Abhijit Ramanujam, MD

Abhijit Ramanujam, MD, introduces Transcranial Magnetic Stimulation (TMS) as an option for treating your patients with hard-to-treat depression.

is a practicing child and adolescent psychiatrist in Sacramento, California, and the Regional Medical Director of

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What are the clinical benefits of TMS? How can you talk to your patients about this option?

Talking to Patients About Transcranial Magnetic Stimulation 

The year 2020 has proven to be a year of challenges and uncertainties thanks to 

 (COVID-19). We started the year relatively unaware of the virus, and now it impacts every aspect of our lives. Although the initial concern was aimed at the oldest and most frail segments of the population, we must not forget our younger patients and the unique psychological challenges that children face during this pandemic.

The reopening debate: in-person versus online learning

One of the most contested issues in the country revolves around the reopening of schools. On the one hand, there are concerns over the social and learning needs of children; on the other are the health risks facing students, teachers, other school personnel, and their respective families.

for in-person school and learning, since schools provide academic, social, and emotional skills and support that are hard to replicate at home.

 However, the AAP also affirmed “science should drive decision-making on safely reopening schools,” and noted “a one-size-fits-all approach is not appropriate for return to school decisions.” The AAP added:

“Reopening schools in a way that maximizes safety, learning, and the well-being of children, teachers, and staff will clearly require substantial new investments in our schools and campuses. We call on Congress and the administration to provide the federal resources needed to ensure that inadequate funding does not stand in the way of safely educating and caring for children in our schools. Withholding funding from schools that do not open in person full-time would be a misguided approach, putting already financially strapped schools in an impossible position that would threaten the health of students and teachers.”

American Academy of Child & Adolescent Psychiatry 

 similarly stated, “In these uncertain times, making educational decisions based on science and community circumstances ensures the mental health needs of our children and adolescents are being addressed, allowing them to feel engaged, safe, secure, supported, and loved.”

 They also acknowledged that “education, including school attendance, is an essential component of successful and healthy development for all children and adolescents” and offered guidelines for reopening. They mentioned ensuring the well-being and educational needs of vulnerable populations like “children with emotional, learning, and physical disabilities as well as those in foster care, poverty, and for whom English is a second language, to mention but a few.”

What is “safe”? Lessons from around the world

The push to open schools in-person was originally based on the theory that children were largely not affected by COVID-19 and that transmission from asymptomatic children was uncommon. However, this assumption came after the strict physical distancing measures and school closures, and the story appears to have changed. The appearance of multisystem inflammatory syndrome, which causes serious, even life-threatening illness in previously healthy children and adolescents, served as a rude wake-up call.

 By August 6, 2020, the Centers for Disease Control received reports of 570 cases and 10 deaths across 40 jurisdictions (

 The affected children were aged 1 to 14 years; their average age was 8 years. Almost all children (96%) with the syndrome tested positive for SARS CoV-2, the virus responsible for COVID-19; the others had been in the vicinity of someone infected with the virus.

New data also show that children are not invulnerable to COVID-19. In the United States, the number of cases in children rose 44% between July 9 and July 23, according to a report which also found that children accounted for 8.4% of US cases.

 With 20 states reporting, researchers found between 0.6% and 9.0% of all juvenile COVID-19 cases resulted in hospitalization, confirming that severe illness was possible in children, albeit rarer than in adults. Similarly, in 8 days in July, Florida saw a 34% increase in new cases and a 23% increase in hospitalizations among children; the test positivity rate among children also increased.

 Recent news reports also tell of thousands of students and teachers quarantined as the number of COVID-19 infections rip through schools in several states after re-opening in person.

Some proponents of a wider in-person school opening have noted that children are less likely to spread the virus, but a new report in 

 The authors found that replication of SARS-CoV-2 in older children resulted in similar levels of viral nucleic acid as in adults, but found significantly greater amounts of viral nucleic acid in children younger than 5 years. Considering behavior and hygiene issues in younger children, the authors said, “Young children can potentially be important drivers of SARS-CoV-2 spread in the general population.”

Lessons can also be learned by looking abroad. Two weeks after reopening schools, Israel saw a spike in COVID-19 cases, with more than 200 cases among students, and 130 cases at a single school.

 Countries including Singapore and South Korea also experienced spikes in cases when schools were reopened.

