![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 10 to 34 of 62. Go back in thread:
Posted by ed_uk on July 30, 2005, at 8:09:24
In reply to Re: Haloperidol (Haldol), posted by med_empowered on July 30, 2005, at 7:12:46
Hi Med,
J Psychopharmacol. 2001 Dec;15(4):251-5.
Determining the optimal dose of haloperidol in first-episode psychosis.Oosthuizen P, Emsley RA, Turner J, Keyter N.
Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa. pieto@samedical.co.za
Uncertainty exists as to the most appropriate dose of haloperidol in first-episode psychosis. This study set out to determine whether ultra-low doses of haloperidol could successfully treat patients with first-episode psychosis. Thirty-five patients with a first episode of psychosis were treated with haloperidol in an open label, fixed protocol over a 12-week period with doses restricted to 1 mg per day for the first 4 weeks. Twenty-nine (83%) remained on haloperidol after 12 weeks at a mean dose of 1.78 mg per day, 16 (55%) had stabilized on 1 mg/day or less. The mean percentage reduction in Positive and Negative Symptom Scale score between baseline and 6 and 12 weeks was 30.3% (SD 20.9%) and 41.4% (SD 16.6%), respectively. There were *no* significant differences in mean extrapyramidal symptom ratings between baseline and 12 weeks. Ultra-low doses of haloperidol are effective and well tolerated in first-episode psychosis. ****Initial doses should be maintained for a sufficient period of time to allow for the medication to take full effect.*****
~Ed
Posted by ed_uk on July 30, 2005, at 12:36:13
In reply to Re: Haloperidol (Haldol), posted by med_empowered on July 30, 2005, at 7:12:46
Hi Med,
>I read a study where 2mgs got good results....
It might have been this, I've posted it a couple of time before.......
Int J Neuropsychopharmacol. 2004 Jun;7(2):125-31. Epub 2004 Mar 5.
A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis.
Oosthuizen P, Emsley R, Jadri Turner H, Keyter N.
Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa. pieto@sun.ac.za
While haloperidol is still widely used in the treatment of psychoses, the optimal daily dose remains a topic of controversy, particularly in first-episode psychosis. Previous studies have suggested that doses as low as 2 mg/d may be effective, whereas others have indicated superiority for higher over lower doses. This double-blinded, randomized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis. Both treatments were equally effective in reducing the PANSS Total and subscale scores. The low dose of haloperidol was better tolerated, with fewer extrapyramidal side-effects, less frequent use of anticholinergic medication and smaller elevations in prolactin levels. Using a low dose of haloperidol is at least as effective as, and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis.
.................................................................................................
Since haloperidol is a very potent D2 antagonist, surprisingly low doses can produce a high level of D2 occupancy (as has been demonstrated using positron emmission tomograph). IMHO, the dose should be precisely titrated (generally within the low dose range) to produce the optimal effect.
2mg haloperidol is not, as many would believe, a homeopathic dose. The potency of haloperidol as a D2 antagonist is often underestimated.
'Seven patients with schizophrenia were treated with 2 mg/day of haloperidol for 2 weeks, and D2 receptor occupancy was measured by [11C]raclopride and positron emission tomography. RESULTS: The patients showed high levels of D2 occupancy (53%-74%); five of them showed substantial clinical improvement, and none showed important side effects. CONCLUSIONS: The findings demonstrate that low doses of haloperidol induce D2 receptor occupancies that are in the putative therapeutic range.'
This is interesting...........
CNS Drugs. 2001;15(9):671-8.
Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies.
Tauscher J, Kapur S.
