Background: schizophrenia is a debilitating mental disorder affecting about 1% of the general
population. About 30% of patients will not react to current drug treatment and defined as
treatment-resistant schizophrenia patients (TRSP). The best studied therapeutic option for
this population is clozapine therapy. Clozapine was shown to be effective than any other
antipsychotic drug in TRSP. Moreover, augmentation of clozapine was not demonstrated to be
more effective than clozapine monotherapy. Albeit Clozapine superiority in TRSP, its use may
be involved with many adverse effects, some of them are life-threatening, and need for
routine blood tests. Amisulpride is an atypical antipsychotic drug with a different mechanism
of action than clozapine, with less adverse effects. No study compared directly amisulpride
and clozapine in TRSP.
Study objective: to compare, for the first time, the broad clinical effectiveness of
clozapine and amisulpride and their combination in TRSP.
Study Design: a clinical, prospective, naturalistic, randomized, comparative study simulating
a real-world approach of clinical decision making.
Methods: a total of 140 TRSP will be recruited from a large regional mental health center.
Participants will be randomized into two treatment groups (70 in each group): clozapine
monotherapy and amisulpride monotherapy. Assessment will be done following 10 and 20 weeks of
treatment. In case of treatment failure (insufficient clinical response or severe adverse
effect) participants will be offered either to switch to clozapine treatment (for failed
amisulpride treatment) or to augment clozapine with amisulpride (for failed clozapine
monotherapy patients). Thereafter, participants will be followed-up for a year. Assessment
will be made using clinician rated scales and self-completed questionnaires, rating the broad
phenomenology of schizophrenia (psychosis, mood, anxiety, obsessive-compulsive, cognitive and
quality of life) and drug-related adverse effects (objective and subjective).
Analysis: comparison of the effectiveness of the three treatment groups: amisulpride,
clozapine and their combination, in the various dimensions of TRSP.