All antipsychotics versus placebo

What are antipsychotics?

This topic includes both first and second generation antipsychotics.

Antipsychotics are effective for the symptoms of schizophrenia. Positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, and motivation. Antipsychotics can also cause side effects. These include extrapyramidal symptoms such as dyskinesias (repetitive, involuntary, and purposeless body or facial movements), Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation), and dystonias (muscle contractions causing unusual twisting of parts of the body, most often in the neck). These effects are caused by the dopamine receptor antagonist action of antipsychotics. Other side effects may include weight, hormonal and metabolic changes, increased sedation, and ventricular anomalies (QTc prolongation).

What is the evidence for any antipsychotic efficacy compared to placebo?

Overall, moderate to high quality evidence shows a medium-sized effect of greater improvement in symptoms with antipsychotic medications than with placebo, with this effect staying reasonably constant over time. Effect sizes were largest in studies with smaller placebo response and in non-industry-sponsored trials. There were also small to medium-sized improvements in quality of life and social functioning, and less all-cause discontinuation with antipsychotics, however antipsychotics produced more extrapyramidal symptoms, sedation, weight gain, prolactin increase, and QTc prolongation.

For specific antipsychotics for symptom improvement, high quality evidence shows a large improvement with clozapine; medium-sized improvements with amisulpride, risperidone, paliperidone, zotepine, haloperidol, quetiapine and aripiprazole; and small to medium-sized improvements with sertindole, ziprasidone, chlorpromazine, asenapine, lurasidone, and iloperidone.

For specific antipsychotics’ effects on weight gain, high quality evidence shows no increases with haloperidol, ziprasidone, and lurasidone; small increases with aripiprazole, amisulpride, asenapine, and paliperidone; and medium-sized increases with risperidone, quetiapine, sertindole, chlopromazine, iloperidone, clozapine, zotepine, and olanzapine.

For specific antipsychotics’ effects on prolactin concentration levels, there were no increases with aripiprazole, quetiapine, asenapine, chlorpromazine, or iloperidone; small increases with ziprasidone and lurasidone; medium-sized increases with sertindole and haloperidol; and large increases with risperidone and paliperidone.

For specific antipsychotics’ effects on QTc prolongation, there were no increases with lurasidone, aripiprazole, paliperidone, or asenapine; small increases with haloperidol, quetiapine, olanzapine, risperidone, and iloperidone; medium-sized increases with ziprasidone, and amisulpride; and a large increase with sertindole.

For specific antipsychotics’ effects on extrapyramidal symptoms, moderate quality evidence shows a small decrease with clozapine; no increases with sertindole, olanzapine, quetiapine, aripiprazole, iloperidone, amisulpride, and asenapine; small increases with ziprasidone, paliperidone, and risperidone; and medium-sized increases with lurasidone, chlorpromazine, zotepine, and haloperidol.

For specific antipsychotics’ effects on sedation, there were no increases with amisulpride, paliperidone, sertindole, and iloperidone; medium to large increases with aripiprazole, lurasidone, risperidone, haloperidol, asenapine, olanzapine, quetiapine, and ziprasidone; and large increases with chlorpromazine, zotepine and clozapine.

October 2019

Last updated at: 5:55 am, 2nd October 2019
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Fact Sheet Technical Commentary

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