World Mental Health Day: Breakthroughs in Schizophrenia Treatment and the Promise of Cobenfy
By Arunima Rajan
In an exclusive interview with Arunima Rajan, Aparna Ramakrishnan, a consultant psychiatrist at Kokilaben Dhirubhai Ambani Hospital, explores the often-overlooked early signs of schizophrenia, the latest advancements reshaping treatment options, and the potential of Cobenfy—a new drug that targets cholinergic receptors, offering new hope for patients who haven't responded to traditional therapies. This conversation highlights the evolving landscape of schizophrenia care in India and underscores the importance of timely intervention in improving long-term outcomes.
Can you elaborate on what schizophrenia is and how its symptoms manifest in patients, particularly in Indian context?
Schizophrenia is one of the most common of the severe mental disorders. In schizophrenia and schizophrenia spectrum and other psychotic disorders, there is a fundamental and characteristic distortion of thinking, perception, affect. Clear consciousness and intellectual capacity is usually maintained though certain cognitive deficits may evolve over a course of time. There is loss of touch with reality. Symptoms of schizophrenia include delusions, hallucinations, disorganisation of speech and behaviour or catatonia, negative symptoms (affective blunting, alogia, avolition, apathy, anhedonia, asociality, inattention). Other symptoms include thought echo, thought insertion/withdrawal/broadcasting and delusional perception. These cause significant distress and socio occupational impairment. A few Indian studies have shown lower prevalence of schizophrenia in India than in the west. One reason for this could be underreporting. Cultural influences have also been seen in symptomatology. Paranoid schizophrenia was the most common subtype. Themes of delusions have also found to be associated with sociocultural background and beliefs of patients with religious delusions being common in Christian societies, magico-religious delusions being common in rural societies, women. First rank symptoms were more frequently found in India. Negative symptoms were reported to be more disturbing in the Indian context.
What are the key early signs of schizophrenia, and how can health care professionals in India encourage timely diagnosis and treatment ?
Aparna Ramakrishnan, Consultant Psychiatrist, Kokilaben Dhirubhai Ambani Hospital
The onset of schizophrenia is mostly post puberty – late teens to early thirties. Onset is slightly earlier for males as compared to females. Some early warning signs may include social isolation wherein a person may withdraw contact with friends and family. They may exhibit decreased sleep, lower academic and work performance. They may complain of reduced focus and attention, may display mood swings, irritability , heightened levels of anxiety or excess thought rumination often up to obsessional levels. They may have trouble organizing thought resulting in irrelevant, incoherent talk and difficulty in maintaining the train of thought. Behavioural changes like muttering to self as if they are having a conversation with someone, smiling to self, mirror gazing may be seen. They may develop odd thoughts, beliefs, suspiciousness, paranoia and delusions. They may developed auditory hallucinations and other abnormal sensory perceptions. Self care is neglected and there is a decline in personal hygiene or appearance. They struggle with activities of daily living and work and academic responsibilities.
Healthcare professionals can encourage timely diagnosis and treatment by providing information about the early signs of schizophrenia to patients ,families and general population so that they can recognize symptoms sooner. Use of standardized screening tools and assessment in routine mental health check-ups also helps in early diagnosis. Health care professionals should provide a safe, supportive non-judgemental environment to all their patients and take a detailed history so that any unusual experiences can be quickly detected and evaluated. Monitoring at risk patients by collaboration with general practitioners, psychologists, social workers can help in early detection. Regular follow ups of at risk patients or patients with mental health issues helps in early diagnosis. Provision of information about mental health, support groups , information about resources available for management of mental health issues can encourage people to seek help as early as possible.
Living with schizophrenia can have profound effects on a person’s ability to function professionally and socially. Can you discuss how the disorder affects day to day life and challenges that patients typically face in India?
