PROJECT REPORT ON PERCEPTIONS OF DOCTORS ABOUT SOLIAN (AMISULPRIDE) FOR THE TRAETMENT OF SCHIZOPHRENIA

MASTER OF BUSINESS ADMINISTRATION (PHARMACEUTICAL MANAGEMENT)

DEPARTMENT OF MANAGEMENT FMIT JAMIA HAMDARD NEW DELHI-110062

Submitted to:

Submitted by:
ADNAN EJAZ MBA (PM)

CHAPTER

CONTENTS

PAGE NO:

CERTIFICATE ACKNOWLEDMENT STUDENTS DECLARATION EXECUTIVE SUMMARY CHAPTER 1 INTRODUCTION

CHAPTER-2

LITERATURE REVIEW RESEARCH METHODOLOGY v SCOPE v OBJECTIVE v RESEARCH DESIGN v LIMITATIONS

CHAPTER-3

CHAPTER-4

DATA ANALYSIS FINDINGS CONCLUSION

CHAPTER-5

CHAPTER-6

BIBLIOGRAPHY

CERTIFICATE FROM FACULTY

ACKNOWLEDMENT
First and the foremost I thank ALMIGHTY for his divine blessings and grace for the successful completion of the project smoothly.

I express my sincere gratitude to Mr. SHIBU JOHN, Faculty of management and information technology, Jamia Hamdard. New Delhi. I express my sincere and profound thanks to SANOFI, MR. PUNEET CHAHBRA & Mr. DHARMVEER (Head- Area Business Manager, Sanofi India) for allowing me to complete my project in this renowned Pharmaceutical Company. I would like to express my gratitude to Dr. N. RAVICHANDRAN , Head of the Department, Department of Management Jamia Hamdard, New Delhi. Words fail to express my love and indebtedness to my beloved parents for the successful completion of this work. Last but not the least, I express my thanks to the Doctors for their cordial behavior and support.

DECLARATION

I hereby declare that the project work entitled PERCEPTIONS OF DOCTORS ABOUT SOLIAN (AMISULPRIDE) FOR THE TRAETMENT OF SCHIZOPHRENIA is based on the original work done by me for the Summer Project of MBA (PM) Program, requirement from JAMIA HAMDARD, New Delhi. This project work is a bonafide record of the carried out work with Sanofi india, delhi branch under the supervision of Mr. Puneet Chahbra & Mr. Dharmveer and under the guidance of Mr. Rahul Jain, Faculty of management and information technology, Jamia Hamdard. New Delhi. No part of this project has been included in any other project submitted for the award of any degree or diploma.

ADNAN EJAZ MBA(P.M)

EXECUTIVE SUMMARY
.

The present report is on PERCEPTIONS OF DOCTORS ABOUT SOLIAN (AMISULPRIDE) FOR THE TRAETMENT OF SCHIZOPHRENIA. To study the current status future acceptance of solian brand. A fair side is brought up about; which constitute the comparative study of Solian (amisulpride) drugs with the different chemical drugs. The methodology has made the report more precise as it would give a fair idea as to what all means were used to gather information. The research tool which used to prepare this report was in-depth interviews from the various Psychiatrist Doctors. A detailed study of the report can be seen in the one to one discussion with the Psychiatrist Doctors in the research methodology section which would constitute a definite aspect in building up title project work. The findings from this report gives us the fair idea about the future market scenario of the same drugs and various reasons about the same.

CHAPTER-1

1. Introduction
Solian tablets and solution contain the active ingredient amisulpride, which is a type of medicine known as an atypical antipsychotic. ( Amisulpride is also available without a brand name, ie as the generic medicine.) It is used to treat schizophrenia. Amisulpride works in the brain, where it affects a neurotransmitter called dopamine. Neurotransmitters are chemicals that are stored in nerve cells and are involved in transmitting messages between the nerve cells. Dopamine is a neurotransmitter known to be involved in regulating mood and behaviour, amongst other things. Schizophrenia is associated with an overactivity of dopamine in the brain, and this may be associated with the delusions and hallucinations that are a feature of this disease. Amisulpride works by blocking the receptors in the brain that dopamine acts on. This prevents the excessive activity of dopamine and helps to control psychotic illness. People with schizophrenia may experience 'positive symptoms' (such as hallucinations, disturbances of thought, and hostility) and/or 'negative symptoms' (such as lack of emotion and social isolation). Amisulpride has been shown to be effective for relieving both positive and negative symptoms of schizophrenia, whereas the conventional antipsychotics are usually less effective against the negative symptoms.

