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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by linkadge on June 4, 2005, at 3:45:35
My mother is taking 100mg of mellaril (thioridazine) How would I find out a similar dose of zyprexa ???
(at least in terms of dopamine blockade)
ThanksLinkadge
Posted by med_empowered on June 4, 2005, at 4:27:23
In reply to mellaril to zyprexa equivilancy, posted by linkadge on June 4, 2005, at 3:45:35
hi! Switching people over from old antipsychotics to the newer agents can be kind of tricky...since the old drugs are more potent D2 blockers (70-90% blockade at average dosages versus 65+% for atypicals) sometimes the best way to go is lowering the dose of the old drug and adding a full-dose atypical. Given that your mom only takes 100mgs, though (the max is 800mgs/day, and severe disorders usually require at least 200mgs) it seems like a switch over should be pretty simple. You could do a taper of the Mellaril (down to 0), a brief washout, and then start introducing the Zyprexa, starting at maybe 2.5 or 5mgs...this would help prevent a number of side effects, since taking 2 antipyschotics at once (even at low-doses) can cause awful side-effects with little or no benefit (though sometimes it is the way to go). On the other hand, if your mother would do better with a cross-taper/titration in which she was *awlays* on at least 1 antipsychotic, and the potential of somewhat increased side-effects is acceptable, you could try cutting the Mellaril *very* gradually--say, 20mgs ever 4 days-1 week, give or take-- while introducing the zyprexa at equally slow, steady intervals. From my (limited) experience with Zyprexa, it seems like cutting a 5mg tablet into 4ths, and introducing 1/4 after each "cut" of the Mellaril might be the way to go. I looked up conversion protocols for switching patients from old APs to new ones; most of them were for severe, hospitalized cases using full-dose anti-psychotics (not your mother's case) and were designed primarily to get the new drug in as fast as possible, while risking side effects (but presumably preventing relapse). Have you considered maybe trying Seroquel? Given its calming, sedating effect, your mom might get the same soothing, calming effects that low-dose Mellaril (theoretically) provides, but without the associated risks. Plus, since they're both low-potency and have very similar dosage ranges, you could do a "cleaner" conversion, more like a 1:1 kind of ratio. My guess would be 150-200+/- mgs of Seroquel would provide similar relief of symptoms, but not necessarily similar D2 blockage--any atypical you substitute will provide less D2 blockage and more serotonin action. I know it must seem from my posts that I work for the Abilify people (I don't), but I do think its good stuff for a lot of people...you could do a short washout and start your mom out on 10mgs, which is effective for full-blown mania and psychosis as well as (presumably) any off-label purposes anti-psychotics are usually used for. The EPS profile isn't as good as Seroquel, but the risk of other serious side effects--diabetes, weight gain, heavy sedation, cognitive impairment,heart "issues," etc.--are considerably better than any other antipsychotic available. Good luck!
Posted by SLS on June 4, 2005, at 8:42:07
In reply to mellaril to zyprexa equivilancy, posted by linkadge on June 4, 2005, at 3:45:35
> My mother is taking 100mg of mellaril (thioridazine) How would I find out a similar dose of zyprexa ???
>
> (at least in terms of dopamine blockade)
>
>
> Thanks
>
> Linkadge
>What condition does your mother take neuroleptics for? It might help to determine how to handle the situation. That's such a low dosage.
Without knowing any details, I would first add Zyprexa and titrate quickly to 10mg. Afterwards, you can gradually remove the thioridizine. Again it is hard to make any suggestions without knowing more about your mother's condition.
- Scott
Posted by ed_uk on June 4, 2005, at 12:41:43
In reply to Re: mellaril to zyprexa equivilancy » linkadge, posted by SLS on June 4, 2005, at 8:42:07
>That's such a low dosage.
But probably an adequate dose! There's been a tendency to prescribe typical APs at grossly excessive doses.
Regards,
ed.
Posted by SLS on June 4, 2005, at 13:32:12
In reply to Re: mellaril to zyprexa equivilancy » SLS, posted by ed_uk on June 4, 2005, at 12:41:43
Hi Ed.
