Posted by Simones on February 22, 2004, at 13:11:05
In reply to anyone over 80mg of Celexa for OCD or Panic??, posted by smittay17 on January 18, 2004, at 17:40:04
I don't usually respond to these things, but I am currently on citaloprom, which doesn't work for me, and trying to get reassigned to a tricyclic like imipramine.
As such the following articles might provide an answer for you. The first one is just background information, the second and third the most important ones - the second one in particular might provide an answer to you. You can research them further yourself.
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National Institutes of Health
National Institute of Mental Health
March 27, 2002 Contact: Jules Asher
NIMH Press Office
(301) 443-4536
NIMHpress@nih.govTiming of Chemical Signal Critical for Normal Emotional Development
A signaling protein suspected of malfunctioning in anxiety and mood disorders plays a key role in the development of emotional behavior, report researchers funded by the National Institute of Mental Health. Mice lacking it in frontal brain circuits during an early critical period fail to develop normal reactions in anxiety-producing situations.
Rene Hen, Ph.D., Columbia University, and colleagues created mice that lacked the protein, which brain cells use to receive signals from the chemical messenger serotonin, by knocking-out the gene that codes for it. As adults, these "knockout" mice were slow to venture into -- or eat in -- unfamiliar environments. By selectively restoring, or "rescuing" certain populations of the receptor proteins, the researchers have now pinpointed when and where they enable the brain to cope with anxiety. Hen, Cornelius Gross, Ph.D., Xiaoxi Zhuang, Ph.D, and colleagues report on their discovery in the March 28, 2002 Nature.
Brain neurons communicate with each other by secreting messenger chemicals, such as serotonin, which cross the synaptic gulf between cells and bind to receptors on neighboring cell membranes. Medications that enhance such binding of serotonin to its receptor (serotonin selective reuptake inhibitors, or SSRIs) are widely prescribed to treat anxiety and depression, suggesting that the receptor plays an important role in regulating these emotions.
Behavior of the animals in the study mimicked human anxiety. The mice bred not to express the gene that codes for the serotonin receptor (5-HT1A) moved around less than normal animals in open spaces, balked at entering elevated mazes, and were slower to begin eating in such novel environments. Yet, the researchers didn't know which of two populations of serotonin receptors -- one in the forebrain and another deep in the brainstem -- was responsible. To find out, they crossed the receptor knockout mice with mice engineered to turn receptor expression on and off in specific brain regions. This gave birth to a line of transgenic animals in which only the forebrain receptors were rescued from the gene knockout. This "rescue" line of mice behaved normally when tested for the anxiety-like behaviors, suggesting a key role for the receptor in forebrain circuits mediating anxiety.
Next, the researchers treated adult mice - knockout, rescue, and normal - with a drug (doxycycline) that shuts off receptor expression. Even without the receptors, the adult rescue mice continued to show normal anxiety-like behavior. The researchers inferred that the receptor "functions earlier in development to establish normal adult anxiety-like behavior."
To find out when this occurs, they gave the receptor-abolishing drug to breeding pairs of rescue mice to turn off receptor expression in their pups during the embryonic and early postnatal period. As adults, these offspring behaved just as anxiously as knockout mice when tested. This, together with the timing of receptor expression in the rescue mice, suggested that the critical period for establishing normal anxiety-like behavior is between 5 and 21 days after birth.
Serotonin stimulation of the forebrain receptor during this period likely triggers "long lasting changes in brain chemistry or structure that are essential for normal emotional behavior throughout life," suggest the researchers. They note a number of studies pointing to such a role for serotonin during this critical time.
Intrigued by evidence that the serotonin receptor may be abnormal in patients with panic disorder and post-traumatic stress syndrome, other NIMH-supported researchers are embarking on brain imaging studies of its function in these anxiety disorders.
The current study was supported under a NIMH grant on the biology of serotonin to Irwin Lucki, Ph.D., University of Pennsylvania. Also participating were: Kimberly Stark, Ph.D., Sylvie Ramboz, Ph.D., Ronald Oosting, Ph.D., Luca Santarelli, M.D., Columbia University; Lynn Kirby, Ph.D., Sheryl Beck, Ph.D., Children's Hospital of Philadelphia.
The National Institute of Mental Health (NIMH) is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
Posted: March 27, 2002
National Institutes of Health
National Institute of Mental Health**************************************************
August 07, 2003 Contact: Jules Asher
NIMH Press Office
301-443-4536
NIMHpress@nih.govCreation of New Neurons Critical to Antidepressant Action in Mice
Blocking the formation of neurons in the hippocampus blocks the behavioral effects of antidepressants in mice, say researchers funded by the National Institutes of Health (NIH). Their finding lends new credence to the proposed role of such neurogenesis in lifting mood. It also helps to explain why antidepressants typically take a few weeks to work, note Rene Hen, Ph.D., Columbia University, and colleagues, who report on their study in the August 8th Science.