1.1

About company:
Sanofi-aventis is one of the leading pharmaceutical companies of the world. We are present in over 100 countries and have about 100,000 employees across the world, all united in the purpose of health. Sanofi-aventis has number of powerful assets to address the new context in the global pharmaceutical market: worldwide presence, an extensive portfolio of prescription medicines, market leadership in vaccines, major biological products, generics medicines, consumer healthcare, animal healthcare, and has a strong and long-established presence in both traditional and emerging markets. Vaccines: Sanofi Pasteur, the vaccines division of sanofi-aventis, offers the broadest range of vaccines in the world, providing protection against over 20 infectious diseases. The division provided more than 1.6 billion doses of vaccine in 2009, supporting vaccination of more than 500 million people worldwide. Sanofi Pasteur is currently the world leader in vaccine production and sales. Sanofi-aventis in India operates through four entities - Aventis Pharma Limited, SanofiSynthelabo (India) Limited, Sanofi Pasteur India Private Limited and Shantha Biotechnics. Sanofi-aventis and its 100% subsidiary Hoechst GmbH are the major shareholders of Aventis Pharma Limited and together hold 60.4% of its paid-up share capital. Sanofi-Synthelabo (India) Limited and Sanofi Pasteur are 100% subsidiaries of sanofi-aventis Group. Aventis Pharma Limited is listed on the Bombay Stock Exchange and the National Stock Exchange. Aventis Pharma Limited was incorporated in May 1956 under the name Hoechst Fedco Pharma Private Limited. Over the years, its name was changed to Hoechst Pharmaceuticals Private Limited, Hoechst India Limited and Hoechst Marion Roussel Limited. The shares of Aventis Pharma Limited are quoted on the Bombay Stock Exchange and the National Stock Exchange. Aventis Pharma Limited [India] has around 2,300 employees. It has state-of-the-art manufacturing facilities in Ankleshwar and Goa, where active pharmaceutical ingredients and formulations are manufactured.

Schizophrenia is a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social or occupational dysfunction. The onset of symptoms typically occurs in young adulthood, with a global lifetime prevalence of about 0.3 0.7%. Diagnosis is based on observed behavior and the patient's reported experiences. Genetics, early environment, neurobiology, and psychological and social processes appear to be important contributory factors; some recreational and prescription drugs appear to cause or worsen symptoms. Current research is focused on the role of neurobiology, although no single isolated organic cause has been found. The many possible combinations of symptoms have triggered debate about whether the diagnosis represents a single disorder or a number of discrete syndromes. Schizophrenia does not imply a "split personality", or "multiple personality disorder" (which is known these days as dissociative identity disorder)a condition with which it is often confused in public perception. Rather, the term means a "splitting of mental functions", because of the symptomatic presentation of the illness. The mainstay of treatment is antipsychotic medication, which primarily suppresses dopamine (and sometimes serotonin) receptor activity. Psychotherapy and vocational and social rehabilitation are also important in treatment. In more serious cases where there is risk to self and othersinvoluntary hospitalization may be necessary, although hospital stays are now shorter and less frequent than they once were. The disorder is thought mainly to affect cognition, but it also usually contributes to chronic problems with behaviour and emotion. People with schizophrenia are likely to have additional (comorbid) conditions, including major depression and anxiety disorders; the lifetime occurrence of substance is almost 50%. Social problems, such as long-term unemployment, poverty and homelessness, are common. The average life expectancy of people with the disorder is 12 to 15 years less than those without, the result of increased physical health problems and a higher suicide rate (about 5%).

Symptoms
A person diagnosed with schizophrenia may experience hallucinations (most reported are hearing voices), delusions (often bizarre or persecutory in nature), and disorganized thinking and speech. The latter may range from loss of train of thought, to sentences only loosely connected in meaning, to incoherence known as word salad in severe cases. Social withdrawal, sloppiness of dress and hygiene, and loss of motivation and judgment are all common in schizophrenia. There is often an observable pattern of emotional difficulty, for example lack of responsiveness. Impairment in social cognition is associated with schizophrenia as are symptoms of paranoia; social isolation commonly occurs. Difficulties in working and long-term memory, attention, executive functioning, and speed of processing also commonly occur. In one uncommon subtype, the person may be largely mute, remain motionless in bizarre postures, or exhibit purposeless agitation, all signs of catatonia. Late adolescence and early adulthood are peak periods for the onset of schizophrenia, critical years in a young adult's social and vocational development. In 40% of men and 23% of women diagnosed with schizophrenia, the condition manifested itself before the age of 19. To minimize the developmental disruption associated with schizophrenia, much work has recently been done to identify and treat the prodromal (pre-onset) phase of the illness, which has been detected up to 30 months before the onset of symptoms. Those who go on to develop schizophrenia may experience transient or self-limiting psychotic symptoms and the non-specific symptoms of social withdrawal, irritability, dysphoria, and clumsiness during the prodromal phase.