Guiding parents and supporting young patients

This is new territory for everyone, and young patients and their parents are likely to experience stress and anxiety as the school year begins. There are several ways parents can prepare themselves and their children for a relatively smooth transition.

First and foremost, clinicians should counsel parents to consider their individual family needs and issues, then develop a clear plan in terms of social distancing.

 Families with at-risk individuals may prefer more stringent rules, while others may err on the side of socialization. Once parents have determined what works best for their family, they should make the socialization rules very clear to their children, discussing realistic and practical strategies to mitigate the chances of infection.

 The approach and discussion should be tailored to the age and maturity of the child.

Children need a sense of safety and stability, so navigating these waters can be tricky. Parents should explain that although schools are reopening, socialization will be a step-by-step process. Regroup as needed with children and adolescents to provide updates, share reminders, and allow for questions.

Children in upper elementary and middle school grades are prone to receiving misinformation, either via friends or social media. Parents should facilitate family conversations, listening carefully to their children’s concerns and helping them separate fact from fiction.

Finally, role play may assist children and adolescents as they negotiate this new school year. It can be difficult even for adults to request that someone maintain their distance or ensure that their mask is properly covering their mouth and nose. Share ways to make the conversations easier. For younger children, you can even make it a game. Act out correct and incorrect behaviors, and see if they can pick out the mistakes.

Special issues associated with psychiatric disorders

Children and adolescents with pre-existing psychiatric disorders may have additional struggles with social distancing, online learning, and the resulting changes and lack of consistency. Although in-person learning is ideal, not all schools will be able to do so. Similarly, even those schools that initially begin in-person learning may need to move to remote learning. Fortunately, there are strategies to help support students with various psychiatric symptoms and disorders.

Children with an attention-deficit/hyperactivity disorder (ADHD) diagnosis. Family confinement and physical distancing may exacerbate ADHD-related risk-taking behavior.

 As much as feasible, additional medication doses should not be used to manage stress related to confinement. Also, steer clear of using any antipsychotic medication to manage disruptive behavior. Instead, use behavioral parenting strategies that have a beneficial effect for children with ADHD and disruptive behavior (

Treatment adherence may become an issue for these patients. Unfortunately, current evidence does not support the use of outpatient telepsychiatry to improve adherence. For 

who are acutely ill, daily home visits by a treatment team member is recommended as an alternative to hospitalization. This allows the child and their family to maintain physical distancing and minimize exposure to COVID-19.

It is quite likely that socially anxious children will refuse to return to school; even under ideal conditions, a new academic year can be a trigger. It is important to validate their feelings and answer questions truthfully, while not offering unnecessary details. Always try to remain calm during these discussions. Whenever possible, parents should avoid excessive reassurance and instead encourage self-reliance. Parents should model how to manage difficult emotions.

It is also important to frame statements in a positive way. For example, avoid phrases like, “There’s nothing to be afraid of,” “It’s not a big deal,” or “You’ll be just fine.” Instead, try, “I would really like for you to go on a bike ride around the neighborhood. The streets are safe.” Additional tips can be found online at the 

Since the world has become a scarier place with so many risks outside of the home, it is important that parents inform their child with anxiety every time they leave the house for work or essential errands. It is also helpful to remind them that frontline workers are addressing the situation.

It is important that parents are fully aware of warning signs and symptoms (

). Children with depression have a tendency to isolate, and social distancing can worsen such. Parents should ensure that their child joins them for family meals. Work with the child to come up with a list of family activities and regularly keep them engaged. Have regular check-ins and monitor media content. Discuss news stories that emphasize strength, hope, and positivity.

It also is important to teach child- ren to recognize their health risk behaviors, such as isolating, excessive sleeping, or lethargy. Encourage them to check in with family or friends. Acknowledge and normalize their distress reactions. For example, parents can share, “I can see that you are very stressed, which is very understandable. Many people are feeling that way.” Other coping strategies are listed in 

The pandemic is causing specific challenges for children with concerns around eating or body image. Disruption in important daily routines such as grocery shopping and exercise can lead to increased anxiety and worsen unhealthy food-related behaviors. These children should remain connected with their therapists, dietitians, and clinicians to create a relapse prevention plan.

I encourage parents to maintain a structure and schedule around the child’s meals and snacks. Families can get creative and encourage a variety of physical activities. The National Eating Disorders Association has extensive offerings of virtual support groups and live meal support.