Schizophrenia-PET Program, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. Jtauscher@camhpet.on.ca
Despite vast clinical experience with antipsychotics, there is no broad consensus on the doses of these substances that should be administered. Currently, most antipsychotics are administered empirically according to clinical dose-finding studies, in which arbitrarily selected doses were tested to find the "most efficient" dose range in a patient population, with no regard for the molecular effects of the tested drug. Brain imaging studies using nuclear medical techniques, such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), can now provide a rationale for doses, directly derived from the central effects of the drugs on neurotransmitter receptors measured in vivo. PET results indicate that occupancy of at least 65% of dopamine D(2) receptors is needed for clinical response to antipsychotics, and that occupancy rates exceeding 72 and 78% are associated with a high risk for elevation of prolactin levels and motor adverse effects, respectively. For example, clinical studies with haloperidol do not point to an advantage of dosages exceeding 5 mg/day. The relevance of D(2) receptor occupancy for drug administration is also borne out by studies relating the effects of antipsychotics to their D(2) receptor occupancy in relevant animal models. Taken together, neuroimaging and clinical studies, as well as animal models, provide a rationale for the use of relatively low doses of typical antipsychotics and equivalent doses of novel antipsychotics. The lower risk of adverse effects with appropriate doses of antipsychotics may further enhance compliance and outcome. This seems to be particularly important in individuals experiencing a first episode of schizophrenia, as they appear to be especially responsive to pharmacotherapy and quite sensitive to adverse effects.
An interesting comparison of Zyprexa 7.5mg versus haloperidol 2.5mg. Haloperidol 2.5mg was superior, producing a better 'subjective experience'............
Am J Psychiatry. 2003 Feb;160(2):303-9.
Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.de Haan L, van Bruggen M, Lavalaye J, Booij J, Dingemans PM, Linszen D.
Academic Medical Center, University of Amsterdam Department of Psychiatry, The Netherlands. l.dehaan@amc.uva.nl
OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.
..................................................................................
In the UK, the recommended starting dose of haloperidol for schizophrenia is 3mg-15mg, a few years ago it was 1.5mg to 20mg.
IMHO, 1.5mg seems like a suitable starting dose for the treatment of a patient suffering from their first episode of schizophrenia. 0.5mg three times a day could be prescribed initially.... Once the patient was stabilised, the drug could be given as a single daily dose in the evening.
Kind regards
~Ed
Posted by ed_uk on July 30, 2005, at 15:46:28
In reply to Re: Haloperidol (Haldol), posted by Declan on July 30, 2005, at 2:48:07
Hi Declan,
What effect did 1.5mg Serenace produce? 0.5mg twice daily is the recommended dose for severe anxiety. It's hardly a first-line treatment for anxiety though, more of a last resort.
In the UK, the smallest Haldol tablet is 5mg!!!!! Thankfully, Serenace comes in 0.5mg capsules. A generic is also available.
~Ed
Posted by Declan on July 30, 2005, at 16:29:27
In reply to Re: Haloperidol (Haldol) » Declan, posted by ed_uk on July 30, 2005, at 15:46:28
Good morning Ed
1.5mg Serenace made me feel numb and restless. As I recall I was taking it for feelings of dread that may in fact have been exacerbated by my benzo use.
Declan
Posted by ed_uk on July 30, 2005, at 17:02:36
In reply to Re: Haloperidol (Haldol), posted by Declan on July 30, 2005, at 16:29:27
>Good morning Ed
Good evening Declan :-)
>1.5mg Serenace made me feel numb and restless........
Yuck. I'm glad they didn't give you a 20mg tablet....... how awful, I hope they get discontinued soon. I guess they're still useful for clinical trials which show atypical APs are better tolerated than 20mg/day haloperidol. Errr, duh! How about using a sensible dose LOL. It makes the atypicals look great though, which I imagine is why they use 20mg.
Kind regards
~Ed
Posted by ed_uk on July 31, 2005, at 14:33:24
In reply to Haloperidol (Haldol), posted by ed_uk on July 29, 2005, at 15:57:15
OK, so we all know that lots of people who've taken typical APs have hated them - especially me and Declan!
I was wondering whether anyone actually liked typical APs????????
I know xbunny likes flupenthixol (Depixol) 6mg for schizophrenia. 6mg flupenthixol is 'equivalent' to about 6mg haloperidol.
Jay likes perphenazine (Trilafon) for agitation. I think he takes 4mg prn. 4mg perphenazine is 'equivalent' to about 1mg haloperidol.
Maxime takes 25mg chlorpromazine prn (Thorazine) for agitation. 25mg chlorpromazine is 'equivalent' to about 0.75mg haloperidol.
River1924 finds trifluoperazine (Stelazine) calming. I think he takes a small dose prn.
CareBear found 0.5-1mg haloperidol (Haldol) to be effective for anxiety.
