Haloperidol studies/trials

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. 

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. 

Tourette s syndrome is a well-studied condition, characterized by motor and phonic tics and by behavioral and psychological problems. While many neurotransmitters were implicated in the etiology of this disorder, it is now believed that the dopaminergic system and noradrenergic systems are involved. Two major clinical trials (Shapiro et ah, 1989 Sallee et al, 1997) indicated that haloperidol and pimozide reduced the severity of tics by 65%. However, these medications are associated with side effects (including possible cognitive impairment, sedation, dysphoria, and tardive dyskinesia) that may limit their effectiveness in children with MR. 

EPS, extrapyramidal side effects HPD, haloperidol MLD, molindone N, total number of subjects in study , number of preschool-age children in study RCT, randomized, double-blind, controlled trial RISP, risperidone SE, side effect TFP, trifluperidol THX, thiothixene. 

Arvanitis LA, Miller BG Multiple fixed doses of Seroquel (quetiapine) in patients with acute exacerbation of schizophrenia a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Biol Psychiatry 42 233-246, 1997... 

Pimozide is FDA-labeled for Tourette s disorder and is particularly interesting in that it is a highly specific DA antagonist that may produce fewer adverse effects than haloperidol. In open studies with adequate doses, this agent has demonstrated efficacy for acute schizophrenia. Several double-blind trials comparing pimozide with other neuroleptics also found it to be an equally effective maintenance therapy ( 34, 35, 36, 37 and 38). We consider this agent to be as effective as the other standard agents, with the same, but perhaps less severe, side effects. 

Janicak et al. (87) studied the relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder. Sixty-two patients (29 depressed type, 33 bipolar type) entered a randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). They found no difference between risperidone and haloperidol in the amelioration of psychotic and manic symptoms nor any significant worsening of mania with either agent. For the total PANSS, risperidone produced a mean decrease of 16 points from baseline, compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively and for the CARS-M mania factor, 3 and 7 points, respectively. 

An international, multicenter, double-blind trial addressed the acute efficacy and safety of a single-dose range of olanzapine (5 to 20 mg/day) compared with a single-dose range of haloperidol (5 to 20 mg/day) (11.6). A total of 1996 patients with a DSM-lll-R diagnosis of schizophrenia (83.1%), schizophreniform disorder (1.9%), or schizoaffective disorder (15%) participated in this study. The primary overall efficacy analysis (i.e., the difference in baseline to endpoint (last observation carried forward [LOCF]) mean change on the BPRS) found olanzapine to be statistically superior to haloperidol (HPDL) (i.e., -10.98 -7.93 p < 0.015). 

Clinically, haloperidol decanoate has been administered to hundreds of chronic schizophrenic patients in several open studies to determine its efficacy, pharmacokinetics, safety, and adverse effects. The trials ranged from 4 months to 2 years, with dosages ranging from 25 to 500 mg given once every 4 weeks. The results of these studies have consistently shown that depot haloperidol ... 

Among the atypical antipsychotics, clozapine has the most convincing evidence of efficacy in children and adolescents with schizophrenia ( 166,167, 170). Kumar and colleagues (171) conducted a double-blind, randomized trial of clozapine versus haloperidol in 21 children and adolescents (mean age = 14 years) whose psychosis had been previously unresponsive to typical antipsychotics. Clozapine at a mean dose of 176 mg per day was superior to haloperidol for both positive and negative symptoms. These results are consistent with an open-label study by Remschmidt and colleagues (172). This group found that clozapine at a mean dose of 154 mg per day produced notable improvement in 27 of 36 (75%) adolescents with schizophrenia previously unresponsive to at least two trials of typical antipsychotics. 

There has been one comprehensive meta-analysis including over 80 studies and over 30 000 patients (814). A meta-analysis of trials of neuroleptic drugs showed the following mean weight gains in kg after 10 weeks of treatment clozapine, 4.5 olanzapine, 4.2 thioridazine, 3.2 sertindole, 2.9 chlorpromazine, 2.6 risperidone, 2.1 haloperidol, 1.1 fluphenazine, 0.43 ziprasidone 0.04 molindone, —0.39 placebo, —0.74... 

Neuroleptics are the drugs of choice in the treatment of tic disorders but they should only be considered in situations where the life of the child is seriously affected and when behavioural treatments have failed. Of the classical neuroleptics which have been used, haloperidol and pimozide have shown success but so far there have been no adequately controlled trials of any neuroleptic to objectively validate their efficacy. It would appear that only low doses of haloperidol are necessary (2-3mg/day) to obtain a significant reduction in tic frequency. It would seem reasonable to consider the use of the atypical antipsychotics for these disorders but, to date, there is no evidence of their efficacy in children. Recently there have been studies in which clonidine was used in the effective treatment of motor tics. The side effects are similar to those seen in the adult and include sedation, headache, irritability and sinus bradycardia. 

Olanzapine has been compared with haloperidol in cannabis-induced psychosis (54), schizoaffective disorder (55), first-episode psychosis (56), and treatment-resistant schizophrenia (57) the two last studies were reanalyses of data from large clinical trials promoted by the manufacturers, Eli Lilly. In all cases olanzapine was better than haloperidol at reducing BPRS scores, but in patients with cannabis-induced psychotic disorders they were similar. Increased appetite was consistently reported more often in olanzapine-treated patients and extrapyramidal signs more often in those treated with haloperidol. 

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