There is much debate and uncertainty regarding how children and adolescents are impacted by the virus. Current research and data from previous epidemics suggest that the pandemic may be directly or indirectly associated with the onset or exacerbation of psychiatric symptoms such as anxiety disorders, depressive disorders, insomnia, and posttraumatic stress disorder.

 For instance, a study conducted in the United Kingdom by 

 found that 80% of youth surveyed reported that the pandemic made their mental health worse.

 About one-third (32%) of respondents said their mental health was “much worse” in March; this number increased to 41% in their summer follow-up survey.

Research also indicates that the pandemic may influence psychological issues associated with EDs. A study conducted recently in Australia found increased restricting, binge eating, purging, and exercise behaviors in patients with eating disorders.

 Similarly, increased restrictive and binge-eating behaviors were found in those without EDs. More than 50% of participants with EDs also demonstrated moderate to extremely severe levels of depression, anxiety, and stress.

Clinicians also need to be aware of a rapidly increasing subset of issues that include substance abuse and domestic violence and child abuse, which have become more prevalent during stay-at-home orders.

 Clinicians should pay special attention to signs of domestic violence or child abuse, including monitoring for parental stress and irritability or harsh and critical responses to child behavior during clinical encounters. Children who live in foster care, as well as gender or sexual minorities, are at a particular risk for violence and adverse mental health effects; extra care should be taken to screen these patients.

Clinicians should be familiar with the psychiatric adverse effects associated with the medications used to treat COVID-19. For example, the corticosteroid dexamethasone has benefited some critically ill patients due to its anti-inflammatory and immunosuppressant effects, but its known adverse effects include emotional lability, insomnia, and sudden mood changes.

Telepsychiatry options can be useful to minimize virus exposure. Even when children are reluctant to try online therapy or if parents view it as an inferior option, clinicians should suggest they try it anyway. Many study results, encouragingly, indicate that outpatients and their psychiatrists are generally satisfied with telemedicine.

An extensive review of 24 studies indicated that the negative effects of quarantine can be lessened when clinicians explain its purpose and how to implement it and when they emphasize the altruistic benefit of quarantine in keeping others safe.

 Depending on age and maturity level, clinicians should consider engaging children and adolescents in such discussions.

Parents also should emphasize that social distancing does not mean emotional distancing. They can offer more hugs and loving and supportive messages.

 Children should be encouraged to stay in touch with their grandparents and extended family via video. Depending on their age, children can connect with peers on social platforms and may also have supervised socially distant playdates. For anxious children, the practice of mindfulness should be considered.

 Clinicians should provide parents with additional general coping strategies (

COVID-19 has presented unusual circumstances and challenges, including the need to balance the physical, emotional, and mental well-being of children and their family members. While there is no perfect one-size-fits-all approach to school reopening and social distancing, clinicians should be prepared to support their younger patients and parents as we all navigate through these choppy waters.

is a practicing child and adolescent psychiatrist in Sacramento, California, and the Regional Medical Director of 

1. Pediatricians, educators and superintendents urge a safe return to school this fall. American Academy of Pediatrics. News release. July 10, 2020. Accessed July 28, 2020. 

https://services.aap.org/en/news-room/news-releases/aap/2020/pediatricians-educators-and-superintendents-urge-a-safe-return-to-school-this-fall

2. American Academy of Child and Adolescent Psychiatry (AACAP) and American Psychiatric Association (APA) detail steps necessary for safely reopening schools this fall. American Academy of Child and Adolescent Psychiatry. News release. July 15, 2020. Accessed July 28, 2020. 

https://www.aacap.org/AACAP/Press/Press_Releases/2020/Needs_Students_During_COVID-19_Era.aspx

3. Feldstein LR, Rose EB, Horwitz SM; Overcoming COVID-19 Investigators and the CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. 

4. Health department–reported cases of multisystem inflammatory syndrome in children (MIS-C) in the United States. CDC. July 15, 2020. Updated August 6, 2020. Accessed July 31, 2020. 

https://www.cdc.gov/mis-c/cases/index.html

5. Children and COVID-19: state-level data report. American Academy of Pediatrics. July 27, 2020. Updated July 30, 2020. Accessed August 10, 2020. 

https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report

6. Flores R, Weisfeldt S, Yan H. Child hospitalizations from Covid-19 surge 23% in Florida as schools statewide must reopen. CNN. Updated July 27, 2020. Accessed July 31, 2020. 

https://www.cnn.com/2020/07/27/health/florida-covid-children-hospitalizations/index.html

7. Walker C, Grayer A, Stuart E. More than 2000 students, teachers and staff quarantined in several schools. CNN August 17, 2020. Accessed August 19, 2020. 

https://www.cnn.com/2020/08/13/us/schools-quarantined-coronavirus/index.html

8. Heald-Sargent T, Muller WJ, Zheng X. Age-related differences in nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in patients with mild to moderate coronavirus disease 2019 (COVID-19). 

