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Dr. Bob is Robert Hsiung, MD,
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Posted by Phillipa on November 28, 2012, at 21:15:04
Hard to believe the study says over 40 is elderly? Phillipa
Medscape Medical News > PsychiatryFour Atypicals Lack Safety, Efficacy in the Elderly
Megan Brooks
Nov 27
Four atypical antipsychotics (AAPs) commonly prescribed off label in older adults lack both safety and efficacy, new research shows.
Conducted by investigators at the University of California, San Diego (UCSD), the study investigated aripiprazole ( Abilify, Otsuka), olanzapine ( Zyprexa, Lilly), quetiapine ( Seroquel, AstraZeneca), and risperidone ( Risperdal, Janssen) in 332 patients older than 40 years who had been diagnosed with psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia.
Dr. Dilip Jeste
"Our study suggests that off-label use of these drugs in older people should be short-term and undertaken with caution," said lead author Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UCSD.
The study was published online November 27 in the Journal of Clinical Psychiatry.
Minimizing Bias
Most antipsychotic prescriptions in people older than 40 years involve off-label use of AAPs, the authors write. There has been "growing concern" about cardiovascular and metabolic morbidity with certain AAPs. The US Food and Drug Administration issued a warning regarding cerebrovascular adverse events and a boxed warning regarding increased mortality with AAP use for dementia-related psychosis.
Because the patients in the current study were all diagnosed with conditions with psychotic symptoms that required antipsychotic drug treatment according to their treating physicians, no placebo was used in the trial.
Instead, the researchers used equipoise stratified randomization a hybrid of complete randomization and a clinician's choice method. This approach allowed patients or their treating psychiatrists to exclude 1 or 2 of the AAPs on the basis of past experience or anticipated risks associated with a particular drug. Optimal dose was determined by the treating physician.
"Our goal," Dr. Jeste explained, "was to ensure clinical relevance. We attempted to make the study as 'user-friendly' as possible, to allow the drugs the best chance of success, while seeking to minimize the amount of bias."
Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter.
Because of a significantly higher incidence of serious adverse events with quetiapine (38.5%) than with the other three AAPs (19.0%), the quetiapine arm of the trial was discontinued midway through the trial, the researchers report.
"Worrisome" Findings
There was a high discontinuation rate following a relatively short duration of AAP use (median of 26 weeks). One half of the patients continued taking the assigned drug for fewer than 6 months, they report.
Moreover, there was no significant improvement in psychopathology on Brief Psychiatric Rating Scale over a 6-month period, and there was a high incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events with AAPs.
"These results are worrisome," the researchers say, "since we had given a choice to the patients and their psychiatrists to exclude one or two of the four AAPs for possible safety or effectiveness concerns. The clinicians could choose the daily dosage and change it as needed at any time. The daily dosages of the AAPs prescribed were relatively low. Thus, we had sought to give all the study AAPs the best chance of proving safe and effective as is done in good clinical practice."
The authors also note that the reported metabolic advantages of aripiprazole compared with olanzapine were not borne out in this study. Irrespective of diagnosis and drug, the overall risk-benefit ratio for the AAPs studied in this population of patients older than 40 years was "not favorable," they report.
The authors acknowledge that the use of AAPs in older patients with psychosis presents a "major clinical dilemma."
Although the researchers say their findings do not suggest that these AAPs should be banned in older patients with psychotic disorders, they do indicate that considerable caution is warranted in off-label, long-term use of the drugs in older persons.
"When these medications are used off-label, they should be given in low dosages and for short durations, and their side effects monitored closely," Dr. Jeste said. "Clearly, there is also a critical need to develop and test new interventions that are safe and effective in older people with psychotic disorders."
No Safer Than Older Agents
Reached for comment, Nicholas Rosenlicht, MD, Department of Psychiatry, University of California, San Francisco, said the side effecttoeffectiveness profile for these newer agents is "just not that good. It seems no better and perhaps worse than the older agents, and I think it's taking a while for this information to filter down to clinicians, especially to nonpsychiatric providers who are doing a lot of prescribing of antipsychotics."
"It's nice that this study is being published," Dr. Rosenlicht added. "These agents do have a place, but we need to be careful; there was this kind of wholesale acceptance and assumption that they worked well and had fewer side effects than the older agents, but really they just tend to have different side effects, except for risperidone, which behaves a lot like an older agent."
The study was funded by the National Institute of Mental Health, in part by the National Institutes of Health, and by the Department of Veteran Affairs. AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen Scientific Affairs LLC donated quetiapine, aripiprazole, olanzapine, and risperidone, respectively. Dr. Jeste and Dr. Rosenlicht have disclosed no relevant financial relationships. A complete list of author disclosures is presented in the article.
J Clin Psychiatry. Published online November 27, 2012
Posted by jono_in_adelaide on November 28, 2012, at 23:10:01
In reply to 4 Atypicals Not Safe In Those Over 40, posted by Phillipa on November 28, 2012, at 21:15:04
I think the way to look at this is that while there are some dangers with taking these drugs, there are a lot more dangers involved in having an untreated schitzophrenia or psychosis.
There are risks with ANY drug you take (Bruce Lee died after taking 2 aspirins for a headache), its about wether the risks are worth it, and I think that in this case, they are.
