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Schizophrenia Research Aug 2015Depot antipsychotics are commonly used to improve adherence and clinical outcomes such as relapse and readmission. Dosing regimens vary but are commonly two- and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depot antipsychotics are commonly used to improve adherence and clinical outcomes such as relapse and readmission. Dosing regimens vary but are commonly two- and four-weekly. To date, the effect of administration at two-weekly or four-weekly intervals on outcome has not been examined in a meta-analysis.
AIMS
A systematic review and meta-analysis on whether the frequency of depot antipsychotic administration (e.g., two- vs four-weekly) makes any difference to compliance and outcome.
METHODS
A systematic search of Medline, EMBASE and PsycInfo for RCTs that compared the frequency of depot administration (e.g., two- vs four-weekly) for an equivalent dose. Outcomes were compliance, psychiatric symptomatology, quality of life, adverse drug reactions (ADRs), patient preference, admission rates, bed-days and costs.
RESULTS
Seven studies from eight papers (n=3994) were found covering olanzapine, paliperidone, risperidone, haloperidol and fluphenazine enanthate/decanoate with follow-up of up to one year. Meta-analyses were possible for psychotic symptoms and ADRs. There were no differences in psychotic symptoms or quality of life between two- and four-weekly doses. Health service use was not reported. For ADRs, the only significant difference detected was that two-weekly injections were less likely to lead to site pain (RR 0.16, 95% CI 0.07-0.38; 2 studies n=1667). There were no differences in other ADRs.
CONCLUSIONS
There were surprisingly little data on the effect of dosing frequency for an equivalent dose on clinical outcomes. There is a need for long-term studies of a wide range of outcomes including cost-effectiveness. Claims for advantages of new preparations over others require careful evaluation.
Topics: Antipsychotic Agents; Drug Administration Schedule; Humans; Patient Compliance; Treatment Outcome
PubMed: 25999043
DOI: 10.1016/j.schres.2015.04.028 -
The Cochrane Database of Systematic... Mar 2018Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat TD.
OBJECTIVES
To determine the effects of cholinergic drugs (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86, tacrine, metoxytacrine, galantamine, ipidacrine, donepezil, rivastigmine, eptastigmine, metrifonate, xanomeline, cevimeline) for treating antipsychotic-induced TD in people with schizophrenia or other chronic mental illness.
SEARCH METHODS
An electronic search of the Cochrane Schizophrenia Group's Study-Based Register of Trials (16 July 2015 and April 2017) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of trials, conference proceedings and dissertations. References of all identified studies were searched for further trial citations.
SELECTION CRITERIA
We included reports identified by the search if they were of controlled trials involving people with antipsychotic-induced TD and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two review authors independently assessed the methodological quality of the trials.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and, where possible, estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We analysed data on an intention-to-treat basis, with the assumption that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported.We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life.
AUTHORS' CONCLUSIONS
TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.
Topics: Antipsychotic Agents; Cholinergic Agents; Dyskinesia, Drug-Induced; Humans; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 29553158
DOI: 10.1002/14651858.CD000207.pub2 -
The Cochrane Database of Systematic... Jun 2018Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades.
OBJECTIVES
To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (23 July 2013, 23 December 2014, 9 November 2016 and 28 December 2017 ) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects.
DATA COLLECTION AND ANALYSIS
For the effects of interventions, a review team inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. Economic studies were searched and reliably selected by an economic review team to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.
MAIN RESULTS
From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). For economic outcomes, we valued outcomes for relapse and presented them in additional tables.
AUTHORS' CONCLUSIONS
The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.
Topics: Administration, Oral; Akathisia, Drug-Induced; Antipsychotic Agents; Fluphenazine; Humans; Placebos; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia
PubMed: 29893410
DOI: 10.1002/14651858.CD006352.pub3 -
Psychopharmacology Oct 2023Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD). (Review)
Review
RATIONALE
Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD).
OBJECTIVES
The review examines the effectiveness of clozapine as a medication for management for severe BPD with high risk of suicide, violence or imprisonment, and aims to help guide clinical practice in managing severe BPD.
