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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by ed_uk on October 3, 2006, at 16:18:42
Arch Gen Psychiatry. 2006;63:1079-1087.
Context Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms.
Objective To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs.
Design A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis.
Setting Fourteen community psychiatric services in the English National Health Service.
Participants Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects.
Interventions Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist.
Main Outcome Measures Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care.
Results The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar.
Conclusions In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
Posted by yxibow on October 3, 2006, at 18:21:36
In reply to QoL: Old versus atypical antipsychotics, posted by ed_uk on October 3, 2006, at 16:18:42
I wouldn't go near a phenothiazine with a ten foot pole again...
But that's just me and my sensitivity to akathisia effects with pretty much everything except for Zyprexa and Seroquel.
Posted by notfred on October 3, 2006, at 20:48:57
In reply to QoL: Old versus atypical antipsychotics, posted by ed_uk on October 3, 2006, at 16:18:42
Conclusions In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
Hmmm, seems to me that the atypicals have not been around long enough to show their negatives, ie movement disorders. It can take decades for TD to show itself, given that AP's both cause and suppress movement disorders. AP's that suppress movement disorders are likely to cause them. Till people have been on atypicals for decades I do not think it is healthy to say they are less likely to cause movement disorders. Nor is there any proof, as people have not been on them long enough, that low doses are safer. It is wishful thinking.
At the same time 1 year is but a drop in a bucket
for schizophrenia.
Posted by Phillipa on October 3, 2006, at 21:11:38
In reply to QoL: Old versus atypical antipsychotics, posted by ed_uk on October 3, 2006, at 16:18:42
Ed should Chris know about this study? Love PJO
Posted by ed_uk on October 4, 2006, at 11:18:36
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by yxibow on October 3, 2006, at 18:21:36
> I wouldn't go near a phenothiazine with a ten foot pole again...
Well no, me neither but evidently some people prefer typical APs. Perhaps they'd rather take haloperidol than end up the size of a house on Zyprexa.
Ed
Posted by Meri-Tuuli on October 4, 2006, at 13:54:41
In reply to Re: QoL: Old versus atypical antipsychotics, posted by ed_uk on October 4, 2006, at 11:18:36
>than end up the size of a house on Zyprexa.
Its so true. My mother in law (well I'm not techically married to my bf, but you know what I mean) is obese - she takes Zyprexa and valium for acute anxiety. Its really sad because she doesn't really realise that she's obese because of the Zyprexa - she somehow blames herself or something. She's totally clueless about pysch meds and doesn't talk about it at all. I only discovered the zyprexa when I opened the wrong cupboard door! She's been on Zyprexa for at least a few years I think. She really has rock bottom self esteem about the obese thing. Well I guess it wasn't much to begin with, but now she's obese...she's virtually house bound too, although they live in remote West Coast Ireland, so there's not exactly much to do....
Anyway.
Kind regards
Meri-Tuuli
Posted by yxibow on October 4, 2006, at 14:37:40
In reply to Re: QoL: Old versus atypical antipsychotics, posted by ed_uk on October 4, 2006, at 11:18:36
> > I wouldn't go near a phenothiazine with a ten foot pole again...
>
> Well no, me neither but evidently some people prefer typical APs. Perhaps they'd rather take haloperidol than end up the size of a house on Zyprexa.
>
> Ed
>There's always Seroquel. Which I have to fight against too, not doing the best at the moment because I had a cold and didn't go to the gym for a while.
Yes, lipid profile is an issue, but quality of life is also one. There is still a difference between the EPS on say, Geodon, and Haldol, for a number of people. If a portion of the population prefers Mellaril, then maybe that's the drug for them. But old line neuroleptics as a whole have a rather nasty set of EPS, especially for those with affective disorders. Pure schizophrenia, there may be a difference.
Posted by Phillipa on October 4, 2006, at 20:06:17
In reply to Re: QoL: Old versus atypical antipsychotics, posted by ed_uk on October 4, 2006, at 11:18:36
Ed and you want me to take zyprexa for anxiety? No way!!!!! I'm getting older and have to think about back problems, heart problems, and other wt issues diabetes another one. Love PJ O
Posted by yxibow on October 5, 2006, at 3:16:50
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by Phillipa on October 4, 2006, at 20:06:17
> Ed and you want me to take zyprexa for anxiety? No way!!!!! I'm getting older and have to think about back problems, heart problems, and other wt issues diabetes another one. Love PJ O
Actually I was more thinking about Seroquel than Zyprexa. But 2.5mg or 5mg of Zyprexa, carefully monitored, temporarily, for a period of weeks is not going to give you diabetes if you watch your weight and consumption.
