All antipsychotics versus placebo

What are 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). Randomised controlled trials compare antipsychotics with placebo to assess their individual effectiveness and side effects.

What is the evidence for antipsychotic efficacy?


High quality evidence shows a large effect of improved symptoms with clozapine compared to placebo. Amisulpride, risperidone, paliperidone, zotepine, haloperidol, quetiapine and aripiprazole all show medium-sized effects for improving symptoms, and sertindole, ziprasidone, chlorpromazine, asenapine, lurasidone, and iloperidone all show small to medium-sized effects.

Side effects

For side effects, high quality evidence shows small effects of weight gain with aripiprazole, amisulpride, asenapine, and paliperidone; medium-sized effects with risperidone, quetiapine, sertindole, chlopromazine, iloperidone, clozapine, zotepine, and olanzapine; and no effect of weight gain with haloperidol, ziprasidone, or lurasidone compared to placebo.

There are small effects of increased prolactin concentrations with ziprasidone and lurasidone; medium-sized effects with sertindole and haloperidol; and large effects with risperidone and paliperidone. No differences were found in prolactin concentrations between placebo and aripiprazole, quetiapine, asenapine, chlorpromazine, or iloperidone.

High quality evidence shows small effects of increased QTc prolongation with haloperidol, quetiapine, olanzapine, risperidone, and iloperidone; medium-sized effects with ziprasidone, amisulpride; and a large effect for sertindole. No differences in QTc prolongation were reported between placebo and lurasidone, aripiprazole, paliperidone, or asenapine.

Moderate quality evidence shows a small effect of less extrapyramidal side-effects with clozapine compared to placebo. Small effects of increased extrapyramidal side-effects are found with ziprasidone, paliperidone, and risperidone; medium-sized effects with lurasidone, chlorpromazine, zotepine, and haloperidol; and no differences are found between placebo and sertindole, olanzapine, quetiapine, aripiprazole, iloperidone, amisulpride or asenapine.

Moderate quality evidence shows medium to large effects of more sedation with aripiprazole, lurasidone, risperidone, haloperidol, asenapine, olanzapine, quetiapine, and ziprasidone than with placebo. Large effects of sedation are found with chlorpromazine, zotepine and clozapine. No effect of sedation is found between placebo and amisulpride, paliperidone, sertindole, and iloperidone.

March 2019

Last updated at: 5:32 am, 22nd March 2019
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