Study of effects of modafinil add-on therapy on excessive day time drowsiness and weight gain in patients on atypical antipsychotics

Abstract

Byline: T. Sudhakar, G. Rao, P. Prasuna, K. Vijay Sagar Introduction Since the introduction of conventional anti-psychotics in the treatment of various psychotic disorders in late 1950's the quest for better molecules continued. The reasons for the betterment resulted in the introduction of second generation antipsychotics (SGA's) which are supposed to be more patient friendly with lesser extra pyramidal symptoms lesser chances of inducing tardive dyskinesia and better impact on affective, cognitive and negative symptoms of the schizophrenia. The initial enthusiasm about SGA's within 5 yrs had settled down towards skeptical optimism to control the unwanted and potentially endangering metabolic side effects. Among the newer drugs except for Aripriprazole and to some extent Ziprasidone all other drugs produce significant weight gain and predispose the individual for hyperglycemia and hyperlipedemia. They also produce significant day time drowsiness which interferes with patients daily occupational activities. The land mark study on antipsychotic efficacy, safety and tolerability namely CATIE study had clearly shown that 74% of the patients discontinued the treatment before 18months of trial. Intolerability was one of the major reason for the discontinuation, weight gain & metabolic effects with Olanzapine was established in phase II, part of the study. However, the trend for metabolic syndrome is also noticed with Clozapine, Risperidone, Olanzapine and to some extent with Quetiapine, Ziprasidone. The other major side effect that discourages the patient to continue the treatment is daytime drowsiness. Though with dose titration this side effect can be minimized, most of the patients do not continue, because day time drowsiness interferes with their daytime work performance. So, to improve the compliance with atypical antipsychotics and to give the patients a better quality of life, it becomes imperative that we should find various strategies including pharmacotherapy and diet control. Modafinil is a novel, non amphetamine psycho stimulant though it is not a typical sympathomimetic amine and has only weak affinity for dopamine uptake carrier site. It also acts on anterior hypothalamic nucleus and adjacent area. It is currently being promoted for excessive daytime sleepiness that occurs in Narcolepsy and also sleep apnoea. In 5% of cases it is known to produce anorexia and increase the alertness. In this, study we are making an attempt to explore whether, a non amphetamine drug like modafinil for reducing daytime drowsiness, would be of any utility in preventing daytime drowsiness associated with atypical antipsychotics. As this drug also has got anorexia and weight loss as adverse events, it would be worth while to see, whether add on therapy of modafinil with atypical especially Olanzapine, Risperidone, Clozapine (widely prescribed atypicals in India) would in anyway influence the daytime sleepiness, weight gain, hyperglycemia & hyperlipidemia. Review of Literature Atypical Anti Psychotics Versus Conventional Antipsychotics. Conventional antipsychotic agents which have been the mainstay of treatment in Schizophrenia and other psychotic disorders for over forty years have a number of limitations. This had prompted a search for new agents with greater efficacy and fewer side effects. So the serotonin dopamine antagonists (SDA) (Janssen et al ,1988) came into the practice which is at present the mainstay of treatment in patients with schizophrenia and other psychoses. But atypical antipsychotics are also not without side effects. Atypicality mainly refers to infrequent occurence of extrapyramidal syndromes in clinical setting. During recent years, it was found that akathisia is still common and tardive dyskinesia is also not uncommon with atypical drugs as earlier thought. Hence Second Generation Anti psychotics would be a better name that was suggested for this group of drugs. …