We're talking about a temporary intervention to a massive anxiety attack that you're apparently having and I was making a suggestion that might provide some immediate relief. Zyprexa acted as an antidepressant and an anxiolytic within 3 days for me. No kidding.
Unfortunately I can't take Zyprexa or I would, some people experience handshaking, some don't.. unfortunately I do.
I wasn't going to suggest Seroquel because its far more sedating, but the lipid changing profile is a fair bit lower than Zyprexa.You could also try a small dose of Geodon -- a number of people are actually calmed by it -- I just happen to get akathisia.
There really isn't anything quicker acting out there than a neuroleptic or a benzodiazepine, and drowning yourself in benzodiazepines only means weeks to remove them. I mean you could even (I can't believe I'm saying this) take seconal or meprobamate but you're not going to get anything different than a benzodiazepine, just much more danger.
-- tidings
Jay
Posted by ed_uk on October 5, 2006, at 16:52:48
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by Phillipa on October 4, 2006, at 20:06:17
Hi PJ,
>Ed and you want me to take zyprexa for anxiety?
Not regularly no, but occasional or short-term use might be helpful.
Love Ed x
Posted by ed_uk on October 5, 2006, at 16:54:29
In reply to Re: QoL: Old versus atypical antipsychotics, posted by Meri-Tuuli on October 4, 2006, at 13:54:41
I'm sorry to hear that Meri. I hope she can get better treatment in future.
Ed x
Posted by ed_uk on October 5, 2006, at 16:56:45
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by yxibow on October 4, 2006, at 14:37:40
Hi Yxi
Seroquel isn't exactly well tolerated. Despite low EPS, the incidence of side effects is high. In addition, clinical trials have revealed a high drop-out rate.
Ed
Posted by Phillipa on October 5, 2006, at 20:06:50
In reply to Re: QoL: Old versus atypical antipsychotics » yxibow, posted by ed_uk on October 5, 2006, at 16:56:45
Well that's it. No antipsychotics for me. I will stubbornly suffer like I always have. The world can't see in my brain. I'm the only one that knows whats going on there. And I don't think I like ad's anymore either. So I guess I'm having a temper tantrum. Love Phillipa it's not you guys
Posted by temoigneur on October 5, 2006, at 22:32:20
In reply to QoL: Old versus atypical antipsychotics, posted by ed_uk on October 3, 2006, at 16:18:42
Hi Ed, everyone....
I was wondering if anyone could tell me the quickest way to get amisulpride in canada, and what dosage would be roughly equivalent to 10mg zyprexa.
On zyprexa and clomipramine I've put on about 30 pounds, I really need to get off zyprexa..
I heard another canadian got it.... hopefully someone might be able to point him out..
thanks so much
Ben
>
>
>
Posted by Phillipa on October 5, 2006, at 22:35:13
In reply to accessing amisulpride in canada » ed_uk, posted by temoigneur on October 5, 2006, at 22:32:20
See I told you zyprexa was fattening. Love Phillipa
Posted by med_empowered on October 6, 2006, at 11:03:06
In reply to Re: accessing amisulpride in canada » ed_uk, posted by Phillipa on October 5, 2006, at 22:35:13
really, all I think this study "proves" is what we've already known: the 2nd generation meds are over-hyped. They're still D2 blockers, afterall, so you're still going to get side effects.
Plus, in the US at least, there was a tendency to way, way, waaaay overprescribe the neuroleptics, both in terms of patient selection (Thorazine for "hyperkinetic" children, for instance) and in terms of dosage (20mgs of Haldol was pretty standard for a long time). So...when the new drugs came out, of course they looked good up against mind-numbing dosages of old-school drugs. I imagine that 10mgs of zyprexa compared to, say, 200mgs of Thorazine wouldn't look nearly so good. Plus, with the built-in serotonin antagonism, you might be suppressing TD and acute EPS more effectively than with other meds (note that Mellaril had low EPS in part b/c of its effects on serotonin; it still caused TD).
I really don't see why we still use neuroleptics. I mean, the whole dopamine theory of schizophrenia is pretty much crap, so why cant docs and drug companies move on?
Posted by yxibow on October 7, 2006, at 4:28:15
In reply to Re: QoL: Old versus atypical antipsychotics » yxibow, posted by ed_uk on October 5, 2006, at 16:56:45
> Hi Yxi
>
> Seroquel isn't exactly well tolerated. Despite low EPS, the incidence of side effects is high. In addition, clinical trials have revealed a high drop-out rate.