METHODS
A database search of the terms "Clozapine" AND "BPD"; "Antipsychotics" AND "BPD"; "Clozapine" AND "Borderline Personality Disorder"; and "Antipsychotics" AND "Borderline Personality Disorder" were performed in CINAHL, Cochrane Library, Embase, Medline, PsychINFO, PubMed, and Web of Science. Full-text articles of clinical clozapine use for BPD were included for review.
RESULTS
A total of 24 articles consisting of 1 randomised control trial, 10 non-controlled trials, and 13 case reports were identified. Most of the studies reported benefits from clozapine when used for severe BPD. Many of the studies focused on clozapine use in BPD patients at high risk of suicide. Results from these non-controlled and case reports support the use of clozapine in patients with severe BPD at high risk of suicide.
CONCLUSION
There may be a role for clozapine in treating severe treatment refractory BPD, especially for those patients at high risk of suicide and frequent hospitalisations.
Topics: Humans; Clozapine; Antipsychotic Agents; Suicide; Borderline Personality Disorder; Randomized Controlled Trials as Topic
PubMed: 37572113
DOI: 10.1007/s00213-023-06431-6 -
Journal of Psychopharmacology (Oxford,... Nov 2018The purpose of this study was to investigate the association of antipsychotic exposure to the incidence and mortality of pneumonia. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
The purpose of this study was to investigate the association of antipsychotic exposure to the incidence and mortality of pneumonia.
METHODS
The design of this study involved meta-analysis of observational studies identified from electronic databases.
RESULTS
In total, 19 studies were included in the systematic review and 14 in the meta-analysis. Risk of pneumonia was increased by first-generation antipsychotics (risk ratio 1.69, 95% confidence interval 1.34-2.15; five studies), second-generation antipsychotics (risk ratio 1.93, 95% confidence interval 1.55-2.41; six studies) and all antipsychotics (risk ratio 1.83, 95% confidence interval 1.60-2.10; seven studies) compared with no antipsychotic use. Pneumonia risk did not differ in seven studies comparing first-generation antipsychotics with second-generation antipsychotics (risk ratio 1.07, 95% confidence interval 0.85-1.35). Case fatality rate was not different in pneumonia cases associated with antipsychotic exposure versus cases without exposure (risk ratio 1.50; 95% confidence interval 0.76-2.96; two studies). All antipsychotics with data from ⩾2 studies allowing meta-analysis, were associated with a significantly increased pneumonia risk (i.e. haloperidol, olanzapine, clozapine, risperidone, quetiapine, zotepine).
CONCLUSION
Exposure to both first-generation antipsychotics and second-generation antipsychotics is associated with an increased pneumonia risk. Clinicians need to be vigilant for the occurrence of pneumonia in patients commencing antipsychotics, especially those with other risk factors for pneumonia including older age, chronic respiratory disease, cerebrovascular disease, dysphagia and smoking.
Topics: Age Factors; Antipsychotic Agents; Cerebrovascular Disorders; Deglutition Disorders; Humans; Incidence; Pneumonia; Respiratory Tract Diseases; Risk; Risk Factors; Smoking
PubMed: 30334664
DOI: 10.1177/0269881118795333 -
The Cochrane Database of Systematic... Nov 2015Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia.
OBJECTIVES
To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies.
SELECTION CRITERIA
Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis.
DATA COLLECTION AND ANALYSIS
We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses.
MAIN RESULTS
We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs.
AUTHORS' CONCLUSIONS
There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine.
Topics: Adult; Antipsychotic Agents; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 26599405
DOI: 10.1002/14651858.CD011458.pub2 -
Schizophrenia Bulletin Jul 2017Antipsychotic switching is routine in clinical practice, although it remains unclear which is the preferable switching method: immediate discontinuation of the current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic switching is routine in clinical practice, although it remains unclear which is the preferable switching method: immediate discontinuation of the current antipsychotic or a gradual tapering approach. The first strategy has been implicated in rebound/withdrawal symptoms and emergence/exacerbation of symptoms, whereas the gradual approach is thought to pose a risk of additive or synergistic side effects if employed in the context of a crossover approach.
