flunarizine and Drug-Related-Side-Effects-and-Adverse-Reactions

Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine, vertigo, and cognitive deficits related to cerebrovascular disorders. Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics. However, its clinical antipsychotic efficacy has never been investigated.. To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in outpatients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder.. Seventy patients from 2 centers were randomly assigned and participated in a double-blind, parallel-group, flexible-dose study comparing flunarizine (10-50 mg/day) and haloperidol (2.5-12.5 mg/day) for 12 weeks. Patients were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Improvement (CGI-I) scale, the Extrapyramidal Symptom Rating Scale (ESRS), a battery for cognitive performance, and laboratory examinations. The study was conducted from September 2004 to May 2007.. Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol. Both groups showed significant symptom improvement during the study, with a reduction of 21% in the flunarizine group and 19% in the haloperidol group in PANSS total scores (p < .05). There were no significant differences in PANSS overall score and all subscales, CGI-I score, or cognitive performance. Dropout rates, ESRS scores, and prolactin levels were not different between groups, but significantly more patients reported emergence of akathisia in the haloperidol group (p = .04), and weight gain was significantly higher with flunarizine (1.2 kg) than with haloperidol (-0.8 kg) (p < .05).. This is the first study evaluating the antipsychotic properties of flunarizine, which showed good efficacy and tolerability for the treatment of schizophrenia, with a possible atypical profile. Its unique pharmacokinetic profile as an oral drug with long half-life (2-7 weeks), low cost, and low induction of extrapyramidal symptoms warrants further investigation, particularly in psychiatric patients with low adherence to treatment.

Topics: Administration, Oral; Adult; Analysis of Variance; Antipsychotic Agents; Dopamine Antagonists; Double-Blind Method; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Flunarizine; Haloperidol; Humans; Male; Metabolic Clearance Rate; Schizophrenia

Topics: Drug-Related Side Effects and Adverse Reactions; Female; Flunarizine; Humans; Male; Migraine with Aura; Pediatrics; Vasodilator Agents

The aim of this study was to report a single-centre experience of flunarizine in childhood migraine with focus on safety and efficacy.. We conducted a retrospective observational audit of 72 individuals (40 male, 32 female; mean age 13y; age range 1y 6mo-17y) at a tertiary paediatric neurology unit between 1998 and 2009. Children were included if they had a diagnosis of migraine and at least one follow-up assessment and a minimum of 3 months' treatment with flunarizine.. Of 102 individuals identified, 30 were excluded for the following reasons: no outcome data (n=13), non-migraineurs (n=9), missing records (n=4), or inadequate treatment duration (n=4). Of the final cohort (72 individuals), 44 had migraine without aura, 15 had migraine with aura or childhood migraine equivalents, eight had sporadic hemiplegic migraine, and five had familial hemiplegic migraine. The median age was 13 years (1y 6mo-17y) and median duration of migraine was 48 months. Starting dose was 5mg. Other doses used were 2.5mg (three individuals), 7.5mg (one individual), and 10mg (six individuals). Treatment duration was 12 months. Successful prophylaxis, defined as at least a 50% reduction in attack frequency, was observed in 57% (41/72). Response rate was higher among those with hemiplegic migraines (85%) than in those who did not have hemiplegic migraines (51%). Side effects were noted in 15 (21%) individuals (depression, n=6; weight gain/increased appetite, n=5; tiredness/sedation, n=2; and worsening headache, n=2), and led to discontinuation of treatment in 13.. In our cohort of children with migraine, flunarizine appears to be more effective in the hemiplegic migraine group. Adverse effects were seen in one-fifth of the individuals, leading to discontinuation in 18%.

Topics: Adolescent; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Flunarizine; Humans; Infant; Longitudinal Studies; Male; Migraine with Aura; Pediatrics; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Vasodilator Agents