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Current Medicinal Chemistry 2018Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a...
BACKGROUND
Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients.
OBJECTIVE
The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD.
METHOD
We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS).
RESULTS
We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies).
CONCLUSION
Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 29278206
DOI: 10.2174/0929867325666171222163645 -
BMC Psychiatry Jul 2015Tic disorders (TDs) are common neuropsychiatric disorders in children. Typical antipsychotics, such as haloperidol and pimozide have been prescribed to control tic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tic disorders (TDs) are common neuropsychiatric disorders in children. Typical antipsychotics, such as haloperidol and pimozide have been prescribed to control tic symptoms as first-line agents. However, adverse effects have led to the use of newer atypical antipsychotics. Aripiprazole is one of alternatives. The aim of this study was to evaluate the efficacy and safety of aripiprazole for children with TDs.
METHODS
Randomized controlled trials (RCTs), quasi-RCTs and control studies evaluating aripiprazole for children with tic disorders were identified from PubMed, Embase, Cochrane library, Cochrane Central, four Chinese database and relevant reference lists. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS
Twelve studies involving 935 participants were included. The general quality of included studies was poor. Only one study used placebo as a control and others used positive drug controls. Participants were aged between 4 and 18 years. The period of treatment ranged from 8 to 12 weeks. Seven studies (N = 600 patients) used the YGTSS scale as the outcome measurement, and there was no significant difference in reduction of the total YGTSS score between the aripiprazole and positive control groups (MD = -0.48, 95 % CI [-6.22, 5.26], P = 0.87, I(2) = 87 %). Meta-analysis of four of the studies (N = 285 patients) that compared aripiprazole with haloperidol showed that there was no significant difference in reduction of the total YGTSS score (MD = 2.50, 95 % CI [-6.93, 11.92], P = 0.60, I(2) = 88 %). Meta-analysis of two studies (N = 255 patients) that compared aripiprazole with tiapride showed that there was no significant difference in reduction of the total YGTSS score (MD = -3.15, 95 % CI [-11.38, 5.09], P = 0.45, I(2) = 86 %). Adverse events (AEs) were reported in 11 studies. Drowsiness (5.1 %-58.1 %), increased appetite (3.2 %-25.8 %), nausea (2 %-18.8 %) and headache (2 %-16.1 %) were common AEs.
CONCLUSION
In conclusion, aripiprazole appears to be a promising therapy for children with TDs. Further well-conducted RCTs are required to confirm this issue.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Haloperidol; Humans; Randomized Controlled Trials as Topic; Tic Disorders; Treatment Outcome
PubMed: 26220447
DOI: 10.1186/s12888-015-0504-z -
Canadian Journal of Psychiatry. Revue... May 2015It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T... (Review)
Review
OBJECTIVE
It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.
METHOD
A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.
RESULTS
A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.
CONCLUSIONS
Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.
Topics: Antipsychotic Agents; Heart Rate; Humans; Polypharmacy
PubMed: 26174525
DOI: 10.1177/070674371506000503 -
Journal of the American Academy of... Jan 2015To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth.
METHOD
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidences of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds, and QTc change >60 milliseconds were also evaluated.
RESULTS
A total of 55 studies were meta-analyzed, evaluating 108 treatment arms covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n = 177; pimozide: studies = 1; n = 25; quetiapine: studies = 5; n = 336; risperidone: studies = 23; n = 2,234; ziprasidone: studies = 10, n = 523; and placebo: studies = 19, n = 962. Within group, from baseline to endpoint, aripiprazole significantly decreased the QTc interval (-1.44 milliseconds, CI = -2.63 to -0.26, p = .017), whereas risperidone (+1.68, CI = +0.67 to +2.70, p = .001) and especially ziprasidone (+8.74, CI = +5.19 to +12.30, p < .001) significantly increased QTc. Compared to pooled placebo arms, aripiprazole decreased QTc (p = .007), whereas ziprasidone increased QTc (p < .001). Compared to placebo, none of the investigated antipsychotics caused a significant increase in the incidence of the 3 studied QTc prolongation measures, but there was significant reporting bias.
CONCLUSION
Based on these data, the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth. Nevertheless, because individual risk factors interact with medication-related QTc effects, both medication and patient factors need to be considered when choosing antipsychotic treatment.
