tissue is not possible while they are alive. So in this study they created mutant mice that were “depressed” and then replace the faulty gene in their brains by inserting a healthy gene and the mice went back to struggling hard to get out of the water, so were declared cured of depression by gene therapy. The mice cannot tell us about how they feel after the gene therapy. They cannot comment on how the therapy has affected their ability to live a normal mouse life. Inserting a gene into the DNA is a permanent action with the possibility of many unintended consequences. I understand that depression is a serious illness and that new approaches are needed because of the unsatisfactory success rate of medications. In trying to be open-minded, this study could be useful in identifying new targets in the brain for treatments like medications that are less invasive, less permanent and less scary.
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Archive for the ‘Depression’ Category
This Study Scares Me
Tuesday, November 16th, 2010Who Gets the Most Benefit from Antidepressants?
Wednesday, January 6th, 2010I seem to be on an anti-depressant theme lately in this blog. Most of the patients I see have some degree of depression and the discussion of whether to use medications is frequent, so perhaps it’s not surprising. I came of age as a psychiatrist when Prozac, the grandmother of modern anti-depressants, was new and we were getting newer drugs almost every year. I felt very optimistic about the medications and their capacity to improve people’s lives. In those early years, there was no data about any serious side-effects and studies showing efficacy for disorders other than depression were abundant. Two decades later, we have data about long term side effects and information about the limitations of these meds, proving there is no such thing as a free lunch.
This week’s Journal of the American Medical Association reports the results of a meta-analysis of the efficacy of anti-depressants and how it relates to the severity of the depression when the person started the med. A meta-analysis is when the results of lots of different studies are pooled and analyzed statistically. The results in this case confirm what I have observed in my practice, that being that the meds are most effective for people with the most severe depression. This can be a frustrating message for people seeking help for milder conditions because they hope and wish that a pill could relieve their distress. Thankfully, psychotherapy can be very effective for these people. No one treatment fits all.
Anti-Depressants and Pregnancy: Results from 2009
Tuesday, January 5th, 2010Studies about the effects of anti-depressants in pregnancy were numerous in 2009. The risk of preeclampsia (gestational hypertension) was elevated to 15.2% in women continuing SSRI medications after the first trimester, compared to 2.4% in women not on the meds. Women who stopped the SSRIs early in pregnancy had only 3.7% risk of preeclampsia, showing that it is not just the effect of the underlying condition i.e., depression.
Risk of cardiac septal defects was increased from 0.5% to 0.9% in babies whose mothers took SSRIs. These heart defects are considered minor, at least as compared to major cardiac defects.
There are conflicting reports about whether the meds cause pre-term birth or whether it is due to the underlying depression.
It is a sobering body of knowledge for me as a prescribing psychiatrist. Prescribing or continuing to prescribe meds during a patient’s pregnancy is a very serious decision. The woman and her partner have to be educated and encouraged to consider all the factors and risks. I am relieved that the pregnant patients I have prescribed meds for have all had normal deliveries and healthy babies.
Long-Term Risks From Anti-Depressants
Friday, December 18th, 2009More studies are coming out on the long-term effects of psychiatric drugs like anti-depressants and the results are mixed. We would like the drugs to have no long-term adverse events. That would make both the people who take the drugs and the docs that prescribe them much more comfortable, but the studies are not giving us simple answers.
Looking at the incidence of stroke and coronary heart disease in post-menopausal women showed no increase in heart disease in women taking anti-depressants. However, there was a small increase of stroke incidence in women on these drugs. There were about 4 strokes for every one thousand person-years for women on anti-depressants, compared to about 3 strokes for women not on anti-depressants. A person-year is the equivalent of one person taking the drug for one year. So, there was about one extra stoke in the thousand that could be due to the medication. This is possibly due to the slight blood-thinning side-effect of the SSRI meds like Prozac, Paxil, Zoloft, Celexa and Lexapro. Another study this year showed variable and increased risk of diabetes in people on anti-depressants, probably associated with drug-related weight gain.
