Improvement in negative symptoms in schizophrenia patients taking clozapine after paliperidone augmentation: a case series

Introduction: Partial response or resistance to treatment is seen in 20-30% of schizophrenic patients after treatment with adequate dose and time of typical and atypical antipsychotic drugs. In treatment resistant schizophrenic patients clozapine is still the best treatment choice but 40-70% of treatment resistant patients still don’t respond to treatment after adequate dose of clozapine. In these patients augmentation with a second drug is usually preferred. Herein we present 5 cases of treatment resistant schizophrenia who were using clozapine and paliperidon augmentation produced improvements in positive and/or negative symptoms of schizophrenia. Table 1 shows each patients’ age, gender, education level, age of diagnosis, comorbid diseases, previous treatment (s), indication for augmentation, dosage of paliperidon, follow up duration, side effects after augmentation, and pre- and post-treatment Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS) and Clinical Global Impression Scale (CGI) values. Discussion: There have been many previous studies including various drugs to augment clozapine in treatment resistant schizophrenic patients. Among them studies about risperidone gave both positive and negative results. Paliperidone is an active metabolite of risperidon and studies have shown improvements in personal and social functioning with paliperidone in schizophrenic patients. Although risperidone and paliperidone have many similar pharmacological properties they have some different actions on firing of serotonergic and noradrenergic neurons. This difference may provide superiority to paliperidone against risperidone for negative and affective syptoms of schizophrenia. To the best of our knowledge there isn’t a randomized, placebo controlled study about paliperidone augmentation of clozapine but we have found 2 case series. Esslinger et al found that paliperidone augmentation improved positive syptoms and allowed to decrease clozapine dosage in some of their patients. Chang et al observed improvements in PANSS, Brief Psychiatric Rating Scale (BPRS), CGI and Personal and Social Performance (PSP) scales. We also found improvements in positive but especially in negative symptoms of schizophrenic patients after augmenting clozapine with paliperidon. Paliperidone augmentation of clozapine may improve positive and negative symptoms of schizophrenia and may allow decreasing dose of clozapine thereby improve metabolic side effects of clozapine. To prove these claims placebo controlled, randomised and blinded studies with large sample sizes are needed.