Schizophrenia can have a significantly impact on day to day life. patients often find it difficult to manage daily tasks, such as personal hygiene, cooking, or cleaning leading to neglect of self-care. Disorganized thinking, concentration issues can affect academic and work performances leading to socio occupational dysfunction. Paranoia, social withdrawal leads to isolation and inability to maintain social relationships. Furthermore, mood swings, anxiety, aggression, apathy effect their own emotional experience and can lead to avoidance by friends and family leading to further social isolation. Cognitive issues make it difficult for them to take decisions, manage finances or even gain or stay employed. Stigma associated with schizophrenia can lead to further isolation and low self-esteem. Comorbid physical health issues are also common in patients with schizophrenia
Indian patients with schizophrenia also face unique challenges foremost of which is stigma and discrimination. This leads to shame and reduced help seeking behaviour and isolation. Lack of awareness about the disorder can result in delayed or misdiagnosis and treatment issues. Access to mental health care and available resources are limited which is another challenge in the Indian context. Financial constraints and cultural beliefs and superstitions may lead to dependence on magico-religious treatment rather than professional help. Non acceptance or lack of support by families, and lack of adequate awareness regarding medications and treatment, fear regarding mental health issues can lead to delay in seeking help and non-adherence to necessary treatment.
Schizophrenia treatment has evolved over the years. Could you share some of the latest advancements in treatment modalities, particularly those relevant to Indian patients and how they improve long term outcomes ?
Antipsychotics remain the mainstay of treatment of schizophrenia. But newer antipsychotics like the 2nd generation and 3rd generation ones are associated with fewer side effects. Long acting injectable antipsychotics can be given monthly or fortnightly which improves treatment adherence. Newer antipsychotics targeting other neurotransmitters like glutamate besides the traditional dopamine are also being considered to improve efficacy and reduce side effects. Other techniques like Deep Brain Stimulation, Transcranial Magnetic Stimulation (which is non-invasive) are new treatments being used in patients. Insight oriented therapy, cognitive behaviour therapy specifically addressing symptoms also show significant effect on treatment. Psychoeducation of patients, families, general population and early intervention strategies in at risk patients improves outcome. Digital health services like apps, telehealth services are useful for treatment, monitoring and follow up and providing access to mental health care all across the country.
These novel strategies help in early diagnosis and intervention, alleviate suffering, reduce socio occupational dysfunction, reduce side effects, improve treatment adherence, prevent relapses and improve long term outcomes in patients.
Diagnosing schizophrenia can be complex. What are some of the unique challenges that Indian psychiatrists face in diagnosing schizophrenia and how can we work towards a more accurate earlier diagnosis?
Some of the unique challenges that Indian psychiatrists face in schizophrenia diagnosis are lack of awareness about the condition among general population and even health care professionals, stigma and cultural belief based interpretation of symptoms. This leads in delayed help seeking, delayed diagnosis or misdiagnosis and treatment. India is a vast country with a diverse cultural and socioeconomic milieu, which makes assessment complicated. Financial constraints and access to mental health care resources especially in rural areas, lack of education can lead to delay in help seeking or patients turning to traditional healers or general practitioners who have limited knowledge of the disorder. Economic factors also affect treatment adherence and lead to relapses. Comorbidities like substance use disorders are very common in patients with schizophrenia, which makes treatment complicated. There is significant shortage of health care professional in our country which leads to evaluation and treatment challenges.
Early and accurate diagnosis of schizophrenia can be done by a Comprehensive Clinical Interview to gather information about the patient's medical history, family history of mental illness, and the onset and progression of symptoms, a thorough mental status examination and observation of symptoms, assessment of impact on personal and socio occupational domains. Standardized tools of assessment like the Positive and Negative Syndrome Scale (PANSS) or the Structured Clinical Interview for DSM-5 (SCID-5), SANS (scale for assessment of negative symptoms), SAPS (scale for assessment of positive symptoms) lend more accuracy to the diagnosis. History should be collected from reliable sources like family, close friends along with the patient. The assessments should be culturally sensitive for accuracy of diagnosis. Other psychiatric disorders (like bipolar disorder, depression with psychosis) or physical conditions that may mimic schizophrenia (like infections, neurological disorders ,substance or drug induced psychosis) should be ruled out. Psychoeducation of family for early signs and signs of relapse should be done and regular follow up should be encouraged for diagnostic confirmation and monitoring as symptoms often evolve over time.
