Haloperidol versus chlorpromazine for schizophrenia.

BACKGROUND: Chlorpromazine and haloperidol are benchmark antipsychotic drugs. Both are said to be equally effective when used at equivalent doses, but have different side-effect profiles. OBJECTIVES: To compare the effects of haloperidol and chlorpromazine for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (August 2006). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of relevant trials. SELECTION CRITERIA: We included all randomised controlled trials that compared haloperidol with chlorpromazine for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by at least two reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. For dichotomous data we calculated the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis using a random-effects model. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately. AUTHORS' CONCLUSIONS: Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required.

Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor.

Cell-binding and internalization studies on neuronal and non-neuronal cells have demonstrated that the 37-kDa/67-kDa laminin receptor (LRP/LR) acts as the receptor for the cellular prion protein (PrP). Here we identify direct and heparan sulfate proteoglycan (HSPG)-dependent interaction sites mediating the binding of the cellular PrP to its receptor, which we demonstrated in vitro on recombinant proteins. Mapping analyses in the yeast two-hybrid system and cell-binding assays identified PrPLRPbd1 [amino acids (aa) 144-179] as a direct and PrPLRPbd2 (aa 53-93) as an indirect HSPG-dependent laminin receptor precursor (LRP)-binding site on PrP. The yeast two-hybrid system localized the direct PrP-binding domain on LRP between aa 161 and 179. Expression of an LRP mutant lacking the direct PrP-binding domain in wild-type and mutant HSPG-deficient Chinese hamster ovary cells by the Semliki Forest virus system demonstrates a second HSPG-dependent PrP-binding site on LRP. Considering the absence of LRP homodimerization and the direct and indirect LRP-PrP interaction sites, we propose a comprehensive model for the LRP-PrP-HSPG complex.

The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein.

Recently, we identified the 37-kDa laminin receptor precursor (LRP) as an interactor for the prion protein (PrP). Here, we show the presence of the 37-kDa LRP and its mature 67-kDa form termed high-affinity laminin receptor (LR) in plasma membrane fractions of N2a cells, whereas only the 37-kDa LRP was detected in baby hamster kidney (BHK) cells. PrP co-localizes with LRP/LR on the surface of N2a cells and Semliki Forest virus (SFV) RNA transfected BHK cells. Cell-binding assays reveal the LRP/LR-dependent binding of cellular PrP by neuronal and non-neuronal cells. Hyperexpression of LRP on the surface of BHK cells results in the binding of exogenous PrP. Cell binding is similar in PrP(+/+) and PrP(0/0) primary neurons, demonstrating that PrP does not act as a co-receptor of LRP/LR. LRP/LR-dependent internalization of PrP is blocked at 4 degrees C. Secretion of an LRP mutant lacking the transmembrane domain (aa 86-101) from BHK cells abolishes PrP binding and internalization. Our results show that LRP/LR acts as the receptor for cellular PrP on the surface of mammalian cells.

Patient Impairment Lexicon: a validation study.

Growth of managed behavioral health organizations (MBHOs) has increased the need for a standardized diagnostic language. The Patient Impairment Lexicon (PIL; Goodman, Brown, & Deitz, 1992, 1996) is intended to address this need. Augmenting previous psychometric assessment (Klewicki, Bjorck, Leucht, & Goodman, 1998), the current study evaluated the PIL's construct validity. Sixteen raters completed impairment inventories; diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R; American Psychiatric Association, 1987); and independent measures of psychiatric functioning for patients in 20 vignettes. Overall rater accuracy was significantly higher for PIL impairments than for diagnoses. As predicted, there were positive correlations between PIL impairments and psychiatric functioning for all 20 vignettes, 11 of which were significant. Results remained significant after controlling variance due to: (a) raters' past experience with similar patients and (b) vignette imaginability. Findings are discussed in terms of MBHO applications and future PIL research.

Patient Impairment Lexicon: a psychometric analysis.

Growth in managed care has magnified the needs for assessment of treatment efficacies and standardized communication regarding treatment needs. Addressing both needs requires a common terminology describing the scope of treatable mental health impairments. The Diagnostic and Statistical Manual of Mental Disorders-IV provides a common categorical language for describing clinical disorders, but its categories are not discrete and do little to facilitate communication regarding specific treatment needs. Goodman, Brown, and Deitz developed a Patient Impairment Lexicon intended to address these limitations. The current vignette study provided initial psychometric assessment of this nomenclature, specifically examining interrater reliability, temporal stability, and content validity. Findings are discussed with respect to both applications in managed care and psychometric research.

Cognitive-behavioral therapy for clinical pain control: a 15-year update and its relationship to hypnosis.

Since Tan's (1982) review of cognitive and cognitive-behavioral methods for pain control was published 15 years ago, significant advances have been made in cognitive-behavioral therapy for pain. The scientific evidence for its efficacy for clinical pain attenuation is now much more substantial and is briefly reviewed. In particular, cognitive-behavioral therapy for chronic pain was recently listed as one of 25 empirically validated or supported psychological treatments available for various disorders. A number of emerging issues are further discussed in light of recent developments and research findings. The relationship of cognitive-behavioral therapy to hypnosis for pain control is briefly addressed, with suggestions for integrating hypnotic and cognitive-behavioral techniques.