9. Estrin D. After reopening schools, Israel orders them to shut if COVID-19 cases are discovered. 

https://www.npr.org/sections/coronavirus-live-updates/2020/06/03/868507524/israel-orders-schools-to-close-when-covid-19-cases-are-discovered

10. Miller G. Managing anxiety during reopening. Child Mind Institute. 2020. Accessed July 31, 2020. 

https://childmind.org/article/managing-anxiety-during-reopening/

11. Sharfstein JM, Morphew CC.The urgency and challenge of opening K-12 schools in the fall of 2020. 

12. Cortese S, Asherson P, Sonuga-Barke E, et al; European ADHD Guidelines Group. ADHD management during the COVID-19 pandemic: guidance from the European ADHD Guidelines Group. 

13. Kozloff N, Mulsant BH, Stergiopoulos V, Voineskos AN. The COVID-19 global pandemic: implications for people with schizophrenia and related disorders. 

14. Silliman Cohen RI, Adlin Bosk E. Vulnerable youth and the COVID-19 pandemic. 

15. Wang G, Zhang Y, Zhao J, et al. Mitigate the effects of home confinement on children during the COVID-19 outbreak. 

16. Coronavirus: impact on young people with mental health needs. YoungMinds. 2020. Accessed July 31, 2020. 

https://youngminds.org.uk/about-us/reports/coronavirus-impact-on-young-people-with-mental-health-needs/

17. Phillipou A, Meyer D, Neill E, et al. Eating and exercise behaviors in eating disorders and the general population during the COVID-19 pandemic in Australia: initial results from the COLLATE project. 

18. Cohen GH, Tamrakar S, Lowe S, et al. Comparison of simulated treatment and cost-effectiveness of a stepped care case-finding intervention vs usual care for posttraumatic stress disorder after a natural disaster. 

19. Wilkinson E. How mental health services are adapting to provide care in the pandemic. 

20. Brooks SK, Webster RK, Smith LE, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. 

21. Ehmke R. Anxiety and coping with the coronavirus. Child Mind Institute. 2020. Accessed August 2, 2020. 

https://childmind.org/article/anxiety-and-coping-with-coronavirus/

22. Glassy D, Tandon P. Getting children and teens outside while social distancing for COVID-19. HealthyChildren.org (American Academy of Pediatrics). June 18, 2020. Accessed August 2, 2020. 

https://www.healthychildren.org/English/health-issues/conditions/COVID-19/Pages/Getting-Children-and-Teens-Outside-While-Social-Distancing.aspx

Articles

Younger patients are facing unique psychological challenges during this pandemic.

For Whom the School Bell Tolls: Helping Youth During the COVID-19 Crisis 

Child and adolescent psychiatrist Abhijit Ramanujam, MD, discusses clinically relevant issues in childhood schizophrenia. Dr Ramanujam is Regional Director of 

Laurie Martin (LEM): How common is schizophrenia in children under the age of 18?

 The worldwide prevalence of early onset schizophrenia,that is symptoms prior to the age of 18yrs is estimated to be about 0.5% of the population,whereas childhood onset or very early onset schizophrenia which begins prior to the age of 13, has been estimated to be around 0.04% in the United States.Much less is known about the prevalence of childhood onset schizophrenia internationally.

LEM: Is there an age in which a child is too young to consider a diagnosis of schizophrenia? What do we know about early detection of schizophrenia and how soon can it be diagnosed?

 Although there is no official age considered too young for a diagnosis of schizophrenia, we have to keep in mind that childhood-onset schizophrenia that starts before aged 13 years is extremely rare.

Whenever a child is suspected of having schizophrenia, the clinical assessment should include a thorough personal, medication, psychosocial and family history as well as physical examination, neurological work-up, laboratory evaluation, and collateral information from family and schools.

