New hope for manic-depression sufferers comes from unlikely source — (Pharmaceutical Business Review)

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Pharmaceutical Business Review

21st November 2006

By PBR Staff Writer

Bipolar disorder sufferers experience swings from severe phases of mania to severe phases of depression and the disorder is treated as essentially two distinct conditions. However, following its US marketing license for the treatment of depressive symptoms, AstraZeneca’s atypical antipsychotic Seroquel could potentially offer a single-pill treatment for both acute phases of the disorder.

‘Content With the creation of the community-based disorders bipolar II disorder and cyclothymia, the inclusion criteria has softened. Without the need for an episode of hospitalization for mania, estimates of the prevalence of bipolar disorder have increased significantly from 1% in 1994, to 2.6% in 2005. As awareness and understanding of bipolar disorder increases, many patients currently diagnosed as suffering from major depressive disorder may be rediagnosed as suffering from bipolar II disorder, the mildest form of the disorder in which the periods of mania can be comparatively benevolent.

[What this means is that people diagnosed as depressed, and treated with antidepressants, become manic and are then diagnosed with bipolar disorder.  In other words, pharma is creating the boom in bipolar disorder with the assistance of physicians who do not see the big picture. – SSRI Stories Ed]

Along with being the most frequently experienced, the depressive phase is thought to be the most problematic phase of the disorder, primarily due to the fear of patients attempting to commit suicide. Depressed bipolar disorder patients are much more likely to attempt suicide than sufferers of classical depression. Antidepressants have a tendency to switch patients from the depressive phase to the manic phase, and are therefore generally not prescribed by psychiatrists.

Why an antipsychotic for a depressive symptom?

The discovery that one of the most commonly prescribed antipsychotics can help treat the depressive symptoms of bipolar disorder may seem like a peculiar twist of fate. Atypical antipsychotics are commonly used to treat schizophrenia and the manic phase of bipolar disorder, so using this class of drug to treat what is in effect an opposing symptom seems counter intuitive. As such, the scientific community has not yet arrived at a consensus of opinion with regards a mode of action for this effect.

However, the use of atypical antipsychotics to treat the depressive symptoms of bipolar disorder may be the result of what was previously thought to be a weakness of this drug class – their relatively unselective targeting of several receptor sub-types. Although atypical antipsychotics are more selective than their traditional predecessors, activity at receptor sub-types largely unrelated to antipsychotic efficacy may result in an antidepressant effect.

New treatments for bipolar depression set to drive near-term growth

Along with the anticipated patient benefit of Seroquel for bipolar depression, pharmaceutical companies will benefit from this new-found use for their atypical antipsychotic franchises. AstraZeneca will reap many of the initial rewards; Seroquel will generate an estimated $1.76 billion from global bipolar disorder sales in 2008, maintaining its leading position as the number one atypical antipsychotic for this disorder in the US, and pushing it from second to first place globally.

However, many of the other drugs in this class will show a similar benefit. With clinical trials investigating the efficacy of Pfizer’s Geodon (ziprasidone) and Bristol-Myers Squibb’s Abilify (aripiprazole) for bipolar depression currently underway, AstraZeneca’s advantage may be short-lived.

Stimulated by sales of the atypical antipsychotics for bipolar depression, the global bipolar disorder market will continue to grow until 2011, when revenues will peak at $6.6 billion. Current treatment for bipolar disorder consists of a diverse range of drug classes borrowed from other conditions. Along with the atypical antipsychotics, which where originally developed for schizophrenia, anticonvulsants are frequently used as ‘mood stabilizers’.

Less than half atypical antipsychotic sales generated from treatment of schizophrenia or bipolar disorder

The atypical antipsychotic class of drug has proved to be one of the most lucrative for pharmaceutical companies. The top six atypical antipsychotic drugs are valued at approximately $10 billion in 2005 in the US alone. Bipolar disorder was the single largest indication for atypical antipsychotic sales, generating $2.7 billion in the US last year. The treatment of schizophrenia only constituted 18% ($1.8 billion) of the total US atypical antipsychotic sales.

Last year, $5.5 billion was generated from a plethora of other conditions, most of which is off-label prescribing. Conditions with sales of atypical antipsychotics of over $1 million include schizoaffective disorder, post traumatic stress disorder, generalized anxiety disorder, anorexia nervosa, obsessive compulsive disorder, sleep disorders and psychosis associated with neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.

Pharmaceutical companies will continue to leverage their atypical antipsychotics by seeking further indication expansions. The recent launch of Seroquel for the depressive phase of bipolar disorder is an example of the continued development of this class of drug. This may also be an indication of the future direction. Clinical trials are underway investigating the efficacy of various atypical antipsychotics against major depressive disorder. ‘End Intelliext