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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 28. This is the beginning of the thread.
Posted by Phillipa on October 23, 2010, at 23:45:41
No Evidence To Support Atypical Antipsychotics over First Generation Antipsychotics. Phillipa
From Medscape Medical News
No Evidence to Support Recommendation to Use Atypicals Over First-Generation Antipsychotic
American Psychiatric Association Practice Guideline Needs Updating, Researcher Says
Deborah BrauserOctober 22, 2010 Second-generation antipsychotics (SGAs), also known as aytypicals, are not superior to the first-generation antipsychotic perphenazine in treating depression in patients with chronic schizophrenia a finding that contradicts the American Psychiatric Association Clinical Practice Guidelines, which specifically recommend SGAs in this population.
Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), the investigators compared the SGAs olanzapine, quetiapine, risperidone, and ziprasidone with perphenazine, but found no significant between-class differences in improvement of depressive symptoms.
These finding "do not lend empirical support" to the recommendation by the American Psychiatric Association in its Clinical Practice Guidelines for schizophrenia that SGAs "may be specifically indicated for the treatment of depression" for this disorder, write the researchers.
Although a significant improvement in depressive symptoms was found in all treatment groups over time, subanalyses found that quetiapine was significantly more effective than risperidone in the patients having a major depressive episode (MDE) at study entry (P = .0056).
"I wasn't surprised at the overall findings, which went against Clinical Practice Guidelines," lead author Donald E. Addington, MD, professor in the Department of Psychiatry at the University of Calgary in Alberta, Canada, told Medscape Medical News.
The recommendation "generally said that [SGAs] are better than first-generation antipsychotics, based on their review of the studies that had been published prior to 2005," added Dr. Addington, was also involved in writing the Canadian clinical practice guidelines for schizophrenia.
"The recommendation needs to be updated," he added. "I think that when using antipsychotics for patients with schizophrenia and depression, clinicians should optimize the reduction in positive and negative symptoms as a first strategy and avoid high doses of antipsychotics that cause extrapyramidal side effects."
The study was published online September 21 in the Journal of Clinical Psychiatry.
The CATIE Project
"Since their introduction in the 1990s, [SGAs] have become the drugs of choice in the treatment of schizophrenia, despite a lack of conclusive evidence of superior efficacy as assessed by measures of general psychopathology," the investigators write.
There were many claims and meta-analyses that suggested that there were some benefits to the [SGAs], but there were very few large, rigorous studies designed to make fair comparisons.
Most SGA trials, "were designed as registration studies, usually having 3 arms: a new antipsychotic, a control active treatment which was usually haloperidol, and placebo," said Dr. Addington. "With those studies, there were many claims and meta-analyses that suggested that there were some benefits to the [SGAs], but there were very few large, rigorous studies designed to make fair comparisons."The original CATIE project was designed to compare the effectiveness of perphenazine to all SGAs available in January 2002 in the United States for the treatment of chronic schizophrenia, with the exception of clozapine.
A total of 1460 patients with schizophrenia between the ages of 18 and 65 years were enrolled between January 2001 and December 2004 at 57 US sites. Of these patients, 1428 were randomly assigned to receive 1 to 4 capsules daily, containing a total of 8 mg perphenazine (n = 256), 7.5 mg olanzapine (n = 328), 200 mg quetiapine (n = 326), 1.5 mg risperidone (n = 332), or 40 mg ziprasidone (n = 182).
"Ziprasidone was approved for use by the US Food and Drug Administration during the trial and was added in January 2002, after 40% of the sample had been recruited," note the study authors.
In addition, "patients with tardive dyskinesia were excluded from the randomization that included perphenazine," they write.
The main results, which were first published in 2005, showed no significant differences in efficacy, tolerability, or neurologic adverse effects between the SGA and perphenazine groups.
However, "patients treated with olanzapine remained on treatment with their medicine longer than those treated with quetiapine or risperidone and were less likely than all of those receiving other drugs to switch drugs for lack of efficacy," report the investigators. The olanzapine-treated patients also experienced substantial weight gain.