.........all these doses are relatively low. I will continue to believe that typical APs are considerably more useful at small doses than at mega-doses, except perhaps in a few isolated cases. Even in schizophrenia, small doses can be useful. It is my belief that these potent dopamine antagonists should be carefully titrated within the low-dose range, to achieve the optimum efficacy without producing disturbing side effects. Of course, even low doses of typical APs appear to result in a high incidence of TD when used on a long-term basis. In a world where the atypical APs are hyped, it's still important that the typical APs remain available for the (small?) proportion of patients who find them more effective or more tolerable than the atypicals.
~ed
Posted by ed_uk on July 31, 2005, at 17:22:14
In reply to Re: Haloperidol (Haldol), posted by med_empowered on July 30, 2005, at 7:12:46
Cochrane Database Syst Rev. 2002;(3):CD001951.
Haloperidol dose for the acute phase of schizophrenia.
Waraich PS, Adams CE, Roque M, Hamill KM, Marti J.
Department of Psychiatry, University of British Columbia, 1081 Burrard St., Rm 306, Comox Building, Vancouver, British Columbia, Canada, V6Z 1Y6. waraich@interchange.ubc.ca
BACKGROUND: Haloperidol is a benchmark, accessible antipsychotic against which the effects of newer treatments are gauged. OBJECTIVES: The primary goal of this review is to determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia. SEARCH STRATEGY: The reviewers searched Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (1999, Issue 2), The Cochrane Schizophrenia Group's Register (December 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1887-1999). They also inspected all references of all identified trials and included studies sought as a citation on SCISEARCH database (1980-1999). Authors of identified studies and pharmaceutical companies were also contacted. SELECTION CRITERIA: Studies were selected if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes. DATA COLLECTION AND ANALYSIS: The reviewers independently and blindly inspected citations (10% reliability check), they ordered papers, and reliably re-inspected and quality assessed the full reports. The reviewers, again working independently, also extracted data. For homogeneous dichotomous data the relative risk (RR), 95% confidence intervals (CI) were calculated on an intention-to-treat basis. Reviewers assumed that people who left the study early or were lost to follow-up had a negative outcome. Weighted mean differences (WMD) were calculated for continuous outcomes that reported intention to treat (ITT), last observation carried forward (LOCF) data. Data was excluded if loss to follow-up was greater than 50%. MAIN RESULTS: Sixteen trials with nineteen different randomised dose comparisons were included. No studies reported data on relapse rates, quality of life and none compared >1.5-3.0 mg/day haloperidol to higher dose ranges. Using low doses (>3-7.5mg/day) did not clearly result in loss of efficacy (no clinically important improvement in global state, versus >7.5-15mg/day n=48, 1 RCT, RR 1.09 CI 0.7 to 1.8; versus >15-35mg/day n=81, 2 RCTs, 0.95 CI 0.8 to 1.2). Doses of haloperidol in the range of >3-7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus >7.5-15mg/day n=64, 2 RCTs, RR 0.12 CI 0.01 to 2.1; versus >15-35mg/day n=144, 3 RCTs RR 0.59 CI 0.5 to 0.8, NNH 3 CI 2 to 6; versus >35mg/day n=86, 2 RCTs, RR 0.70 CI 0.5 to 1.1). All other comparisons between dose ranges did not yield statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences. REVIEWER'S CONCLUSIONS: No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.
3mg-7.5mg haloperidol is an effective treatment for schizophrenia. IMHO, further research regarding the efficacy of doses <3mg would be very valuable. Haloperidol is a cheap drug. In many parts of the world, atypicals APs are not readily available.... they're far too expensive.
~Ed
Posted by JACJ on July 31, 2005, at 19:00:06
In reply to Re: Haloperidol (Haldol) dose for schizophrenia, posted by ed_uk on July 31, 2005, at 17:22:14
What is a high incidence for TD when using atypical AP even at low doses? Also, what is considered long term?
Thanks,
JACJ
Posted by ed_uk on August 1, 2005, at 13:43:13
In reply to Re: For Ed, posted by JACJ on July 31, 2005, at 19:00:06
Hi J,
Atypical APs cause TD at a rate of less than 1% per year (of continuous AP treatment) in young adults. TD is *much* more common in the elderly. TD is very rare in patients treated with APs for less than 3 months, 1 month in the elderly.
Am J Psychiatry. 2004 Mar;161(3):414-25.
Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.Correll CU, Leucht S, Kane JM.
Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Schneider Children's Hospital, Glen Oaks, NY 11004, USA. ccorrell@lij.edu
OBJECTIVE: Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic. METHOD: Studies of treatment with second-generation antipsychotics lasting > or =1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed. RESULTS: In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of double-blind, randomized trials (N=4); and open label (N=4). Of the four trials that had a comparator (all involving adults with schizophrenia spectrum disorders), three used haloperidol (N=408) and one used placebo (N=71). Studied populations included children (N=77), adults (N=1,419), adults and elderly persons (N=794), and exclusively patients age 54 years or older (N=479). The weighted mean annual incidence of tardive dyskinesia for second-generation antipsychotics was 0% in the children, 0.8% (range=0.0%-1.5%) in the adults, 6.8% in the mixed adult and elderly population, and 5.3% (range=0.0%-13.4%) in the patients age 54 years and older, compared to 5.4% (range=4.1%-7.4%) in adults treated with haloperidol. CONCLUSIONS: Results from 11 long-term studies support the idea that second-generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotics, although the doses of haloperidol used in the comparator studies were relatively high. More carefully designed studies, ideally lasting beyond 1 year and comparing the effects of different second-generation antipsychotics in patients who have never taken first-generation antipsychotics, are needed to estimate the true risk. It would not appear premature for clinicians to consider these findings in making long-term treatment decisions.
~Ed
Posted by JACJ on August 1, 2005, at 14:54:22
In reply to Re: For Ed » JACJ, posted by ed_uk on August 1, 2005, at 13:43:13
Hi Ed,
Thanks for that info. Say you are on 2-3 Atypical's. Would that risk increase to 2-3 percnt a year since you are on more than one? Also, what is the culmulative risk if you were on AP's for 2.5 years?Thanks,
J
Posted by ed_uk on August 1, 2005, at 15:12:19
In reply to Re: For Ed, posted by JACJ on August 1, 2005, at 14:54:22
Hi J,
>Say you are on 2-3 Atypical's. Would that risk increase to 2-3 percnt a year since you are on more than one?
AFAIK, no.
>Also, what is the culmulative risk if you were on AP's for 2.5 years?
I don't know. I'd guess about 2%. TD appears during AP treatment or shortly (eg. 1-2 weeks) after withdrawal. I know you haven't taken an AP for a long time - if you haven't developed TD yet, you'll never develop TD.
Kind regards
~Ed
Posted by JACJ on August 1, 2005, at 16:02:51
In reply to Re: For Ed » JACJ, posted by ed_uk on August 1, 2005, at 15:12:19
> Hi J,
>
> >Say you are on 2-3 Atypical's. Would that risk increase to 2-3 percnt a year since you are on more than one?
>
> AFAIK, no.
>
> >Also, what is the culmulative risk if you were on AP's for 2.5 years?
>
> I don't know. I'd guess about 2%. TD appears during AP treatment or shortly (eg. 1-2 weeks) after withdrawal. I know you haven't taken an AP for a long time - if you haven't developed TD yet, you'll never develop TD.
>
> Kind regards
>
> ~EdHi Ed,
What does AFAIK mean? I am going back to school and am studying about neuroleptics. I have a great interest in them as you well know. :) These drugs scare me so much b/c I was given them out of a medical mistake and now am still payingn some price. I am off all drugs for about 16 months and still have w/d effects even though I think the benzo is causing alot of this. Anyways, didn't mean to get off track but now that I am drug free I am afriad to take any drugs thinking it will cause TD or some other movement disorder to show up. What drug(s) should I stay away so that this doesn't happen? i.e. dopamine activating drugs I know some anesthesia meds can cause CNS dispution too. My CNS system is so fragile right now. The reason I am concerned is b/c I am about to give birth and what if I need anesthesia?Since I was on neuroleptics is my brain more fragile if I ever went on AP's again? I guess what I am getting at is this: is my brain suseptible to TD since I was on AP's or has the brain recovered? This isn't just about my casee but I just wanted to know some answers. I am thinking of seeing a neurologist to get some answers. Does the brain grow new cells in replaced to what was damaged? Is my brain chemistry changed? I know these are extremely difficult questions but my mind and body need to get past this and I can't until I know some answewrs.