Topics: Adolescent; Antipsychotic Agents; Child; Clinical Trials as Topic; Electrocardiography; Humans; Long QT Syndrome
PubMed: 25524787
DOI: 10.1016/j.jaac.2014.10.002 -
The Cochrane Database of Systematic... Dec 2013Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. This is an update of a review first published in 2006 and previously updated in 2011.
OBJECTIVES
To systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia.
SEARCH METHODS
On 20 May 2013, for this updated review, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 4), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013) and the Chinese Biomedical Retrieval System (1978 to May 2013). We searched clinical trials registries for ongoing trials.
SELECTION CRITERIA
We included double-blind, randomised controlled trials in which the active drug was used either alone or in combination with other non-antiepileptic drugs for at least two weeks.
DATA COLLECTION AND ANALYSIS
Two authors decided which trials fitted the inclusion criteria and independently graded risk of bias. We assessed the quality of the evidence according to the GRADE criteria for this update.
MAIN RESULTS
In this 2013 update, we updated the searches, but identified only two new ongoing studies. The review includes four trials involving 139 participants. The primary outcome measure in each was pain relief. Three trials compared one of the oral non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. The quality of evidence for all outcomes for which data were available was low. In a trial of tizanidine involving 12 participants (one dropped out due to unrelated disease), one of five participants treated with tizanidine and four of six treated with carbamazepine improved (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.05 to 1.89). Few side effects were noted with tizanidine. For pimozide, there was evidence of greater efficacy than carbamazepine at six weeks. Up to 83% of participants reported adverse effects but these did not lead to withdrawal; the report did not provide comparable data for carbamazepine. Limited data meant that we could not assess the effects of tocainide; however, data from non-randomised studies (not included in this review) indicate that serious haematological adverse events can occur. A trial involving 47 participants compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show any significant benefits, again according to low-quality evidence. The report did not mention adverse events. The proparacaine trial was at low risk of bias; the other trials were at unclear risk of bias overall.
AUTHORS' CONCLUSIONS
There is low-quality evidence that the effect of tizanidine is not significantly different than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more effective than carbamazepine, although the evidence is of low quality and the data did not allow comparison of adverse event rates. There is also low-quality evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over placebo. Limitations in the data for tocainide prevent any conclusions being drawn. There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.
Topics: Amitriptyline; Analgesics; Anticonvulsants; Baclofen; Carbamazepine; Clomipramine; Clonidine; Humans; Pimozide; Propoxycaine; Randomized Controlled Trials as Topic; Tocainide; Trigeminal Neuralgia
PubMed: 24297506
DOI: 10.1002/14651858.CD004029.pub4 -
International Review of Neurobiology 2013Forty years of research and clinical practice have proved dopamine (DA) receptor antagonists to be effective agents in the treatment of Tourette's syndrome (TS),... (Review)
Review
Forty years of research and clinical practice have proved dopamine (DA) receptor antagonists to be effective agents in the treatment of Tourette's syndrome (TS), allowing a significant tic reduction of about 70%. Their main effect seems to be mediated by the blockade of the striatal DA-D2 receptors. Various typical and atypical agents are available and there is still discord between experts about which of them should be considered as first choice. In addition, there are suggestions to use DA receptor agonists such as pergolide or non-DA-modulating agents. The present chapter is focusing on the clinical pharmacology of DA-modulating agents in the treatment of TS. The introduction outlines their clinical relevance and touches on the hypotheses of the role of DA in the pathophysiology of TS. Subsequently, general information about the mechanisms of action and adverse effects are provided. The central part of the chapter forms a systematic review of all DA-modulating agents used in the treatment of TS, including an overview of studies on their effectiveness, and a critical discussion of their specific adverse effects. The present chapter closes with a summary of the body of evidence and a description of the resulting recommendations for the pharmacological treatment of TS.
Topics: Animals; Dopamine; Dopamine Agents; Humans; Tourette Syndrome
PubMed: 24295625
DOI: 10.1016/B978-0-12-411546-0.00010-X -
The Cochrane Database of Systematic... Nov 2013Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained death. Electrocardiogram monitoring is now required before and during use.
