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Expert Opinion on Drug Safety May 2016Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing antipsychotic monotherapy with antipsychotic co-treatment in ≥20 adults with schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks), antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002), constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006), drooling/hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001), prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004).
EXPERT OPINION
No double-blind evidence for altered AE burden associated with antipsychotic co-treatment was found. However, AEs were insufficiently and incompletely reported and follow-up duration was modest. Adjunctive partial D2-agonists might be beneficial for counteracting several AEs. High-quality, long-term studies that comprehensively assess AEs are needed.
Topics: Adult; Antipsychotic Agents; Dopamine D2 Receptor Antagonists; Drug Partial Agonism; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Receptors, Dopamine D2; Schizophrenia
PubMed: 26967126
DOI: 10.1517/14740338.2016.1165668 -
Frontiers in Cellular Neuroscience 2016Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination... (Review)
Review
Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination of axons. Cells of the oligodendrocyte lineage are generated in the germinal zone from migratory bipolar oligodendrocyte precursor cells (OPCs), and acquire cell surface markers as they mature and respond specifically to factors which regulate proliferation, migration, differentiation, and survival. Loss of myelin underlies a wide range of neurological disorders, some of an autoimmune nature-multiple sclerosis probably being the most prominent. Current therapies are based on the use of immunomodulatory agents which are likely to promote myelin repair (remyelination) indirectly by subverting the inflammatory response, aspects of which impair the differentiation of OPCs. Cells of the oligodendrocyte lineage express and are capable of responding to a diverse array of ligand-receptor pairs, including neurotransmitters and nuclear receptors such as γ-aminobutyric acid, glutamate, adenosine triphosphate, serotonin, acetylcholine, nitric oxide, opioids, prostaglandins, prolactin, and cannabinoids. The intent of this review is to provide the reader with a synopsis of our present state of knowledge concerning the pharmacological properties of the oligodendrocyte lineage, with particular attention to these receptor-ligand (i.e., neurotransmitters and nuclear receptor) interactions that can influence oligodendrocyte migration, proliferation, differentiation, and myelination, and an appraisal of their therapeutic potential. For example, many promising mediators work through Ca(2+) signaling, and the balance between Ca(2+) influx and efflux can determine the temporal and spatial properties of oligodendrocytes (OLs). Moreover, Ca(2+) signaling in OPCs can influence not only differentiation and myelination, but also process extension and migration, as well as cell death in mature mouse OLs. There is also evidence that oligodendroglia exhibit Ca(2+) transients in response to electrical activity of axons for activity-dependent myelination. Cholinergic antagonists, as well as endocannabinoid-related lipid-signaling molecules target OLs. An understanding of such pharmacological pathways may thus lay the foundation to allow its leverage for therapeutic benefit in diseases of demyelination.
PubMed: 26903812
DOI: 10.3389/fncel.2016.00027 -
International Journal of Clinical... Sep 2015To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD). (Review)
Review
Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'brexpiprazole' OR 'OPC-34712', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
Brexpiprazole is a new dopamine D2 receptor partial agonist that received approval for the treatment of schizophrenia and for adjunctive use for the treatment of MDD based on a clinical trial development programme that included two pivotal Phase III trials of brexpiprazole monotherapy in acute schizophrenia, and two pivotal Phase III trials of adjunctive brexpiprazole in acute MDD in patients who demonstrated inadequate response to standard antidepressant therapy. In addition, results from a 52-week relapse prevention/maintenance randomised placebo-controlled withdrawal study in patients with schizophrenia are available. In these trials, brexpiprazole was administered once daily and titrated to target doses. The recommended dose for the treatment of schizophrenia is 2-4 mg/day and that for MDD, 2 mg/day. Pooling together all the available data for the recommended target dose of brexpiprazole for acute schizophrenia from the above studies, the percentage of responders is 45.5% vs. 31.0% for placebo, yielding a NNT of 7 (95% CI 5-12). In the relapse prevention/maintenance trial, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in a NNT of 4 (95% CI 3-8). When the results for brexpiprazole 1, 2 and 3 mg from the two Phase III MDD trials are pooled together, 23.2% of the patients receiving brexpiprazole were responders, vs. 14.5% for placebo, yielding a NNT of 12 (95% CI 8-26). Brexpiprazole was well tolerated - for schizophrenia, discontinuation rates because of an adverse event (AE) were overall lower for patients receiving brexpiprazole vs. placebo, and for MDD a total of 3% of brexpiprazole-treated patients and 1% of placebo-treated patients discontinued because of AEs, resulting in a NNH of 53 (95% CI 30-235). Although the most commonly encountered AE noted in product labelling was akathisia (5.5% in the acute schizophrenia trials and 8.6% in the MDD trials), differences from placebo were small, generating a non-significant NNH of 112 for patients with schizophrenia and a modest NNH of 15 (95% CI 11-23) for patients with MDD. Short-term weight gain appears modest; however, more outliers with an increase of ≥ 7% of body weight were evident in open-label 52-week safety studies. Effects on glucose and lipids were small. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QT interval were evident.