“If antidepressants work by stimulating the production of new neurons, there’s a built-in delay,” explained Hen, a grantee of NIH’s National Institute of Mental Health (NIMH) and National Institute on Drug Abuse (NIDA). “Stem cells must divide, differentiate, migrate and establish connections with post-synaptic targets – a process that takes a few weeks.”
“This is an important new insight into how antidepressants work,” added NIMH director Thomas Insel, M.D. “We have known that antidepressants influence the birth of neurons in the hippocampus. Now it appears that this effect may be important for the clinical response.”
Chronic stress, anxiety and depression have been linked to atrophy or loss of hippocampal neurons. A few years ago, Hen’s colleague and co-author Ronald Duman, Ph.D., Yale University, reported that some antidepressants promote hippocampal neurogenesis. But to what effect? To begin to demonstrate a causal relationship between these newly generated cells and relief from depression, researchers would have to find a way to prevent their formation in a behaving animal.
The researchers first showed that mice become less anxious – they begin eating sooner in a novel environment – after four weeks of antidepressant treatment, but not after just 5 days of such treatment. Paralleling the delay in onset of antidepressant efficacy in humans, the chronically-treated mice, but not the briefly-treated ones, showed a 60 percent boost in a telltale marker of neurogenesis in a key area of the hippocampus.
To find out if the observed neurogenesis is involved in antidepressants’ mechanism-of-action, Hen and colleagues selectively targeted the hippocampus with x-rays to kill proliferating cells. This reduced neurogenesis by 85 percent. Antidepressants had no effect on anxiety and depression-related behaviors in the irradiated mice. For example, fluoxetine failed to improve grooming behavior, as it normally does, in animals whose behavior had deteriorated following chronic unpredictable stress. Evidence suggested that this could not be attributed to other effects of x-rays.
Neurons communicate with each other by secreting messenger chemicals, or neurotransmitters, such as serotonin, which cross the synaptic gulf between cells and bind to receptors on neighboring cell membranes. Medications that enhance such binding of serotonin to its receptors (serotonin selective reuptake inhibitors, or SSRIs) are widely prescribed to treat anxiety and depression, suggesting that these receptors play an important role in regulating emotions.
By knocking out the gene that codes for a key subtype of serotonin receptor (5-HT1A), the researchers created a strain of “knockout” mice that as adults show anxiety-related traits, such as a reluctance to begin eating in a novel environment. While unaffected by chronic treatment with the SSRI fluoxetine, the knockout mice became less anxious after chronic treatment with tricyclic antidepressants, which act via another neurotransmitter, norepinephrine, suggesting an independent molecular pathway.
While chronic fluoxetine treatment doubled the number of new hippocampal neurons in normal mice, it had no effect in the knockout mice. The tricyclic imipramine boosted neurogenesis in both types of mice, indicating that the serotonin 1A receptor is required for neurogenesis induced by fluoxetine, but not imipramine. Chronic treatment with a serotonin 1A-selective drug confirmed that activating the serotonin 1A receptor is sufficient to spur cell proliferation.
Although the new findings strengthen the case that neurogenesis contributes to the effects of antidepressants, Hen cautions that ultimate proof may require a “cleaner” method of suppressing this process, such as transgenic techniques that will more precisely target toxins at the hippocampal circuits involved.
“Our results suggest that strategies aimed at stimulating hippocampal neurogenesis could provide novel avenues for the treatment of anxiety and depressive disorders,” suggest the researchers.
Also participating in the study were: Luca Santarelli, Michael Saxe, Cornelius Gross, Stephanie Dulawa, Noelia Weisstaub, James Lee, Columbia University; Alexandre Surget, Catherine Belzung, Universite de Tours, France; Fortunato Battaglia, Ottavio Arancio, New York University.
In addition to NIMH and NIDA, the research was also supported by the National Alliance for Research on Schizophrenia and Depression (NARSAD).
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NIMH and NIDA are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
Posted: August 07, 2003
Clinical & Research News
Missing Gene in Anxiety-Ridden Mice Could Point Way to New Treatments
Joan Arehart-Treichel
A particular gene—the gene for the serotonin-1A receptor—appears to cause excessive anxiety in stressful situations, at least in mice. But how does the gene do it?
Although the day will probably soon come when scientists find that a faulty gene, or lack of a gene, underlies a certain psychiatric disorder, that information alone won’t lead to successful therapy for it.**************************************************
Joshua Gordon, M.D, Ph.D.: "We can’t just throw drugs at a gene."
