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Re: Haloperidol (Haldol) med_empowered

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


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poster:ed_uk thread:535356
URL: http://www.dr-bob.org/babble/20050728/msgs/535626.html