tag:blogger.com,1999:blog-7772182113499451603.post695044144349756760..comments2024-03-27T10:50:53.692-05:00Comments on Real Psychiatry: Dangerous Medications 3: No - New IS Better Than OldGeorge Dawson, MD, DFAPAhttp://www.blogger.com/profile/03474899831557543486noreply@blogger.comBlogger16125tag:blogger.com,1999:blog-7772182113499451603.post-4963642383828299132014-07-05T19:34:42.887-05:002014-07-05T19:34:42.887-05:00I suppose it's possible that that was Dr. Lieb...I suppose it's possible that that was Dr. Lieberman's agenda alone, and i confused it with the organization he was president of. He has been very active to promote "early innervation and prevention" of a schizophrenia for decades.<br /><br />Thank you for the link, I have actually read that paper. <br />Here was a paper I was referring to, reviewing 13 more recent voxel MRI studies to compare FGAs and SGAs:<br />http://www.ncbi.nlm.nih.gov/pubmed/23157636<br /><br />It was published in a chemistry journal called "Current Medical Chemistry" in the Netherlands. The full paper is available for free. There is a minor conflict of interest declared; Eli-Lilly has an anti-psychotic called Zyprexa on the market.clarknoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-57779822948613755692014-07-05T01:01:01.508-05:002014-07-05T01:01:01.508-05:00Well I guess you would be wrong then Clark.
Ionna...Well I guess you would be wrong then Clark.<br /><br />Ionnadides paper on most published research being false clearly applies to practically all research studies involving brain volumes in psychiatric disorders and they go back at least 30 years. And keep in mind that I am not somebody who just reads about it in the papers. For those 30 years I actually went down and looked at all of the brain scans I ordered and did the measurements. I think what most people fail to realize is that differences are subtle and that schizophrenia is a very heterogenous disorder. I am not aware of any brain volume studies stratified on endophenotypes, but I can easily find out.<br /><br />As far as your remark about unmedicated schizophrenia goes, there are many neuropathological studies from before the time of medications and there are many studies that disagree with your statement. I reference one at the end here. Serial MRI scans looking a volumetric analysis would produce what you expect them to. A percentage of people with "cortical atrophy"and everyone else with normal scans. If you talk with any neuroradiologist (as I have) they will tell you it is a nonspecific finding. That is the reason the studies were not included in CATIE (at least in addition to the fact that the researchers did not seem capable of keeping anyone in the study to image them a second time) and why they are not done clinically.<br /><br />As far as the APA "selling" some idea about medications - you have not been paying attention. They don't seem to be able to sell the idea that it might be reasonable to increase psychiatric services. Selling an idea about medications is not even on their agenda.<br /><br />Harrison PJ. The neuropathology of schizophrenia. A critical review of the<br />data and their interpretation. Brain. 1999 Apr;122 ( Pt 4):593-624. Review.<br />PubMed PMID: 10219775.George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-40742467006757556242014-07-05T00:09:58.623-05:002014-07-05T00:09:58.623-05:00I would disagree that the newer drugs are necessar...I would disagree that the newer drugs are necessarily less toxic. They do after-all have the same mechanism of action to produce sedation as the old. Some of the anti-psychotic side effects appear to be unique to blocking dopamine, such as brain volume reduction. There are about 13 'placebo' controlled studies on brain shrinkage with anti-psychotics drugs published. Their quality is higher then those without placebo groups (maybe, some used automated voxel imaging). Interestingly, none found brain volume changes in untreated schizophrenics.<br /><br />But, would it not make more sense to just introduce routine MRI scans every so many months? Brain shrinkage is very significant with these drugs, and that would provide a means to falsify an anecdotal observation concerning neurotoxicity. Then again, I'm aware the APA is trying to sell brain shrinkage as 'schizophrenia' itself... I guess there's a reason these tests have not been made available for this purpose in the first place, possibly the same reason placebo groups are not included in studies like CATIE.<br /><br />None the less, I'm not sure how "knowing what to look for" could be realistically applied to many physicians who clearly do not and probably never will either. Maybe there's no solution?<br /><br />I mean, since the FDA refuses to take these drugs off the market in the first place.