Medications
Antipsychotic medications are the most effective treatment for schizophrenia. They change the balance of chemicals in the brain and can help control symptoms. These medications are usually helpful, but they can cause side effects. Many side effects can be managed, and they should not prevent you from seeking treatment for this serious condition. Common side effects from antipsychotics may include:

Dizziness Feelings of restlessness or "jitters" Sleepiness (sedation) Slowed movements Tremor Weight gain

Long-term use of antipsychotic medications may increase your risk for a movement disorder called tardive dyskinesia. This condition causes repeated movements that you cannot control, especially around the mouth. Call your health care provider right away if you think you may have this condition. When schizophrenia does not improve with several antipsychotics, the medication clozapine can be helpful. Clozapine is the most effective medication for reducing schizophrenia symptoms, but it also tends to cause more side effects than other antipsychotics. Schizophrenia is a life-long illness. Most people with this condition need to stay on antipsychotic medication for life. The most common salt used for Schizophrenia treatment are Amisulpride Olanzapine Risperidone Quetiapine

Amisulpride
Amisulpride (sold as Solian, Sulpitac, Amitrex, Soltus or Amazeo), is an atypical antipsychotic used to treat psychosis in schizophrenia and episodes of mania in bipolar disorder. In small doses it is also used to treat depression. It was introduced by Sanofi-Aventis in the 1990s.Amisulpride is not approved for use in the United States. Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms

Pharmacology
Amisulpride functions primarily as a D2 and D3 receptor antagonist. It has high affinity for these receptors with dissociation constants of 2.8 nM and 3.2 nM, respectively. Although standard doses in the 400 to 1200 mg a day range used to treat psychosis inhibit dopaminergic neurotransmission, low doses in the 50 to 200 mg range preferentially block inhibitory pre-synaptic autoreceptors. This results in a facilitation of dopamine activity, and for this reason, low dose amisulpride has also been used to treat clinical depression. Amisulpride and its relative sulpiride have been shown to bind to and activate the GHB receptor at doses that are used for therapeutic purposes. Activation of the GHB receptor is known to inhibit the release of dopamine and even appears to have neuroleptic effects itself. For this reason it is believed that amisulpride and sulpiride's action at this receptor may contribute to their efficacy in treating psychosis. Another recent study concludes that amisulpride is an appropriate first-line treatment for the management of acute psychosis.

Quetiapine
Quetiapine (branded as Seroquin, Quel, Pincalm, Qutpin-SR), is an atypical antipsychotic approved for the treatment of schizophrenia, bipolar disorder, and as an add-on to treat depression. Annual sales are approximately $5.7 billion worldwide, with $2.9 billion in the United States. The U.S. patent, which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012. Quetiapine fumarate is used to treat either schizophrenia or bipolar disorder. Some users have even reported a pleasant side effect that entails a numbing of or contraction of the tongue, especially in human males.
MEDICAL USES

Schizophrenia It is debatable whether, as a class, typical or atypical antipsychotics are better. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. Bipolar disorder In those with bipolar disorder, it is used for depressive episodes, acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium, valproate or lamotrigine), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex) Alzheimer's Quetiapine is ineffective in reducing agitation among people with Alzheimer's, whose usage of the drug once constituted 29% of sales. Quetiapine worsens cognitive functioning in the elderly with dementia and therefore is not recommended. Other It is sometimes used off-label, often as an augmentation agent, to treat conditions such as obsessive-compulsive disorder, post-traumatic stress disorder, autism, alcoholism, borderline personality disorder, depression, Tourette syndrome, and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Risperidone
Risperidone (Risperdal, and generics) is a dopamine antagonist of the secondgeneration or atypical antipsychotic class, possessing antiserotonergic, antiadrenergic and antihistaminergic, which is mainly used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism. It is associated with significant weight gain and metabolic problems, as well as tardive dyskinesia and neuroleptic malignant syndrome. Risperidone and other antipsychotics also increase the risk of death in patients with dementia. The drug was developed by JanssenCilag and first released in 1994 Medical uses Risperidone is used for the treatment of schizophrenia, bipolar disorder and behavior problems in people with autism. In autism, however, it does not improve conversational ability or social skills, and does not appear to reduce obsessive behavior in most autistic people. Due to its strong serotonin, dopaminergic, and adrenergic antagonism, risperidone was approved by the United States Food and Drug Administration(FDA) in 1993 for the treatment of schizophrenia. On August 22, 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youths, ages 1317; it was also approved that same day for treatment of bipolar disorder in youths and children, ages 1017,joininglithium. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. In 2003, the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006, the FDA approved risperidone for the treatment of irritability in children and adolescents with autism. The FDA's decision was based in part on a study of autistic people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern. Like other atypical antipsychotics, risperidone has also been used off-label for the treatment of anxiety disorders, such as obsessivecompulsive disorder, severe, treatment-resistant depression with or without psychotic features, Tourette syndrome, disruptive behavior disorders in children, and eating disorders, among others.

