India's No.1 PU & Degree With Integrated IAS & IPS(UPSC/PSC) Training College.
FDA Approval for Cobenfy Casts Light on Schizophrenia’s Wickedness
Relevance: GS – 3 : Science and Technology – developments.
Why in the News?
- On September 26, the U.S. FDA approved Cobenfy for the treatment of schizophrenia.
- Cobenfy is notable for its novel mechanism of action, targeting cholinergic receptors instead of dopamine receptors.
- This makes Cobenfy the first antipsychotic that does not rely on dopamine receptor modulation.
- The drug is a combination of xanomeline and trospium chloride.
- It is designed to avoid many of the side-effects associated with older antipsychotics, though it has its own unique side-effects.
Understanding Schizophrenia
- Schizophrenia is one of the most serious psychiatric disorders, leading to life-altering consequences.
- Key impacts include social isolation, stigma, and reduced chances of forming relationships.
- Individuals with schizophrenia have a life expectancy 13-15 years shorter, due to factors like: Weight gain, Poor dietary habits, Smoking, Comorbid substance use.
- 5% of people with schizophrenia die by suicide.
- It affects 1 in 100 people over their lifetime.
- New research indicates it is slightly more common in men than women.
- Schizophrenia typically develops in late adolescence and early adulthood:
- In men, it peaks in the early 20s.
- Women may experience new cases in their mid- to late 40s.
- To appreciate Cobenfy’s novelty and potential, it is essential to understand the effects of schizophrenia, its diagnosis, and evolving scientific views on its causes.
Clinical Symptoms of Schizophrenia
- Historical contributions:
- Paul E. Bleuler (1911): defined schizophrenia using the “four As”—affect, associations, ambivalence, and autism.
- Kurt Schneider: identified “first rank” symptoms, including third-person auditory hallucinations and experiences of external control over actions, sensations, or emotions.
- Cognitive impairment: Common across patients, impacting judgement, attention, memory, and general intellectual abilities.
- Prodromal symptoms:
- Precede the onset of schizophrenia and last for under 12 months.
- Include feelings of inner change, new spiritual or philosophical interests, anger, irritability, anxiety, depression, and social withdrawal.
- Clinical phenotype is categorized into three groups:
- Reality distortion (positive symptoms):
- Delusions and hallucinations.
- Formal thought disorder: disorganized speech patterns that are difficult to follow.
- Disorganisation symptoms:
- Disorganized behaviour, formal thought disorder (also a positive symptom).
- Inappropriate affect: emotional responses that are out of context.
- Catatonia (now rare): abnormal motor behaviour accompanied by stupor or excitement, seen in other psychiatric conditions as well.
- Negative symptoms:
- Reduced speech, goal-directed activities, motivation (apathy), energy (anergia), and pleasure.
- Reduced emotional expression.
Causes of Schizophrenia
- Schizophrenia is a multifactorial disorder, meaning it results from a combination of factors, not a single cause.
- Genetics plays a significant role in the disorder’s pathophysiology:
- Genetic variants influence brain development and function by altering gene expression.
- Unlike single-gene disorders (e.g., Huntington’s disease, cystic fibrosis), schizophrenia is polygenic, involving hundreds or even thousands of genes with small effect sizes.
- Some rare genetic variants with moderate to large effect sizes have also been identified.
- A 2014 genome-wide association study identified 108 genetic loci linked to schizophrenia, though correlation doesn’t necessarily imply causation.
Neurodevelopmental Theory
- Neurodevelopmental theory suggests that schizophrenia’s causes include events occurring early in life, at birth, or even during pregnancy (in utero).
- Prenatal and perinatal complications are significant environmental risk factors for developing schizophrenia.
- The interaction between genetic risk and early-life complications can increase the likelihood of developing schizophrenia by up to fivefold.
- Discoveries of risk-conferring genes and insights into the neurodevelopmental origins of schizophrenia have enhanced our understanding of its pathophysiology.
Xanomeline and Trospium: Neurotransmitters
- Dopamine and glutamate have been implicated in the development of schizophrenia, but research findings have been conflicting.
- The dopamine hypothesis arose from observations that amphetamine abuse stimulates dopamine release and mimics schizophrenia symptoms, leading to antipsychotics being developed to block dopamine receptors.
- Evolution of the dopamine hypothesis: The original version of the dopamine hypothesis has been discredited due to new evidence showing that individuals with established schizophrenia exhibit increased dopamine synthesis capacity. Only one study has failed to replicate these findings.
- Cobenfy: Recently approved by the FDA, Cobenfy is the first antipsychotic to target cholinergic receptors instead of dopamine receptors, marking a shift in treatment approaches.
- Xanomeline and Trospium:
- Xanomeline was initially developed for Alzheimer’s and schizophrenia but faced discontinuation due to adverse effects. It regained interest when combined with trospium.
- Xanomeline acts as an agonist of muscarinic receptors in the parasympathetic nervous system, potentially improving all types of schizophrenia symptoms.
- Trospium, an antimuscarinic agent, is expected to mitigate the adverse effects of xanomeline.
- Side effects and pricing:
- The most common side effects of Cobenfy include nausea, indigestion, hypertension, tachycardia, and dizziness.
- The drug is produced by Bristol Myers Squibb and is priced at $1,850 per month.
Associated Article
https://universalinstitutions.com/recasting-care-models-for-mental-illness-and-homelessness/
Mains question
What is the significance of antipsychotics in the treatment of schizophrenia, considering its side effects, and implications for future therapies. Discuss it in line with the mental health perspective. (250 words)
