Second-generation antipsychotic drugs are not necessarily better than the first-generation drug haloperidol at treating a first episode of schizophrenia. This is the conclusion of authors of an Article in this week’s issue of The Lancet.
Second-generation drugs, introduced over a decade ago, are purported to be more effective and less likely to induce motor side-effects, such as stiffness and tremors, than first-generation drugs. Whether or not this is true, however, is still debatable. Results from studies comparing the two types of drugs so far have not been reliable because of factors such as over-representation of men, and under-representation of people with other issues such as drug abuse, or because the trials were too short. The question is important for cost issues (many of the newer drugs are more expensive) and for making treatment recommendations to doctors.
René Kahn (University Medical Centre, Utrecht, Netherlands) and colleagues did an open randomised trial in 14 countries (13 European countries and Israel), which included 498 patients aged 18–40 years. The participants were randomly assigned to one low-dose first-generation drug (haloperidol), or one of four higher-dose second-generation drugs (amisulpride, olanzapine, quetiapine, or ziprasidone).
Over the following 12 months, more patients discontinued treatment in the haloperidol group (63 individuals), than in the others: amisulpride (32), olanzapine (30), quetiapine (51), and ziprasidone (31). However, the reductions in all symptoms were about the same for all groups, at around 60%—what the authors describe as “a clinically meaningful response”. When the authors further analysed the data according to sex, tendencies towards suicide, and substance abuse, they found no significant differences between the drugs.
The authors conclude: “although the high continuation rates for several of the second-generation antipsychotic drugs suggest that clinically meaningful long-term antipsychotic treatment is achievable in the first episode of schizophrenia, it cannot be concluded that second-generation antipsychotic drugs are more efficacious than haloperidol in the treatment of these patients.”
In an accompanying Comment, Dr Robert A Rosenheck, VA Connecticut Health Care System, USA says: “Whether use of atypical antipsychotics in either chronic or first-episode schizophrenia should be limited to situations in which they are specifically indicated (eg, in the presence of tardive dyskinesia, akathesia, or pseudoparkinsonism*) is a question that must now be faced head-on. Addressing this question poses a major challenge to both cost-effectiveness assessment and to mental-health policy making.”
http://multimedia.thelancet.com/pdf/press/Schizophrenia.pdf
Professor René S Kahn, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, Germany. r.kahn@umcutrecht.n
Comment Robert A Rosenheck, VA Connecticut Health Care System, West Haven, CT 06516, USA; robert.rosenheck@yale.edu
Note to Editors
*These three conditions are side-effects of antipsychotics: tardive dyskinesia is where a person has involuntary movements as a result of long-term or high-dose antipsychotics that can continue even after the drugs are stopped; akathesia is characterised by excessive, usually repetitive, movements such as pacing, foot tapping and rocking; pseudoparkinsonism is a condition that mimics, but is not, parkinsonism, which is a neurological syndrome characterised by tremor, physical rigidity and postural instability.
Journal
The Lancet