Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.
"At 12 weeks, olanzapine but not haloperidol, was associated with a reduced response with regard to their psychotic symptomatology in those abusing alcohol compared with those not abusing alcohol. No data regarding substance use at the 2 year end point was reported (Green et al., 2006). In other small trials, no clinically meaningful differences were found, (Sayers et al., 2005; Smelson et al., 2006) (Ib). "
[Show abstract][Hide abstract] ABSTRACT: The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
Journal of Psychopharmacology 05/2012; 26(7):899-952. DOI:10.1177/0269881112444324 · 3.59 Impact Factor
"Haloperidol, risperidone, olanzapine and quetiapine were the only drugs assessed in more than one trial (Figure 1). In terms of FGAs, seven trials assessed haloperidol (Crespo-Facorro et al., 2006, 2011; Emsley 1999; Gaebel et al., 2007; Green et al., 2006; Kahn et al., 2008; Lieberman et al., 2003b; Möller et al., 2008; Sanger et al., 1999; Schooler et al., 2005), one assessed zuclopenthixol (Glenthoj et al., 2007) and one assessed chlorpromazine (Lieberman et al, 2003a). "
[Show abstract][Hide abstract] ABSTRACT: This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (≤ 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (≥ 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research.
"In two large studies of FEP1,2) the patient's decision to discontinue medication against the preferences of the treating clinician was a common reason for discontinuation, occurring in 22.9% of patients (30/131) on olanzapine in the study by Green et al.1) and 41.5% of all patients (166/400) in the CAFE study.2) "
[Show abstract][Hide abstract] ABSTRACT: "All-causes discontinuation" refers to discontinuation of treatment for any reason, and medication adherence is an important component of this measure. Similar to our previous results, we found that almost 30% of patients with first-episode psychosis (FEP) discontinue medication in the first 9 months of treatment, a finding that has important implications for long-term outcomes. Many newer second-generation antipsychotics have not been studied in FEP. The self-reported Drug Attitude Inventory may help identify patients at heightened risk for medication discontinuation. In addition to vigilant monitoring for and adequate treatment of psychopathology and medication side effects, Relapse Prevention Therapy and the use of long-acting injectable agents may be effective interventions decrease discontinuation rates in FEP. There is currently no consensus on how long a patient should remain on an antipsychotic medication following remission of FEP. Studies are needed to identify predictors of which patients in remission from FEP are less likely to relapse when medication is discontinued. Taken together, our findings presented here underscore the importance of addressing medication discontinuation both as a means of preventing long-term morbidity and enhancing remission and functional recovery in FEP.
Clinical Psychopharmacology and Neuroscience 08/2011; 9(2):45-53. DOI:10.9758/cpn.2011.9.2.45
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