In terms of diagnosis, DSM-5 diagnostic criteria for schizophrenia in childhood and adolescence are the same as those used for adult disorders. They include the presence of significant positive and negative symptoms during a 1-month period (such as delusions or hallucinations, disorganized speech, catatonic behavior, and negative symptoms such as lack of motivation and lack of socialization). Disturbance of functioning in 1 or more major areas and continued signs of disturbance for at least 6 months, as well as the exclusion of other psychiatric or medical diagnoses.

Although the diagnostic criteria used in children are the same as those for adults, there are some key differences in clinical presentation:

• Usually hallucinations are much more common than delusions in youth with schizophrenia as compared to adults. The most common hallucinations are auditory with comments or commands. These are often accompanied by visual and tactile hallucinations.

• Although hallucinations are more common, they are least likely to reported. Many youths may not disclose auditory hallucinations since they are scared that the voices may harm them.There may also be delusions associated with it such as "The voices tell me that they will kill me if I talk about them to anyone."

• Children and adolescents are more likely to exhibit negative symptoms such as being socially aloof or having a flat affect which can sometimes be mistaken for depression or lack of motivation for plain laziness as I have actually heard some of the parents describe it.

• Cognitive decline, in particular verbal memory, attention, and concentration, is significantly affected. Delay in language, motor, and social development, and delay or deviation in developmental milestones may be pronounced as well in childhood-onset schizophrenia; although these delays are not diagnostic, they are commonly observed.

LEM: What are the most commonly confused causes of schizophrenia-like behaviors?

 There are many other disorders that can be confused with schizophrenia-like behaviors.

The most common one I see is PTSD. PTSD symptoms can include flashbacks which some patients may describe as auditory hallucinations. Hypervigilance and flashbacks together can often be misinterpreted as paranoia and hallucinations. However, you will notice less disorganized thinking and usually symptoms begin after a traumatic event.

Another area is autism spectrum disorders. Misdiagnosis of autism spectrum disorders as a psychotic disorder also occurs very commonly. Common features such as impairment in social communication can be misinterpreted as negative symptoms of psychosis. Stereotyped use of language seen in autism can be confused with disorganized speech.

It is very important to obtain a thorough developmental history and a baseline thought processes which helps distinguish these 2 diagnoses.

Some patients may have a comorbid diagnosis of autism spectrum disorder and schizophrenia. In these cases, you will see a new onset delusion or hallucination lasting longer than 1 month. Disordered or delusional thinking will be distinctly different from the baseline. We usually notice a significant deterioration of social and general functioning with comorbid diagnoses. I sometimes noticed this in children who have been through multiple foster homes. A baseline thought process is difficult to establish in this case since past history is not readily available. These children are more likely to be wrongly diagnosed as having a disorganized thinking process as opposed to a social communication issue.

Schizoaffective disorder can be a difficult one to differentiate since a psychotic syndrome continues to evolve as a child progresses through the developmental process. Again, a thorough longitudinal symptom assessment would help distinguish the 2.

Major depressive disorders with psychotic features or bipolar disorder with psychosis should also be considered very carefully. Usually in depression with psychotic features, the psychosis is generally seen when the depressive disorder has significantly worsened. Guilt dominates in depressive psychosis. In case of bipolar disorder with psychotic features, you generally see psychosis during severe episodes of mood and not during lucid intervals.

Another area that is very important to remember is that in very young children before the age of 6, anxiety can itself present as hallucinations. Many children with symptoms of anxiety report, "Someone called my name;" they may also report visual hallucinations such as "Mama, I see a shadow every night passing by." Most of these children are healthy and nonpsychotic.

Anxiety-related visual hallucinations are very common in preschool children. Usually in the history, you will notice that there will be a precipitating event such as watching a scary movie or video game that triggered such reactions. Whereas in early-onset schizophrenia, you will notice a decline in cognitive function, attention, and concentration, as well as the presence of negative symptoms which indicate psychosis.

Sometimes, substance-induced psychosis that is secondary to steroid use can present very similarly to a primary psychotic disorder. Urine toxicology screens are very important. It is also important to remember that many of the newer recreational drugs may not be detected in current screens; hence a thorough history will help us distinguish between the 2.

In case of delirium, look for waxing and waning of symptoms or evidence of ingestion of substance or any other metabolic abnormalities, since these are usually seen in delirium and not a psychotic illness.

Other medical conditions may also mimic psychotic symptoms. Those include:

• Autoimmune disorder, such as systemic lupus erythematosus

• Metabolic disorder, such as Wilson disease

I am only mentioning the positive pertinent factors in each of the following 3 cases for the sake of brevity. All names and identifying factors have been changed. This is for clinical purposes only.