Depression Analysis
For this analysis, the investigators sought to specifically examine the effect of the different treatments on depressive symptoms in the same overall study population, as well as in a subgroup meeting criteria for a MDE at baseline (n = 448).
Depression was assessed using the Calgary Depression Scale for Schizophrenia, which was developed by Dr. Addington. All patients were evaluated at baseline and followed-up for 18 months.
Although the results showed no significant differences between any of the treatment groups, there was "a significant interaction found between treatment and experiencing an MDE at baseline (P = .05)," the investigators report.
"The main finding of this study is that we found no evidence of a class benefit of the use of SGAs compared with [first-generation antipsychotics] in the treatment of symptoms of depression, even in the subset that was above the baseline threshold for MDD," they summarize.
However, "depression was not the primary outcome measure for this study, and the sample size was not powered for this outcome. Thus, these analyses should be considered descriptive," they add.
Dr. Addington reported that he would now like to see research on the relationship between patients and extrapyramidal symptoms.
"We also need to look more carefully at the antidepressant effects of the different antipsychotics. That merits further basic laboratory and animal studies to understand whether this is a general property of antipsychotics or whether it's more specific to some of them rather than others," he explained.
Slight Depression Reduction "Distressing"
"These results were very similar to the primary results found in the earlier CATIE study, where basically the first-generation drug did pretty much as well as second-generation drugs," Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.
Dr. Pigott, who was not involved in this study, noted that the overall CATIE project showed that 74% of the patients discontinued the study by the end of the 18-month trial either because of lack of efficacy or intolerable adverse effects.
"What's interesting to me in this study is that there's a slight decrease in overall depressive symptoms over the course of the 18 months, but that's really only for those who were continuing in the study," he said. "By definition, those should be the ones who are doing better. So that slight decline in symptoms over time is really underwhelming."
He also noted interest in the subgroup with MDE. "By the end of 18 months, they basically only had a 1- to 2-point reduction on their depressive score, which again is distressing because I would think you would expect much more.
Overall, clearly we haven't made much improvement in terms of going from first-generation meds to second-generation meds.
"Overall, clearly we haven't made much improvement in terms of going from first-generation meds to second-generation meds."Dr. Pigott recently conducted a review of 4 meta-analyses of FDA trials, including the large Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which found that antidepressants were only marginally better than placebo.
He noted that this new study reminds him of a recent paper written by the director of the National Institute of Mental Health, Thomas R. Insel, MD (J Clin Invest. 2009;119:700-705).
"In 1 portion of it, Dr. Insel basically reviews various comparative effectiveness studies that the National Institute of Mental Health has funded, including the CATIE and the STAR*D studies. He makes the observation that despite their added costs, the second-generation psychotropic medications have been found to be no better than first-generation ones," said Dr. Pigott.
"His quote that resonates with me is, 'the unfortunate reality is that current medications help too few people to get better and very few people to get well.' And what we concluded in the STAR*D analysis was similar."
We really need to take more seriously looking at different combination therapies, different kinds of approaches to treatment if we're going to be able to make some meaningful improvement in patients' lives.
"I think we really need to [start] more seriously looking at different combination therapies, different kinds of approaches to treatment, if we're going to be able to make some meaningful improvement in patients' lives," said Dr. Pigott.The original CATIE project was supported by the National Institute of Mental Health. Dr. Addington has disclosed no relevant financial relationships. However, 5 of the other 7 study authors report several potential conflicts, which are listed in the original article. Dr. Pigott reported consulting for CNS Response, Amen Clinics, EEG Spectrum, Neuronetics, and International Society of Neurofeedback and Research.
J Clin Psychiatry. Published online September 21, 2010.
Posted by SLS on October 24, 2010, at 5:18:17
In reply to Atypicals No Better Than First Generation Per Stud, posted by Phillipa on October 23, 2010, at 23:45:41
For me, there is no comparison in the way I felt on first-generation neuroleptics to the newer atypical neuroleptics. The older ones made me feel weird. They produced a heavy-duty drugged-up feeling. I guess it would be likened to having done a chemical lobotomy. I have not had this kind of unwanted reaction to any of the atypicals. I feel more like myself when I take these drugs.