> >That's such a low dosage.
> But probably an adequate dose! There's been a tendency to prescribe typical APs at grossly excessive doses.I'm not so sure about that. I think it depends on what condition you are treating. Most of us here are using these drugs as adjuncts to antidepressants, as anxiolytics, as hypnotics, and as mood-stabilizers. There are fewer of us who use them to treat schizoid disorders and affective psychoses. Trust me, for these latter people, the dosages advocated in the PDR or in general practice is not excessive, but necessary.
Linkadge's mom might, perhaps, be using thioridizine as an anxiolytic and mental filter to help prevent anxious rumination. Lower dosages of neuroleptics are probably sufficient to deal with this.
- Scott
Posted by ed_uk on June 4, 2005, at 15:19:47
In reply to Re: mellaril to zyprexa equivilancy » ed_uk, posted by SLS on June 4, 2005, at 13:32:12
Hi Scott,
>There are fewer of us who use them to treat schizoid disorders and affective psychoses.
That's true but most p-babblers take atypical APs eg. for insomnia etc. In my post, I was specifically referring to typical neuroleptics.
>Trust me, for these latter people, the dosages advocated in the PDR or in general practice is not excessive, but necessary.
I think pdocs have a tendency to increase the dose before they've given the low dose chance to work. In the treatment of schizophrenia, an AP can take several weeks to have a good effect..... docs may increase the dose every few days in some cases.
Haloperidol (Haldol) in particular has often been prescribed at very high doses. 30mg/day was not unusual and doses of up to 200mg have been prescribed. The problem is, once someone is on a very high dose, it might be difficult to reduce it. Haloperidol, like most typical APs, is a potent D2 antagonist. The dose needs to be carefully titrated in order to optimise efficacy and minimise adverse effect. High doses (of typical APs) are useful for some patients (eg those who have low plasma concentrations on low doses) but in general, high doses of typical APs frequently produce severe/disturbing side effects and may not be any more effective than low doses.
*****2-3mg/day haloperidol (Haldol) is claimed to be 'equivalent' to 75-100mg thioridazine (Mellaril).
Here's some interesting stuff................
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.
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Even very low doses of haloperidol produce a high level of D2 occupancy.....
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.
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Am J Psychiatry. 1996 Jul;153(7):948-50.
High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study.
Kapur S, Remington G, Jones C, Wilson A, DaSilva J, Houle S, Zipursky R.
PET Centre, Clarke Institute of Psychiatry, Toronto, Ont., Canada. kapur@clarke-inst.on.ca
OBJECTIVE: The purpose of this study was to determine the dopamine D2 receptor occupancy induced by low-dose haloperidol treatment in a prospective trial. METHOD: 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. In combination with recent empirical trials, these findings should encourage clinicians to initiate treatment of psychotic episodes with low (2-4 mg haloperidol equivalent) doses of typical neuroleptics, particularly for first-episode patients.
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Careful titration of the dose may be very important to minimise side effects by avoiding excessive D2 occupancy......................
Am J Psychiatry. 2000 Apr;157(4):514-20.
Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.Kapur S, Zipursky R, Jones C, Remington G, Houle S.
Department of Psychiatry, University of Toronto, ON, Canada.
OBJECTIVE: Since all antipsychotics block dopamine D(2) receptors, the authors investigated how well D(2) receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. METHOD: In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2. 5 mg/day of haloperidol. After 2 weeks of treatment, D(2) receptor occupancy was determined with [(11)C]raclopride and positron emission tomography, and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. RESULTS: The patients showed a wide range of D(2) occupancy (38%-87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects.
*****The likelihood of clinical response, hyperprolactinemia, and extrapyramidal side effects increased significantly as D(2) occupancy exceeded 65%, 72%, and 78%, respectively.*****
CONCLUSIONS: The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment. The data are consistent with a "target and trigger" hypothesis of antipsychotic action, i.e., that the D(2) receptor specificity of antipsychotics permits them to target discrete neurons and that their antagonist properties trigger within those neurons intracellular changes that ultimately beget antipsychotic response. While limited to haloperidol, the relationship between D(2) occupancy and side effects in this study helps explain many of the observed clinical differences between typical and atypical antipsychotics.