Olanzapine
Olanzapine (trade name Zyprexa or in combination with fluoxetine Symbyax) is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder. Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. The olanzapine formulations are manufactured and marketed by the pharmaceutical company Eli Lilly and Company; the drug went generic in 2011 Medical uses Oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or valproate) Intramuscular formulation like Zyprexa IntraMuscular: acute agitation associated with schizophrenia and bipolar I mania in adults. Oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults FDA approved uses Treatment of the manifestations of psychotic disorders (September 1996 - March 2000). Short-term treatment of acute manic episodes associated with bipolar I disorder (March 2000) Short term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders (March 2000) Treatment in combination with fluoxetine disorder (December 2003) of depressive episodes associated with bipolar

CHAPTER-2

2.LITERATURE REVIEW

The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study
Miguel Herrera-Estrella Date: 3 may 2005

Background The treatment of schizophrenia has shown important improvements since the introduction of new antipsychotics. These drugs, also called atypical or second generation antipsychotics (SGAs) bring the possibility of a better quality of life for patients affected with schizophrenia, because they have been associated with a better efficacy over negative symptoms, probably less cognitive impairment and lower probability of extrapyramidal symptoms (EPS) , which is one of their main advantages.

The SGAs increase the release of dopamine in the prefrontal cortex and the hippocampus. This effect of SGAs is critical to improve negative symptoms and cognition, and to decrease the EPS. The principal hypothesis of their mechanism of action has been attributed to the antagonism of 5-HT2A receptors coupled to weaker antagonism of dopamine D2 receptors. Their effect as 5-HT1A receptor agonist has also been suggested to contribute to an atypical antipsychotic profile.

Nevertheless, amisulpride represents an important contrast on the theory of the 5HT2A receptor antagonism. Amisulpride, is a benzamide with high affinity for dopamine D2 and D3 receptors without affinity for serotonin, muscarinic or alpha-adrenergic receptors Amisulpride also shows selectivity for dopamine receptors in limbic and hippocampal structures, rather than striatal region.

At low doses (100300 mg/d), amisulpride binds preferentially on D2/D3 presynaptic autoreceptors, increasing dopaminergic transmission in the prefrontal cortex, which is believed to be associated with improvement of primary negative symptoms. Doses between 400800 mg/d result in antagonism of postsynaptic dopamine receptors, leading to an improvement of positive symptoms of schizophrenia with less EPS development.

The limbic selectivity of amisulpride is similar to the observed with clozapine, and is secondary to its high affinity for D3 receptors and the short isoform of the D2 receptor, which are highly distributed in these regions . This selectivity has been documented in animal models. In addition, PET studies have shown that receptor D2 occupancy in striatal regions is around 14% when amisulpride is prescribed at doses between 50100 mg/d.A decreased amisulpride plasma concentration induces a low percentage of occupancy in striatal and increased occupancy in limbic regions.

The improvement of negative symptoms has been documented in clinical studies with doses between 50100 mg/d. Until now, amisulpride is the only antipsychotic that has shown scientific evidence of its efficacy over the primary negative symptoms of schizophrenia . Several clinical trials have shown that amisulpride has similar efficacy and better tolerability in comparison to haloperidol and flupentixol as well as similar efficacy and safety when compared to olanzapine and risperidone . Additionally, amisulpride has shown a positive effect over depressive symptoms and the cognitive impairment related to schizophrenia.

These data support that amisulpride is also an 'atypical' antipsychotic despite having a different receptor-affinity profile. However, there is a lack of studies about the efficacy and tolerability of amisulpride in latin populations. We decided to perform a 3-month open trial to determine these parameters on a sample of Mexican patients, using the five-factor model of schizophrenic psychopathology, a previously determined useful strategy for the evaluation of drug efficacy.

A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers.

P. Rosenzweig*, M. Canal

Date:23 JAN 2002

Amisulpride binds selectively to dopamine D2 and D3 receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D2/D3-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50300mg/day), and also on the positive symptoms of the disease at high dosages (400800mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of 12h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (50mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4mg/day and is consistent with a weak blocking effect on striatal D2 receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered. Copyright 2002 John Wiley & Sons, Ltd.

Second-Generation (Atypical) Antipsychotics and Metabolic Effects. A Comprehensive Literature Review

Newcomer, John W. CNS Drugs, Volume 19, 2005, pp. 1-93(93)

Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications. Substantial evidence from a variety of human populations, including some recent confirmatory evidence in treated psychiatric patients, indicates that increased adiposity is associated with a variety of adverse physiological effects, including decreases in insulin sensitivity and changes in plasma glucose and lipid levels. Comparison of mean weight changes and relative percentages of patients experiencing specific levels of weight increase from controlled, randomised clinical trials indicates that weight gain liability varies significantly across the different second generation antipsychotic agents. Clozapine and olanzapine treatment are associated with the greatest risk of clinically significant weight gain, with other agents producing relatively lower levels of risk. Risperidone, quetiapine, amisulpride and zotepine generally show low to moderate levels of mean weight gain and a modest risk of clinically significant increases in weight. Ziprasidone and aripiprazole treatment are generally associated with minimal mean weight gain and the lowest risk of more significant increases. Published studies including uncontrolled observations, large retrospective database analyses and controlled experimental studies, including randomised clinical trials, indicate that the different second-generation antipsychotics are associated with differing effects on glucose and lipid metabolism. These studies offer generally consistent evidence that clozapine and olanzapine treatment are associated with an increased risk of diabetes mellitus and dyslipidaemia. Inconsistent results, and a generally smaller effect in studies where an effect is reported, suggest limited if any increased risk for treatment-induced diabetes mellitus and dyslipidaemia during risperidone treatment, despite a comparable volume of published data. A similarly smaller and