Case presentation 1: Oppositional or something else?

PR is a 17-year-old boy who initially brought in by his father with chief complaints of “very oppositional, up to something, secretive, and angry.”

The father appeared remorseful due to his "busy schedule" for the last 3 to 4 years. His being away also coincided with a gradual deterioration of his son.

PR refused to talk other than state, "I hate them" [my parents].

Neuropsychological tests, detailed medical examinations, laboratory tests, and a urine drug screen came back negative; the clinical picture became clearer as we obtained collateral information.

The mother described her son demonstrated bizarre behavior. She also hesitatingly disclosed family psychiatric issues (many relatives with schizophrenia), which was initially minimized. “It is a taboo and we do not talk about it,” she said.

His siblings disclosed they are fearful of him "Since he stays up all night and talks to himself. He does not seem like our brother anymore."

School reported he was growing increasingly isolative and suspicious of other kids. His grades kept falling. Teachers also responded behavior that was indicative of PR being internally preoccupied.

The approach of the parents changed from “the boy just needs good disciplining” to a gradual understanding and compliance with the treatment plan.

I will discuss the treatment plan further below. But before that I would like to say that PR is doing much better than he was 3 years ago.

Case presentation 2: “The adopted boy who was ‘psychotic.’”

A was adopted at age 3 and was brought in for an evaluation by his adoptive mother at age 9. The adoptive mother insisted he was “psychotic” and fearful of ingesting food because he thought his mother had poisoned it.

On examination, the boy was found to have significant anxiety, ADHD symptoms, and social communication disorder.

His fear of contamination was misinterpreted as paranoia and delusional. He had also watched a “cold cases” forensic science documentary along with his brother a few months ago which was the precipitating factor. Further information revealed he had a family history of anxiety disorder but no family history of schizophrenia.

Case presentation 3: “My daughter is hearing voices.”

SK is a 7-year-old girl who was brought in for auditory hallucinations. A detailed history revealed a traumatic past (she had witnessed domestic violence). Although currently she lives in a safe environment, she continued to experience flashbacks in the form of auditory hallucinations. There was no family history of psychotic disorders.

After 6 months of cognitive behavioral therapy and trauma-related behavioral therapy, the patient is doing significantly better.

LEM: What are some of the common therapeutic approaches in the treatment of childhood schizophrenia?

In this stage, medications are aimed at delaying or stopping progression to psychotic disorder amongst children who are considered high risk or those that have prodromal symptoms, such as disorganized behavior, paranoia or suspicion, or any unusual thought content that is below the threshold of a full-blown psychotic disorder.

Several medications have been tested in clinical trials. Trials of omega-3 fatty acids have shown mixed results. However, although clinical trials are mixed given the positive potential effects as well as the limited adverse effects of omega-3 fatty acids make it a good choice to consider.

Selective serotonin reuptake inhibitor antidepressants have been shown to be helpful in two naturalistic studies but have not been tested in a clinical trial. Initiating SSRIs along with omega-3 fatty acids is a grade 2 recommendation which basically means this is a suggestion, but clinicians could choose a reasonable alternative.

Clinical trials have not found antipsychotics to be efficacious in terms of delaying or preventing progression to psychosis.

Antipsychotics are first-line treatment for confirmed schizophrenia. Several randomized trials have shown that antipsychotics reduce positive symptoms of schizophrenia, such as hallucinations and delusions. Antipsychotics eliminate or reduce the symptoms to a tolerable level in about 70% of the patients with schizophrenia.

Negative symptoms of schizophrenia, such as diminished emotional expression or lack of motivation is a little more difficult to treat.

We generally follow the age guidelines from the indications approved by the FDA in the United States which were based on the age of enrollees in the efficacy trials of antipsychotics in children with schizophrenia. These medications are aripiprazole, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, 

, and the first-generation agents, chlorpromazine, haloperidol, and perphenazine.

The current recommendation is to start with a second-generation antipsychotic with lower sedation and fewer problems with metabolic syndrome.

Clinical trials have not consistently found any one antipsychotic more effective than the others except clozapine, but due to adverse effects, it is reserved for use in treatment-resistant schizophrenia.

Hence, clinicians can select 1 amongst the above medications, based on patient age and medication adverse effect profile.