<br /><br />Happy independence day, btwclarknoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-58981853693612227902014-07-03T23:13:23.831-05:002014-07-03T23:13:23.831-05:00I think that there is scant evidence that supersen...I think that there is scant evidence that supersensitivity psychosis occurs. The diagnostic criteria for this disorder are so vague that they could basically include anybody with increased symptoms and a movement disorder. In many of the studies of this phenomenon - low to moderate doses of antipsychotics are used. The only condition I have seen that resembles a supersensitivity psychosis is a person with a severe movement disorder typically from first generation antipsychotics who also has psychotic symptoms. In that case the dose of the medication is not necessarily the factor that leads to problems it is probably the genetics of the person taking the medication.<br /><br />That is the message of this post - it is currently possible to determine who is sensitive on a clinical basis by a person who knows what to look for. There is no one size fits all approach and people have to be carefully monitored for the first signs of toxicity. With regard to CNS effects - second generation drugs are less toxic.George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-63359801412542498732014-07-03T19:49:52.232-05:002014-07-03T19:49:52.232-05:00I have a question about these drugs.
What happens...I have a question about these drugs.<br /><br />What happens to patients today who have been made sick by anti-psychotics, specifically in the case of "dopamine super-sensitivity psychosis"?<br /><br />In the past, persistent drug-induced psychosis was usually treated with dangerous doses of the same drugs that caused it, or ablative treatments. Is this still the case today?clarknoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-60641687773175723402014-06-18T21:17:06.673-05:002014-06-18T21:17:06.673-05:00Haloperidol is an FGA. Clozapine was the original...Haloperidol is an FGA. Clozapine was the original SGA.<br /><br />The only thing that matters in clinical practice is the outcomes of individual practitioners. There is no clinical trial that predicts that and as I have pointed out the CATIE technology is incredibly crude. The ratio of prescribing FGAs and SGAs is fairly meaningless.<br /><br />Prescribing SGAs does require a lot more effort on the part of the psychiatrist and close monitoring and intervention to prevent weight gain. Apart from the biases that is about all the CATIE study meant to me. George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-8244979074673808822014-06-18T21:07:46.822-05:002014-06-18T21:07:46.822-05:00Obviously I disagree. If you read through my post...Obviously I disagree. If you read through my post - you can see the biases in the CATIE study and they are significant. The other issue with the CATIE study was time to drug discontinuation as the primary outcome measure. If anything it proves how crude clinical trials are. I guess if my goals was to treat people for 18 months it might apply. If you have treated as many people with disabling movement disorders as I have and you know how to manage metabolic side effects that is a reason to prescribe SGAs first. The other clinical issue is that most patients prefer olanzapine over other antipsychotics and that was probably why it was the "most effective" int he CATIE study.<br /><br />Your quote of the British psychiatrist saying that the Americans would eat their own words seems strangely biased to me. The goal here is patient care not some kind of political argument. If you feel strongly about first generation antipsychotics - feel free to use them as first line agents. Just have a movement disorder specialist that you can refer patients to who predictably develop tardive dyskinesia and other movement disorders.George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-67970866874930672542014-06-18T19:52:11.210-05:002014-06-18T19:52:11.210-05:00And a lot of the psychiatrists do notice a lot mor...And a lot of the psychiatrists do notice a lot more obese schizophrenics in the psychiatric wards than when the FGAs were around, I side with NIH and the UK's CUTLASS study, SGAs, though less associated with extra pyramidal symptoms, the weight gain is significant and, overall, that FGAs are on par with the SGAs.<br /><br /><br />And I agree with the NIH statement that " (the CATIE study) will provide valuable information to help physicians and patients choose the most appropriate medication for them" and the added negative effects--again diabetes and obesity, compensates for the slight advantages that the SGAs deliver.<br /><br />So, in summary, I think there is no real reason for your belief that the SGAs should be more prescribed than the FGAs, they are, at the very least, roughly equivalent and a *personalized* approach (what treatment is best for the *individual* patient , FGA or SGA) must be taken.