CONCLUSIONS
Clinical trials of brexpiprazole support its efficacy at the recommended target dose of 2-4 mg/day for the treatment of schizophrenia, and at the recommended target dose of 2 mg/day as adjunct to antidepressant medication for the treatment of MDD. Head-to-head comparisons with other available agents among patients with schizophrenia and MDD in the 'real world' are needed.
Topics: Antidepressive Agents; Antipsychotic Agents; Chemotherapy, Adjuvant; Clinical Trials as Topic; Depressive Disorder, Major; Dopamine Agonists; Humans; Quinolones; Schizophrenia; Thiophenes
PubMed: 26250067
DOI: 10.1111/ijcp.12714 -
Frontiers in Microbiology 2014Toxoplasma gondii is the causal agent of toxoplasmosis in which one third of the world's population has been infected. In pregnant women, it may cause abortion and... (Review)
Review
BACKGROUND
Toxoplasma gondii is the causal agent of toxoplasmosis in which one third of the world's population has been infected. In pregnant women, it may cause abortion and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, simultaneously progesterone and 17β-estradiol also increase. Thus, it has been suggested that these hormones can aggravate or reduce parasite reproduction. The aim of this study was reviewing the relationship between hormones and infection caused by T. gondii in several experimental animal models and humans, focused mainly on: (a) congenital transmission, (b) parasite reproduction, (c) strain virulence, (d) levels of hormone in host induced by T. gondii infection, and (e) participation of hormone receptors in T. gondii infection. Are the hormones specific modulators of T. gondii infection? A systematic review methodology was used to consult several databases (Pub Med, Lilacs, Medline, Science direct, Scielo, Ebsco, Sprinker, Wiley, and Google Scholar) dated from September, 2013 to March, 2014.
RESULTS
Thirty studies were included; eight studies in humans and 22 in animals and cell cultures. In the human studies, the most studied hormones were testosterone, progesterone, prolactin, and 17β-estradiol. Type I (RH and BK) and Type II (Prugniaud, SC, ME49, T45, P78, and T38) were the most frequent experimental strains.
CONCLUSIONS
Thirty-five years have passed since the first studies regarding T. gondii infection and its relationship with hormones. This systematic review suggests that hormones modulate T. gondii infection in different animal models. However, given that data were not comparable, further studies are required to determine the mechanism of hormone action in the T. gondii infectious process.
PubMed: 25346725
DOI: 10.3389/fmicb.2014.00503 -
Evidence Report/technology Assessment Nov 2010The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the... (Review)
Review
OBJECTIVES
The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers.
DATA SOURCES
We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence.
REVIEW METHODS
Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles.
RESULTS
Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development. Fifteen cell line studies suggested the following mechanisms: Increased hormonal receptor levels. Increased cell proliferation. A direct stimulatory effect. DNA adduct formation. Increase cyclic adenosine monophosphate (camp). Change in potassium channels. Modulation of gene expression. Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions. Among 19 animal studies the mechanisms considered included: Mucosal damage after ethanol consumption. Increased degradation of folate. Stimulation of rectal carcinogenesis. Increased cell proliferation. Increased effect of carcinogens. Ten cell line studies suggested: Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell death. DNA adduct formation. Cell differentiation. Modulation of gene expression. One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms.
CONCLUSIONS
Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.
Topics: Alcohol Drinking; Animals; Breast Neoplasms; Cell Proliferation; Colorectal Neoplasms; Estrogens; Ethanol; Female; Humans; Male; Mammary Neoplasms, Animal; Oxidative Stress; Prolactin; Receptors, Estrogen; Risk
PubMed: 23126574
DOI: No ID Found -
Endocrine Reviews Feb 2010Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid... (Review)
Review
Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.
Topics: Analgesics, Opioid; Animals; Endocrine System; Endocrine System Diseases; Female; Humans; Hypogonadism; Male; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 19903933
DOI: 10.1210/er.2009-0009 -
Recent Results in Cancer Research.... 2009Elevated mammographic density measures are a well-established, relatively strong risk factor for breast cancer development. A systematic review of prospective cohort... (Review)
Review
Elevated mammographic density measures are a well-established, relatively strong risk factor for breast cancer development. A systematic review of prospective cohort studies and cross-sectional studies strikingly establishes parallels between the associations of combined postmenopausal estrogen and progestin replacement therapy with, on the one hand, mammographic densities and, on the other hand, breast cancer risk. Other parallel observations were the inverse associations of both mammographic density and breast cancer risk with the selective estrogen receptor modulator tamoxifen, and direct associations with prolactin. Paradoxically, however, high mammographic density has been found associated with higher risks of both estrogen- and progesterone-receptor positive (ER+/ PR+) and negative (ER-/PR-) breast cancers, while hormone replacement therapy (HRT) use, but also circulating (blood) levels of androgens, estrogens, and prolactin appear to be associated more specifically to the risk of ER+ tumors. The effects of aromatase inhibitors and gonadotropin-releasing hormone agonists on breast density, as well as on breast cancer risk, still require further investigation. Regarding circulating levels of insulin-like growth factor (IGF)-I or IGFBP-3, studies did not show fully consistent relationships with mammographic density measures and breast cancer risk. In view of these various findings, it is impossible, at present, to propose mammographic density measures as an intermediate risk-related phenotype, integrating the effects of exogenous and/or endogenous hormones on the risk of developing breast cancer.
