Scrip's Complete Guide to CNS Disorders

Scrip's Complete Guide to CNS Disorders

Therapeutic

A comprehensive overview of the global market for current and forthcoming CNS drugs, this report covers the major areas: Alzheimer's disease, Parkinson's disease, depression, schizophrenia and anxiety. Six volumes supply you with invaluable information on CNS drugs in R&D and the global market for CNS therapies.

Access:

Extensive R&D information on over 150 products in clinical trials for CNS disorders
R&D details for over 200 drugs in preclinical research
Relative market share of products and sales forecasts to 2002 for each disease
18 top company profiles
Sales figures for the top 30 CNS drugs currently on the market

Each major disease area is covered in a separate volume containing definitions, pathogenesis, risk factors and epidemiology. The report also supplies descriptions of current treatments and information on their advantages and disadvantages.

Profiles of the 18 companies most active in the CNS field allow you to undertake accurate competitor analysis - and evaluate opportunities for strategic collaborations.

PUBLISHED: AUGUST 1999
REF: BS1023E
PAGES: 600+
PRICE: Complete six-volume set �990/$1,995/�238,000

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CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
METHODOLOGY
ABBREVIATIONS
GLOSSARY

CHAPTER 1 INTRODUCTION
1.1 Overview of central nervous system disorders
1.2 Alzheimer's disease
1.2.1 Current treatments
1.2.2 Recent developments and potential treatments
1.2.3 Dementia
1.3 Parkinson's disease
1.3.1 Current methods of treatment
1.3.2 Recent developments and potential treatments
1.4 Depression
1.4.1 Current methods of treatment
1.4.2 Recent developments and potential treatments
1.5 Bipolar disorder
1.5.1 Current methods of treatment
1.5.2 Recent developments and potential treatments
1.6 Schizophrenia
1.6.1 Current methods of treatment
1.6.2 Recent developments and potential treatments
1.7 Other psychoses
1.8 Anxiety
1.8.1 Current methods of treatment
1.8.2 Recent developments and potential treatments
1.9 Multiple sclerosis
1.9.1 Current methods of treatment
1.9.2 Recent developments and potential treatments
1.10 Amyotrophic lateral sclerosis
1.10.1 Current methods of treatment
1.10.2 Recent developments and potential treatments
1.11 Epilepsy
1.11.1 Current methods of treatment
1.11.2 Recent developments and potential treatments
1.12 Huntington's chorea
1.13 Narcolepsy
1.13.1 Current treatments
1.13.2 Recent developments and potential treatments
1.14 Insomnia
1.14.1 Current methods of treatment
1.14.2 Recent developments and potential treatments
1.15 Attention deficit hyperactivity disorder
1.15.1 Current methods of treatment
1.15.2 Recent developments and potential treatments
1.16 Migraine
1.16.1 Current methods of treatment
1.16.2 Recent developments and potential treatments

CHAPTER 2 THE MARKET
2.1 Worldwide pharmaceutical market value
2.1.1 Market value by major geographic region
2.1.2 Market value by therapeutic category
2.1.3 Market value and rate of growth for the world's major drug classes
2.1.4 Market value by major geographical region
2.2 CNS market value
2.2.1 CNS market value by geographical region
2.2.1.1 North America
2.2.1.2 Europe
2.2.1.3 Japan
2.2.1.4 Australia
2.2.2 CNS market value by therapeutic category
2.2.2.1 Comparison of net present values
2.2.2.2 Comparison by actual sales
2.2.3 The impact of demographic changes on market share - an example
2.3 Growth of the CNS market
2.3.1 CNS market growth by therapeutic category
2.3.2 Growth projections for currently marketed CNS drugs
2.3.2.1 Drugs for Parkinson's disease
2.3.2.2 Drugs for Alzheimer's disease
2.3.2.3 Drugs for depression
2.3.2.4 Drugs for schizophrenia
2.3.2.5 Drugs for anxiety
2.3.3 Growth projections for CNS drugs currently in development
2.4 Market structure
2.4.1 Market structure by disease area
2.4.1.1 Neurological disorders
2.4.1.2 Psychiatric disorders
2.4.2 Relative importance of the leading companies in the CNS market
2.4.3 Major products
2.4.4 Leading anti-depressants
2.5 Market influences
2.5.1 Generic competition
2.5.2 Neuropharmacogenetics
2.5.3 Market trends for individual disease areas
2.5.3.1 Alzheimer's disease and dementia
2.5.3.2 Parkinson's disease
2.5.3.3 Depression
2.5.3.4 Schizophrenia
2.5.3.5 Anxiety
2.6 Epidemiology
2.6.1 Current statistics
2.6.1.1 The ageing population
2.6.1.2 Developing countries
2.6.1.3 The public health burden of disease
2.6.1.4 The cost of illness to society
2.6.1.5 Estimated costs of individual CNS diseases
2.6.2 Population and mortality
2.6.2.1 Mortality figures for CNS disorders
2.6.3 Global incidence of CNS disorders
2.6.4 Global prevalence CNS disorders
2.7 Summary