<br /><br /><br />And I recall that one of the psychiatrists who was involved with the CUTLASS study (that preceded America's CATIE study) looked forward to "Americans eating their own words" when CATIE's results were published. And eat their own words many American psychiatrists did, I remember reading some go as far as saying that the perceived advantages of the SGAs were just a result of drug companies marketing their products. Also, CATIE was , if I recall correctly, the largest follow up study that was *not* funded by the drug companies, and combine that with the consistent findings the similar (long term) follow up study the British conducted( CUTLASS), I saw there is little evidence supporting your claims that there is more reason to prescribe SGAs more commonly than the first generation ones.<br /><br />And I conclude with saying that, from my experience, that your opinion that the CATIE studies (and the CUTLASS study you failed to mention) are no reason to view Second generation antipsychotics as inherently superior is a minority view, even in America (the land of the drug company funded studies).<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-76046241592619663902014-06-18T19:51:52.495-05:002014-06-18T19:51:52.495-05:00What about the weight gain, and diabetes, associat...What about the weight gain, and diabetes, associated with the second generation anti-psychotics?<br /><br />I remember hearing a podcast where Robin Murray (a British psychiatrist) commenting that even though Tardive Dyskinesia is associated with the first generation antipsychotics, second generation ones are associated with significant weight gain, increase in blood cholesterol, triglyercide levels, etc. And the important thing to note is a lot of patients with schizophrenia live sedentary lifestyles, which can be attributed to negative affect, just counselling them on how to avoid weight gain (when we know that anhedonia, avolition, etc.) could very well prevent these patients from exercising. Likewise, studies in Canada show that, due to the excess weight gain caused by second generation antipsychotics (and combine that with the sedentary lifestyle most patients with schizophrenia have....) Also, the drugs themselves cause raised glucose, triglycerides and cholesterol by themselves, in fact one of Olazapine's potential side effects is glucose in urine, due to the hyperglycemia, and again, I think you too are aware in your practice (and the many other psychiatrists note) patients with schizophrenia tend to live more sedentary lifestyles. I think just educating them on the risks of weight gain won't do too much because, again, negative affect, and there is no real proven treatment for that (yet) is there?<br /><br />Also, clozapine isn't prescribed as a first line treatment, in fact I recall that the reason why it only is used in treatment resistant schizophrenia is because of the chance of agranulocytosis, and the economic cost for the monitoring to make sure that does not happen.<br /><br />In fact, I remember clozapine was initially rejected because of the high rate of death, it wasn't only until investigators observed its effects in the treatment resistant population that it was *cautiously* used again.That is why it is not used as front line treatment.<br /><br />Also the CATIE study was not the first study to show that the first generation antipsychotics were on par with the second generation antipsychotics, it was the CUTLASS study done in the UK, where clozapine was judged to be the only superior second generation antipsychotic, but with the risk of agranulocytosis, it is a drug of last resort ( real term by the way).<br /><br />In fact, here in Canada, we only prescribe clozapine if (at least) two other antipsychotics have failed,and why it is only used for treatment resistant cases.<br />Also, the CATIE study wasn't the first one that demonstrated second generation antipsychotics were not superior to the first generation ones, it was the CUTLASS study done in the UK where only clozapine was judged to be superior out of the second generation bunch. And again, the British too view it as a drug of last resort.<br /><br />I say there is no clinical justification to view the second generation antipsychotics (aside from clozapine) as more effective than first generation antipsychotics, and coincidentally the non drug company funded studies (such as CATIE and CUTLASS) showing no significant advantage between first and second generation antipsychotics, whereas (purely coincidental) it's the drug companies' studies that show the "superior" advantages of *their* drugs means psychiatrists should take a more personalized approach to the treatment of our patients.<br /><br />Also, SGAs such as haloperidol are associated with inducing mania. Again, personalized approaches to patients, I'm sure some patients benefit more from SGAs than FGAs, but the opposite is true as well. Which is why the British don't prescribes SGAs: FGAs in 9:1 ratios like the Americans, but more of a 50/50 (if I recall correctly) and I think their CUTLASS study, along with America's subsequent CATIE study, support their claims.