Haloperidol efficacy

Metoclopramide, administered at doses higher than those required to inhibit apomorphine-induced emesis, was more effective than haloperidol in antagonizing cisplatin-induced emesis in dogs [80]. This was observed despite the fact that metoclopramide was considerably weaker than haloperidol as a D2-dopamine antagonist [43]. Subsequently, antiemetic efficacy of metoclopramide administered at high doses has been reported in cancer patients... 

Metoclopramide may be considered as a prototype 5-HT3 antagonist because its antiemetic efficacy both in animals and man could not be adequately explained by D2-dopamine blockade. In fact, metoclopramide was considerably weaker as a D2-antagonist than haloperidol or domperidone and yet it was effective against emesis induced by anticancer agents both in animals [43, 80] and cancer patients [135]. 

Some first-generation agents, such as haloperidol, are rather specific for one subtype of dopamine receptor, D2. This suggests that some degree of both efficacy and side effects are associated with dopamine antagonism at this receptor. However, the situation is complex, as usual. There are five classes of dopamine receptors known Di through D5. To complicate matters further, several of these classes have subclasses. In total, there are at least 15 dopamine receptors. Which of these is important for relief of the symptoms of schizophrenia Which is responsible for movement disorders The answers to these questions are incomplete. We do have a few hints. 

Antipsychotics. It was recognized some years ago that high potency typical anti-psychotics, that is, haloperidol (Haldol) and pimozide (Orap), were effective in treating OCD patients who had a comorbid tic disorder. The efficacy of these agents, however, is primarily in redncing the tics rather than the core symptoms of OCD. 

Reports of efficacy in acutely relapsed schizophrenia and schizoaffective disorder, and has an improved tolerability profile compared to haloperidol... 

Shapiro, A.K. and Shapiro, E. (1982). Clinical efficacy of haloperidol, pimozide, penfluridol, and clonidine in the treatment of Tourette syndrome. Adv Neurol 35 383-386. 

Campbell, M., Small, A.M., Green, W.H., Jennings, S.J., Perry, R., Bennett, W.G., and Anderson, L. (1984) Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorder. Arch Gen Psychiatry 41 650-656. 

Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette s disorder. Am J Psychiatry 154 1057-1062. 

Of the atypical antipsychotics, clozapine, olanzapine, and risperidone have been studied the most. Clozapine was used to treat 10 treatment refractory acutely manic patients and 15 schizomanic patients. Using reduction in the YMRS score as the outcome measure, 72% improved (non-rapid cycling, bipolar patients). Comparison of olanzapine (5-20 mg) with placebo showed significant reduction of the YMRS in 49% vs. 24% of subjects by 3 weeks, with significant change evident by the first week. In a trial comparing risperidone at 6 mg with haloperidol at 10 mg and low-dose lithium (800-1200 mg/day) efficacy was similar over the 28 days of the trial. 

Fluphenazine, a typical neuroleptic of the phenothi-azine class, has been less widely used for treatment of tics than haloperidol or pimozide. A controlled trial of haloperidol, fluphenazine, and trifluoperazine found comparable tic-reducing efficacy, but greater sedation and extrapyramidal side effects for haloperidol fluphenazine was the best tolerated (Borison et al., 1982). In an open-label trial with 21 subjects who had an unsatisfactory response to haloperidol, fluphenazine had a superior side effect profile to that of haloperidol in the dose range employed (mean dose of fluphenazine, 7 mg/day, range 2-15 mg/day) (Goetz et al., 1984). In this group selected for an unsatisfactory response to haloperidol, 11 of the 21 subjects (52%) had a better response to fluphenazine than haloperidol, 6 subjects had a comparable response, and 2 subjects preferred haloperidol. 

Sallee, F.R., Nesbitt, L., Jackson, C., Sine, L., and Sethuraman, G. (1997) Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette s disorder. Am Psychiatry 154 1057-1062. 

Efficacy in short-term treatment. From studies in adult schizophrenia, it is evident that clozapine treatment has at least the same or superior antipsychotic effect, compared to typical antipsychotics. In some studies, clozapine was superior with regard to symptom reduction in severe and acute schizophrenic patients. As the guidelines do not allow the use of clozapine as a first-choice drug, most patients have been treated before with at least two atypical or typical antipsychotics. Only one controlled trial has assessed the efficacy of clozapine in child and adolescent psychiatry. In this study (Kumra et ah, 1996), clozapine was found to be superior to haloperidol in all measures of psychosis, and showed a striking superiority for both positive and negative symptoms. 

Atypical neuroleptics have a better side-effect profile, and several studies have confirmed their efficacy. Risperidone has been found effective in the treatment of dementia in patients with agitation (N. Hermann et al. 1998 Jeanblanc and Davis 1995 Jeste et al. 1996 I. R. Katz et al. 1999 Lavretsky and Sultzer 1998), in patients with Lewy body disease (Geizer and Ancill 1998), or in patients with L-dopa-induced hallucinations (Meco et al. 1994). Risperidone has better tolerability than classic neuroleptics such as thioridazine and haloperidol (Frenchman and Prince 1997). No studies of the efficacy of olanzapine in the treatment of agitation in patients with dementia have been done, but its use is widely advocated. 

Caine ED, Polinsky RJ Haloperidol induced dysphoria in patients with Tourette syndrome. Am J Psychiatry 236 1216-1217, 1979 Caine ED, Weingartner H, Ludlow EA, et al Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 74 74-80, 1981 Calabrese JR, Delucchi GA Spectrum of efficacy of valproate in 55 rapid-cycling manic depressives. Am J Psychiatry 147 431-434, 1990 Calabrese JR, Markowitz PJ, Kimmel SE, et al Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. J Clin Psychopharmacol 12 (suppl 53-56, 1992... 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

In a double-blind, multicenter, prospective study, Csernansky et al. (2002) showed that among patients with clinically stable chronic schizophrenia or schizoaffective disorder the risk of relapse was significantly lower with risperidone than with haloperidol (34% vs. 60%, P < 0.001). The means of daily doses of risperidone ( 4.9mg) and haloperidol (11.7mg) were similar to those used in clinical practice (Csernansky et al.y 2002). The reduced risk of relapse found with risperidone could be due to its superior efficacy, better tolerability or both (Csernansky et al.y 2002). 

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