There is often confusion between bipolar disorder and schizophrenia as both can invoke episodes of psychosis. Could you explain the key differences between these two conditions and how a psychiatrist in India approaches differential diagnosis and treatment for each ?
Bipolar disorder is mainly a disorder of mood and affect. It is usually characterised by episodes of mania or hypomania and depression with relatively normal periods of stable mood in between. In a manic episode there is usually mood elevation or irritability, elevated self-esteem, grandiosity, overtalkativeness, flight of ideas and racing thoughts, increased goal directed activity, impulsivity, decreased need for sleep, increased energy levels, overfamiliarity etc. A depressive episode is characterised by pervasive sadness of mood, loss of interest, fatigue, decreased sleep or hypersomnia, decreased appetite and weight loss or increased appetite and weight gain, negative thought ruminations, ideas of helplessness, hopelessness, worthlessness, death wishes and often suicidal ideations and acts. It usually starts in late adolescence or early adulthood, usually has an episodic course, causes less socio occupational dysfunction as compared to schizophrenia. Schizophrenia is mainly a disorder of thought and perception characterised by delusions, hallucinations, disorganised thought/speech, disorganized behaviour, negative symptoms and catatonia. Its primarily a psychotic disorder and though mood symptoms may occur, they are not the primary or defining feature. Age of onset is late teens to early adulthood. Symptoms must persist for at least six months, including at least one month of active-phase symptoms (e.g., hallucinations, delusions). The course may be chronic, with symptoms sometimes fluctuating in intensity.
Accurate diagnosis is through thorough history taking, comprehensive clinical interview with patient and other reliable sources, mental status examination, physical examination and history to rule out other psychiatric and medical disorders which may mimic these conditions, use of standardised assessment scales.
Bipolar disorders are usually treated with antipsychotics, antidepressants, mood stabilizers, benzodiazepines and psychotherapy. Schizophrenia is usually treated with antipsychotics and psychosocial interventions.
A new drug called Cobenfy developed by Bristol Myers Squibb targets cholinergic receptors instead of traditional dopamine receptors used in most schizophrenia treatments. How significant is this shift in treatment approach and what impact could this have on schizophrenia care particularly for Indian patients who may not respond to existing dopamine targeted therapies ?
COBENFY (xanomeline and trospium chloride) is a drug recently approved by US food and drug administration for oral use in treatment of schizophrenia in adults. It targets cholinergic receptors. Research conducted over a period of 5 weeks showed that patients who received Cobenfy had a meaningful reduction in PANSS score that measures symptoms of schizophrenia. Some of the advantages purported are fewer side effects (especially the ones related to dopamine blockade like tremors, rigidity, movement disorders ) and blocks muscarinic receptors in peripheral tissues. It has been shown to decrease negative symptoms of schizophrenia. It’s the first new approach to schizophrenia treatment in decades. It can be a game changer for people with treatment resistant schizophrenia or the ones having intolerable side effects like extra pyramidal symptoms, weight gain, metabolic issues and can improve treatment adherence. Having said that longer trials with more subjects is required for accurately determining the efficacy, safety and long term effectiveness of this drug.
Many patients worry about weight gain due to medication for schizophrenia. Could you shed light on this issue and discuss other common side effects associated with schizophrenia treatment
Antipsychotic induced weight gain is a major management problem for clinicians and patients often leading to non-compliance to treatment. Antipsychotics can also impair glucose metabolism, increase cholesterol and triglyceride levels and increase arterial hypertension leading to metabolic syndrome. Clozapine and olanzapine – 2nd generation antipsychotics have been identified with highest weight gain. Actions on Serotonin (5HT2A,5HT2C) dopamine D2, D3, Histamine H1 and muscarinic M1 receptors is associated with weight gain. Antipsychotics also affect neuropeptides associated with appetite control and energy metabolism which in turn affect weight.
Other side effects of various antipsychotics are anticholinergic effects (dry mouth , constipation, urinary retention) , akathisia, extrapyramidal symptoms like tremors, rigidity, dyskinesia, excess salivation, orthostatic hypotension, changes in blood counts, sedation, increased prolactin levels, sexual dysfunction, myocarditis, agranulocytosis, deranged sugar levels. They vary according to type of drug, dosage, individual vulnerability.
