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Second-generation antipsychotics have been thought to cause fewer
extrapyramidal side-effects (EPS) than first-generation antipsychotics,
but recent pragmatic trials have indicated equivalence.
To determine whether second-generation antipsychotics had better outcomes
in terms of EPS than first-generation drugs.
We conducted an intention-to-treat, secondary analysis of data from an
earlier randomised controlled trial (n = 227). A
clinically significant difference was defined as double or half the
symptoms in groups prescribed first- v.
second-generation antipsychotics, represented by odds ratios greater than
2.0 (indicating advantage for first-generation drugs) or less than 0.5
(indicating advantage for the newer drugs). We also examined EPS in terms
of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had
resolved at these time points.
At baseline those randomised to the first-generation antipsychotic group
(n = 118) had similar EPS to the second-generation
group (n = 109). Indications of resolved Parkinsonism
(OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR
= 2.2) in the second-generation drug group at 12 weeks were not
statistically significant and the effects were not present by 52 weeks.
Patients in the second-generation group were dramatically (30-fold) less
likely to be prescribed adjunctive anticholinergic medication, despite
equivalence in terms of EPS.
The expected improvement in EPS profiles for participants randomised to
second-generation drugs was not found; the prognosis over 1 year of those
in the first-generation arm was no worse in these terms. The place of
careful prescription of first-generation drugs in contemporary practice
remains to be defined, potentially improving clinical effectiveness and
avoiding life-shortening metabolic disturbances in some patients
currently treated with the narrow range of second-generation
antipsychotics used in routine practice. This has educational
implications because a generation of psychiatrists now has little or no
experience with first-generation antipsychotic prescription.
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