Second versus second generation

What are second-generation antipsychotics?

Second-generation ‘atypical’ antipsychotics are a newer class of antipsychotic than first-generation ‘atypical’ antipsychotics. Both are effective for the positive symptoms of schizophrenia, including the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). It is sometimes claimed that they are more effective than first-generation antipsychotics in treating the negative symptoms of schizophrenia. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation.

What is the evidence for second-generation antipsychotics?

Moderate to high quality evidence suggests olanzapine may be superior to aripiprazole, quetiapine, risperidone and ziprasidone for overall symptoms. Risperidone may be superior to quetiapine and ziprasidone for overall symptoms, amisulpride may be superior to risperidone for negative symptoms, and clozapine may be superior to risperidone for less drop-outs due to inefficiency. Moderate quality evidence suggests amisulpride may be superior to ziprasidone for less drop-outs due to inefficiency, and quetiapine may be superior to clozapine for negative symptoms.

Moderate to high quality evidence finds fewer hospitalisations with clozapine than with other second-generation antipsychotics combined. There were also less extrapyramidal side effects or anticholinergic use with clozapine, however clozapine was associated with greater risk of cardiometabolic-related outcomes.

For long-term psychopathology (over 6 months), moderate quality evidence finds aripiprazole was superior to quetiapine and ziprasidone. Clozapine was superior to quetiapine and risperidone. Lurasidone was superior to quetiapine. Olanzapine was superior to paliperidone and risperidone. Paliperidone was superior to aripiprazole and ziprasidone. For long-term side effects, clozapine, olanzapine, and risperidone were the best for reducing all-cause discontinuation, while quetiapine was the worst. Risperidone was the best for intolerability-related discontinuation, and clozapine was the worst. Olanzapine was the worst for weight gain, followed by risperidone. Risperidone and amisulpride were the worst for prolactin increase. Olanzapine was superior to risperidone for parkinsonism. Clozapine and quetiapine were the worst for sedation.

October 2020

Last updated at: 2:06 am, 15th October 2020
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