CHAPTER 3 COMPANY PROFILES
3.1 Pharmaceutical sales and R&D expenditure by company
3.2 Companies developing and marketing neurological products
3.2.1 Akzo Nobel
3.2.1.1 R&D highlights and agreements
3.2.2 American Home Products
3.2.2.1 R&D highlights and agreements
3.2.3 AstraZeneca
3.2.3.1 R&D highlights and agreements
3.2.4 Bristol-Myers Squibb
3.2.4.1 R&D highlights and agreements
3.2.5 Eli Lilly
3.2.5.1 R&D highlights and agreements
3.2.6 Glaxo Wellcome
3.2.6.1 R&D highlights and agreements
3.2.7 Johnson & Johnson
3.2.7.1 R&D highlights and agreements
3.2.8 Knoll
3.2.8.1 R&D highlights and agreements
3.2.9 Merck & Co
3.2.9.1 R&D highlights and agreements
3.2.10 Novartis
3.2.10.1 R&D highlights and agreements
3.2.11 Pfizer
3.2.11.1 R&D highlights and agreements
3.2.12 Pharmacia & Upjohn
3.2.12.1 R&D highlights and agreements
3.2.13 Roche
3.2.13.1 R&D highlights and agreements
3.2.14 Sanofi
3.2.14.1 R&D highlights and agreements
3.2.15 Schering
3.2.15.1 R&D highlights and agreements
3.2.16 SmithKline Beecham
3.2.16.1 R&D highlights and agreements
3.2.17 Synth�labo
3.2.17.1 R&D highlights and agreements
3.2.18 Warner-Lambert
3.2.18.1 R&D highlights and agreements

CHAPTER 4 COMPANY DIRECTORY

REFERENCES

WEBSITES

APPENDIX 1 GUIDANCE FOR CLINICAL TRIALS
A.1 Regulatory requirements for drugs for treating central nervous system disorders
A.2 Guidance for clinical investigation of treatments for depression
A.2.1 Short-term studies
A.2.2 Long-term studies
A.2.3 End-points
A.2.4 Specific groups of patients
A.3 Guidance for clinical investigation of treatments for bipolar disorder
A.4 Guidance for clinical investigation of treatments for Alzheimer's disease
A.4.1 Phase I - early pharmacology and pharmacokinetic studies
A.4.2 Phase II - initial therapeutic trials
A.4.3 Phase III - controlled clinical trials
A.4.4 Adjustment for prognostic variables
A.4.5 Concomitant treatments
A.5 Guidance on clinical investigation of treatments for schizophrenia
A.5.1 Specific considerations for developing antischizophrenia products
A.5.1.1 Use of placebo
A.5.1.2 Negative symptoms
A.5.1.3 Extrapolation
A.5.1.4 Recurrence/episodic symptoms and relapse
A.5.1.5 Study design in therapy-resistant schizophrenic patients
A.5.1.6 Special groups
A.5.2 Assessment of efficacy criteria
A.5.2.1 Improvement in symptomatology
A.5.2.2 Relapse/recurrence prevention
A.5.2.3 Negative symptomatology
A.5.3 Methods to assess efficacy
A.5.4 Study design
A.5.4.1 Short-term clinical trials
A.5.4.2 Maintenance therapy
A.5.4.3 Neurological adverse events
A.6 Guidance for clinical investigation of treatments for Parkinson's disease
A.6.1 Design of the clinical studies
A.6.1.1 Symptomatic relief in early-stage Parkinson's disease before levodopa+ treatment
A.6.1.2 Symptomatic relief in patients with Parkinson's disease on levodopa+
A.6.1.3 Therapies aimed at reducing disease progression
A.6.2 Dosage
A.6.3 Polytherapy
A.6.4 Assessment of efficacy criteria
A.6.5 Methods to assess efficacy criteria