"We can’t just throw drugs at a gene," said Joshua Gordon, M.D., Ph.D., a research fellow in psychiatry at Columbia University. So what has to be done? Find out how the quirky gene or missing gene causes the illness, then target drugs at the process, Gordon believes.
Gordon and his colleagues, in fact, are practicing that philosophy—at least in mice. They have conducted an experiment to find out how a gene missing in anxious mice actually triggers the rodents’ anxiety. Their results suggest that the missing gene does so by putting neurons in the hippocampal region of the brain into overdrive.
Gordon reported these results at the 14th Annual Scientific Symposium of the National Alliance for Research on Schizophrenia and Depression, held in New York City last month. NARSAD organized the symposium to showcase Gordon and some of its other young investigators who it believes are doing promising psychiatric research.
Mice have been bred to lack the gene that makes one of the various nerve receptors that receive messages from the neurotransmitter serotonin. Mice lacking the gene for serotonin-1A receptor appear to be more anxious than their littermates with the gene, and if they are given antianxiety medications, they seem to calm down. Thus, lack of the serotonin-1A gene and of the serotonin-1A receptor in turn appear to be responsible for excessive anxiety in these mice.
Gordon and his colleagues decided to conduct an experiment to see what happens to the brains of the mice lacking the serotonin-1A receptor gene when they are placed in an anxiety-inducing situation. In other words, they hoped to identify brain activity provoked by the missing gene that might explain the animals’ excessive anxiety.
First, they obtained mice lacking the serotonin-1A receptor gene, as well as some of the mice’s littermates that had the gene. They then operated on each of the mice to implant electrodes in the two hippocampi of its brain. The hippocampus was formerly thought to be involved only in learning and memory, but now it seems to be implicated in schizophrenia, bipolar disorder, depression, and anxiety as well. What’s more, the hippocampus is normally rich in serotonin-1A receptors. The scientists were also careful to implant the electrodes in such a way that they could record electrical signals from individual neurons in each mouse’s hippocampi.
After the mice had recovered from surgery, the researchers gave them the opportunity to explore an open maze. Mice generally prefer closed mazes to open ones, probably because they feel more secure in the former, and these mice were no exception. However, the mice lacking the serotonin-1A receptor gene were even more reluctant to go into the open maze than their littermates with the gene.
As the mice approached the open maze, electrical signals were recorded from neurons in their hippocampi. The hippocampal neurons of the mice without the gene gave off more electrical signals than did the hippocampal neurons of the mice with the gene, the researchers discovered.
Thus, a lack of the serotonin-1A gene may lead to excessive neuronal activity in the hippocampus during stressful situations, and the excessive neuronal activity in turn may switch on anxiety, Gordon and his colleagues concluded. If this conclusion is correct, Gordon explained at the symposium, hippocampal neurons might constitute good targets for new kinds of antianxiety drugs.
"This is state-of-the-art genetic work" combined with electrophysiology, said Frances Benes, M.D., Ph.D., a professor of psychiatry at Harvard University, at the symposium.
"This is a powerful experimental paradigm that Dr. Gordon has put together," she commented, ". . .and it is a model for individuals who have had anxiety since the time they are born."
The research was funded by a NARSAD Young Investigator Award, a National Institute of Mental Health Institutional Training Fellowship, and an APA-Wyeth Ayerst M.D./Ph.D. Fellowship.*************************************************
> i have OCD and panic disorder and i am currently on 80mg of Celexa, i just switched from Imipramine and im having massive panic attacks now. How come a Imipramine worked for me for 8 years and this SSRI seems to not?? Has anyone ever heard of anybody going up to 100mg of Celexa like this post below?? Please let me know, i feel like i made 6 moths of transition only to have it not work, im so discouraged...
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> > Ben,
> > I currently take 100mg of Celexa for OCD which is not that abnormal considering that OCD requires higher dosages than depression. My pdoc told me that he has some patients that use up to 140mg a day with great results. I could not sustain a good drug level until I hit 100mg and now I am very pleased with the results. According to my doctor, some people just have higher tolerances (depending on their physiology and specific mental illness) than others and they require higher doses to relieve their symptons. I even tried to go up to 120mg a day to see if I could acheive even better results, but the side effects were a little too much (the only real side effect was a little more drowsiness than I wanted)so I dropped back down. I am still very satisfied with the results 100mg has given me and I feel a ton better. Celexa is a great drug and should be equally as effective on your depression as it was on my OCD. Good luck!
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poster:Simones
thread:49689
URL: http://www.dr-bob.org/babble/20040218/msgs/316480.html