Calcium channel blockers for antipsychotic-induced tardive dyskinesia (review)

BackgroundSchizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. ObjectivesTo determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic‐induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. Search methodsWe searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteriaWe selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. Data collection and analysisWe independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. Main resultsPrevious versions of this review included no trials. From the 2015 search, we identified three cross‐over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD ‐0.71, 95% CI ‐2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. Authors' conclusionsAvailable evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic‐induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well‐designed randomised trials

Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia

Background: Antipsychotic medication can cause tardive dyskinesia (TD) – late-onset, involuntary, repetitive movements, often involving the face and tongue. TD occurs in > 20% of adults taking antipsychotic medication (first-generation antipsychotics for > 3 months), with this proportion increasing by 5% per year among those who continue to use these drugs. The incidence of TD among those taking newer antipsychotics is not different from the rate in people who have used older-generation drugs in moderate doses. Studies of TD have previously been found to be limited, with no treatment approach shown to be effective. Objectives: To summarise the clinical effectiveness and safety of treatments for TD by updating past Cochrane reviews with new evidence and improved methods; to undertake public consultation to gauge the importance of the topic for people living with TD/the risk of TD; and to make available all data from relevant trials. Data sources: All relevant randomised controlled trials (RCTs) and observational studies. Review methods: Cochrane review methods, network meta-analysis (NMA). Design: Systematic reviews, patient and public involvement consultation and NMA. Setting: Any setting, inpatient or outpatient. Participants: For systematic reviews, adults with TD who have been taking a stable antipsychotic drug dose for > 3 months. Interventions: Any, with emphasis on those relevant to UK NHS practice. Main outcome measures: Any measure of TD, global assessments and adverse effects/events. Results: We included 112 studies (nine Cochrane reviews). Overall, risk of bias showed little sign of improvement over two decades. Taking the outcome of ‘TD symptoms improved to a clinically important extent’, we identified two trials investigating reduction of antipsychotic dose [n = 17, risk ratio (RR) 0.42, 95% confidence interval (CI) 0.17 to 1.04; very low quality]. Switching was investigated twice in trials that could not be combined (switching to risperidone vs. antipsychotic withdrawal: one RCT, n = 42, RR 0.45, 95% CI 0.23 to 0.89; low quality; switching to quetiapine vs. haloperidol: one RCT, n = 45, RR 0.80, 95% CI 0.52 to 1.22; low quality). In addition to RCTs, six observational studies compared antipsychotic discontinuation with decreased or increased dosage, and there was no clear evidence that any of these strategies had a beneficial effect on TD symptoms (very low-quality evidence). We evaluated the addition to standard antipsychotic care of several treatments, but not anticholinergic treatments, for which we identified no trials. We found no clear effect of the addition of either benzodiazepines (two RCTs, n = 32, RR 1.12, 95% CI 0.6 to 2.09; very low quality) or vitamin E (six RCTs, n = 264, RR 0.95, 95% CI 0.89 to 1.01; low quality). Buspirone as an adjunctive treatment did have some effect in one small study (n = 42, RR 0.53, 95% CI 0.33 to 0.84; low quality), as did hypnosis and relaxation (one RCT, n = 15, RR 0.45, 95% CI 0.21 to 0.94; very low quality). We identified no studies focusing on TD in people with dementia. The NMA model found indirect estimates to be imprecise and failed to produce useful summaries on relative effects of interventions or interpretable results for decision-making. Consultation with people with/at risk of TD highlighted that management of TD remains a concern, and found that people are deeply disappointed at the length of time it has taken researchers to address the issue. Limitations: Most studies remain small and poorly reported. Conclusions: Clinicians, policy-makers and people with/at risk of TD are little better informed than they were decades ago. Underpowered trials of limited quality repeatedly fail to provide answers. Future work: TD reviews have data from current trials extracted, tabulated and traceable to source. The NMA highlights one context in which support for this technique is ill advised. All relevant trials, even if not primarily addressing the issue of TD, should report appropriate binary outcomes on groups of people with this problem. Randomised trials of treatments for people with established TD are indicated. These should be large (> 800 participants), necessitating accrual through accurate local/national registers, including an intervention with acceptable treatments and recording outcomes used in clinical practice. Study registration: This study is registered as PROSPERO CRD4201502045. Funding: The National Institute for Health Research Health Technology Assessment programme

Benzodiazepines for Psychosis-Induced Aggression or Agitation

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The platelet polyphosphoinositide system in schizophrenia

Imperial Users onl

Psychosis as an adverse effect of antibiotics

Adverse neuropsychiatric effects of antibiotic medications have been well documented. There is evidence suggesting a direct relationship between acute psychosis and antibiotic exposure. Conversely, the tetracycline antibiotic minocycline has been associated with improvements in psychopathology in patients with psychotic disorders. The purpose of the present study was to investigate the prevalence of spontaneously reported adverse drug reactions (ADRs) of psychotic symptoms in adults for antibiotics and the odds of psychosis compared to minocycline for individual antibiotics and antibiotic classes. We searched the publicly available U.S. F.D.A. Adverse Event Reporting System (FAERS) from inception through March 2020 for which an antibiotic was the suspected agent of an adverse drug reaction (ADR). We investigated 23 different antibiotics, comprising 183,265 adverse event reports and 2955 psychosis ADRs. For individual antibiotics, the prevalence of psychosis ADRs ranged from 0.3 to 3.8%. Fifteen antibiotics were associated with a significantly increased odds of psychosis (OR ​= ​1.67–9.48), including penicillins, fluoroquinolones, macrolides, cephalosporins, and doxycycline. Our results suggest that psychosis is a potential adverse effect of antibiotic treatment, but risks vary by specific agents. Future studies in this area are needed to identify specific underlying biological mechanisms that contribute to these associations. Findings may also inform on clinical decisions regarding the selection of antibiotic therapy in vulnerable patient populations