A comparison of efficacy, mechanism, and side effects of clozapine and risperidone in patients with schizophrenia

Abstract

Schizophrenia is a chronic psychotic disorder characterized by the presence of psychotic symptoms (hallucinations, delusions), negative symptoms (decreased expressiveness), and cognitive symptoms (lack of executive function). The exact etiology of schizophrenia is unknown, although it is thought to be linked to increased dopaminergic activity in the mesolimbic neuronal pathway and decreased dopaminergic activity in the prefrontal cortical pathway. Treatment of schizophrenia includes both pharmacological and psychosocial intervention. Nonpharmacological treatments are effective in treating the negative and cognitive symptoms of schizophrenia and increasing patient adherence to medications. The first-generation “conventional” antipsychotic drugs are high-affinity antagonists of dopamine D2 receptors that are most effective against psychotic symptoms and atypical agents differ pharmacologically from previous antipsychotic agents in their lower affinity for dopamine D2 receptors Clozapine and risperidone both are atypical antipsychotics. Clozapine has weak D2 blocking action. It mainly acts by blocking 5-HT2, alpha-adrenergic, and D4 receptors. Risperidone acts by blocking 5-HT, alpha-adrenergic and D2 receptors. It is a more potent D2 blocker than clozapine and can cause extrapyramidal symptoms at a high dose. Aggravation of seizures more with olanzapine and fewer chances with risperidone. Clozapine is a high potential atypical antipsychotic to cause metabolic side effects, while risperidone is a low potential antipsychotic to cause metabolic side effects. Clozapine is used in the treatment of resistant schizophrenia and risperidone is the most potent atypical antipsychotic agent available in long-acting injectable form.