inconsistent signal suggests limited if any increased risk of diabetes or dyslipidaemia during quetiapine treatment, but this is based on less published data than is available for risperidone. The absence of retrospective database studies, and little or no relevant published data from clinical trials, makes it difficult to draw conclusions concerning risk for zotepine or amisulpride, although amisulpride appears to have less risk of treatment-emergent dyslipidaemia in comparison to olanzapine. With increasing data from clinical trials but little or no currently published data from large retrospective database analyses, there is no evidence at this time to suggest that ziprasidone and aripiprazole treatment are associated with an increase in risk for diabetes, dyslipidaemia or other adverse effects on glucose or lipid metabolism. In general, the rank order of risk observed for the second-generation antipsychotic medications suggests that the differing weight gain liability of atypical agents contributes to the differing relative risk of insulin resistance, dyslipidaemia and hyperglycaemia. This would be consistent with effects observed in nonpsychiatric samples, where risk for adverse metabolic changes tends to increase with increasing adiposity. From this perspective, a possible increase in risk would be predicted to occur in association with any treatment that produces increases in weight and adiposity. However, case reports tentatively suggest that substantial weight gain or obesity may not be a factor in up to one-quarter of cases of new-onset diabetes that occur during treatment. Pending further testing from preclinical and clinical studies, limited controlled studies support the hypothesis that clozapine and olanzapine may have a direct effect on glucose regulation independent of adiposity. The results of studies in this area are relevant to primary and secondary prevention efforts that aim to address the multiple factors that contribute to increased prevalence of type 2 diabetes mellitus and cardiovascular disease in populations that are often treated with second-generation antipsychotic medications.

Antipsychotic medication, functional outcome and quality of life in schizophrenia: focus on amisulpride.
Nuss P, Tessier C. Date: 2010 Apr

Only one dedicated study assessing functional outcome or quality of life as a primary outcome criterion was identified. This demonstrated significant improvement in subjective well-being in patients with schizophrenia initiating treatment with amisulpride, and a correlation between this improvement and amelioration of psychopathology. In addition, functional outcome rating scales were used as secondary outcome measures in eight randomised clinical trials, and two naturalistic observational studies. Amisulpride treatment was associated with improvement in functional outcome, with effect sizes that were comparable between studies. Improvements in functional outcome are consistently greater than those observed in patients treated with haloperidol and similar in magnitude to those seen with three other atypical antipsychotics, namely olanzapine, ziprasidone and risperidone. A patient-reported outcome measure was used in only one comparative study, and demonstrated perception of a superior benefit with amisulpride compared to haloperidol. These findings could to some extent be replicated in several large naturalistic studies under standard conditions of care. The data from studies on functional outcome and subjective well-being provide consistent information supporting the use of amisulpride for the treatment of schizophrenia in order to improve social functioning, integration into the community and autonomy, which are critical for the overall quality of life of patients with schizophrenia.

Treatment of negative symptoms in schizophrenia by amisulpride

Plissolo A, Krebs MO, Oli JP Date: 1996 May-Jun

The deficit forms of schizophrenia have given rise to important research and controversy for the last 15 years. It is now recognized that some negative symptoms in schizophrenia are part of a pure and primary deficit syndrome which could be related to decreased dopaminergic function and which is not well improved by standard antipsychotic drugs. Amisulpride is a substituted benzamide neuroleptic with an original pharmacologic profile. Prescription of high doses (6001 200 mg/day) yields to an usual antipsychotic activity on positive symptoms, through the blockage of post-synaptic dopamine receptors. At low doses, amisulpride preferentially blocks presynaptic dopamine autoreceptors, with a poor affinity for striatal sites. Three recent doubleblind placebo controlled studies have suggested an efficacy of low doses (50-300 mg/day) of amisulpride in deficit forms of schizophrenia. The first study was carried out in young nevertreated schizophrenic patients, and showed a significant improvement of negative symptoms with a 6-week amisulpride treatment. In the second study, subjects with a long-course deficit schizophrenia were included after a 6-week wash-out period. Reduction of scores of negative symptoms (Andreasen's scale) was about twice as important in the amisulpride group compared to the placebo group, whereas positive symptoms, modest at inclusion, remained unchanged. Finally, the efficacy of amisulpride was shown in another double-blind long-term study over 6 months in patients with predominantly negative symptoms. The overall safety profile of amisulpride in these studies was good, in particular with a low incidence of extrapyramidal symptoms. Thus, amisulpride at low doses appeared to be a well tolerated treatment for various deficit forms of schizophrenia, with a short-term and long-term efficacy.