It is important to keep the idea of risk in perspective. Every automobile ride comes with some risk of injury or death. We all accept that readily in our daily lives to reap the benefits of rapid transportation. There is a low risk of death in childbirth, but women choose to have children. Life is just a risky proposition. When it comes to drug treatment for anything, not just psychiatric conditions, we need to weigh the risks and benefits and make the best choice we can.
Flu-Related Depression
Thursday, November 5th, 2009I have always thought that having the flu affects mood more than one would expect. It seems to go beyond feeling run-down and tired. I have experienced this personally and seen it in patients as well as family and friends. I wondered if the flu virus itself got into the brain and unbalanced the neurotransmitters. Some new studies are throwing light on how any inflammatory process could affect mood. For my non-medical readers, inflammation is the body’s reaction to particular kinds of stress like infections. Sticking with the flu example, the white blood cells in the immune system notice the invading organism and go on the attack. The attacking cells release various chemicals in their attempt to beat the infection and some of these chemicals make us feel crummy. We get a fever, ache all over, lose our appetites and sometimes feel depressed. Some of these chemicals are called cytokines and are the focus of the studies I am referencing today. The researchers are interested in exploring the details of where these chemicals act in the brain and how they make us depressed. They also suggest that perhaps cytokines make us depressed as part of a massive reorganization of body resources to fight the infection. One paper called this “reorienting the central motivational state”. This translates as making you feel so sick you can’t waste energy on anything but staying alive. So if you are home sick with the flu and reading this blog, have a cup of tea, pull the covers over your head and take a nap and let your cytokines do their thing.
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Delonte West and Why People Don’t Take Their Medications
Monday, October 5th, 2009Delonte West is a talented young man who plays in the NBA for the Cleveland Cavaliers. He has been in the news in Cleveland lately because he was arrested for carrying firearms and secondly because of missing the start of training camp. Delonte West has said he has Bipolar Disorder and when he reported to training camp he said he was back on his medication regimen now. I don’t know this young man personally but I have known many people with Bipolar disorder. It’s not hard to imagine that being off his medications may have contributed to getting arrested with the guns. In the past, he has missed time on the court because of his mood disorder.
It got me to thinking about why people don’t take their medications. Some can’t afford the meds. Others cannot tolerate the side effects. For some people it’s the idea of being on meds, the stigma. People with Bipolar Disorder can be particularly prone to stopping their medications because there are enjoyable aspects to the highs of mania (high energy, euphoria, increased libido, feeling powerful).
I hope Delonte West’s medication regimen works and that he is consistent with it. It would be a shame to watch Bipolar Disorder sink his career. He is a valuable part of the Cavaliers and fun to watch. So I will be watching with my fingers crossed, rooting for him in more ways than one, because in some way he is one of mine.
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Fighting Seasonal Depression
Thursday, October 1st, 2009It’s that time of year in northeast Ohio when the days get shorter and darker. I have heard that Cleveland is the second cloudiest city in the US after Seattle and I believe it. Too often the sky is a featureless nondescript gray that I call “Cleveland gray”. I can clearly see the effects of seasonal change on my patients’ moods. People who have been doing fine come in and tell me how their meds aren’t working so well anymore or how they cannot seem to cope with that difficult boss or that impossible spouse. From where I sit, it’s not hard to believe in Seasonal Affective Disorder. Simply put, Seasonal Affective Disorder (SAD) is a disorder of mood associated with the light deprivation common in the winters of northern climates. It seems that light travels down the optic nerve to deep centers in our brains and activates biochemical cascades that improve our mood. Less light equals worse mood.
Since we cannot all move to sunnier places, what can we do to deal with this? Therapeutic interventions include med adjustments or using a therapy light. A daily dose of about 30-40 minutes of bright light (10,000 lux) directly in the eyes can be helpful especially if done first thing in the morning. Adverse effects of light therapy can be eyestrain and headache. Very few of my patients stick with light therapy because it is inconvenient to spend that amount of time daily essentially staring at a light. And the 10,000 lux light systems are pricey.
