Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.
OBJECTIVE
Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic.


METHODS
Studies of treatment with second-generation antipsychotics lasting > or =1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed.


RESULTS
In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of double-blind, randomized trials (N=4); and open label (N=4). Of the four trials that had a comparator (all involving adults with schizophrenia spectrum disorders), three used haloperidol (N=408) and one used placebo (N=71). Studied populations included children (N=77), adults (N=1,419), adults and elderly persons (N=794), and exclusively patients age 54 years or older (N=479). The weighted mean annual incidence of tardive dyskinesia for second-generation antipsychotics was 0% in the children, 0.8% (range=0.0%-1.5%) in the adults, 6.8% in the mixed adult and elderly population, and 5.3% (range=0.0%-13.4%) in the patients age 54 years and older, compared to 5.4% (range=4.1%-7.4%) in adults treated with haloperidol.


CONCLUSIONS
Results from 11 long-term studies support the idea that second-generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotics, although the doses of haloperidol used in the comparator studies were relatively high. More carefully designed studies, ideally lasting beyond 1 year and comparing the effects of different second-generation antipsychotics in patients who have never taken first-generation antipsychotics, are needed to estimate the true risk. It would not appear premature for clinicians to consider these findings in making long-term treatment decisions.
Department of Psychiatry Research, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Schneider Children's Hospital, Glen Oaks, NY 11004, USA. ccorrell@lij.edu
Christoph U
CU
Correll
Stefan
S
Leucht
John M
JM
Kane
D000293:Adolescent; D000328:Adult; D000368:Aged; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000209:etiology*; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D013469:Sulpiride; D000077582:Amisulpride; D006220:Haloperidol; D000077152:Olanzapine