Thanks,
J
Posted by ed_uk on August 1, 2005, at 16:21:21
In reply to Re: For Ed, posted by JACJ on August 1, 2005, at 16:02:51
Hi,
>What does AFAIK mean?
As far as I know.....
>What drug(s) should I stay away so that this doesn't happen?
If you want to avoid all dopamine antagonist drugs, stay away from metoclopramide (Reglan) and prochlorperazine (Compazine) - two widely used anti-nausea drugs.
>The reason I am concerned is b/c I am about to give birth and what if I need anesthesia?
Dopamine antagonists such as Compazine are widely used to treat/prevent post-op nausea and vomiting. Numerous alternatives are available though, you don't have to take any dopamine antagonists if you don't want to.
>I guess what I am getting at is this: is my brain suseptible to TD since I was on AP's.........
No, I don't believe it is.
>Does the brain grow new cells in replaced to what was damaged?
You don't have TD, I don't think the APs will have damaged any brain cells. Anyway, the brain can grow new cells in a process called neurogenesis.
>Is my brain chemistry changed?
No, I don't think so.
Kind regards
~Ed
Posted by JACJ on August 1, 2005, at 17:29:30
In reply to Re: For Ed » JACJ, posted by ed_uk on August 1, 2005, at 16:21:21
Thanks Ed for that info. It isn't that I am worried. I am past that. :) It is just I want to learn as much about these types of drugs as possible. Any good research or websites that I can learn from that are objective? It seems most info about these drugs are extreme.
Hope you are well.
Hugs,
J
Posted by ed_uk on August 2, 2005, at 13:55:09
In reply to Re: For Ed, posted by JACJ on August 1, 2005, at 17:29:30
Hi J,
You can search on pubmed.........
www.pubmed.com
Kind regards
~Ed
Posted by ed_uk on August 2, 2005, at 15:42:07
In reply to Haloperidol (Haldol), posted by ed_uk on July 29, 2005, at 15:57:15
Schizophrenia.....
Most trials which have compared atypical APs with haloperidol (the 'gold standard' antipsychotic) have been financed by the manufacturers of the atypical APs and have used very high doses of haloperidol (which are clearly not well tolerated). A new study aims to compare numerous atypical APs with each other and with lower, more appropriate doses of haloperidol.
Schizophr Res. 2005 Jul 28; [Epub ahead of print]The European First Episode Schizophrenia Trial (EUFEST): Rationale and design of the trial.
Fleischhacker WW, Keet IP, Kahn RS; EUFEST Steering Committee.
Department of Biological Psychiatry, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
BACKGROUND: Most studies comparing second generation antipsychotics with classical neuroleptics have been conducted in more or less chronic schizophrenia patients. Such studies were usually conducted in highly selected samples, and were generally designed and financed by the manufacturer of the drug tested. These and other facts have stimulated discussions regarding the effectiveness of the new generation of antipsychotics. AIMS: The aim of the European First Episode Schizophrenia Trial (EUFEST) is to compare treatment with amisulpride (Solian), quetiapine (Seroquel), olanzapine (Zyprexa) and ziprasidone (Geodon) to a low dose of haloperidol (Haldol, Serenace) in an unselected sample of first episode schizophrenia patients with minimal prior exposure to antipsychotics. METHODS: 500 patients between the ages of 18-40 meeting DSM-IV criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder are randomly allocated to one year of treatment with one of the drugs under study. The primary outcome measure is retention in treatment, defined as time to discontinuation of study drug. Loss of retention can be the result of insufficient clinical effect, or lack of tolerability or acceptance. Secondary measures include changes in different dimensions of psychopathology, side effects, compliance, social needs, quality of life, substance abuse and cognitive functions. CONCLUSIONS: At present, more than 400 patients have been recruited and randomized in the following countries: Austria, Belgium, Bulgaria, Czech Republic, Germany, France, Israel, Italy, the Netherlands, Poland, Rumania, Spain, Sweden and Switzerland: The study should be finished by the end of 2006 and it is expected that results will yield relevant clinical information with regard to the effectiveness of the second generation antipsychotics. This effort represents the first independently designed trans-European schizophrenia treatment trial.