>
> EdWell I've driven on an accidental dose of 1600 mg so I can tell you that it was tolerated. Not pleasant.
I have to take Seroquel because there is nothing below it but Clozaril and I don't want a) $9000 a year in expenses and b) drooling.
There's nothing wrong with a short course of Zyprexa, Jan. They're approved for those sorts of purposes for mania with Bipolar. Like 30 days. And we're talking about doses 1/4 to 1/8 of what would be used in Schizophreniform disorders.
-- Jay
Posted by yxibow on October 7, 2006, at 4:40:52
In reply to Atypicals vs old-school meds..., posted by med_empowered on October 6, 2006, at 11:03:06
> really, all I think this study "proves" is what we've already known: the 2nd generation meds are over-hyped. They're still D2 blockers, afterall, so you're still going to get side effects.
>
> Plus, in the US at least, there was a tendency to way, way, waaaay overprescribe the neuroleptics, both in terms of patient selection (Thorazine for "hyperkinetic" children, for instance) and in terms of dosage (20mgs of Haldol was pretty standard for a long time).
Yes, and people were locked up in wards and injected with insulin, but this isn't 1949...
So...when the new drugs came out, of course they looked good up against mind-numbing dosages of old-school drugs. I imagine that 10mgs of zyprexa compared to, say, 200mgs of Thorazine wouldn't look nearly so good. Plus, with the built-in serotonin antagonism, you might be suppressing TD and acute EPS more effectively than with other medsActually with the built in anticholinergic properties probably... I've always been curious about that with Seroquel.
(note that Mellaril had low EPS in part b/c of its effects on serotonin; it still caused TD).
And it still has a dangerous Qtc profile compared to Geodon which was rechallenged.
>
>
> I really don't see why we still use neuroleptics. I mean, the whole dopamine theory of schizophrenia is pretty much crap, so why cant docs and drug companies move on?
Where do you get the idea that psychosis because you're seeing things at visual D2 pathways, among other dopamine receptors is crap?Evidence based psychiatry has clearly shown that Clozaril, the gold standard, binds heavily at D4. and even more at D2 despite its nearly zero TD profile than Zyprexa or Seroquel.
(Antipsychotic drugs. In: Pharmacology, 4th edition. Rang HP, Dale MM and Ritter JM. Edinburgh, UK: Harcourt Publishers Ltd, 2001:539–549.)
Posted by ed_uk on October 9, 2006, at 14:09:19
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by yxibow on October 7, 2006, at 4:28:15
Hi Jay,
I thought you said Seroquel makes you very tired? It doesn't sound particularly tolerable.
Ed
Posted by yxibow on October 9, 2006, at 18:34:02
In reply to Re: QoL: Old versus atypical antipsychotics » yxibow, posted by ed_uk on October 9, 2006, at 14:09:19
> Hi Jay,
>
> I thought you said Seroquel makes you very tired? It doesn't sound particularly tolerable.
>
> EdIt does, but I'm used to it. And it wouldn't if I could take caffeine, but my particular sticky situation means that enough of it raises my visual problems. For others, and when I didn't have this, I'd just carry a thermos.
Despite the fatigue, which can be alleviated by taking the medicine earlier in the evening instead of late night, it is far more tolerable than the sheer hell of akathisia from horrible phenothiazine and other related compounds. Not to mention the aggregate data on all of the newer atypicals is less than 5% TD per year, with Seroquel in the noise level. Can't say that about haloperidol.
-- Jay
Posted by ed_uk on October 10, 2006, at 15:05:04
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by yxibow on October 9, 2006, at 18:34:02
Hi J
>...........it is far more tolerable than the sheer hell of akathisia from horrible phenothiazine and other related compounds.........
In 'CATIE', discontinuation rates were 64% for Zyprexa, 75% for perphenazine, 82% for Seroquel, 74% for Risperdal, and 79% for Geodon. As you can see, less patients discontinued the high-potency neuroleptic perphenazine that Seroquel. In fact, more patients discontinued Seroquel than any of the other APs.
Ed
Posted by yxibow on October 11, 2006, at 10:27:40
In reply to Re: QoL: Old versus atypical antipsychotics » yxibow, posted by ed_uk on October 10, 2006, at 15:05:04
> Hi J
>
> >...........it is far more tolerable than the sheer hell of akathisia from horrible phenothiazine and other related compounds.........
>
> In 'CATIE', discontinuation rates were 64% for Zyprexa, 75% for perphenazine, 82% for Seroquel, 74% for Risperdal, and 79% for Geodon. As you can see, less patients discontinued the high-potency neuroleptic perphenazine that Seroquel. In fact, more patients discontinued Seroquel than any of the other APs.