If we were to take into consideration only how effective neuroleptics are to reducing shizoid and psychotic symptoms, we miss a great deal in evaluating how these drugs affect the quality of life.
- Scott
Posted by linkadge on October 24, 2010, at 12:44:10
In reply to Re: Atypicals No Better Than First Generation Per Stud, posted by SLS on October 24, 2010, at 5:18:17
I don't want to negate your experiences, but the research has simply not shown that atypicals are at all superior for negative symptoms either.
That is, although it was assumed that the 5-ht2 antagonism yadia yada resulted in improved cognative performance, mood etc, the research does not really support this either.
The only typical I was on was perphenazine and it was better (for me) than any of the atypicals. I didn't feel as yukky on perphenazine vs. any atypical.
Linkadge
Posted by SLS on October 24, 2010, at 14:05:05
In reply to Re: Atypicals No Better Than First Generation Per Stud » SLS, posted by linkadge on October 24, 2010, at 12:44:10
> I don't want to negate your experiences, but the research has simply not shown that atypicals are at all superior for negative symptoms either.
Well, that's why I tried to frame my words such that they be applied to my experiences only. It is tempting for me to generalize my own experiences to the majority, but the only thing I have to go by is how these drugs affected me personally. Like you, I found perphenazine to be relative inoffensive. However, I definitely felt as if my mind were somehow being filtered so that I could could not concentrate on my thoughts. I know that sounds good at first, but my consciousness felt like it was stuck in mud. It is interesting to see how differently two people can feel on the same drug. However, it confounds the efforts made to understand and treat mental illness.
- Scott
Posted by Christ_empowered on October 24, 2010, at 14:40:01
In reply to Re: Atypicals No Better Than First Generation Per Stud » linkadge, posted by SLS on October 24, 2010, at 14:05:05
I mean, its one thing when they're very careful with the dosage of perphenazine (or other old-school AP); its quite another when you have some hospital shrink who just drugs people up with the cheapest available drug (yes, it happened to me).
I think a lot of the "conventional" neuroleptics would probably have a much better reputation if docs had given them in small tranquilizing doses back in the day instead of dosing all the way up to EPS/Parkinson's as a matter or routine.
That said: I've been on what I think was relatively low-dose Haldol, along with Ativan and Benadryl (hospital situation, not my idea). When I got switched over to Risperdal the next day, I immediately felt somewhat better...when I got switched over to Abilify, I felt even better.
Posted by linkadge on October 24, 2010, at 15:53:15
In reply to I think dosing is an issue..., posted by Christ_empowered on October 24, 2010, at 14:40:01
Well, the funny thing too is that some of the "typicals" such as perphenazine and thioridazine (taken off the market) actually have moderate 5-ht2 antagonism.
See:
Linkadge
Posted by rogerk on October 24, 2010, at 16:33:04
In reply to Atypicals No Better Than First Generation Per Stud, posted by Phillipa on October 23, 2010, at 23:45:41
dude i just posted this. lol
thanks for jacking it!
Posted by sigismund on October 24, 2010, at 16:58:34
In reply to I think dosing is an issue..., posted by Christ_empowered on October 24, 2010, at 14:40:01
>instead of dosing all the way up to EPS/Parkinson's as a matter or routine.
In the 70s there was a school of thought that held that by increasing the dose greatly the risk of EPS was diminished. That's how you ended up with 50mg (or something) haloperidol a day
Posted by maxime on October 24, 2010, at 19:29:36
In reply to Re: I think dosing is an issue... » Christ_empowered, posted by sigismund on October 24, 2010, at 16:58:34
> >instead of dosing all the way up to EPS/Parkinson's as a matter or routine.
>
> In the 70s there was a school of thought that held that by increasing the dose greatly the risk of EPS was diminished. That's how you ended up with 50mg (or something) haloperidol a dayThat is what I going to say. When Thorazine was first used they were giving patients 1000mg! No wonder the patients just sat there drooling. I have been on 50 mg of Thorazine and it was very good for calming me and keeping hallucinations at bay (when I am REALLY depressed I suffer from hallucinations).