~Ed
Posted by ed_uk on August 2, 2005, at 15:58:02
In reply to STUDY IN PROGRESS: haloperidol versus atypical APs, posted by ed_uk on August 2, 2005, at 15:42:07
Am J Psychiatry. 2005 May;162(5):947-53.
Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.Schooler N, Rabinowitz J, Davidson M, Emsley R, Harvey PD, Kopala L, McGorry PD, Van Hove I, Eerdekens M, Swyzen W, De Smedt G; Early Psychosis Global Working Group.
Hurwich Professor, Bar Ilan University, Ramat Gan, Israel.
OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.
~ed
Posted by ed_uk on August 2, 2005, at 15:59:40
In reply to Re: Haloperidol (Haldol) » Declan, posted by ed_uk on July 30, 2005, at 17:02:36
I thought you might be interested in this.....
Neuropsychobiology. 2003;47(1):37-46.
Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients.Hertling I, Philipp M, Dvorak A, Glaser T, Mast O, Beneke M, Ramskogler K, Saletu-Zyhlarz G, Walter H, Lesch OM.
Department of Psychiatry, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
OBJECTIVE: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics. METHODS: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). RESULTS: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group. CONCLUSIONS: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.
~Ed
Posted by xbunny on August 2, 2005, at 18:31:27
In reply to A post for xbunny...., posted by ed_uk on August 2, 2005, at 15:59:40
> I thought you might be interested in this.....
thanks that is pretty interesting and its interesting to see flupenthixol represented as a atypical/typical crossover drug.
I was also interested by your discussion of haldol and dopamine receptor site occupation. Does the same hold true for flupenthixol or is it weaker? What does it really mean that say 70% of the receptor sites are occupied by the drug? What would happen if 100% were occupied? is there an optimal value? Oh and whilst I am asking questions, the TD thread got me wondering what are my chances of getting TD given that I take 6-9mg of flupenthixol and 20mg of pericyazine daily? Does the fact that I have been taking the flupenthixol for some years mean I am less likely to develop it? I was also wondering if theres any reason why I shouldnt take my flupenthixol as a single morning dose as I have been doing? does flupenthixol hang around long enough to build up and not require split doses like recommended in the leaflet? certainly I havent noticed any ill effects!Lots of questions tonight lol hope you are well.
Buns
Posted by ed_uk on August 3, 2005, at 15:16:08
In reply to Re: A post for xbunny.... » ed_uk, posted by xbunny on August 2, 2005, at 18:31:27
Hi Buns!
>Does the same hold true for flupenthixol or is it weaker?
Flupenthixol is said to be similar in antipsychotic potency to haloperidol. 6mg flupenthixol is said to be approximately 'equivalent' to 6mg haloperidol. However.......... no dose of flupenthixol is truly equivalent to haloperidol because flupenthixol and haloperidol have different receptor affinities. Haloperidol is a selective D2 antagonist whereas flupenthixol antagonises D1, D2 and (less so) 5-HT2 receptors.
>What does it really mean that say 70% of the receptor sites are occupied by the drug?
At any one time, 70% of D2 (dopamine type 2) receptors in the brain are occupied by a flupenthixol molecule. Flupenthixol binds to the D2 receptors but doesn't active the receptors like dopamine would. Flupenthixol simply 'sits' on the receptors and prevents them from being activated by dopamine ie. if flupenthixol is bound to a receptor, dopamine can't bind.
>What would happen if 100% were occupied?
Marked side effects would be present eg. dystonia, dysphoria, akathisia, parkinsonism, elevated prolactin levels.
>Does the fact that I have been taking the flupenthixol for some years mean I am less likely to develop it?
Since you can tolerate flupenthixol without taking an anticholinergic, the extrapyramidal side effects must be very mild. This is a good sign. The absence of EPS suggests that TD may be less likely to occur. Watch out for involuntary movements of the tongue, jaw and mouth. Fine (involuntary) movements of the tongue can be an early sign of TD.
>I was also wondering if theres any reason why I shouldnt take my flupenthixol as a single morning dose as I have been doing?
No, that's fine. Twice daily dosing is recommended initially but most people on long term maintenace treatment can take it as a single daily dose.
>..does flupenthixol hang around long enough to build up and not require split doses like recommended in the leaflet?
Yes, it has a long half-life - about 35 hours.