APPENDIX 2 CONFERENCE CALENDAR

LIST OF TABLES
Table 1.1 Memory enhancing drugs marketed for Alzheimer's disease and other dementias
Table 1.2 Drugs marketed for Parkinson's disease as a first indication
Table 1.3 First indication antidepressant drugs marketed for depression
Table 1.4 Summary of marketed antidepressants specifically indicated for bipolar disorder
Table 1.5 Antipsychotics marketed for schizophrenia and other psychoses
Table 1.6 Anxiolytic drugs marketed for anxiety
Table 1.7 Drugs marketed for MS for which there is only one first indication
Table 1.8 Neuroprotective drugs marketed for amyotrophic lateral sclerosis
Table 1.9 The frequency of epilepsy in the developed world population
Table 1.10 Drugs marketed for epilepsy
Table 1.11 Psychostimulant drugs marketed for narcolepsy
Table 1.12 Hypnotic and sedative drugs marketed for insomnia
Table 1.13 Drugs marketed for ADHD
Table 1.14 Drugs marketed for migraine

Table 2.1 World ethical pharmaceutical sales by major geographical region, 1998
Table 2.2 The top five CNS drugs in the US by sales value, 1998
Table 2.3 The top three CNS drugs in the US by numbers of prescriptions written, 1998
Table 2.4 The top four prescription CNS drugs in Canada by sales value, 1998
Table 2.5 NPV values of various therapeutic categories considering medical need versus patient population
Table 2.6 CNS market value compared with the total pharmaceutical sales of the major companies involved within that category, 1998
Table 2.7 CNS market value by selected company and projections to 2002 ($ million)
Table 2.8 Total drug sales figures and total NPVs from major therapeutic categories, 1997 and forecasts to 2002 ($ million)
Table 2.9 The importance of therapeutic category as calculated by overall company sales, 1998
Table 2.10 Worldwide sales of individual antiparkinsonian agents since 1997 and projections to 2002 ($ million)
Table 2.11 Worldwide sales of individual memory enhancers since 1997 and projections to 2002 ($ million)
Table 2.12 Worldwide sales of individual antidepressants since 1997 and projections to 2002 ($ million)
Table 2.13 Worldwide sales of individual antipsychotics since 1997 and projections to 2002 ($ million)
Table 2.14 Worldwide sales of individual anxiolytics since 1997 and projections to 2002
($ million)
Table 2.15 Potential worldwide sales in 2002 and overall peak sales of antiparkinsonian agents to be released ($ million)
Table 2.16 Potential worldwide sales in 2002 and overall peak sales of memory enhancers to be released ($ million)
Table 2.17 Potential worldwide sales in 2002 and overall peak sales of antidepressants/anxiolytics to be released ($ million)
Table 2.18 Potential worldwide sales in 2002 and overall peak sales of antipsychotics to be released ($ million)
Table 2.19 Potential worldwide sales in 2002 and overall peak sales of anxiolytics to be released ($ million)
Table 2.20 NPV of a given company's CNS drugs, and their percentage of the calculated total CNS market
Table 2.21 Top 30 CNS drugs worldwide, ranked according to sales predictions for 1999
($ million)
Table 2.22 Median age by major geographical region for 1950, 1998 and 2050 (median variant projections)
Table 2.23 Leading causes of years lived with a disability worldwide, 1990
Table 2.24 Rank of selected conditions among all causes of disease burden, estimates for 1998
Table 2.25 Estimated direct and indirect economic costs of CNS-related illnesses in the US, 1999 ($ billion)
Table 2.26 Male and female mortality associated with CNS diseases in WHO Member States, 1998
Table 2.27 Mortality associated with CNS diseases in low- and high-income WHO Member States, 1998
Table 2.28 Summary of WHO incidence figures for CNS disorders worldwide, 1995
Table 2.29 Summary of WHO prevalence figures for CNS disorders worldwide, 1995