CHAPTER-3

3. Objective of study
3.1 SCOPE OF STUDY The scope of this project is to understand and describe the factors which would play major role in market acceptance of Solian. Amisulpride is one of the foremost amongst future economy drivers. It is committed to deliver high quality drugs and formulation at an affordable price for the general public, so that majority of people can afford it. The report also gives a realistic picture of the strengths and limitations of the solian, indicating those product groups whose strengths are set to last.

SPECIFIC OBJECTIVE

PERCEPTIONS OF DOCTORS ABOUT SOLIAN (AMISULPRIDE) FOR THE TRAETMENT OF SCHIZOPHRENIA

3.1 SUB OBJECTIVE

To study the perception of doctors about solian drugs when other molecules are also present for the treatment of schizophrenia.. To study problems faced by solian in market acceptance. To comparative study about the solian with other similar drugs available in the market.

CHAPTER 4

4.1 RESEARCH DESIGN

There is a huge array of alternative research designs that can satisfy research objectives. The key is to create a design that enhances the value of the information obtained, whilst reducing the cost of obtaining it. Marketing research can be classified one of three categories: 1. 2. Exploratory research Conclusive research : a) Descriptiveresearch b) Causal research These classifications are made according to the objective of the research. In some cases the research will fall into one of these categories, but in other cases different phases of the same research project will fall into different categories. 1. Exploratory research has the goal of formulating problems more precisely, clarifying concepts, gathering explanations, gaining insight, eliminating impractical ideas, and forming hypotheses. Exploratory research can be performed using a literature search, surveying certain people about their experiences, focus groups, and case studies. When surveying people, exploratory research studies would not try to acquire a representative sample, but rather, seek to interview those who are knowledgeable and who might be able to provide insight concerning the relationship among variables. Case studies can include contrasting situations or benchmarking against an organization known for its excellence. Exploratory research may develop hypotheses, but it does not seek to test them. Exploratory research is characterized by its flexibility. 2. Conclusive research is the research design which leads us to conclusion. It is classified into: a) Descriptive research. b) Causal research

a) Descriptive research is more rigid than exploratory research and seeks to describe users of a product, determine the proportion of the population that uses a product, or predict future demand for a product. As opposed to exploratory research, descriptive research should define questions, people surveyed, and the method of analysis prior to beginning data collection. In other words, the who, what, where, when, why, and how aspects of the research should be defined. Such preparation allows one the opportunity to make any required changes before the costly process of data collection has begun.

There are two basic types of descriptive research: longitudinal studies and crosssectional studies. Longitudinal studies are time series analyses that make repeated measurements of the same individuals, thus allowing one to monitor behavior such as brand-switching. However, longitudinal studies are not necessarily representative since many people may refuse to participate because of the

commitment required. Cross- sectional studies sample the population to make measurements at a specific point in time. A special type of cross-sectional analysis is a cohort analysis, which tracks an aggregate of individuals who experience the same event within the same time interval over time. Cohort analyses are useful for long-term forecasting of product demand.

b) Causal research seeks to find cause and affect relationships between variables. It accomplishes this goal through laboratory and field experiments.

Research Design Used in the ProjectDescriptive format of conclusive research. Data Collection Sampling Procedure: Doctors (Psychiatrist). Primary data: It was collected through well structured questionnaire from Doctors. The questionnaire design was such that it motivated the respondents to cooperate, become involved, and provide complete, Honest and accurate answers. Secondary Data: It includes information obtained from literature review, articles in the Newspapers, magazines and internet. Data Presentation-It is based on statistical analysis of the feedbacks obtained. v Research Duration:60 Days v Time line No: of days Line of action 10 5 30 15 Secondary research Questionnaires Designing Field work Report preparation

v Research Design: Exploratory Research v Sampling Frame: Psychiatrist Doctors v Sampling Size:150 v Research Location: Delhi v Research instrument: Questionnaires (open ended) v Mode of data collection: One to One interview and Discussion .

4.2 LIMITATIONS
v v v v v v In-depth interviews only with the Doctors who were ready to give appointments.. Deviation from the topic. Snowballing effect resulted in unnecessary discussions. Not easy to get appointments. Entries in Hospitals, without appointments were not allowed. Only point of view, of Doctors is taken.

4.3 QUESTIONNAIRE DESIGN

Date: Name: ADNAN EJAZ

Your opinion matters!

PERSONAL DETAILS: Doctor: Contact no. Place:

Q.1 In Schizophrenia, the molecules you prefer, kindly rank? Olanzapine Amisulpride Risperidone Quetiapine

Q.2. In Amisulpride which brand you prefer?