<br /><br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-44731781207218919542014-06-18T16:20:37.102-05:002014-06-18T16:20:37.102-05:00I hate to switch meds unless its bothersome side e...I hate to switch meds unless its bothersome side effects. Two months, costs, and dropout problems. I'll at least give LMTF a shot before doing that. Here's another link in the form of summary article:<br /><br />http://www.medscape.com/viewarticle/805018James O'Brien, M.D.https://www.blogger.com/profile/14994350319492582321noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-15362278590381594622014-06-18T13:25:36.537-05:002014-06-18T13:25:36.537-05:00Oh, and one other area where new is better: sleepe...Oh, and one other area where new is better: sleepers, specifically Lunesta which is now off patent (not a fan of Ambien). However, i don't get the FDAs latest recc on dosage, which is ridiculously low in my experience. <br /><br />The UAB researcher is Shelton. Here's one of his newer articles on LMTF and biomarkers (subs req).<br /><br />http://www.researchgate.net/publication/262225339_Effect_of_adjunctive_L-methylfolate_15_mg_among_inadequate_responders_to_SSRIs_in_depressed_patients_who_were_stratified_by_biomarker_levels_and_genotype_results_from_a_randomized_clinical_trial<br /><br />James O'Brien, M.D.https://www.blogger.com/profile/14994350319492582321noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-66947326461386585932014-06-18T13:09:41.328-05:002014-06-18T13:09:41.328-05:00I looked into the 5 Hour Energy and concluded it w...I looked into the 5 Hour Energy and concluded it was a placebo - except for the caffeine which would not be sustained.<br /><br />Most of what I do these days is stop or replace antidepressants, typically for either the wrong diagnosis and side effects. There are a significant number of people who do not tolerate SSRIs and should not take them. I use the augmentation only if the antidepressant is well tolerated (no detectable side effects) and there is evidence of some partial response.George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-39440096852088037082014-06-18T12:02:52.411-05:002014-06-18T12:02:52.411-05:00I make my own antidepressants at home. Have you lo...I make my own antidepressants at home. Have you looked into the components of 5 hr energy? I think it may be the tyrosine that has worked for some where caffeine alone didn't work.<br /><br />Also, have you ever not augmented an antidepressant and instead replaced it?<br />RBnoreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-69785570501765175772014-06-17T17:38:50.943-05:002014-06-17T17:38:50.943-05:00My experience is similar to that of Stahl...I like...My experience is similar to that of Stahl...I like everything about Buspar except efficacy.<br /><br />I almost never use antipsychotics for this purpose. <br /><br />In the last couple years LMTF has expanded beyond MTHFR polymorphism into waist size as a biomarker. I think there is an article on this by a research from Alabama Birmingham on this. James O'Brien, M.D.https://www.blogger.com/profile/14994350319492582321noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-5017114578089468802014-06-17T12:21:40.511-05:002014-06-17T12:21:40.511-05:00I did some extensive research on L-methylfolate so...I did some extensive research on L-methylfolate some years ago for a colleague. If I can find that e-mail I will post it later. I seem to recall that the purported genotypes supporting this approach were rare and that made me a skeptic of the research at the time. That said, I have had people tell me that they tried all sorts of augmentation strategies on their own with good to great results. The most unusual was 5 Hour Energy drinks that totally eradicated low energy and depression at the same time (just 1-2 drinks per day). My preferred strategy has been buspirone and I think that works pretty well. I have consulted on a lot of people using aripiprazole including some who clearly developed TD from it. I use it only in special circumstances.<br /><br />Maybe a good study would be L-methylfolate versus buspirone as augmentation? George Dawson, MD, DFAPAhttps://www.blogger.com/profile/03474899831557543486noreply@blogger.comtag:blogger.com,1999:blog-7772182113499451603.post-46296359759128815492014-06-17T11:40:32.185-05:002014-06-17T11:40:32.185-05:00I know this article focused on antipsychotics, but...I know this article focused on antipsychotics, but I wondered about your take on experience with antidepressant augmentation.<br /><br />Some of the studies on L-methyl-folate I find deeply flawed because of the use of the PHQ-9 which is a joke for research. However, in practice I find that it works very well at the 15 mg for partial responders and for the overweight/obese depressed. Conceding limited sample size, anecdotal, all of that.<br /><br />The good news is that it's incredibly safe, the bad news is the cost.James O'Brien, M.D.https://www.blogger.com/profile/14994350319492582321noreply@blogger.com