Kind regards
~Ed
Posted by ed_uk on August 3, 2005, at 16:36:30
In reply to Flupenthixol (Depixol) » xbunny, posted by ed_uk on August 3, 2005, at 15:16:08
Psychiatr Prax. 2003 May;30 Suppl 2:S94-6.
[Comparative effectiveness of flupenthixol and risperidone on negative symptoms of schizophrenia]
[Article in German]
Philipp M, Lesch OM, Schmauss M, Dose M, Glaser T.
Bezirkskrankenhaus Landshut, Prof.-Buchner-Strasse 22, 84034 Landshut.
The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.
Fortschr Neurol Psychiatr. 2000 Apr;68 Suppl 1:S38-41.
[Flupenthixol--a partial atypical neuroleptic?]
[Article in German]
Kuhn KU, Meyer K, Maier W.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie Rheinische Friedrich-Wilhelms-Universitat Bonn. k.u.kuehn@uni-bonn.de
There is no really clear-cut definition for "atypical" neuroleptics. The most convincing definition is draft by characterization of the receptor-binding profile. Most important are: the combined antagonism of D2 and 5-HT2 receptors, the preferential binding to D4 and D3 receptors and a balanced relation of D2 to D1 antagonism. Flupentixol fits into this description as well as some modern neuroleptics widely considered as "atypical" neuroleptics. Clinical criteria--like the absence of EPMS and the improvement of negative symptoms--offer no clear-cut distinction between "typical" and "atypical" neuroleptics, too, because some modern "atypical" neuroleptics lead--dose-dependent--to EPMS, and there is no proven efficacy for some atypical neuroleptics in the treatment of negative symptoms. So, neuroleptics are labelled "atypical" if there is a favourable relation between antipsychotic activity and the degree of EPMS, and if there is at least some efficacy in the treatment of negative symptoms. In this regard, Flupentixol has to be labelled at least a "partial atypical neuroleptic".
~ed
Posted by ed_uk on August 6, 2005, at 13:53:51
In reply to Haloperidol (Haldol), posted by ed_uk on July 29, 2005, at 15:57:15
Hi Zeugie!
I just found this..........
'I took a typical antipsychotic (Trilafon) many years ago. The problem as you mention was dosage: at one point I was on 48 mg a day and all I wanted to do was sleep. It probably had a 'calming' effect..........'
Wow, 48mg! That's a LOT! Probably far too much! Can you tell us more about how it affected you? How were you affected by lower doses?
Kind regards
~Ed
Posted by ed_uk on August 6, 2005, at 14:12:55
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
Posted by ed_uk on August 6, 2005, at 14:19:54
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
Hi Scott,
You mentioned in a previous post that you'd been on chlorpromazine (Thorazine), perphenazine (Trilafon) and fluphenazine (Prolixin).
Were you prescribed these drugs to treat acute mania? What doses did you take? Were they effective? Side effects?
~ed
Posted by zeugma on August 6, 2005, at 15:58:35
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
> Hi Zeugie!
hi Ed! Been a long time, huh? A crazy stretch of months- but then, there has been no stretch of my life longer than, say, five minutes that is truly otherwise...
>
> I just found this..........
>
> 'I took a typical antipsychotic (Trilafon) many years ago. The problem as you mention was dosage: at one point I was on 48 mg a day and all I wanted to do was sleep. It probably had a 'calming' effect..........'
>
> Wow, 48mg! That's a LOT! Probably far too much! Can you tell us more about how it affected you? How were you affected by lower doses?
>I had severe Parkinsonism, for which I was on a massive dose of benztropine (no 'dumb-drug' euphoria that I remember, alas). If I am normally one stage away from comatose, then Trilafon had me in a coma. It became increasingly difficult to stay awake as the dosage was increased, and the already huge quantities of coffee that I was drinking became proportionally ineffective as the dose the was raised. I believe that my constant requests to have the 'free time' I was allowed (I was in a hospital) to be spent in bed were interpreted by the staff as antisocial behavior, and so the dose went up, 'antisocial' symptoms presumably a sign of schizophrenia.
I did not like Trilafon at any dose. But I think that maybe if the dosage had not escalated so drastically that I might have been less miserable on it. I was lethargic and 'out of it' on trilafon at any dose, but then I am 'out of it' when not on stimulants anyway.
-best,
z
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