Q.3. Have you tried Solian for your patient of Schizophrenia? Yes No

Q.4 What comes in your top of the mind, when it comes to solian? Positive Symptoms Negative Symptoms Add on Acute Psychosis Early intervention

Q.5 What characteristics differentiate Solian from competition. How is it set apart from competing brands? Value added CMES Quality Representation from Sanofi Efficacy & Safety of brand

Q.6 What do you think Solian as a brand of Amisulpride molecules? Excellent Product Very Good Product Good Product Average Product Poor Product

Q.7 How and what does Solian communicate instantly? Sustained Symptom Control Lower Risk Of Side Effects Improve Functioning Towards a new beginning

Q.8 What are the factor that gives you more confidence to Rx Solian to more patients?

.. ..

Q.9 Do you want Sanofi to represent in your clinic? Preferred Day: Preferred Time:

Thank you

CHAPTER-5

DATA ANALYSIS AND FINDINGS FROM INDEPTH INTERVIEWS

TOTAL NUMBER OF SAMPLES.

TOTAL NUMBER OF DOCTORS

NON- RESPONSE 45%

RESPONSE 55%

FINDINGS:
Total number of sample are 145. Out of which 80 Psychiatrist responded constituting to 55% of response and remaining 45% turned out to be non-responder. The data would have been more accurate, meaningful and statistically significant if the response rate was higher.

Q1. In Schizophrenia, the molecules you prefer, kindly rank?

OLANZAPINE RESPERIDONE QUETIAPINE AMISULPRIDE 47 40 60 60 Rank 1 Rank 2 Rank 3 Rank 3

60 50 40 30 20 10 0

OLANZAPINE

RESPERIDONE

AMISULPRIDE

QUETIAPINE

FINDINGS:
Among four molecules, Olanzapin is the most preferred molecule for the treatment of schizophrenia. The survey shows that the molecule Amisulpride comes under top 3 selling molecules by the doctors for the treatment of schizophrenia. Other molecules preffered for the treatment are Resperidone and Quetiapine

Q.2. In Amisulpride which brand you prefer?

SULPRIDE 1%

PREFFERD BRANDS
NO COMMENTS 18% SOLIAN 35%

AMPRIDE 1% GENERIC 6% SOLTUS 6% AMIGOLD 11% SULPITAC 22%

FINDINGS:
When surveyed thoroughly, it is found that Solian is the most preferred brand that use Amisulpride molecule. The brand Solian is registered product from Sanofi. Other preferred brands for Amisulpride molecules are namely Sulpitac and Amigold leading in the market. They represent big names in the market such as Lupin and Sun Pharma. The survey clearly puts Solian as a leading brand among all with 35% practitioner recommending it and this is followed by Sulpitac with 22% and Amigold 11% and few of them preferring others like Generic brands, Ampride, Soltus and Sulpride. About 24% of practitioners did not want to reveal their preferred brand.

Sanofi leads ahead of Lupin and Sun Pharma and constitute major player in the field.

Q.3. Have you tried Solian for your patient of Schizophrenia?

NUMBER OF DOCTORS TRIED SOLIAN

NO 6%

YES 94%

FINDINGS:
The survey shows that all practitioners and doctors are well aware of the existence of brand Solian as one of the treatment option for schizophrenic patients. The result shows that more than 90% of doctors have tried Solian on their patients for the treatment of subsets of schizophrenia. There is awareness of brand and the product among the doctors makes Solian as a product which holds positive aspect for the future growth and progress in the market.

Q.4 What comes in your top of the mind, when it comes to solian?

EARLY INTERVENTION 5% ACUTE PSYCHOSIS 12%

SOLIAN MAINLY USED FOR

NEGATIVE SYMPTOMS 32% ADD ON 24% POSITIVE SYMPTOMS 27%

FINDINGS:
When asked about the functional aspect of Solian, there were mixed responses from the field regarding its usage. 32% of the practitioners said that Solian is mainly used for negative symptoms in the treatment of schizophrenia Positive symptoms and add on are the some other areas where solian is also prescribed. Acute Psychosis and Early intervention symptoms are the area where solian have to work really hard to acquire all the segment of the market for the treatment of schizophrenia.

Q.5 What characteristics differentiate Solian from competition? How is it set apart from competing brands?

DIFFERENT CHARACTERISTIC OF SOLIAN FROM COMPETITION

EFFICACY & SAFETY OF BRAND 14% RESPRESENTATION FROM SANOFI 25% QUALITY 33%

VALUE ADDED CME'S 28%

FINDINGS:
Quality of the product is the main characteristic that differentiate Solian from its competing brands. Value added CMEs are the second most preferred factor that differentiates solian from its competing brand. Representation from a big pharma name like Sanofi add value to Solian and give it an edge over other prevailing brands in the market. Safety and Efficacy of brand comes under the quality category.

Q.7 How and what does Solian communicate instantly?