There are lifestyle interventions that can soften the effects of winter on our spirits. The trick is to make friends with the winter. Let whatever light there is out there come inside by opening curtains and blinds. Get out of the house nearly every day, if only to do a few laps around an indoor mall, preferably one with atrium styling so there’s lots of natural light. Walk outside, with proper clothes and footwear. I will concede that there are days in Cleveland when walking outside would be inadvisable, or maybe would fall into the category of Extreme Sports. But there are many more days when it is just fine, if you are prepared. They even sell compact warmer packs to fit inside gloves and sox. Winter sports like skiing and snow-shoeing can make you look forward to a good snowfall. Indoor hobbies and projects are indispensable when the sun sets at 5pm. Catch up on reading or movies, sewing or jigsaw puzzles, baking or computer games. Just keep moving and resist the urge to collapse on the sofa and give in to the winter blues. Above all remember that it won’t last forever.
When is Sadness Depression?
Wednesday, July 1st, 2009Sadness is a normal human emotion, experienced by all of us at times of loss, hurt, disappointment, grief, etc. Where is the boundary between sadness and clinical depression? Mental health practitioners utilize a diagnostic handbook called the DSM to help make the distinction. The DSM is the Diagnostic and Statistical Manual published by the American Psychiatric Association and has undergone many revisions through the years. One of the benefits of having a manual like this is to attempt to give psychiatrists, counselors, physicians, and psychologists a common vocabulary so that we can be more sure we are talking about the same condition when we use a word like depression. All fields of medicine have diagnostic categories. For example, the staging system used by oncologists to describe how far a cancer has progressed or the categories of heart disease. Doctors even have staging categories for normal processes like how far along children are in their adolescent sexual development or how childbirth is progressing.
In general, the DSM distinguishes sadness from depression by the intensity, the duration and the impact it has on a person’s functioning. Depression is pervasive sadness for at least two weeks that affects the person’s interests and activities, appetite, sleep, energy, and ability to think clearly. Feelings of agitation, being slowed down, worthlessness or excessive guilt are also symptoms. Suicidal thinking can be a very serious component. Not all people with depression experience all the symptoms listed above.
I decided to write about this after reading an article in the New York Times Magazine on May 10, 2009 by Daphne Merkin about her lifelong struggle with depression. She captures in words the inner experience of severe depression. She compares depression to “thick black paste”, “the muck of bleakness”, “as if in exiting the womb I was enveloped in a gray and itchy wool blanket instead of a soft, pastel-colored bunting”. Her piece is intense and painful at times to read. Thankfully, not all depressions are as severe and chronic as hers has been. Her article is worth reading if you are interested in understanding the subjective experience of depression. Here’s the NYT link.
Pain and Depression
Tuesday, June 9th, 2009More support for the mind-body connection. A study treated patients in primary care settings who had both chronic pain and depression symptoms. The control group received usual care and the target group received anti-depressant treatment combined with therapy sessions for 12 weeks for chronic pain management techniques. At the end of the study and at one year followup, the treatment group had less depression and less pain. It is amazing that this study had to be done. It makes common sense to me that chronic pain and depression go hand in hand and for people to do well, both need to be addressed. It is evidence of the continuing bias in Western Medicine to view people through the dualistic lens of mind separate from body.
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Anti-depressants and pregnancy
Monday, May 11th, 2009The March 2009 issue of the American Journal of Psychiatry contains an article describing new risks associated with the use of some anti-depressants in pregnancy. Women taking SSRI’s in late pregancy had higher rate of hypertension and preeclampsia than women not taking these medications. The SSRI’s (serotonin reuptake inhibitors) are the most commonly prescribed group of anti-depressants and include Prozac, Zoloft, Paxil, Lexapro, and Celexa. These results make the decisions surrounding treating depression in pregnancy even more difficult. I would like to see a study done to determine the outcomes of depressed pregnant women treated with psychotherapy rather than medication. Some interesting data is out there that indicates that elderly people with anxiety do just as well with psychotherapy as they do with meds. This was a helpful study because using medication in the elderly comes with a elevated risk profile, just like using meds in pregnancy is more complicated.
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