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    Antidepressants Work and Don't Boost Suicide Risk

    Antidepressants Work and Don't Boost Suicide Risk
    Sun Jan 1, 2005
    by Steven Reinberg, HealthDay

    SUNDAY, Jan. 1 (HealthDay News) -- Contrary to what has been feared, the antidepressants known as serotonin reuptake inhibitors (SSRIs) are initially effective in as many as one-third of depressed patients and don't appear to increase the risk of suicide, two new studies claim.

    The reports, both of which were funded by the National Institute of Mental Health, appear in the January issue of the American Journal of Psychiatry.

    The suicide findings seem to challenge a 2004 advisory by the U.S. Food and Drug Administration that warned that suicidal behavior may increase after treatment with SSRIs. However, the study did find that suicide attempts were higher among teens than adults, a finding borne out by other research.

    The first report is based on early data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest study of its kind. This research looked at the benefits of antidepressants in "real world" settings.

    "About a third of the patients achieved remission," said lead researcher Dr. Madhukar Trivedi, director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center, in Dallas. "An additional 10 to 15 percent achieved a response."

    The object of the study was to provide physicians with guidelines for treating depression, Trivedi said. "The goal is to have patients provided with an adequate dose of medication for an adequate time," he explained. "Treatment would be tailored for each individual patient to get the most benefit from treatment."

    For the study, researchers looked at the results of prescribing the SSRI Celexa to 2,876 patients with major depression. These patients also had other physical and psychological problems. The researchers found that about a third of the patients had their depression cured during the first 12 weeks of treatment.

    In addition, another 10 percent to 15 percent of the patients showed a response to the medication, or reduction of at least half their symptoms. For patients who did not improve, later phases of the trial will use other medications or combinations of medications to see what might help those who did not benefit from the drug used in the first phase of the trial.

    "These antidepressants in routine clinical care produce outcomes comparable with what is seen in research settings," Trivedi said. "These treatments do work in routine clinical care. There also has to be careful monitoring of side effects. In addition, you have to monitor dose and duration of the treatment, based on the patient's progression."

    One expert thinks this study will eventually provide guideposts for treating depression that physicians can follow.

    "This study, when it is all finally published, will give us a very good idea of how to treat treatment-resistant depression, and what the next step is after the SSRI fails," said Dr. David L. Dunner, director of the University of Washington's Center for Anxiety and Depression.

    In the second study, researchers found the risk of suicide attempts and of successful suicides actually dropped in the weeks following the start of SSRI therapy.

    "The risk of a serious suicide attempt in people who start taking antidepressant medication is, fortunately, quite low -- less than one in 1,000," said lead author Dr. Greg Simon, a researcher at the Group Health Cooperative, in Seattle. "The risk actually goes down after people start antidepressant medication."

    The study also found no increase in suicide risk with the newer antidepressants, such as SSRIs, Simon added. "If anything, our data suggests that with the newer antidepressants there is less risk than with the older antidepressants," he said.

    For the study, Simons's team collected data on 65,103 patients who had prescriptions for antidepressants between 1992 and 2003.

    The researchers found the number of suicide attempts dropped by 60 percent in adults in the first month after starting treatment. The suicide rate continued to drop in the succeeding five months.

    Among all the patients, there were 31 suicides in the six months after starting antidepressant therapy. That rate did not change from one month after starting treatment or in subsequent months.

    However, teens had more suicide attempts than adults. Simon's group found that in the first six months of antidepressant treatment, the suicide rate was 314 attempts per 100,000 in teens, vs. 78 attempts per 100,000 in adults. For teens and adults, the rate was highest in the month before treatment and dropped by about 60 percent after treatment began, the researchers found.

    In its 2004 warning, the FDA said people taking antidepressants should be closely monitored because of the risk of suicide.

    "People should be closely monitored, but not because these drugs are especially risky," Simon said. "The real problem in the treatment of depression is that people start medicine and the medicine has side effects or the medicine doesn't work right away, and they get discouraged and they drop out."

    Dunner agreed that close monitoring is essential when prescribing patients antidepressants. "Monitoring depression is very important," he said. "Often people come in for treatment when they are starting to get worse."

    Monitoring is needed more for side effects from the drugs than to watch for suicidal behavior, Dunner said. "Suicide is a pretty rare event," he said. "It is more important to monitor for side effects and adherence to the medication."

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    Antidepressants Work and Don't Boost Suicide Risk

    About a third of the patients achieved remission," said lead researcher Dr. Madhukar Trivedi, director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center, in Dallas. "An additional 10 to 15 percent achieved a response."
    I find this really surprising...I thought that antidepressants (SSRI) were effective for most people. Doesn't this mean that they only help less than half of the people who have depression? Is that typical for other medication? I wonder how effective SSRIs have been shown to be for other disorders that they are used for, like anxiety.

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    Antidepressants Work and Don't Boost Suicide Risk

    That figure's low, in my experience. I've been working with depressed clients for many years and in my experience the majority of them are helped by one of the SSRI medications.