OBJECTIVES
To review the effects of pimozide for people with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.A secondary objective was to examine the effects of pimozide for people with delusional disorder.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (28 January 2013).
SELECTION CRITERIA
We sought all relevant randomised clinical trials (RCTs) comparing pimozide with other treatments.
DATA COLLECTION AND ANALYSIS
Working independently, we inspected citations, ordered papers and then re-inspected and assessed the quality of the studies and of extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and mean differences (MDs) for continuous data. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence.
MAIN RESULTS
We included 32 studies in total: Among the five studies that compared pimozide versus placebo, only one study provided data for global state relapse, for which no difference between groups was noted at medium term (1 RCT n = 20, RR 0.22 CI 0.03 to 1.78, very low quality of evidence). None of the five studies provided data for no improvement or first-rank symptoms in mental state. Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (1 RCT, n = 19, RR 5.50 CI 0.30 to 101.28, very low quality of evidence) or at medium term (1 RCT n = 25, RR 1.33 CI 0.14 to 12.82, very low quality of evidence), or for Parkinsonism (tremor) at medium term (1 RCT n = 25, RR 1 CI 0.2 to 4.95, very low quality of evidence). No data were reported for quality of life at medium term.Of the 26 studies comparing pimozide versus any antipsychotic, seven studies provided data for global state relapse at medium term, for which no difference was noted (7 RCTs n = 227, RR 0.82 CI 0.57 to 1.17, moderate quality of evidence). Data from one study demonstrated no difference in mental state (no improvement) at medium term (1 RCT n = 23, RR 1.09 CI 0.08 to 15.41, very low quality evidence); another study demonstrated no difference in the presence of first-rank symptoms at medium term (1 RCT n = 44, RR 0.53 CI 0.25 to 1.11, low quality of evidence). Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (6 RCTs n = 186, RR 1.21 CI 0.71 to 2.05,low quality of evidence) or medium term (5 RCTs n = 219, RR 1.12 CI 0.24 to 5.25,low quality of evidence), or for Parkinsonism (tremor) at medium term (4 RCTs n = 174, RR 1.46 CI 0.68 to 3.11, very low quality of evidence). No data were reported for quality of life at medium term.In the one study that compared pimozide plus any antipsychotic versus the same antipsychotic, significantly fewer relapses were noted in the augmented pimozide group at medium term (1 RCT n = 69, RR 0.28 CI 0.15 to 0.50, low quality evidence). No data were reported for mental state outcomes or for extrapyramidal symptoms (EPS). Data were skewed for quality of life scores, which were not included in the meta-analysis but were presented separately.Two studies compared pimozide plus any antipsychotics versus antipsychotic plus placebo; neither study reported data for outcomes of interest, apart from Parkinsonism at medium term and quality of life using the Specific Level of Functioning scale (SLOF); however, data were skewed.Only one study compared pimozide plus any antipsychotic versus antipsychotics plus antipsychotic; no data were reported for global state and mental state outcomes of interest. Data were provided for Parkinsonism (rigidity and tremor) using the Extrapyramidal Symptom Rating Scale (ESRS); however, these data were skewed.
AUTHORS' CONCLUSIONS
Although shortcomings in the data are evident, enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with efficacy similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. No data support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Delusions; Humans; Pimozide; Psychotic Disorders; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Schizophrenic Psychology
PubMed: 24194433
DOI: 10.1002/14651858.CD001949.pub3 -
The Cochrane Database of Systematic... Mar 2013Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this indication. Their effectiveness is limited and there is concern about adverse effects, including higher mortality with long-term use. When behavioural strategies have failed and drug therapy is instituted, regular attempts to withdraw these drugs are recommended. Physicians, nurses and families of older people with dementia are often reluctant to try to stop antipsychotics, fearing deterioration of NPS. Strategies to reduce antipsychotic use have been proposed, but a systematic review of interventions aimed at withdrawal of antipsychotic agents in older people with dementia has not yet been performed.
OBJECTIVES
To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia in community or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older people with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on behaviour.