One of the most significant challenges in managing schizophrenia is when patients refuse to seek help or adhere to their prescribed medication. What strategies can caregivers, psychiatrists and health care system implement to encourage consistent treatment and address this issue particularly in India where mental health awareness is still growing ?
Psychiatrists can psycho-educate the patients and caregivers about the disorder, need for treatment and long term benefits. Building a rapport with patients and caregivers can be of great use during treatment and results in treatment adherence. Tailor treatment plans according to patients lifestyle, preferences and needs. Psycho-educate the patients and caregivers about the purpose of the medication, mechanism of action, effects, side effects and address their concerns patiently and honestly. Use simple drug regimens, consider long acting injectable formulations. Address side effects and manage them adequately. Involve family in the treatment process to ensure compliance, encourage patients to use reminders like apps, alarms, pill organizers to take medication. Ensure regular follow up to monitor progress, alter medications if needed, evaluate and address reasons for non-compliance.
Caregivers can ensure treatment compliance by psycho-educating themselves about schizophrenia and helping their loved ones who are suffering from this condition to understand the importance of treatment. They can foster a supportive environment for the patient where he or she can express their concerns without fear or judgement. They can help the patient set a routine for medication, therapy, activities and help them set reminders to take the medications. They can monitor the progress and warning signs of relapse and can encourage patients to be an integral part of their own treatment process. They can foster a calm, supportive living condition which improves the treatment process. They can facilitate regular check-ups and follow ups with the mental health professionals and approach them for help if compliance remains a challenge.
Health care system can facilitate programmes for mental health awareness, provide affordable and accessible mental health care to all those in need and promoted an integrated health care model combining services for physical and mental health – promoting that a sound mind and a sound body go hand in hand.
As people with schizophrenia age, do the symptoms of the disease tend to become milder or do they persist with the same intensity? How should treatment strategies evolve for older patients with schizophrenia ?
As you get older some studies suggest that positive symptoms of schizophrenia like delusions and hallucinations are likely to improve but negative symptoms may persist. However this varies from person to person. Negative symptoms may persist or worsen deteriorating the quality of life. Cognitive issues become more pronounced as you age and so do physical health issues and comorbidities. This can lead to more medication related side effects and inability to use some medications in view of the physical health issues. Social support systems may diminish as the individual gets older leading to isolation and its bad impact on mental health. On the bright, many a time symptoms may stabilize and patient may gain more insight into his/her illness leading to better treatment compliance and maintenance of quality of life.
For older patients with schizophrenia, medical management has to be done very carefully. Lowest effective doses of medications with least side effects and least drug-drug interactions should be used because older patients may have several physical comorbidities and may be on treatment for the same. Regular monitoring ,follow ups for efficacy and side effects should be done. Family involvement is integral in the treatment process especially to monitor the patient and watch out for any side effects and to ensure medication compliance. Psychosocial interventions and supportive therapy should be done. Access to community support like support groups, social services will reduce isolation. Rehabilitation including cognitive rehabilitation should be a part of the treatment process. Collaboration with the patients other health care providers is a must for holistic care of the older patient.
Are there online support groups or resources available for patients and caregivers of people with schizophrenia in India? How can they benefit from these communities and what role do they play in the overall management of the disorder ?
Yes, there are several online support groups and resources available for patients with schizophrenia and their caregivers including SCARF (Schizophrenia research foundation) India, Schizophrenia Awareness Association (SAA) which provides support and resources for individuals with schizophrenia and their families including educational materials and support options. Mental Health Foundation India offers resources, articles, and online support for various mental health conditions, including schizophrenia. They also have community outreach programs. Indian Psychiatric Society (IPS) website includes resources for mental health, including links to support groups and information about local mental health services.
There are also several Instagram and Facebook and WhatsApp support groups which provide platforms to share experiences and have a sense of community. Telehealth services offer online consultations with mental health professionals. Podcasts on you tube and other social media platforms help provide awareness and guidance . hospitals and NGOs also have support groups for patients and caregivers.
Such platforms offer support, educational material, offer a sense of community, guidance all of which goes a long way in inclusivity of the patient into society and easing caregiver burden too.