    However, I can see some factors that could account for the discrepancy:

    1. the study notes that "about a third of the patients achieved remission", meaning "complete cure" or a "complete remission of symptoms" with medication alone - most of my clients, of course, are combining medication with psychotherapy, which we know from other research is more effective than medication alone. Additionally, the study reported that "an additional 10 to 15 percent achieved a response", meaning they benefited from the medication but in the time frame of the study did not achieve a "complete cure" from medication alone. But that means that even in this restricted study, 43% to 48% of patients showed some improvement from medication alone.

    2. the study notes that "for patients who did not improve, later phases of the trial will use other medications or combinations of medications to see what might help those who did not benefit from the drug used in the first phase of the trial". In other words, the patients in this study were tested on a single medication and if they did not show a positive responsethey would have been counted as failures. In the real world, it's not uncommon for patients to require some trial and error, so they may not show benefits from the first medication they try but they do from the second or third. In cases where there is a dual diagnosis (e.g., depression plus anxiety or something else), this may be especially true. The study notes that "these patients also had other physical and psychological problems" but we do not know from this report what those additional problems or issues were.

    3. the study looked at the effectiveness of a single SSRI: Celexa. Depending on the specific history and how the patient responds, Celexa is not necessarily the best or most effective medication - it makes sense as a starting point for a study like this because it tends to have fewer side effects than others and interacts well with other medications (remember the comment above about these patients having other physical problems).

    My conclusions from reading this study:

    (a) the reports of increased risk of suicide are NOT substantiated: the previous reports were not research findings but rather anectdotal reports - the current study tells us that the fears are overstated and misguided

    (b) even under restricted circumstances, these medications do work for a substantial number of patients - if the conditions are less restrictive, I would expect more patients to show a positive response - I would see the figures cited as being a minimum of what to expect from these medications, rather than an upper limit

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    Antidepressants Work and Don't Boost Suicide Risk

    Thanks so much for such a thorough explanation. It makes a lot more sense to me now and fits much more with my prior understanding and also matches your explanations of anti depressant effectiveness on other threads. I had understood from the article that the suicide risk was not substantiated, but like you said I thought those figures were really low as far as effectiveness. Now that you've explained the specifics I totally understand and it makes a lot more sense=) Thank you=)

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    Antidepressants Work and Don't Boost Suicide Risk

    See the NAMI and NIMH story on these studies here.

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    Antidepressants Work and Don't Boost Suicide Risk

    I have a question, too. I take Effexor (75mg/qd) and have taken it for about 10 years, excepting while pregnant. I have been on the same dose for all that time. Also, when I have been off, it's been a roller coaster of a ride. Therefore, I haven't d/c'd its use, and in fact have been really reluctant to, especially now with all that's going on in life/school/kids/marraige/psychological. My question is, how common is it for someone to be on a med like this for so long, and is it likely to lose its efficacy after time? I mean, since I am feeling so stressed latley, if I were your patient, would you reccommend a doasge increase? Or do you think a patient should ride it out for a few months and see what happens? I'm worried that if I were to ask for an increase in strength, that they might want to switch me all together. I have seen too many people going around zoned out, and it's scary to think I might not be able to function normally b/c of a new/stronger medication. In fact, i don't think I need a new medication, just maybe to try a larger dose of this one for a while. Is this common-- to increase a dose after being on one for so long? Or is it wise?-- Poohbear

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    Antidepressants Work and Don't Boost Suicide Risk

    I'm curious about efficacy (particularily with effexor) too. I've been on effexor (my dosages have gone up and down throughout the years)for just over 10 years. i recnetly had a depression that was comparable to the one i experienced right after my sister's death. Could part of my second major depression have been attributed to my body getting used to effexor and therefor it not being as effective?

    ps...not planning on going off anytime soon :)

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    Antidepressants Work and Don't Boost Suicide Risk

    Some people are on antidepressants for a year or two and never need them again. Others seem to need to remain on them for extended periods of time, although the dose does tend to increase and decrease over time. For example, some people find they need more in the winter months and less in the summer. Others may need more at times of unusual stress or trigger points.

    I don't know of anything to suggest that your body will "get used to it" to the point where it won't work any more. If you're worried about this, discuss it with your doctor but I doubt that it's an issue.

    Just out of curiosity, Poohbear, you indicate that you have been taking "Effexor (75mg/qd)" - do you mean 300 mg/day (75 mg qid)? If so, that's a standard dose for the non-XR version. If you meant 75 mg/day, that's a very low dose.

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    Antidepressants Work and Don't Boost Suicide Risk

    Thanks for your response, Dr Baxter.

    And just as a side note poobear, I'm on 225mg XR. I think this is a pretty high dose, but I'm also continuing to emerge from a major depression.

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    Antidepressants Work and Don't Boost Suicide Risk

    Quote Originally Posted by healthbound
    I'm on 225mg XR. I think this is a pretty high dose, but I'm also continuing to emerge from a major depression.
    It's not really high, healthbound. I would say that most people taking Effexor XR are on either 150 or 225 mg/day, some as high as 300 mg/day. The XR version is usually prescribed at a slightly lower dose than the non-XR version.

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