Topics: Breast Neoplasms; Female; Hormones; Humans; Mammography; Risk Factors
PubMed: 19213565
DOI: 10.1007/978-3-540-69297-3_14 -
The Cochrane Database of Systematic... 2000Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making... (Review)
Review
BACKGROUND
Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making important inroads into this approach. Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders and raise serum prolactin. There is some suggestion that the different adverse effect profiles of atypical antipsychotic group make them more acceptable to people with schizophrenia. Ziprasidone is one of the newer atypicals with a high serotonin receptor affinity.
OBJECTIVES
To determine the effects of ziprasidone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies (Pfizer - the manufacturer of ziprasidone - and the manufacturers of all comparator drugs) and first authors of all included trials were contacted.
SELECTION CRITERIA
All randomised controlled trials that compared ziprasidone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment.
DATA COLLECTION AND ANALYSIS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity.
MAIN RESULTS
Data for this compound range from very short (one week) studies of the intramuscular preparation, to trials lasting over six months. For measures of mental state ziprasidone seems more effective than placebo (RR 0.8 CI 0.7-0.9) and as effective as haloperidol (RR 0.8 CI 0.7-1). It is less likely than haloperidol to cause movement disorders (RR 0.4 CI 0.2-0.6), but causes more nausea and vomiting (RR 2.1 CI 1.2-3.8). The injected form of the drug causes more pain at the injection site than haloperidol (RR 5.3 CI 1.3-22).
REVIEWER'S CONCLUSIONS
Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also, however, causes more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use.
Topics: Antipsychotic Agents; Humans; Piperazines; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles
PubMed: 11034737
DOI: 10.1002/14651858.CD001945 -
The Cochrane Database of Systematic... 2000Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making... (Review)
Review
BACKGROUND
Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making important inroads into this approach. Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Ziprasidone is one of the newer atypicals with a high serotonin/dopamine receptor affinity.
OBJECTIVES
To determine the effects of ziprasidone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted.
SELECTION CRITERIA
All randomised controlled trials that compared ziprasidone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment.
DATA COLLECTION AND ANALYSIS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity.
MAIN RESULTS
Data for this compound range from very short (1 week) studies of the intramuscular preparation, to trials lasting over six months. For measures of mental state ziprasidone seems more effective than placebo (RR 0.8 CI 0.7-0.9) and as effective as haloperidol (RR 0.8 CI 0.7-1). It is less likely than haloperidol to cause movement disorders (RR 0.4 CI 0.2-0.6), but may cause more nausea and vomiting (RR 2.1 CI 1.2-3.8). The injected form of the drug may cause more pain at the injection site than haloperidol (RR 5.3 CI 1.3-22).
REVIEWER'S CONCLUSIONS
Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also may, however, cause more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use.
Topics: Antipsychotic Agents; Humans; Piperazines; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles
PubMed: 10796670
DOI: 10.1002/14651858.CD001945 -
The Cochrane Database of Systematic... 2000Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making... (Review)
Review
BACKGROUND
Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making important inroads into this approach. 'Atypical' is a term widely used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Molindone has a similar profile to quetiapine (a novel atypical antipsychotic), with very low binding to all receptors. Some authors have suggested that molindone is safer than other 'typical' antipsychotics in that extrapyramidal adverse effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as an atypical antipsychotic.
OBJECTIVES
To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of molindone and authors of trials were contacted.
SELECTION CRITERIA
All randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment.
DATA COLLECTION AND ANALYSIS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity.
MAIN RESULTS
Thirteen studies were included in the review. Data for this compound range from very short (10 day) studies of the intramuscular preparation to trials lasting over three months. For measures of global state available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics no difference in effectiveness was evidenced (doctors' RR 1.13, CI 0.69 to 1.86; nurses' RR 1.23, CI 0.82 to 1.86). It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99).
REVIEWER'S CONCLUSIONS
The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. At present there is no evidence to suggest that it may have an atypical profile.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Molindone; Schizophrenia
PubMed: 10796464
DOI: 10.1002/14651858.CD002083