Background


Prevalence


Treatment


Current Drugs



Background


Schizophrenia (derived from the Greek for "split mind") is a chronic mental disorder affecting both cognition and emotion. Symptoms are generally categorized into three domains: positive, negative, and cognitive. Positive symptoms include delusions and auditory/visual hallucinations. (Note that "positive" refers to the addition of unwanted mental processes rather than beneficial ones.) Negative symptoms include blunted emotional responses and decreased motivation. Cognitive symptoms (although rarely associated with the disease by the general public) are widely observed in patients with schizophrenia and highly debilitating. They may include an inability to concentrate, poor short-term memory, and deficits in executive function, a term which refers to an individual's ability to integrate information and make appropriate decisions. With a typical onset in early adulthood and persistence throughout the lifespan, the disease has a devastating effect on patients and their families.


Prevalence


Schizophrenia affects nearly 2.5 million Americans, comprising 1.1% of the adult population. Individuals with schizophrenia occupy up to half of all psychiatric inpatient beds and account for 5-10% of all hospital patient-days. They make up a disproportionate number of the incarcerated or jailed and constitute about a third of the homeless population. Taken together, the estimated total economic costs in the United States for schizophrenia are more than $60 billion annually.


Treatment


Schizophrenia is usually treated with a combination of psychotherapy and medication. Antipsychotic drugs are thought to provide their beneficial effects by reducing levels of the signaling molecule dopamine in certain brain regions. Common side effects of these treatments include blurred vision, drowsiness, weight gain, and metabolic disruption. Importantly, these side effects can produce significant increases in diseases like diabetes, high cholesterol (hypercholesterolemia), and tremors (tardive dyskinesia). All of these factors contribute profoundly to decreased medication adherence--nearly 50% of patients choose to stop taking their medication during the course of treatment, causing relapse and difficulty in re-establishing control over the disease. Thus, novel medications with diminished side effects that address both the negative and cognitive symptoms of schizophrenia are in great need.



Current FDA-Approved Drugs


Drug Name Brand Name
(Company)
Peak
US Sales
Year
Approved
Generic Class Structure
Quetiapine Seroquel
(AstraZeneca)
$3,747M
(2010)
1997 Yes Dopamine
Antagonist
Olanzapine Zyprexa
(Eli Lilly)
$2,496M
(2010)
1996 Yes Dopamine
Antagonist
Aripiprazole Abilify
(Otsuka)
$2,082M
(2009)
2002 Yes Partial
Dopamine Agonist
Risperidone Risperdal
(Janssen)
$1,790M
(2007)
1993 Yes Dopamine
Antagonist
Ziprasidone Geodon
(Pfizer)
$1,309M
(2011)
2001 Yes Dopamine
Antagonist
Paliperidone Invega
(Janssen)
$319M
(2011)
2006 No
(2017)
Dopamine
Antagonist