I’m of the belief that the English language can’t describe the devastation caused by schizophrenia. It’s a crippling illness, one capable of lowering lifespan by 20 years. Patients with schizophrenia are more likely to commit suicide, end up in jail, and become homeless than individuals in the general population. A mental illness so severe that its name translates into ‘splitting of the mind’ in Greek.
The true pathophysiology of schizophrenia remains poorly understood. The use of dopamine and serotonin antagonists to suppress hallucinations and delusions appears to support the hypotheses that describe neurotransmitter imbalances. Yet, a true understanding of these imbalances remains elusive. Schizophrenia is too complex. A single pharmaceutical agent capable of treating the disease is likely impossible. The disease process occurring in the brain can‘t be “cured“ with a receptor activator or inhibitor. Rather, current medications act as a stopgap. By essentially “turning off“ certain cortical pathways via receptor blockade we stop the psychosis. Stopping psychosis often comes at a cost: we radically change our patient‘s personality and exacerbate symptoms of depression and apathy.
The First Antipsychotics
A 1962 advertisement for the first generation antipsychotic Thorazine
The early antipsychotic medications were discovered in the 1950s and 1960s. Haloperidol and chlorpromazine were touted to practitioners as ways to control patients. By blocking neurotransmitter receptors, these drugs could stop delusions, hallucinations, and acute manic behavior. The sedating effects of these drugs led the American Psychiatric Association president to testify in front of Congress that they were a “Godsend” in 1962. Widespread use of these and the subsequent political pressure encouraged the closing of numerous ‘insane . The argument was that patients treated with these medications could now be treated with less intensive care, in either community based inpatient facilities or even as an outpatient.
The drugs, however, came with nasty side effects. Tremors, abnormal movements, and uncontrollable muscle spasms often inhibited their widespread use in psychotic patients. First generation medications were never a “Godsend.” They failed to cure schizophrenia and were unable to magically conjure up a sustainable mental health system within the United States.
They Were Supposed to Be Different
An early 2000s advertisement for Zyprexa, a second generation antipsychotic
Perhaps no medication better highlights the second-generation antipsychotics better than Zyprexa. The advertising campaigns launched by Eli-Lilly in the early 2000s emphasized Zyprexa’s efficacy and tolerability over the first-generation antipsychotics. Physicians quickly bought into the hype, and Zyprexa was soon prescribed for numerous conditions ranging from depression to dementia. Within a couple short years, Zyprexa became a hit.
Mood stabilizers and antipsychotics remain potent money–makers for pharmaceutical companies. Millions of Americans and bipolar disorder, and the American Psychiatric Association recommends long term medical treatment for these disorders. Developing a drug for mood regulation taps into a revenue stream that won’t run dry for 20 years. For Eli-Lilly, Zyprexa fit the bill as that wonder drug. As Eli-Lilly’s bestselling drug, it netted over in sales in 2005.
Unfortunately, Zyprexa wasn’t a wonder drug. Side effects soon emerged, and prescriptions fell by 50% from 2003 to 2007. The link between the development of diabetes and Zyprexa soon became undeniable, and Eli Lilly paid over to settle lawsuits. The off-label use of Zyprexa to help control dementia patients soon came under scrutiny, and Eli Lilly ultimately pled guilty to illegal marketing of Zyprexa for use in dementia.
The story of Zyprexa isn’t a unique one. Antipsychotic medications are one of the most profitable classes of medication, and pharmaceutical companies are often willing to settle any potential lawsuits that arise from their aggressive marketing campaigns and drug side effect profiles. The market is simply too lucrative, and physicians remain all too willing to prescribe multiple powerful mood altering medications in the name of health.
Despite costly marketing campaigns and medications that were touted as improved over typical antipsychotics, the industry