Posted by jane d on November 29, 2012, at 4:52:56
In reply to Re: 4 Atypicals Not Safe In Those Over 40, posted by jono_in_adelaide on November 28, 2012, at 23:10:01
> I think the way to look at this is that while there are some dangers with taking these drugs, there are a lot more dangers involved in having an untreated schitzophrenia or psychosis.
>
> There are risks with ANY drug you take (Bruce Lee died after taking 2 aspirins for a headache), its about wether the risks are worth it, and I think that in this case, they are.If these drugs were only being used for acute psychosis I'd agree with you. But here at least they are being used for anxiety, depression, sedation of the institutionalized etc. And the argument for doing it has not been that the benefit outweighs the risk - the argument is that there WAS no significant risk. And that has distorted all the decisions about when to use them.
Posted by Dinah on November 29, 2012, at 10:20:47
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » jono_in_adelaide, posted by jane d on November 29, 2012, at 4:52:56
Risperdal has made my life far better. Even though I already have diabetes, I see it as well worth the cost. After all, stress raises blood sugar as well, and can wreak havoc on the various body systems.
Maybe instead of condemning atypicals altogether, it would be better to see how low a dose can be helpful. Does it need to be prescribed daily for anxiety? There are cycles in most mental illnesses. There are some meds that do need to be taken daily to be effective. But I don't see that as necessary with atypicals for something like anxiety.
Psychosis is probably different.
Is it just atypicals? I thought it was also an issue with the older AP's. I remember it being discussed in my family a very long time ago.
Posted by jane d on November 29, 2012, at 12:02:12
In reply to Re: 4 Atypicals Not Safe In Those Over 40, posted by Dinah on November 29, 2012, at 10:20:47
> Risperdal has made my life far better. Even though I already have diabetes, I see it as well worth the cost. After all, stress raises blood sugar as well, and can wreak havoc on the various body systems.
>
> Maybe instead of condemning atypicals altogether, it would be better to see how low a dose can be helpful. Does it need to be prescribed daily for anxiety? There are cycles in most mental illnesses. There are some meds that do need to be taken daily to be effective. But I don't see that as necessary with atypicals for something like anxiety.
>
> Psychosis is probably different.
>
> Is it just atypicals? I thought it was also an issue with the older AP's. I remember it being discussed in my family a very long time ago.I know it's vital to you. And it doesn't look like they included people who use it the way you do. Hopefully that eliminates or reduces the risk.
The older APs had huge problems. I don't remember anything about diabetes specifically. But they were also much less widely prescribed because everybody knew about the problems. At least that's my vague recollection.
ps. Isn't it fun to be the included with the population that gets the headline "elderly"? Over 40 is elderly? We've let these kiddies get way out of hand!
Posted by Phillipa on November 29, 2012, at 18:29:14
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » Dinah, posted by jane d on November 29, 2012, at 12:02:12
That is what struck me 40 as being elderly as thought the new 40 was being 60? Best years of my life were 40's. Phillipa
Posted by herpills on November 29, 2012, at 21:33:45
In reply to 4 Atypicals Not Safe In Those Over 40, posted by Phillipa on November 28, 2012, at 21:15:04
This part stuck out to me-
"Because of a significantly higher incidence of serious adverse events with quetiapine (38.5%) than with the other three AAPs (19.0%), the quetiapine arm of the trial was discontinued midway through the trial, the researchers report."
With this high incidence of serious adverse events, it makes me wonder...didn't these serious adverse events show up in the clinical trials for FDA approval? How did it get approved if it is so dangerous? herpills
Posted by jono_in_adelaide on November 29, 2012, at 22:12:11
In reply to Re: 4 Atypicals Not Safe In Those Over 40, posted by herpills on November 29, 2012, at 21:33:45
Perhaps it was a statistical fluke?
Posted by ed_uk2010 on December 2, 2012, at 12:57:35
In reply to Re: 4 Atypicals Not Safe In Those Over 40, posted by Dinah on November 29, 2012, at 10:20:47
>Is it just atypicals? I thought it was also an issue with the older APs.
All typical antipsychotics can cause weight gain and metabolic problems, but some are clearly worse than others. Haloperidol (Haldol) tends to cause minimal weight gain whereas chlorpromazine (Thorazine) is associated with larger gains.
Amongst the atypicals, clozapine (Clozaril) and olanzapine cause the most weight gain. Clozapine is generally the most effective medication for schizophrenia and related psychoses. We don't hear much about it on p-babble because it's not normally used off-label.
Posted by Phillipa on December 2, 2012, at 20:21:51
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » Dinah, posted by ed_uk2010 on December 2, 2012, at 12:57:35
Too many serious side effects as agranlatosis. Phillipa
Posted by Phil on December 3, 2012, at 10:56:55
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » Dinah, posted by ed_uk2010 on December 2, 2012, at 12:57:35
Quetiapine does a pretty impressive job all by itself.
Posted by ed_uk2010 on December 3, 2012, at 12:06:16
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » ed_uk2010, posted by Phillipa on December 2, 2012, at 20:21:51
> Too many serious side effects as agranlatosis. Phillipa
Clozapine is widely used in schizophrenia though because it's more effective than other treatments.
Posted by Phillipa on December 3, 2012, at 20:11:39
In reply to Re: 4 Atypicals Not Safe In Those Over 40 » Phillipa, posted by ed_uk2010 on December 3, 2012, at 12:06:16
Yes I recommended it for a lot of schizophrenics that nothing else worked for and they did get better. Phillipa
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