Table 3.1 Pharmaceutical sales and R&D expenditure for companies involved in CNS products, 1997-1998
Table 3.2 Total sales revenue and R&D expenditure for companies involved in CNS product development, 1997-1998
Table 3.3 Akzo Nobel's financial results, 1994-1998 (NLG million)
Table 3.4 Pharmaceutical sales by division, 1997-1998 (NLG million)
Table 3.5 Akzo Nobel's main marketed neurological products
Table 3.6 Akzo Nobel's major neurological products in development
Table 3.7 American Home Products' financial results, 1993-1998 ($ million)
Table 3.8 Major neurological products manufactured by Wyeth-Ayerst
Table 3.9 Major neurological products manufactured by American Cyanamid
Table 3.10 American Home Products' neurological products in development
Table 3.11 AstraZeneca's financial results, 1998 ($ million)
Table 3.12 Astra's financial results, 1994-1997 (SKr million)
Table 3.13 Zeneca's financial results, 1994-1997 (� million)
Table 3.14 AstraZeneca's marketed neurological products
Table 3.15 AstraZeneca's neurological products in development, 1998-1999
Table 3.16 Bristol-Myers Squibb's financial results, 1994-1998 ($ million)
Table 3.17 Bristol-Myers Squibb's sales by therapeutic category, 1996-1998 ($ million)
Table 3.18 Major neurological products manufactured by Bristol-Myers Squibb
Table 3.19 Bristol-Myers Squibb's major neurological products in development
Table 3.20 Eli Lilly's financial results, 1994-1998 ($ million)
Table 3.21 Eli Lilly's sales by therapeutic category, 1997 ($ million)
Table 3.22 Some of the major neurological products marketed by Eli Lilly
Table 3.23 Eli Lilly's neurological products in development, 1998-1999
Table 3.24 Glaxo Wellcome's financial results, 1994-1998 (� million)
Table 3.25 Some of the major neurological products marketed by Glaxo Wellcome
Table 3.26 Glaxo Wellcome's neurological products in development, 1998-1999
Table 3.27 Johnson & Johnson's financial results, 1994-1998 ($ million)
Table 3.28 Johnson & Johnson's marketed neurological products
Table 3.29 Johnson & Johnson's major neurological products in development
Table 3.30 BASF Group's financial results, 1994-1998 (DM million)
Table 3.31 Knoll's major neurological products
Table 3.32 Knoll's major neurological products in development
Table 3.33 Merck's financial results, 1994-1998 ($ million)
Table 3.34 Merck's major neurological products
Table 3.35 Merck's major neurological products in development
Table 3.36 Novartis' financial results, 1996-1998 (SFr million)
Table 3.37 Novartis' sales by division, 1997-1998 (SFr billion)
Table 3.38 Novartis' healthcare sales by product area, 1997-1998 (SFr million)
Table 3.39 Some of the major neurological products marketed by Novartis
Table 3.40 Novartis' major neurological products in development
Table 3.41 Pfizer's financial results, 1994-1998 ($ million)
Table 3.42 Pfizer's major marketed neurological products
Table 3.43 Pfizer's major neurological products in development
Table 3.44 Pharmacia & Upjohn's financial results, 1994-1998 ($ million)
Table 3.45 Some major neurological products manufactured by Pharmacia & Upjohn
Table 3.46 Pharmacia & Upjohn's major neurological products in development
Table 3.47 Roche's financial results, 1994-1998 (SFr million)
Table 3.48 Roche's marketed neurological products
Table 3.49 Roche's major neurological products in development
Table 3.50 Sanofi's financial results, 1994-1998 (Fr million)
Table 3.51 Sanofi's major neurological products
Table 3.52 Sanofi's major neurological products in development
Table 3.53 Schering's financial results, 1994-1998 (DM million)
Table 3.54 Schering's neurological products in development
Table 3.55 SmithKline Beecham's financial results, 1994-1998 (� million)
Table 3.56 SmithKline Beecham's sales by business sector, 1997-1998 (� million)
Table 3.57 SmithKline Beecham's sales by therapeutic category, 1997-1998 (� million)
Table 3.58 Major neurological products manufactured by SmithKline Beecham
Table 3.59 SmithKline Beecham's major neurological products in development
Table 3.60 Synth�labo's financial results, 1994-1998 (Fr million)
Table 3.61 Synth�labo's major neurological products with sales figures, 1997-1998
(Fr million)
Table 3.62 Synth�labo's neurological products in development
Table 3.63 Warner-Lambert's financial results, 1993-1998 ($ million)
Table 3.64 Warner-Lambert's major marketed neurological products
Table 3.65 Warner-Lambert's major neurological products in development