Low doses of haloperidol can be an effective treatment for psychosis in some patients..........................................................
Int J Neuropsychopharmacol. 2004 Jun;7(2):125-31. Epub 2004 Mar 5. Related Articles, Links
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.
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A Cochrane review said.................
'Haloperidol dose for the acute phase of schizophrenia.'
'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).'
'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.'
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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.
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****75-100mg thioridazine is claimed to be 'equivalent' to about 100mg chlorpromazine (Thorazine).
'What is the best maintenance dose of neuroleptics in schizophrenia?'
'..........Most long-term studies involved patients diagnosed as chronic schizophrenics and used phenothiazines; responses, dose requirements, and probably diagnosis were highly heterogeneous. Data from controlled studies permitting estimates of the equivalent dose of chlorpromazine to be plotted vs. reduction of relapse rates revealed no significant dose effect between 100 and over 2,000 (median = 310) mg/kg day, no mean difference in outcome at doses above vs. below 310 mg..........'
Kind regards,
Ed.
Posted by SLS on June 4, 2005, at 17:52:10
In reply to Suitable doses of typical APs..... Haldol » SLS, posted by ed_uk on June 4, 2005, at 15:19:47
Hi Ed.
That's a lot of interesting stuff you gathered. It will take me a while to go through. It would be nice if things worked out the way these studies suggest. They are indeed very optimistic.
In my line of "work", I get to see many people with schizoid disorders several times a week. I have been able to follow the courses of treatment vs. outcome as real stories. These people are not so ill as to need institutionalization, but they are ill enough to require typical, and sometimes supra-typical dosages of neuroleptics to maintain an adequate response. We are talking about using typicals as well as atypicals. Their doctors frequently try lowering dosages when they are first admitted into the program. Ultra-low dosages of these drugs don't seem to work. This is all anecdotal stuff, of course. Most of these people are not medication naive and it is generally not their index episode. Perhaps that has something to do with it. No one wants to see these people be "overmedicated". Unfortunately, to be undermedicated does not bring about an acceptable outcome.
Typical doses used for schizophrenia and schizoaffective disorder:Zyprexa 10-20mg
Seroquel 400-800mg
Risperdal 3-6mg
Geodon (rarely used)
Abilify 20-30mg
Clozaril (rarely used)
Posted by linkadge on June 4, 2005, at 18:57:26
In reply to Re: Suitable doses of typical APs..... Haldol » ed_uk, posted by SLS on June 4, 2005, at 17:52:10
She is taking lithium 900 and was given mellaril a while back as an adjunctive. She has a terrable time sleeping and I suggested swapping zyprexa for mellaril, since it has additional 5-ht antagonistic properties. She's so stubborn. On the one hand she begs people for help with straightening out her meds, but then when people suggest a change, she gets defensive and will not part with her current regime.
Linkadge
Posted by ed_uk on June 5, 2005, at 2:33:39
In reply to Re: Suitable doses of typical APs..... Haldol » ed_uk, posted by SLS on June 4, 2005, at 17:52:10
Hi Scott,
>Ultra-low dosages of these drugs don't seem to work.
.........but perhaps they work for some people...........other people will require much higher doses.
>Most of these people are not medication naive and it is generally not their index episode.
Once someone is on a high dose of a typical neuroleptic, it can be difficult to reduce the dose due to withdrawal symptoms. Of course, this is by no means the only reason why some people need high doses but I do think it is an important factor for some patients. Withdrawal symptoms seem to be a particular problem with low-potency typical APs such as thioridazine.
>Unfortunately, to be undermedicated does not bring about an acceptable outcome.
Of course not! :-) I was just saying that *some* patients might do well on doses of haloperidol that would previously have been considered homeopathic.