SEARCH METHODS
ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources were searched on 23 November 2012. The search included the following terms: antipsychotic* or neuroleptic* or phenothiazines or butyrophenones or risperidone or olanzapine or haloperidol or prothipendyl or methotrimeprazine or clopenthixol or flupenthixol or clothiapine or metylperon or droperidol or pipamperone or benperidol or bromperidol or fluspirilene or pimozide or penfluridol or sulpiride or veralipride or levosulpiride or sultopride or aripiprazole or clozapine or quetiapine or thioridazine combined wither terms such as discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*.ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA
Randomised, placebo-controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia.
DATA COLLECTION AND ANALYSIS
Review authors independently assessed trials for inclusion, rated their risk of bias and extracted data.
MAIN RESULTS
We included nine trials with 606 randomised participants. Seven trials were conducted in nursing homes, one trial in an outpatient setting and one in both settings. In these trials, different types of antipsychotics prescribed at different doses were withdrawn. Both abrupt and gradual withdrawal schedules were used. The risk of bias of the included studies was generally low regarding blinding and outcome reporting and unclear for randomisation procedures and recruitment of participants.There was a wide variety of outcome measures. Our primary efficacy outcomes were success of withdrawal (i.e. remaining in study off antipsychotics) and NPS. Eight of nine trials reported no overall significant difference between groups on the primary outcomes, although in one pilot study of people with psychosis and agitation that had responded to haloperidol, time to relapse was significantly shorter in the discontinuation group (Chi(2) = 4.1, P value = 0.04). The ninth trial included people with psychosis or agitation who had responded well to risperidone therapy for four to eight months and reported that discontinuation led to an increased risk of relapse, that is, increase in the Neuropsychiatric Inventory (NPI)-core score of 30% or greater (P value = 0.004, hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.09 to 3.45 at four months). The only outcome that could be pooled was the full NPI-score, used in two studies. For this outcome there was no significant difference between people withdrawn from and those continuing on antipsychotics at three months (mean difference (MD) -1.49, 95% CI -5.39 to 2.40). These two studies reported subgroup analyses according to baseline NPI-score (14 or less versus > 14). In one study, those with milder symptoms at baseline were significantly less agitated at three months in the discontinuation group (NPI-agitation, Mann-Whitney U test z = 2.4, P value = 0.018). In both studies, there was evidence of significant behavioural deterioration in people with more severe baseline NPS who were withdrawn from antipsychotics (Chi(2) = 6.8; P value = 0.009 for the marked symptom score in one study).Individual studies did not report significant differences between groups on any other outcome except one trial that found a significant difference in a measure of verbal fluency, favouring discontinuation. Most trials lacked power to detect clinically important differences between groups.Adverse events were not systematically assessed. In one trial there was a non-significant increase in mortality in people who continued antipsychotic treatment (5% to 8% greater than placebo, depending on the population analysed, measured at 12 months). This trend became significant three years after randomisation, but due to dropout and uncertainty about the use of antipsychotics in this follow-up period this result should be interpreted with caution.
AUTHORS' CONCLUSIONS
Our findings suggest that many older people with Alzheimer's dementia and NPS can be withdrawn from chronic antipsychotic medication without detrimental effects on their behaviour. It remains uncertain whether withdrawal is beneficial for cognition or psychomotor status, but the results of this review suggest that discontinuation programmes could be incorporated into routine practice. However, two studies of people whose agitation or psychosis had previously responded well to antipsychotic treatment found an increased risk of relapse or shorter time to relapse after discontinuation. Two other studies suggest that people with more severe NPS at baseline could benefit from continuing their antipsychotic medication. In these people, withdrawal might not be recommended.