Table A2.1 Forthcoming CNS-related conferences

LIST OF FIGURES
Figure 1.1 Classification and percentage frequency of the different forms of epileptic seizure, in all ages

Figure 2.1 Pharmaceutical sales in 12 leading markets, 1998
Figure 2.2 Sales by therapeutic category (for 12 of the world's leading markets), 1998
Figure 2.3 Estimated worldwide drug classes driving growth, 1998
Figure 2.4 World drug purchases of retail pharmacies by therapeutic category and major geographical region in the 12 months to March 1999
Figure 2.5 Market value of therapeutic categories by major geographical region, in the 12 months to August 1997
Figure 2.6 Changing importance of the world's major Alzheimer's disease markets (1995 and 2005)
Figure 2.7 Projected worldwide sales for CNS products for the top 29 companies involved in this sector
Figure 2.8 Worldwide sales of psychiatric products by market segment, 1997
Figure 2.9 Estimated market share of leading antidepressant drugs for 1998
Figure 2.10 DALYs attributable to non-communicable diseases in low and middle income countries, estimates for 1998

Figure 3.1 Number of neurological projects in development, 1995-1998

This volume, Market Overview, is part of a series forming Scrip's Complete Guide to CNS Disorders. The other volumes in this series are:
Volume 2: Alzheimer's Disease and Other Dementias (BS1025)
Volume 3: Parkinson's Disease (BS1026)
Volume 4: Depression and Bipolar Disorder (BS1027)
Volume 5: Schizophrenia and Other Psychoses (BS1028)
Volume 6: Anxiety (BS1029)

EXECUTIVE SUMMARY
This report investigates the market for central nervous system (CNS) drug therapies which are the third highest selling therapeutic category behind cardiovascular and alimentary/metabolic products. It focuses particularly on the neurodegenerative disorders -Alzheimer's and Parkinson's disease - and the neuropsychiatric disorders - schizophrenia, depression and bipolar disorder - and anxiety. Overall, new classes of drugs are transforming the way these disorders are treated but an individual approach to treatment is necessary and alternative strategies will always be required for non-responsive patients.

Debate continues over the use of less costly, well established drugs as opposed to newer compounds with fewer side effects but which cost more whose clinical experience is limited. This is especially the case for the antipsychotics and antidepressants. Many novel drug strategies under development could, for the neurodegenerative disorders, slow the progression of the disease's course rather than just temporarily treat the symptoms.

The worldwide market for CNS drugs, which is currently over $30 billion, is predicted to double to over $62 billion by 2002. This represents a growth rate of 14-15% per annum, double the rate of growth of the pharmaceutical market as a whole (Lehman Brothers, 1998). By far the largest factor influencing the steep market increase, for neurodegenerative-related drugs at least, is the increasing elderly population, which is occurring globally. Because the incidence rates for Alzheimer's and Parkinson's diseases increases with age, the growing number of these patients will place a higher demand for treatments in both market segments.

The potential for neuropsychiatric disorders to cause severe disability and contribute largely to the overall burden of disease to society is now being recognised. Previously, such conditions as schizophrenia, bipolar disorder, depression and anxiety were not included in cause of death lists and were therefore never considered to be a tremendous burden. For example, depression is the second highest-ranking disorder contributing to disease burden in developed countries.

