Deaths with risperidone

Several adverse events, including one death (no further information provided), have been described with risperidone in a study in which elderly patients with schizophrenia (mean age 70 years) were randomly assigned to risperidone (n = 32) or olanzapine (n = 34) for 4 weeks (33). 

Stroke is a matter of increasing concern with some antipsychotic drugs, and the Canadian Medicine Agency has issued a warning that there is a risk of stroke with risperidone (116). On April 2005, the FDA issued an alert and asked the company to add the following information to both the oral and depot formulations The FDA has found that older patients treated with atypical neuroleptic drugs for dementia had a higher chance for death than patients who did not take the medicine. This is not an approved use (117). In some countries, the use of... 

A post hoc analysis of 64 studies with risperidone and paliperidone assessed risk of sudden death, cardiovascular and cerebrovascular events [33" ]. The overall risk was significantly increased compared to placebo for adverse events including syncope, tachycardia, palpitations, oedema peripheral, dysarthria and transient ischaemic attack. 

Atypical antipsychotics may be helpful in managing the delusions and agitated behavior that can accompany dementia. These medications, include risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and olanzapine (Zyprexa). All antipsychotics, typical and atypical, appear to increase the risk of death in patients with dementia and psychosis. This appears as a warning in the package inserts of the newer drugs. A prudent approach is to discuss this risk with the caregiver, use the lowest effective dose, and monitor for effectiveness. 

Research indicates that typical and atypical neuroleptic drugs increase the vulnerability of neurons to cell death and even kill brain cells and that the risk increases in patients already suffering from brain disorders such as Alzheimer s (chapter 5). Consistent with this, Sechi et al. (2000) reported on a case of NMS following exposure of a patient with familial dementia with Lewy bodies to low doses of risperidone. 

Note. None of these medications have FDA indication for the treatment of Alzheimer s disease. The literature and practice guidelines support the use of these medications for specific target symptoms. The FDA has issued a black box warning regarding the use of certain antipsychotic medications in the elderly, especially haloperidol, olanzapine, and risperidone. The warning notes that the use of these drugs is associated with an increase in death rates when used by the elderly patients with dementia. 

Of 524 inquiries received by the National Poisons Information Service concerning new neuroleptic drugs over 9 months, only 45 cases involved overdose with a single agent (olanzapine, n — 10 clozapine, n — 8 risperidone, n — 10 sulpiride, n = 16) (503). There were no deaths or cases of convulsions. Cardiac dysrhythmias occurred only with sulpiride. Symptoms were most marked with clozapine most patients had agitation, dystonia, central nervous system depression, and tachycardia. Most of the patients who had taken risperidone were asymptomatic. 

Death Deaths associated with commonly prescribed antipsychotic drugs [SEDA-32, 89 SEDA-33, 90] have been assessed in a 5-year retrospective study using US Veterans National Healthcare data [54 ]. The exposed subjects, who were predominantly male, aged 65 and older and with a diagnosis of dementia, were compared with randomly selected controls. Those who were exposed to haloperidol (n = 2217), olanzapine ( = 3384), quetiapine (n = 4277), or risperidone ( = 8249) had more co-morbidities than the controls. During the first 30 days, there was a significant increase in mortality in those who took doses of haloperidol over 1 mg/day (HR=3.2 95% Cl = 2.2, 4.5), olanzapine over 2.5 mg/day (HR = 1.5 95% CI=1.1, 2.0), or risperidone over 1 mg/day... 

Psychiatric The incidence of suicide-related events in patients with schizophrenia or bipolar disorder taking aripiprazole has been studied using administrative data from three US sources [65 "]. Suicide attempts and death by suicide were assessed in patients aged at least 18 years. Among 20489 antipsychotic drug users (8985 patient-years), unadjusted suicide event rates per 1000 patient-years were 21 for aripiprazole 24 for olanzapine 32 for quetiapine 20 for risperidone and 49 for ziprasidone. Compared with current users of the other antipsychotic... 

Cardiovascular Cardiovascular disease mortahty in patients with chronic schizophrenia treated with cloz ine has been retrospectively assessed [71 ]. Patients with schizophrenia who started to take clozapine ( = 1084) were compared with patients who took risperidone and had never taken clozapine ( = 602). During the follow-up period of 6-10 years 43 deaths were attributed to cardiovascular disease. There was no difference in cardiovascular mortality in patients aged under 55 years at the start of treatment (clozapine 1.1% and 2.7% versus risperidone 1.0% and 2.8% at 5 years and 10 years respectively). Patients who started treatment at an age of at least 55 years had higher cardiovascular mortality... 

Comparative studies The SCoP study was a prospective, randomized, partially blinded, active-controlled, multinational trial, designed to assess the safety of sertindole in the treatment of schizophrenia under normal conditions of use risperidone was the comparator. Results are now emerging. For instance, sertindole did not increase allcause mortality, but cardiac mortality was higher and suicide attempts possibly lower with sertindole [147. The study comprised 9858 selected patients with schizophrenia, and after 14147 person-years the major findings were (i) no statistically significant difference between sertindole ( = 4905) and risperidone (n = 4904) in the two co-primary outcomes, i.e. all-cause mortality (sertindole 64 deaths, risperidone 61 deaths HR=1.12 90% Cl = 0.83, 1.5) and cardiac events... 

A systematic review of case reports of risperidone-induced or -associated QTc prolongation and torsade de pointes identified 15 cases in 1 case of a 37-year-old female QTc prolongation was confirmed by three separate challenges and she was on low-dose risperidone with no additional risk factors other than sex. There were six deaths, three of which were attributed torsade de pointes [248 ]. 

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