>
> Ed
A 3 point discontinuation rate between Geodon and Seroquel is within the margin of error. Secondly, if we are quoting scholarly articles,"It is crucial to point out that equivalent does not mean identical: 25 percent of patients may respond to risperidone and 25 percent to perphenazine, but they are not the same 25 percent. These initial results from CATIE speak to the need for treatment options—not restrictions, such as closed formularies or fail-first requirements."
Psychiatr Serv 57:139, January 2006
Jeffrey A. Lieberman, M.D. and John K. Hsiao, M.D
This is the same investigator in
NEJM 353:1209-1223Also from the NEJM article
"The fact that a higher proportion of patients assigned to quetiapine and ziprasidone received the maximal dose allowed in the study suggests that these agents are either less effective or require higher doses (Table 2). The dose range of perphenazine was chosen to minimize the potential for extrapyramidal symptoms that may have biased previous comparisons of first- and second-generation drugs"
This suggests to me that the phenothiazine drug used in the study was used at its MED (minimum effective dose).Have you ever tried a bone chilling dose of Compazine, Ed ? Its staggering.
I'm only glad that there are medications out there that have low EPS levels, regardless of how much I have to use the treadmill.
Yes, Zyprexa has a huge problem with type 2 diabetes in long term use -- I wouldn't suggest it but for short term mania in those especially susceptible to diabetes, but EPS and TD rise markedly up to Risperdal, as well as to old line antipsychotics.
This study also does not focus particularly on affective disorders, where neuroleptics weigh a heavier toll of EPS and TD.
CATIE is a worthwile study, but it doesn't suggest to me that just because 3/4 of patients discontinued atypicals, that as noted it is the not necessarily the same 3/4 that would discontinue non-atypicals. There is no one size fits all.
I'm talking about effects in myself, not what others choose to take, what risks they take in informed consent (old line drugs which have now been out for 50 years show markedly higher TD rates than new medications that have been out for only a decade.)
Posted by ed_uk on October 11, 2006, at 12:34:15
In reply to Re: QoL: Old versus atypical antipsychotics » ed_uk, posted by yxibow on October 11, 2006, at 10:27:40
>A 3 point discontinuation rate between Geodon and Seroquel is within the margin of error.
I wasn't comparing Seroquel with Geodon, just noting the very high drop out rate with Seroquel.
>The dose range of perphenazine was chosen to minimize the potential for extrapyramidal symptoms that may have biased previous comparisons of first- and second-generation drugs" This suggests to me that the phenothiazine drug used in the study was used at its MED (minimum effective dose).
Well yes, that's good, excessively high doses would have been inappropriate.
>Have you ever tried a bone chilling dose of Compazine, Ed ? Its staggering.
No, I took a high dose of Thorazine though and it landed me in the hospital with VERY severe akathisia. I once took a low dose of Compazine (5mg orally) and didn't have any side effects. Side effects of neuroleptics are usually dose dependent.
You seem to be missing the point. If typical APs are used, clearly they should not be given at 'bone chilling' doses.
>I'm only glad that there are medications out there that have low EPS levels, regardless of how much I have to use the treadmill.
I'm glad they're available too, but they are not *universally* superior to typicals.
>TD rise markedly up to Risperdal, as well as to old line antipsychotics
I don't actually know of any evidence that the risk of TD is any higher with Risperdal than with any of the other atypicals. Acute EPS seems to be more common with Risperdal but that does not necessarily apply to TD. The evidence I've seen suggests that the risk of TD is similar among all the atypicals, including Seroquel and Risperdal.
>This study also does not focus particularly on affective disorders, where neuroleptics weigh a heavier toll of EPS and TD
I think this is probably a myth. Psychotic patients tend to be more ill and less capable of reporting EPS.
>I'm talking about effects in myself, not what others choose to take, what risks they take in informed consent (old line drugs which have now been out for 50 years show markedly higher TD rates than new medications that have been out for only a decade.)
In the treatment of schizophrenia, I believe that an atypical AP should be used first-line. Among the atypicals, I would not choose Seroquel first.
Ed
Posted by yxibow on October 12, 2006, at 2:53:10
In reply to Re: QoL: Old versus atypical antipsychotics » yxibow, posted by ed_uk on October 11, 2006, at 12:34:15
> >A 3 point discontinuation rate between Geodon and Seroquel is within the margin of error.
> I wasn't comparing Seroquel with Geodon, just noting the very high drop out rate with Seroquel.
