flunarizine and Dyskinesia--Drug-Induced

Schizophrenia 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.. To 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.. We 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.. We 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.. We 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.. Previous 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.. Available 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.

Topics: Antipsychotic Agents; Calcium Channel Blockers; Diltiazem; Dyskinesia, Drug-Induced; Flunarizine; Humans; Randomized Controlled Trials as Topic; Schizophrenia

Tardive dyskinesia (TD), a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB) drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphine was rated. The CCB drugs were administered in acute (in the 28th day) and chronic (for 8 days, after the 25th day) experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD.

Topics: Animals; Apomorphine; Drug Evaluation, Preclinical; Dyskinesia, Drug-Induced; Flunarizine; Haloperidol; Male; Rats; Rats, Wistar; Stereotyped Behavior; Verapamil

Topics: Aged; Dyskinesia, Drug-Induced; Female; Flunarizine; Humans

Over the last few years, cases of movement disorders induced by flunarizine and cinnarizine have been increasingly reported. We describe a series of 101 patients, whose ages ranged from 37 to 84 years (mean 69.1), developing abnormal movements frequently associated with depression, secondary to treatment with either or both drugs. Symptoms closely resembled those induced by neuroleptic drugs and remitted on drug discontinuance in all but five cases after 5-22 months' follow-up. Whether or not such undesirable side effects are attributable to calcium antagonism and/or dopamine receptor blockade, long-term treatment with flunarizine or cinnarizine should be discouraged, particularly in the elderly.

Topics: Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Cinnarizine; Depression; Dyskinesia, Drug-Induced; Dystonia; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Tremor

Topics: Dyskinesia, Drug-Induced; Female; Flunarizine; Headache; Humans; Middle Aged

12 subjects, 8 women and 4 men, presented with extrapyramidal motor signs and psychic depression after treatment with flunarizine for between 3 weeks and 15 months. One woman presented with severe symptoms and 20 months after stopping flunarizine she still had dyskinesia and akathisia. The other patients showed partial or complete improvement after withdrawal of the drug.

Topics: Aged; Akathisia, Drug-Induced; Cinnarizine; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Psychoses, Substance-Induced