LEM: Can you talk about cardiometabolic risks or any other risks of treatment with antipsychotics, and do they outweigh clinical benefits?

The adverse effect profiles of individual antipsychotic drugs vary widely. Children and adolescents compared with adults are at a high risk of many of the adverse effects associated with antipsychotic use

Common adverse effects associated with second-generation antipsychotics include weight gain and related metabolic effects, sedation, anticholinergic symptoms, elevated prolactin levels and extrapyramidal symptoms, cardiac effects, and sexual dysfunction.

Many of these drugs increase appetite and alter metabolic control. Children who are more vulnerable to these adverse effects are those with pre-existing conditions, such as obesity, diabetes, or elevated cholesterol. Clozapine and olanzapine carry significantly higher risk than other antipsychotics, whereas lurasidone and to an extent aripiprazole are associated with the lowest risk.

Clinicians should conduct routine short and long-term monitoring of weight, waist circumference, blood pressure, fasting glucose, and lipid profile of patients taking any of the antipsychotic drugs. For patients in whom weight gain is a concern, we tend to prescribe lurasidone. Whenever possible, we tend to avoid medication such as olanzapine which has a higher rate of metabolic abnormality.

Tardive dyskinesia is characterized by involuntary movements of the mouth, tongue, face, extremities, or trunk (including lip-smacking, tongue, and jaw movements, and facial grimacing). The symptoms are often initially mild; however, they can progress and become disfiguring or disabling. Tardive dyskinesia risk increases with age, time of exposure to medications, and prior development of extrapyramidal symptoms (EPS).

 is less common in youth compared with adult and older adult populations—0.4% versus 6.8%.

The risk of tardive dyskinesia in children appears to be the greatest with first-generation antipsychotics with minimal or no risk seen with second-generation antipsychotics.

 Clozapine has not shown to cause tardive dyskinesia. Patients on these medications should be formally assessed for tardive dyskinesia at least annually. Older adults should be assessed every 6 months.

Nausea and sedation are common adverse effects of antipsychotic treatment in all patients, but they often remit over time and should not be considered a reason to terminate treatment. As mentioned earlier although no one antipsychotic is better than the other, for patients with prominent insomnia we tend to use quetiapine.

Clinicians should routinely assess for fall risks in vulnerable population, given that many of these medications cause sedation as well as orthostatic hypotension. Anticholinergic effect, such as constipation, dry mouth, blurry vision, and urinary retention are fairly common. In the case of clozapine sialorrhea rather than dry mouth is common.

 Second-generation antipsychotics have reduced incidence of akathisia, rigidity, bradykinesia, dysphagia, tremor, and acute dystonic reactions that constitute EPS. Among the second-generation antipsychotics, risperidone carries the highest risk, especially at doses greater than 4 mg/day; elevated risk is also noted with aripiprazole, asenapine, and lurasidone. Quetiapine and clozapine are preferred agents in patients with high risk for EPS. Patients on second-generation agents should be asked about restlessness, slow movements, shaking, and rigidity at baseline and weekly during dose increases.

We usually start with a second-generation antipsychotics because of their lower rates of extrapyramidal symptoms and tardive dyskinesia compared with the first-generation antipsychotics.

Prolactin elevation can occur in both men and women. Accordingly, patients may experience gynecomastia, galacturia, menstrual disturbance sexual dysfunction and infertility. Risperidone and paliperidone are more strongly associated with elevated prolactin. Olanzapine and aripiprazole, clozapine and quetiapine show little or no change in prolactin levels.

Patients on risperidone and paliperidone should be asked about changes in sexual function and abnormal lactation at each visit for 12-week and annually thereafter. A serum prolactin level is indicated if the patient develops signs of sexual dysfunction or galacturia.

Sexual adverse effects that cause dysfunction in all phases of sexual activity are quite common. It seems to be highest on patients who are prescribed risperidone and least amount patients were on aripiprazole. Clinicians are encouraged to ask about sexual functioning initially and at least annually thereafter.

QT prolongation can happen with many of the medications. A corrected QT interval greater than 500 or an increase in QT of 60 or more during antipsychotic treatment indicates significant risk. Ziprasidone appears to have a somewhat greater risk of QT prolongation. Olanzapine and risperidone have been associated with mild QT prolongation but neither carries a specific caution on this issue. Lurasidone and Abilify are the least likely to cause cardiac arrhythmias.

