flunarizine and Basal-Ganglia-Diseases

Flunarizine and cinnarizine have been well documented to cause EPS. Other CCBs, on rare occasions, also have been reported to cause EPS. Theoretical explanations for these events include the inhibition of calcium influx into striatal cells and direct dopaminergic antagonistic properties. In addition, the chemical structures of flunarizine and cinnarizine, which are related to neuroleptics, may explain the relatively greater incidence of EPS with these agents. Suggested risk factors for acquiring EPS with flunarizine or cinnarizine use appear to be age, although experience with using these agents in younger patients is limited, and a family history of tremors and/or Parkinson's disease. The onset and type of presentation is unpredictable and, in most instances, discontinuation of the medication relieves the symptoms within a few days to months. Pharmacologic management of EPS with continued use of the offending agent generally has not been of clinical benefit. In conclusion, patients receiving CCBs, particularly flunarizine and cinnarizine, should be monitored for EPS.

Topics: Basal Ganglia Diseases; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Flunarizine; Humans; Parkinson Disease; Risk Factors

A 68 year-old woman had been taking flunarizine 10 mg daily for 10 weeks when she developed severe bradykinesia and rigidity, resting tremor of both hands, akathisia, buccolinguofacial dyskinesias and depressed mood. Flunarizine was discontinued. After 3 months the patient was asymptomatic. This case and data from the literature suggest that extrapyramidal symptoms and depression may be observed even at the recommended daily dose of 10 mg. Flunarizine should be avoided in patients with Parkinson's disease. Patients on flunarizine should be watched for depressive and extrapyramidal signs, especially those aged over 60.

Topics: Aged; Basal Ganglia Diseases; Female; Flunarizine; Humans

A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort. Propranolol was somewhat better than flunarizine in reducing the severity of migraine attacks, although this may have been due to a selection bias. Discontinuations of therapy due to events considered likely to be treatment-related were mostly due to the recognized side effects of the two drugs. As regards the occurrence of depressions, a total of 58 patients had depressive events, 34 in the flunarizine cohort and 24 in the propranolol cohort. Whereas migraine itself appears to be associated with an increased risk of depression, the number of previous migraine treatments was shown to be an additional risk factor for the development of depression in patients receiving flunarizine as was a history of depression. Overall, there was no appreciable difference in the risk/benefit ratio between flunarizine and propranolol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Belgium; Child; Cohort Studies; Depression; Fatigue; Female; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Netherlands; Propranolol; Prospective Studies; Risk Factors; Safety; Treatment Outcome; Vasodilator Agents; Weight Gain

1. Calcium channel blockers (CCBs) are reported to affect extrapyramidal motor behavior in mammals. Since sex related differences are a common feature in the pharmacological properties of several centrally active drugs, the authors decided to investigate the effects of verapamil (VER), flunarizine (FLU) and nimodipine (NIM), three pharmacologically different CCBs, on neuroleptic-induced catalepsy in male and female albino mice. 2. Catalepsy was induced with haloperidol (0.75 mg/kg, i.p.) and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle, for the controls) were injected i.p. 20 min before haloperidol, with each animal being used only once. 3. VER (1, 5 and 10 mg/kg) did not significantly affect catalepsy in male mice. In females, however, a significant attenuation of catalepsy was found at the two higher doses. 4. FLU (1, 5 and 10 mg/kg) did not significantly affect catalepsy in male mice, whilst a significant attenuation was observed in females with the doses of 1 and 5 mg/kg (but not with the dose of 10 mg/kg). 5. NIM (3, 10 and 30 mg/kg) potentiated neuroleptic-catalepsy in males at the doses of 10 and 30 mg/kg. In females, however, only the higher dose of NIM caused a potentiation of catalepsy. 6. These results demonstrate the existence of sex related differences in the extrapyramidal effects of CCBs in mice. Further, this sex related effect might depend, among other factors, on the particular channel involved.

Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; Calcium Channel Blockers; Catalepsy; Dose-Response Relationship, Drug; Female; Flunarizine; Haloperidol; Male; Mice; Nimodipine; Sex Factors; Verapamil

This international postmarketing observational study of flunarizine was designed to evaluate, in routine clinical practice, the risk/benefit ratio of flunarizine in its approved indications, namely prophylaxis of migraine and treatment of vertigo. Comparator drugs were propranolol in migraine and betahistine in vertigo. The study was carried out by 498 general practitioners in Belgium, The Netherlands and Germany, whose participation had been requested by mail. In total 3186 patients were entered: 1601 in the two migraine cohorts and 1585 in the two vertigo cohorts.. In the migraine study, treatment results with propranolol tended to be somewhat better than those with flunarizine, but a selection bias cannot be excluded. There was no clear difference regarding efficacy between flunarizine and betahistine in the vertigo study. The safety evaluation focused on extrapyramidal symptoms (EPS) and depression. Overall, EPS were noted in only four patients, two in the vertigo-betahistine and two in the migraine-flunarizine cohort. A total of 70 patients developed depressive symptoms (34 in the flunarizine and 24 in the propranolol migraine cohorts, but only 7 in the flunarizine and 5 in the betahistine vertigo cohorts). Patients with migraine were clearly more prone to depression than patients with vertigo, regardless of their treatment. Additional risk factors for depression were a history of depression, and, in the migraine flunarizine cohort, a high number of previous migraine treatments.

Topics: Basal Ganglia Diseases; Betahistine; Cohort Studies; Depression; Female; Flunarizine; Histamine H1 Antagonists; Humans; Male; Migraine Disorders; Product Surveillance, Postmarketing; Propranolol; Prospective Studies; Risk Factors; Vasodilator Agents; Vertigo

Topics: Aged; Basal Ganglia Diseases; Cinnarizine; Depressive Disorder; Female; Flunarizine; Follow-Up Studies; Humans; Male; Middle Aged

Topics: Aged; Basal Ganglia Diseases; Female; Flunarizine; Humans; Movement Disorders

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: Aged; Basal Ganglia Diseases; Flunarizine; Humans

Apathy, mood depression and extrapyramidal signs consisting of akinesia, amimia, gait apraxia, slight rigidity and tremor were induced in 10 patients by long-term treatment with flunarizine for trivial complaints. These symptoms suggest a mild antidopaminergic activity of flunarizine. Long-term administration of flunarizine should be avoided particularly in the elderly and in patients with extrapyramidal disorders.

Topics: Aged; Basal Ganglia Diseases; Depression; Female; Flunarizine; Humans; Male; Middle Aged

Topics: Basal Ganglia Diseases; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders

Topics: Basal Ganglia Diseases; Cinnarizine; Clinical Trials as Topic; Flunarizine; Humans; Patient Education as Topic; Placebos; Random Allocation

Topics: Aged; Anticonvulsants; Basal Ganglia Diseases; Cinnarizine; Flunarizine; Humans; Middle Aged

Topics: Adult; Aged; Akathisia, Drug-Induced; Basal Ganglia Diseases; Cinnarizine; Depression; Female; Flunarizine; Humans; Male; Middle Aged; Vasodilator Agents

Topics: Adult; Aged; Aged, 80 and over; Basal Ganglia Diseases; Cerebrovascular Disorders; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Placebos