Fair enough
> >The dose range of perphenazine was chosen to minimize the potential for extrapyramidal symptoms that may have biased previous comparisons of first- and second-generation drugs" This suggests to me that the phenothiazine drug used in the study was used at its MED (minimum effective dose).
>
> Well yes, that's good, excessively high doses would have been inappropriate.Oh, but the idea of dosing beyond the MED (minimum effective dose) is still in practice. Dial it up until something happens, even if it goes beyond what should be tolerable EPS.
> >Have you ever tried a bone chilling dose of Compazine, Ed ? Its staggering.
>
> No, I took a high dose of Thorazine though and it landed me in the hospital with VERY severe akathisia. I once took a low dose of Compazine (5mg orally) and didn't have any side effects. Side effects of neuroleptics are usually dose dependent.True enough, but I was given a "normal" dose of Compazine in the hospital for uncontrollable vomiting due to flu. You go to a hospital to get sicker apparently, and it wasnt long before I hit the nurse button and they remembered to give me an IV of Benadryl. Wore off, akathisia was through the roof I couldnt think in the hospital signout desk, barely made it in a taxi home and I think my current beau/friend at the time came over to visit later in the morning while I was still writhing on the sofa. Finally got some Klonopin somehow from my psychiatrist.
> You seem to be missing the point. If typical APs are used, clearly they should not be given at 'bone chilling' doses.
Well it was.
> >I'm only glad that there are medications out there that have low EPS levels, regardless of how much I have to use the treadmill.
>
> I'm glad they're available too, but they are not *universally* superior to typicals.Didn't say universally, but they are far less likely to cause TD over a long period of time.
> >TD rise markedly up to Risperdal, as well as to old line antipsychotics
>
> I don't actually know of any evidence that the risk of TD is any higher with Risperdal than with any of the other atypicals. Acute EPS seems to be more common with Risperdal but that does not necessarily apply to TD. The evidence I've seen suggests that the risk of TD is similar among all the atypicals, including Seroquel and Risperdal.Mean rate aggregate chart, 2% across all studies. Elderly patients were found to be higher. One study of 1,964 patients found under 1%.
Am J Psychiatry 161:414-425, March 2004> >This study also does not focus particularly on affective disorders, where neuroleptics weigh a heavier toll of EPS and TD
>
> I think this is probably a myth. Psychotic patients tend to be more ill and less capable of reporting EPS.B*llshit, this is a disservice to the functioning of patients with schizophreniform disorders -- the same still applies, if you're really aware of something that is TD, it isn't likely to be so, and I think the average higher functioning person can definately complain about akathisia.
And it is not a myth that the brain structure of schizophrenic patients is different from those not psychotic with affective disorders (anxiety, depression). There is a difference, perhaps not completely understood, in the way that dopamine is manipulated, and rates of EPS and TD are higher among affective disorders treated with neuroleptics with higher D2 affinities.
> >I'm talking about effects in myself, not what others choose to take, what risks they take in informed consent (old line drugs which have now been out for 50 years show markedly higher TD rates than new medications that have been out for only a decade.)
>
> In the treatment of schizophrenia, I believe that an atypical AP should be used first-line. Among the atypicals, I would not choose Seroquel first.Possibly, because it is the most sedating of all atypicals, I would agree, and less effective at lower doses for extremely psychotic patients.
On the other hand, Risperdal at its highest doses is basically its chemical cousin Haldol. At extremely low doses it can actually be a dopamine increaser.
My experience with a combination of Risperdal and Prozac is still 5 years later, my right index finger twitches uncontrollably, just slightly. We discontinued it after that. Alas, too late. Zyprexa was a bust with pseudoparkinsonism at any dose and the second time challenged at a lower dose, it took months for my hands to stop shaking when using power tools or under hot water in the shower.
So I'm now at Seroquel.
And across the pond there was a study of Zyprexa:
The British Journal of Psychiatry 174: 23-30 (1999)
"Based on data following the initial six weeks of observation (during which patients underwent medication change and AIMS assessments as frequently as every three days), the one-year risk was 0.52% with olanzapine (n = 513) and 7.45% with haloperidol (n = 114). The relative risk throughout this follow-up period was 11.37 (95% CI = 2.21-58.60). CONCLUSION: Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol."
So while there is no guarantees, I can live with Seroquel for the time being, not being a perfect drug -- Zyprexa would be. Extrapolating from that, Seroquel probably has a 1/4% risk or lower.
But who knows. I could always challenge with clozapine, but somehow the idea of peeing in my pants and $9000 a year monitoring is not in the cards. Not yet anyhow.
-- tidingsJay
This is the end of the thread.
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