I think like all meds, some people will respond well to the older APs while others will respond to the new generation of APs.
Posted by Christ_empowered on October 24, 2010, at 20:59:02
In reply to Re: I think dosing is an issue... » sigismund, posted by maxime on October 24, 2010, at 19:29:36
Yeah, the author of "Mad in America" writes about neuroleptic dosing in a couple chapters.
Apparently, docs in France used around 100mgs/day Thorazine, docs in the UK up to 300mgs/day, and docs in the US...sometimes a couple grams, although there was huge variation between patients and docs. Docs in the US were more inclined to see evidence of Parkinson's as a biological indicator of "successful" therapy, whereas it seems that European docs were really just looking to calm people down and get them to do talk therapy, vocational rehab, or just be quiet.
Posted by SLS on October 25, 2010, at 5:08:06
In reply to I think dosing is an issue..., posted by Christ_empowered on October 24, 2010, at 14:40:01
> I mean, its one thing when they're very careful with the dosage of perphenazine (or other old-school AP); its quite another when you have some hospital shrink who just drugs people up with the cheapest available drug (yes, it happened to me).
>
> I think a lot of the "conventional" neuroleptics would probably have a much better reputation if docs had given them in small tranquilizing doses back in the day instead of dosing all the way up to EPS/Parkinson's as a matter or routine.
>
> That said: I've been on what I think was relatively low-dose Haldol, along with Ativan and Benadryl (hospital situation, not my idea). When I got switched over to Risperdal the next day, I immediately felt somewhat better...when I got switched over to Abilify, I felt even better.
>
>Just remember what was the target population when the antipsychotics first were discovered. They were used primarily for severe schizophrenia, many suffers of which were chronically institutionalized. I think the dosage guidelines were formulated empirically for these subjects rather than people with depression or anxiety.
It is not unusual for the clinical properties of a drug to become better elucidated as it is used over the years. I would be interested to see something describing the dosage differences used between the severest forms of schizophrenia versus affective or anxiety disorders for both old and new neuroleptics.
- Scott
Posted by bleauberry on October 25, 2010, at 17:22:11
In reply to Atypicals No Better Than First Generation Per Stud, posted by Phillipa on October 23, 2010, at 23:45:41
The way these researchers gathered their data and interpreted it is so full of flaws an entire book could be written on it.
Also, do you know the purpose of the study? Who was behind it? Why they pursued it? Who funded it and why? No, we don't. Yellow flag.
You'll be hard pressed in the real world to find anyone that agrees with this study. The best source would be to ask patients, which they didn't do. A visit to pbabble would have yielded much more accurate results than what they did.
Sorry, but when it comes to meds like Zyprexa and Abilify, sometimes Ziprasidone or Seroquel or Risperdal, and definitely Amisulpride, the old ones don't even come close to the superior effects on depression these newer ones have.
It's fun to surf and look at studies though. Best to take them with a grain of salt. They never give you enough details in an abstract to fully judge the entire thing. Crucial details are usually left out of those abstracts.
Posted by Phillipa on October 25, 2010, at 20:00:15
In reply to Re: Atypicals No Better Than First Generation Per Stud, posted by bleauberry on October 25, 2010, at 17:22:11
The studies are from a site I subscribe to and offer testing for doctors, nurses, and pharmacists at the end of each which I do not include for my own privacy issues as they contain the test questions and my personal amount of CME's I have from online testing. Site recommended to me by my internist who uses it to obtain his CME's Phillipa
Posted by ed_uk2010 on October 26, 2010, at 15:34:24
In reply to Re: Atypicals No Better Than First Generation Per Stud, posted by bleauberry on October 25, 2010, at 17:22:11
>Also, do you know the purpose of the study? Who was behind it? Why they pursued it? Who funded it and why? No, we don't. Yellow flag.
....so like the studies which suggest that atypicals are superior?