Topics: Aged; Antipsychotic Agents; Dementia; Humans; Mental Disorders; Psychomotor Agitation; Randomized Controlled Trials as Topic; Recurrence
PubMed: 23543555
DOI: 10.1002/14651858.CD007726.pub2 -
Neuroscience and Biobehavioral Reviews Jul 2013We conducted a meta-analysis of randomized, placebo-controlled trials to determine the efficacy of antipsychotic and alpha-2 agonists in the treatment of chronic tic... (Review)
Review
We conducted a meta-analysis of randomized, placebo-controlled trials to determine the efficacy of antipsychotic and alpha-2 agonists in the treatment of chronic tic disorders and examine moderators of treatment effect. Meta-analysis demonstrated a significant benefit of antipsychotics compared to placebo (standardized mean difference (SMD)=0.58 (95% confidence interval (CI): 0.36-0.80). Stratified subgroup analysis found no significant difference in the efficacy of the 4 antipsychotic agents tested (risperidone, pimozide, haloperidol and ziprasidone). Meta-analysis also demonstrated a benefit of alpha-2 agonists compared to placebo (SMD=0.31 (95% confidence interval CI: 0.15-0.48). Stratified subgroup analysis and meta-regression demonstrated a significant moderating effect of co-occurring ADHD. Trials which enrolled subjects with tics and ADHD demonstrated a medium-to-large effect (SMD=0.68 (95%CI: 0.36-1.01) whereas trials that excluded subjects with ADHD demonstrated a small, non-significant benefit (SMD=0.15 (95%CI: -0.06 to 0.36). Our findings demonstrated significant benefit of both antipsychotics and alpha-2 agonists in treating tics but suggest alpha-2 agonists may have minimal benefit in tic patients without ADHD.
Topics: Adrenergic alpha-Agonists; Age Factors; Animals; Antidiarrheals; Attention Deficit Disorder with Hyperactivity; Clinical Trials as Topic; Humans; Meta-Analysis as Topic; PubMed; Tic Disorders
PubMed: 23099282
DOI: 10.1016/j.neubiorev.2012.09.008 -
The Journal of Clinical Psychiatry Jun 2012To assess the utility of antipsychotics for weight gain and improvement of illness-related psychopathology in patients with anorexia nervosa. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the utility of antipsychotics for weight gain and improvement of illness-related psychopathology in patients with anorexia nervosa.
DATA SOURCES
PubMed, the Cochrane Library databases, and PsycINFO citations from the inception of the databases until March 27, 2012, were searched without language restrictions using the following keywords: randomized, random, randomly, and anorexia nervosa. In addition, we hand-searched for additional studies eligible for inclusion in this meta-analysis and contacted authors for unpublished data.
STUDY SELECTION
Included in this study were randomized placebo- or usual care-controlled trials of antipsychotics in patients with anorexia nervosa.
DATA EXTRACTION
Two independent evaluators extracted data. The primary outcome of interest was body weight, expressed as the standardized mean difference (SMD) between the 2 groups in baseline to endpoint change of body mass index (BMI), endpoint BMI, or daily weight change. SMD, risk ratio (RR), and number needed to harm (NNH) ± 95% confidence interval (CI) were calculated.
RESULTS
Across 8 studies (mean duration = 9.6 weeks; range, 7-12 weeks), 221 patients (mean age = 22.5 years, 219 [99.1%] females) with anorexia nervosa were randomly assigned to olanzapine (n = 54), quetiapine (n = 15), risperidone (n = 18), pimozide (n = 8), sulpiride (n = 9), placebo (n = 99), or usual care (n = 18). Both individually (P = .11 to P = .47) and pooled together (SMD = 0.27, 95% CI, -0.01 to 0.56; P = .06, I2 = 0%; 7 studies, n = 195), weight/BMI effects were not significantly different between antipsychotics and placebo/usual care. Moreover, pooled antipsychotics and placebo/usual care did not differ regarding scores on questionnaires related to anorexia nervosa (P = .32, 5 studies, n = 114), body shape (P = .91, 4 studies, n = 100), depressive symptoms (P = .08, 4 studies, n = 103), and anxiety (P = .53, 4 studies, n = 121). Individually, quetiapine (1 study, n = 33) outperformed usual care regarding eating disorder attitudes (P = .01) and anxiety (P = .02). While rates of dropout due to any reason (P = .83, I2 = 0%) and due to adverse events (P = .54, I2 = 5%) were similar in both groups, drowsiness/sedation occurred significantly more often with antipsychotics than placebo/usual care (RR = 3.69, 95% CI, 1.37-9.95; I2 = 67%, P = .01; NNH = 2, P = .001; 5 studies, n = 129), but most other adverse effects were only sparsely reported.
CONCLUSIONS
Although limited by small samples, this meta-analysis failed to demonstrate antipsychotic efficacy for body weight and related outcomes in females with anorexia nervosa.
Topics: Anorexia Nervosa; Antipsychotic Agents; Body Weight; Controlled Clinical Trials as Topic; Humans
PubMed: 22795216
DOI: 10.4088/JCP.12r07691