METHODS
MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining immediate vs gradual antipsychotic discontinuation in antipsychotic switching in patients with schizophrenia and/or schizoaffective disorder were selected. Data on clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, were extracted.
RESULTS
A total of 9 studies involving 1416 patients that met eligibility criteria were included in the meta-analysis. No significant differences in any clinical outcomes were found between the 2 approaches (all Ps > .05). Sensitivity analyses revealed that the findings remained unchanged in the studies where switching to aripiprazole was performed or where immediate initiation of the next antipsychotic was adopted, while some significant differences were observed in switching to olanzapine or ziprasidone.
CONCLUSIONS
These findings indicate that either immediate or gradual discontinuation of the current antipsychotic medication represents a viable treatment option. Clinicians are advised to choose an antipsychotic switching strategy according to individual patient needs. This said, immediate discontinuation may be advantageous both for simplicity and because a stalled cross-titration process in antipsychotic switching could end up in antipsychotic polypharmacy.
Topics: Antipsychotic Agents; Drug Substitution; Humans; Schizophrenia
PubMed: 28044008
DOI: 10.1093/schbul/sbw171 -
Schizophrenia Research Mar 2018How antipsychotics should be initiated/titrated in patients with acute schizophrenia as well as patients undergoing an antipsychotic switch remains a question. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
How antipsychotics should be initiated/titrated in patients with acute schizophrenia as well as patients undergoing an antipsychotic switch remains a question.
METHODS
MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining rapid vs. slow antipsychotic initiation in patients with schizophrenia were selected. Data on study discontinuation, psychopathology, extrapyramidal symptoms (EPS), and treatment-emergent adverse events (TEAEs) were extracted and synthesized in studies including clinically different populations of acute patients and stable patients undergoing an antipsychotic switch.
RESULTS
Among 11 studies that met eligibility criteria, 8 and 3 studies involving 809 and 777 patients were identified as acute patient studies and stable patient switching studies, respectively. Rapid antipsychotic initiation was not significantly different from slow antipsychotic initiation in acute patient studies for all-cause study discontinuation, while the former was significantly inferior to the latter in stable patient switching studies (N=3, n=777, RR=1.45, 95% CI=1.05-2.00, P=0.02). In contrast, rapid initiation was significantly superior to slow initiation for all psychopathology outcomes including the PANSS/BPRS total score (N=3, n=336, SMD=-0.28, 95% CI=-0.51--0.05, P=0.02) in acute patient studies, but not different in stable patient switching studies. Any other outcomes except for nausea did not significantly differ between the 2 groups.
CONCLUSIONS
Rapid initiation of antipsychotics may represent a reasonable option for the treatment of acute schizophrenia, while slower initiation may be a safer strategy when switching antipsychotics in stable schizophrenia. Because of the low to very low quality of evidence, findings should be considered preliminary.
Topics: Antipsychotic Agents; Databases as Topic; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28844639
DOI: 10.1016/j.schres.2017.08.012 -
Schizophrenia Research Mar 2015Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side... (Review)
Review
Despite extensive study over the past decades, available treatments for schizophrenia are only modestly effective and cause serious metabolic and neurological side effects. Therefore, there is an urgent need for novel therapeutic targets for the treatment of schizophrenia. A highly promising new pharmacological target in the context of schizophrenia is the endocannabinoid system. Modulation of this system by the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol (CBD) may have antipsychotic properties, and thus may be a promising new agent in the treatment of schizophrenia. Here we review studies that investigated the antipsychotic properties of CBD in human subjects. Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use. These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomised clinical trials will be needed before this novel therapy can be introduced into clinical practice.
Topics: Antipsychotic Agents; Brain; Cannabidiol; Humans; Psychotic Disorders
PubMed: 25667194
DOI: 10.1016/j.schres.2015.01.033 -
Journal of Child and Adolescent... Feb 2022Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this... (Meta-Analysis)
Meta-Analysis Review
Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs = 4; OLS = 4; observational studies = 7; case reports = 3). Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.
Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain
PubMed: 35099269
DOI: 10.1089/cap.2021.0092