>Zyprexa 10-20mg
Seroquel 400-800mg
Risperdal 3-6mg
Geodon (rarely used)
Abilify 20-30mg
Clozaril (rarely used)I 'agree' with all these doses. I don't believe that people are often overmedicated with atypical APs. I do believe that people have often been overmedicated with haloperidol though (particularly in the past). Doses in excess of 30mg/day haloperidol start to look disturbing!
Kind regards.
Ed.
Posted by med_empowered on June 5, 2005, at 5:53:20
In reply to Re: Suitable doses of typical APs..... Atypicals » SLS, posted by ed_uk on June 5, 2005, at 2:33:39
hi! There seems to be a little bit of controversy here regarding appropriate dosages, lol...I think that's great, since its a great way to share information. Anyway, my 2.5-5mgs zyprexa recommendation is based on my assumption that your mother is in need of minor dopamin-blocking action and something calming. Its probably also a good idea to take into account her current weight, eating habits, and whether she has diabetes or is at risk of developing it for any reason (genetics, lifestyle, whatever). Since you wrote that she needs something seddating, my #1 choice would be seroquel. Its usually dosed 2X daily, but I tried it at 3X daily and it worked well with less sedation...150-200mgs could be divvied up into 3rds so the nite time dose was relatively large (100mgs) while each daytime dose was relatively small (50mgs, perhaps). Still, because of the diabetes problems associated with the new antipsychotics, I still think Abilify at could be a good choice. Low-end therapeutic doses (10-15mgs) don't have many side-effects, and Abilify seems pretty harmless in terms of weight changes (very slight increase in weight over course of long-term treatment) and diabetes. For calming purposes, she could try a benzo+sleeping med, or something with less addictive potential, like hydroxyzine at low dases in the day and a higher dose at nite. If your mother doesn't responde well to atypicals and it appears that an older neuroleptic may be the way to go, I'd personally recommend loxapine (Loxitane in the US). It hasn't ever been that popular, especially compared to Haldol, but it seems to have something of an "atypical" profile in terms of side-effects and serotonin/dopamine action. Its also sedating. If your mother has depression issues and does best on old anti-psychotics, low-dose Triavil (perphenazine+Elavil) might be a good call. Traditionally, its used at high-end doses for "moody schizophrenia," schizoaffective disorder, and some more severe cases of psychotic depression. At lower end doses, its used for severe anxiety, agitation, severe depression, etc. Because of the Elavil content, Triavil does have the potential for "activating" mania, and Tricyclics can also induce or exacerbate psychosis; however, the Elavil dose is pretty low and the perphenazine acts as a sort of built-in mood-stabilizer....your mother's lithium would also help prevent unwanted side-effects. The final option I thought of was Asendin, or amoxapine. This is a tricyclic chemically related to loxapine that acts as a mild neuroleptic and antidepressant all in one pill. Like Triavil, its used for agitation, severe anxiety, and psychotic depression; recent research has found it useful for schizophrenia/schizoaffective disorders, and it seems to be a sort of "atypical" antipsychotic with strong antidepressant properties. Anyway, since its a tricyclic the small daytime doses could have a calming effect, while the larger nite time dose could act as something of a sedative. Loxapine and Amoxapine do carry the usual anti-psychotic risks, including neuroleptic malignancy sydrome and EPS+TD, but these risks appear to be less frequent than in other "conventional" antipsychotics. Triavil in low doses would carry about the same TD risk as low-dose Mellaril, but would have a higher EPS risk b/c perphenazine is an intermediate-potency neuroleptic. BTW- No matter what anti-psychotic your mother ends up taking, she might want to take antioxidants. Some research, and anecdotal evidence, suggests that Vitamin E supplements (small dose-200 IU or so) reduce the risk of TD. This makes sense, since a 1994 Harvard Study suggested that TD, as well as the changes in brain structure seen with prolonged administration of conventional neuroleptics, may be due to an "oxidizing" effect from the antipsychotics. Personally, I take a combo Vitamin C/Vitamin E softgel along with a multi-vitamin just in case (There have been scattered reports of possible TD from newer anti-depressants). I also make sure to eat plenty of fruit+vegetable and drink lots of red, black, green or white tea. Good luck!
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