TOWARDS A NEW BEGINNING 3%

SOLIAN COMMUNICATES INSTANTLY

SUSTAINED SYMPTOM CONTROL 25%

IMPROVE FUNCTIONING 33%

LOWER RISK OF SIDE EFFECTS 39%

FINDINGS:
When surveyed for Solian about its mode of action and other associated factors, the finding has an impressive result. Solian is mainly picked up by doctors owing to its lower risk of side effects which accounts for its success. The lower side effect is one of the major criteria for any drug to be included and prevail in the course of treatment where Solian scored maximum response.

Besides, Solian is also found to be effective in treatment owing to its improve functioning and sustained symptoms control.

Q.8 What are the factor that gives you more confidence to Rx Solian to more patients?

FACTORS TO Rx SOLIAN
FACTORS TO Rx SOLIAN

28 21 14 4 QUALITY LESS SIDE EFFECT EVIDENCE BASE SAFETY OF PRODUCT 4 IMPROVE FUNCTIONING 3 IMPROVE -VE SYMPTOMS

FINDINGS:
When asked about the overall factors contributing to Solian for giving it an edge over other products running in the market, the response comes out to be satisfying in all necessary areas of consideration. The major factor contributing to Solian success is its Quality comes first in consideration. The other majorimportant considerations are its Less Side Effect followed by Evidence Based, Safety Issues and Improve Functioning over other similar products.

CONCLUSION
Amisulpride is currently being used as one of the potent molecule for the treatment of schizophrenia as it is clinically effective on various symptoms of this acute disease. Exhibiting no detrimental effect even at the high dose makes it one of the favorite molecules currently being employed in the area. Owing to its strong clinical relevance background with significant viable clinical human trials, we decided to study its hold in the current market focusing on various factors it associated with it. Amisulpride is currently being available as a brand name Solian under the banner of Sanofi-Aventis, a leading pharmaceutical company of the world. To have a realistic picture we decided to conduct a survey in and around the area of National Capital Region of Delhi among different doctors/practitioners to express their views on Solian for the treatment of schizophrenic patients. The questionnaire was prepared keeping in mind about various issues that a new drug can face while being employed for treatment, focussing majorly on its ability to act on subject and perceptions associated with it. The final aim was to highlight the areas where Solian is facing problem in market acceptance and the comparative study with other drugs to further improve its availability and launching strategies. In the first response where choosing a molecule for the treatment of schizophrenia is concerned, the first name that comes into the practitioners mind is Olanzapin followed by Resperidone. This clearly shows that Amisulpride is not one of the favorite molecule that is considered for this treatment. Being at spot third among other molecules, it clearly shows that further awareness about the effectiveness of this molecule has to be highlighted. This can be done by including more human clinical trials (already done or currently being done), research studies and highlighting the advantageous features over others. But when it comes to choose a brand within Amisulpride, Solian is the first name that strikes in their mind which states its clear dominance in the category of this molecule. The other brand falling under this molecule are Sulpitac and Amigold which are leading in the market representing big pharma names such as Lupin and Sun Pharma. This depits the picture that Solian has to maintain its effectiveness under all categories failing to which it may succumb to its rival brand. In order to do so, the marketing value, pricing slot and proper launch in wide spectrum of Solian has to be maintained foreseeing all factors. The survey result shows that all practitioners and doctors are well aware of Solian as the treatment option for schizophrenic patients making it as one of the favorite brand. The awareness and knowledge of this brand among the doctors makes Solian as a product which holds positive aspect for the future growth and progress in the market. Therefore we need to more focus on its stable availability globally even making them within the reach of remote areas by consulting doctors, holding meetings, conducting surveys with proper presentations with and among experts in the field. We have surveyed and seen that the quality of the product is the main characteristics which differentiate Solian from its competing brands.

Besides, value added CMEs and representation from a big pharma name such as SanofiAventis add value to Solian giving it an edge over other prevailing brands in the market. Also Solian is found to be mainly the reason of choice among doctors due to the least side effect if offers where safety and efficacy of a drug play a major role. Overall Solian is the leading brand among all Amisulpride molecule currently in the market according to this research survey. However this finding open a new window of opportunities to enhance its strength in the area by creating more awareness about its positive role, more research analysis, systematic surveys, comparative analysis among its competing brands, availability in global spectrum, long term effectiveness and strategic marketing approach in current level playing field.

REFRENCES
wikipedia.com google.com http://www.netdoctor.co.uk/brain-and-nervous-system/medicines/solian.html http://journals.lww.com/intclinpsychopharm/Abstract/2004/03000/A_double_blind,_rand omized_comparative_trial_of.2.aspx http://www.drugsupdate.com/brand/showavailablebrands/709 http://www.sanofipasteur.in/ www.sanofi.com www.sanofi-aventis.in http://onlinelibrary.wiley.com/doi/10.1002/hup.320/abstract http://www.ncbi.nlm.nih.gov/pubmed/20121655 http://www.ingentaconnect.com/content/adis/cns/2005/00000019/a00101s1/art00001 http://www.ncbi.nlm.nih.gov/pubmed/8767050 Through questionnaires presented before doctors and responses there from. Personal interview