Posted by maya3 on October 26, 2010, at 15:38:55
In reply to Re: I think dosing is an issue..., posted by linkadge on October 24, 2010, at 15:53:15
Linkadge, do you happen to know when and why thioridazine was taken off the market?Thanks,
Maya.
Posted by bleauberry on October 26, 2010, at 17:22:43
In reply to Re: Atypicals No Better Than First Generation Per Stud » bleauberry, posted by ed_uk2010 on October 26, 2010, at 15:34:24
> >Also, do you know the purpose of the study? Who was behind it? Why they pursued it? Who funded it and why? No, we don't. Yellow flag.
>
> ....so like the studies which suggest that atypicals are superior?
>I don't use those studies either. They are good for curiosity, and for sort of putting things in perspective within a larger picture. But I do not at all put any significant weight on them.
Posted by linkadge on October 26, 2010, at 17:29:42
In reply to Re: I think dosing is an issue... » linkadge, posted by maya3 on October 26, 2010, at 15:38:55
In Canada, thioridazine was taken off (about 3-4 years ago ?) due to cardiac effects (I think QTc prolongation).
Linkadge
Posted by Phillipa on October 26, 2010, at 20:56:21
In reply to Re: I think dosing is an issue..., posted by linkadge on October 26, 2010, at 17:29:42
I thought thorazine was still available? Phillipa ps shows how long it's been since nursing if not as we used it. But not often
Posted by Christ_empowered on October 26, 2010, at 20:59:35
In reply to Re: I think dosing is an issue... » linkadge, posted by Phillipa on October 26, 2010, at 20:56:21
thorazine (chlorpromazine) is still around, but Mellaril (thioridazine) isn't, at least not in the US or canada. I guess now that its old, off-patent, and there are lots of other options, there wasn't really any justification in keeping it on the market.
Posted by ed_uk2010 on October 27, 2010, at 17:19:39
In reply to Re: I think dosing is an issue... » linkadge, posted by maya3 on October 26, 2010, at 15:38:55
Thioridazine was discontinued in the UK in 2005 due to the elevated risk of cardiac arrhythmias. Melleril was very widely used here for many years, and was prescribed like the atypicals are now for a variety of non-psychotic conditions. The more things change the more they stay the same.
Posted by Maxime on October 27, 2010, at 17:28:16
In reply to Re: I think dosing is an issue... » linkadge, posted by Phillipa on October 26, 2010, at 20:56:21
> I thought thorazine was still available? Phillipa ps shows how long it's been since nursing if not as we used it. But not often
Not Thorazine ....thioridazine. Two different meds. I still take Thorazine at times and it is my emergency if I have a hypertensive reation.
Posted by Phillipa on October 27, 2010, at 19:35:31
In reply to Re: I think dosing is an issue... » Phillipa, posted by Maxime on October 27, 2010, at 17:28:16
No wonder so many med errors even by pharmacists spellings to close. Thorazine is also used for intractible hiccups and I knew you had taken it. Must google this other spelling. Thanks Phillipa
Posted by Phillipa on October 27, 2010, at 20:30:14
In reply to Re: I think dosing is an issue... » Phillipa, posted by Maxime on October 27, 2010, at 17:28:16
If it's mellaril we used it for schizophrenia or acute manic phase of bipolar. What happened to the barbituates? and miltowns which were available and what I was given when first had panic anxiety. Was also given by ob-gyn two seconals in false labor in the hospital and nothing wrong with my third child?. Phillipa
Posted by ed_uk2010 on October 28, 2010, at 14:13:29
In reply to Re: I think dosing is an issue... » Maxime, posted by Phillipa on October 27, 2010, at 20:30:14
>What happened to the barbituates?
Short acting barbiturates such as Seconal are very dangerous in overdose. As a result, they fell out of favour once doctors became familiar with benzodiazepines.
Posted by Phillipa on October 28, 2010, at 20:18:26
In reply to Re: I think dosing is an issue... » Phillipa, posted by ed_uk2010 on October 28, 2010, at 14:13:29
Ed yes so why are they now using atypical antipsychotics that have diabetes and weight gain etc. I just don't get it. PJXX
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