Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia

Summary

Schizophrenia is a mental health problem usually starting in the late teens/early twenties, and often lasting many years. The standard medication ('antipsychotics') for this problem is usually helpful, and if taken continually can keep people well, reducing the likelihood of further episodes. However, in up to one in three people with schizophrenia, the illness does not show much improvement with antipsychotic medication. For some of these 'resistant' illnesses, one particular antipsychotic, clozapine, can work well, but one disadvantage is the risk of a severe blood side effect which means that regular blood testing is necessary. If the response to clozapine treatment is disappointing, there is some evidence that adding another antipsychotic can sometimes produce more improvement. However, it seems that the added antipsychotic may need to be taken by the person for at least 10 weeks in order to work well. The investigators plan to test carefully the possible benefits and problems when the antipsychotic amisulpride or a dummy tablet ('placebo') is added to clozapine for 12 weeks in people whose schizophrenia illness has not been helped much by any antipsychotic medication on its own, and who are now taking clozapine, but again with not much improvement. The investigators have chosen amisulpride because its pharmacological action may be complementary to that of clozapine, and also it is less likely than some other antipsychotics to compound some of the characteristic side effects of clozapine, such as sedation, weight gain and other metabolic problems.

Adjunctive amisulpride or placebo will be randomly assigned. The investigators expect that adding amisulpride will be more likely to cause an improvement than adding placebo. But the investigators should learn more about the risks and side effects of combining these two medications. Also, the investigators should gain a greater understanding of the possible benefits of adding another antipsychotic to clozapine in relation to particular problem symptoms, and a person's ability to live and work in the community.

Conditions

• Schizophrenia

Interventions

DRUG

Amisulpride

Clozapine augmentation with another second-generation antipsychotic, amisulpride (400mg amisulpride for the first 4 weeks, then the option of titrating up to 800mg amisulpride for the remaining 8 weeks).

DRUG

placebo

Clozapine augmentation with 1 capsule placebo for the first 4 weeks, then the option of titrating up to 2 capsules placebo for the remaining 8 weeks).

Sponsors & Collaborators

• University of Manchester

  collaborator OTHER

• University College, London

  collaborator OTHER

• Imperial College London

  lead OTHER

Principal Investigators

• Thomas R Barnes, MD · Imperial College London

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-09-30

Primary Completion

2015-03-31

Completion

2015-03-31

Countries

• United Kingdom

Study Locations