. . . Alzheimer's
The worldwide market for Alzheimer's disease was $600 million in 1997, accounting for 25% of neurology-related products, and is predicted to reach $3.25 billion in 2002. Because Alzheimer's disease has an incidence rate that increases with age, it will be a high priority for improved drugs and treatment strategies. Annual healthcare costs are estimated at $50 billion per annum, most of which can be attributed to nursing home costs, which is a common additional healthcare option for most patients in the advanced stage of disease. Moreover, Alzheimer's disease is the fourth leading cause of death in the Western world.

The World Health Organization (WHO) has estimated that there are currently around
22 million people with dementia and so the market value could in fact be a higher, with Alzheimer's disease being the most common form of dementia. Dementia occurring as a result of stroke in the elderly may also show an upward trend, as increasing numbers of patients are diagnosed, leading to increased treatment demands.

Current treatment options focus on prolonging the action of acetylcholine or blocking its degradation at the synapse. The most promising treatments in current use are the acetylcholinesterase inhibitors, which are dominating the market. Potentially competing products are looking to adopt a dual mode of action to enhance efficacy - for example the drug, galantamine, which is an acetylcholinesterase inhibitor and which also stimulates nicotine receptors. As further understanding of the complex genetic basis of Alzheimer's disease is gained and abnormalities identified, opportunities for drug development will naturally widen.

As strategies that are more diverse are being tested, drugs in development remain varied. The theory that anti-inflammatory compounds may alter immune mechanisms has led to the cyclooxygenase-2 (COX-2) inhibitors being tested (two of which have recently been approved for treating pain in arthritis) in trials for Alzheimer's disease. Glutamate inhibitors, monoamine oxidase B (MAO-B) inhibitors and neuroprotective compounds are also in development.

. . . Parkinson's
The worldwide market for Parkinson's disease was $700 million in 1997, accounting for 22% of neurology-related products, and is predicted to reach $1.5 billion in 2002. Parkinson's disease also has an incidence rate that increases with age and will be a high priority for improved drugs and treatment strategies.

There is an ongoing debate about the use of the current gold standard treatment - levodopa -and whether its use should be delayed in younger patients to avoid inevitable movement problems later on in treatment.

Treatments are being developed, both as monotherapies to postpone the need for levodopa until later, and as adjunctive compounds to reduce the dosage of levodopa required - both with the common goal of preventing the 'on-off' fluctuations characteristic of lengthy treatment with levodopa. Other compounds on the market include the dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors and monoamine oxidase (MAO) inhibitors.

Recent setbacks involving serious side effects with the COMT inhibitor, Tasmar (tolcapone), which aimed to reduce the need for levodopa, have left scope for improvement in this area. As with most disorders, there are opportunities for more convenient drug formulations. This is especially the case with Parkinson's disease, because the nature of the symptoms means that swallowing an oral formulation can be difficult for some patients.

Alternative strategies are also being employed such as dopamine reuptake inhibitors, glutamate antagonists, adenosine A2 antagonists and the use of levodopa prodrugs.

. . . depression and bipolar disorder
Estimated to affect up to 50% of the population at some time in their lives, depression is a common problem affecting all age groups and sometimes resulting in suicide. Antidepressants are estimated to account for 47% of worldwide psychiatric-related drug sales, by far the largest market segment. The worldwide market for antidepressants was approximately $7.1 billion in 1997 and is predicted to reach $15 billion in 2002.

This market doubling may predict the anticipated changes in treatment - from generic tricyclic antidepressants (TCAs) which have declining sales but are still widely used, to newer compounds.

The selective serotonin reuptake inhibitors (SSRIs) currently dominate most markets and have just reached Japan, where, until recently, there had been no SSRIs on the market. They have proved successful due to fewer side effects than TCAs but again they are more expensive and still do not fulfil the gap for an antidepressant that does not need an induction phase of a few weeks to work effectively.

Opportunities are also expanding with regard to the co-existence of anxiety-related disorders with depression. A strategy for targeting treatment-resistant depression is in development, which involves the well-established antidepressant fluoxetine in combination with the antipsychotic olanzapine. It is expected that this combinatorial approach could treat 30% of non-responsive depressed patients.

