Effect of Olanzapine and Risperidone on clinical and biochemical profile of persons with Schizophrenia.

The study will be conducted in Department of Psychiatry, Government Medical College and Hospital, Sector-32 (GMCH-32), Chandigarh. A total of 74 consecutive patients diagnosed with schizophrenia as per ICD-11 coming to OPD or IPD will be evaluated based upon the inclusion and exclusion criteria mentioned above. After obtaining informed consent of the patients or their nominative representative they will be randomly assigned to Group A (Risperidone) and B (Olanzapine)by using computer generated random number table. Both of these medications are available free of cost at GMCH pharmacy. Dosage of respective drugs will be kept in therapeutic range of 2-16mg and 5-20mg for Risperidone and olanzapine respectively. For risperidone, initial approved recommendation being 2-4mg/day going up to 16mg/day and for olanzapine initial dose of 5-10mg/day, maximum 20mg/day. The attending clinician will reach the maximum tolerable therapeutic dose within 2-4 weeks of initiation of pharmacotherapy. Patient will be started with minimum effective dose of 2mg for risperidone and 5mg for olanzapine. Patient will then be evaluated at 1 week for side effects by administering Glasgow Antipsychotic Side-effect Scale (GASS) and response to treatment. Thereafter, dose can be up-titrated at this time depending on clinical status and symptomatology. On the next follow up at 2weeks on the basis of their response to treatment they will be labelled early responders (≥20% reduction in PANSS Score) and early non-responders. In both early responders and early non-responders the dose will be further up-titrated to maximum tolerable dose by the end of 4 weeks. If during up titration of dose, patient is unable to tolerate, the dose will be reduced to half and gradual escalation will be done. And if at any point of time if patient develops severe side effects or the patient withdraws his consent to continue in the study, the patient will be dropped out from the study and managed accordingly. If any patient gets pregnant during the course of this study, then that patient will be dropped out from the study and managed accordingly. After reaching maximum tolerable dose by 4weeks the patients will be kept at same dose for the next 6weeks. Patients will be followed up at week 1,2,4,6,8 and 10. A reminder call will be given a day prior to follow up to ensure continuation of treatment and patients will be asked to bring empty medicines strips to check compliance to medication. Depending upon the level of improvement at 10 weeks patients will be labelled as responders (≥50% improvement in PANSS) and non-responders (<50% improvement in PANSS). The dosage will be kept in therapeutic range by the treating clinicians. During the study, concomitant medications like anticholinergic drugs for extrapyramidal symptoms and benzodiazepine for sleep disturbance and agitation will be permitted whenever required and doses of such medications will be documented in each group. 

The levels of TNF-alpha, IL-1beta and IL-6 will be assessed at 0week, 2weeks and 10weeks. The Quality of life and sexual well being will be assessed at 0week and 10weeks. This study will widen our understanding of the disease process by the use of both clinical parameters and inflammatory markers(TNF-alpha, IL-6, IL-1beta) concurrently while predicting treatment response by two weeks. This study will also explore quality of life in terms already established determinants while also providing us a new opportunity to study the role of TNF- α and interleukins in determining the quality of life in persons with schizophrenia. Sexual well-being in persons with schizophrenia and the effect of treatment on it will also be explored in this study.