Routine monitoring of ECG with antipsychotics is not usually required in patients without cardiac risk factors. Rarely, cases of myocarditis and cardiomyopathy have been reported with quetiapine, Risperdal, and ziprasidone.

Orthostatic hypotension is frequently observed with clozapine, quetiapine, iloperidone, and paliperidone. This is somewhat less so with olanzapine, risperidone, and ziprasidone. It very rarely occurs with aripiprazole. The symptoms are generally benign and self-limiting but, in some cases, may necessitate a slowing in the rate of dose titration. Seizures have been associated with several second-generation antipsychotics and is dose dependent. Clozapine carries the 

 among the second-generation antipsychotics.

Some of the less common adverse effects include 

, cardiomyopathies, and cataracts. The use of antipsychotics in children should always be started with extreme caution at a low dose and titrated slowly.

LEM: Are there family or genetic factors to consider? What about trauma, sexual abuse, or domestic violence? Do these factors have any effect on children’s propensity to develop early-onset psychosis or psychotic symptoms?

 In terms of predisposing factors, genetic vulnerability, environmental factors, obstetric complications, trauma, social adversities, and substance use can all contribute to the risk for acquiring a primary psychotic disorder. Studies have shown the presence of a substance use disorder and co-occurring psychotic symptoms indicate an increased risk for developing a primary psychotic disorder.

Cannabis in particular has the potential to cause psychotic symptoms, although the studies are limited. However, the body of evidence is consistently increasing.

The birth cohort study of patients with schizophrenia reported an association between hypoxia during birth complications and early onset schizophrenia but not of adult-onset schizophrenia. Prematurity was found in 17% of early-onset psychosis in a schizophrenia spectrum disorder study.

Two large systematic studies demonstrate that 30% to 50% of patients with childhood onset schizophrenia had premorbid features of autism or had comorbid diagnoses of pervasive developmental disorders.

 However, youth with early-onset schizophrenia frequently showed greater premorbid deficits in attention, learning, and socialization compared with their counterparts with adult-onset schizophrenia.

A meta-analysis reported strong evidence that childhood adversity was associated with an increased risk for psychosis in adults, although psychotic symptoms may also be present in PTSD.

 Twin studies suggest that childhood-onset of schizophrenia may have a substantial genetic component.

 A number of psychiatric disorders occur in higher frequency amongst first-degree relatives of children with schizophrenia.

For example, bipolar disorder prevalence is 6% in first degree relatives versus 2.4% in the general population. The same can be said for schizophrenia spectrum disorder: 10% in first-degree relatives versus 3.5% in general population. Anxiety disorders prevalence is 15% in first degree relatives versus 7.3% in the general population.

LEM: Is it too early to talk about long-acting injectable antipsychotic agents, or LAI, treatments?

 In terms of long-acting injectable antipsychotics, they have not been sufficiently studied in younger children to recommend their use.

LEM: From a child’s perspective, how do we build a daily routine of taking oral medications? What can one expect when there is a patient stops treatment abruptly?

 I strongly recommended a multimodal instead of medication-alone approach for a better outcome. First psychoeducation is key and is best provided early in treatment and frequently reviewed, provide children and their parents or guardian information about the illness, medications, and other interventions. It is highly useful to integrate family members and educate them to better support youth.

There are a few variables in terms of our approach based on the clinical presentation of the patient.

For patients with schizophrenia who have had a recent psychotic episode and have significant ongoing contact with family members, we recommend patients and family members receive a family intervention for at least 6 to 9 months. During family intervention, patient's family members receive education about the nature course treatment of schizophrenia.

It also involves correcting the erroneous notion that poor parenting was the cause of schizophrenia. Many parents are left to wonder what they could have done wrong to cause the illness and need help transitioning from the guilt and blame to acceptance and support.

Many times, family members may perceive the negative symptoms of schizophrenia, such as lack of motivation and asociality, as laziness. Furthermore, the clinician should teach early warning signs and explain the importance of medication adherence.

2. If the patient has had multiple relapses of schizophrenia and reside in a particularly stressful family environment, a more intensive problem-solving family therapy has been developed. 

In these cases, we identify and correct overly hostile and critical parent-patient interaction. Sometimes stressful family dynamics can be mitigated by finding outside rehabilitative activities or supported employment for the patient.

Although the diagnostic criteria used in children are the same as adults, there are some key differences in clinical presentation of psychotic features. More in this podcast about childhood schizophrenia.

Abhijit Ramanujam, MD

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