Drugs are also being developed with increased receptor specificity such as reversible MAOIs as opposed to the older style irreversible products, which irreversibly block the inactivation of tyramine and so have the potential to cause a fatal hypertensive crisis. To illustrate further the variety of receptors being targeted, the dual-acting serotonin and noradrenaline reuptake inhibitor compound (SNRI), venlafaxine, has provided a successful alternative method for treating more severe cases of depression, and noradrenaline reuptake inhibitors (NARIs) and noradrenaline and selective serotonergic antidepressant (NASSA) compounds have also been released.

Alternative mechanisms of action and new developments include melatonin compounds, substance-P antagonists, corticotrophin-releasing factor compounds, single isomer versions of well established SSRIs, herbal remedies, AMPAkines (a novel drug class), thyrotrophin-releasing hormone compounds and sigma receptor agonists.

Bipolar disorder (manic depression) is a growing market as attempts to improve the mainstay treatment, lithium, are in progress. Characterised by periods of depression and periods of mania, both antidepressants and antipsychotics have an important role in drug treatment. Since the success of Depakote (divalproex sodium), the potential for anticonvulsants in treating this disorder is now being realised with Lamictal (lamotrigine) which is in late-stage trials for this disorder.

. . . schizophrenia
With 1% of the world's population suffering from schizophrenia at any one time, and
$40 billion per annum spent on US healthcare alone, schizophrenia is a costly disorder in terms of drugs and hospital care. Furthermore, it is also a major contributor to suicide. The potential for successful drugs to reduce time spent in hospital and therefore reduce overall costs is enormous. The worldwide market for schizophrenia was approximately $2.2 billion in 1997 and is predicted to reach $6.1 billion in 2002. This increase in cost may predict the anticipated changes in treatment - from generics to newer compounds.

The market is currently divided between the older, well-established 'typical antipsychotics' such as generic haloperidol and the newer, more expensive 'atypical' antipsychotics, which claim less severe side effects, leading to improved quality of life.

The market for antipsychotics is in transition and more head-to-head studies and increased patient awareness of these reduced side effects will help determine whether the newer compounds will outsell older ones. Advances in understanding the causes of schizophrenia are ongoing and opportunities for improved drug development will undoubtedly arise from these findings. Considering that 90% of patients who successfully respond to treatment and then stop, eventually relapse, there is scope for improvement using maintenance therapy. Further advances in overall treatment can always be achieved by developing more convenient dosing regimens. For example, longer-acting depot formulations are likely to improve patient compliance and there is again a greater chance that a patient will take their medication if the side effects are more tolerable (ie no extrapyramidal symptoms).

. . . anxiety
The worldwide market for anxiolytics was approximately $1.6 billion in 1997 and is predicted to increase to $1.9 billion in 2002. Anxiety also accounted for 16% of the worldwide sales for psychiatry products in 1997, only 1% less than antipsychotics. With the predicted overall decline in sales of benzodiazepines by 2000, there is a great deal of scope for new and improved compounds. Older compounds may now be re-released or in development as alternative formulations to maintain their market share (eg Buspar (buspirone) as a transdermal patch).

Co-morbid anxiety with depression or other psychiatric disorders is a growing area of interest. The apparent non-specific treatment response between the subtypes of the major disease areas suggests that certain types of anxiety and certain types of depression are either different expressions of a similar disorder with a common neurobiological substrate; discrete diagnostic entities that respond to independent pharmacological effects of the same drugs, or a combination of the two. Research is increasing in this area and could open up new opportunities for other drugs that are already on the market.

One of the major emerging trends is the scope for the SSRI antidepressants to be used for treating anxiety. Furthermore, the dual-acting SNRI compound, venlafaxine, has been approved to anxiety disorder. Increasing numbers of antidepressants are gaining additional indications for more than one anxiety-related disorder in many cases. Despite anxiety being an add-on for products indicated for depression, it is becoming a major therapeutic area in its own right, with the associated conditions, generalised anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, seasonal affective disorder and panic disorder gaining ground as individual disorders.

Drugs with alternative mechanisms of action in development include melatonin compounds, cholecystokinin B (CCKB) receptor antagonists and corticotrophin-releasing factor compounds.