Matcheri S. Keshavan, MD

It is not new for viruses to have both mental and physical health consequences. 

 is a notable example in recent times, with 38 million individuals currently living with the virus and an estimated 35 million who have died from AIDS-related illnesses.

 As many as half of people living with HIV have at least 

 Today, after more than a year since the pandemic started, the magnitude of the public health impact of the current COVID-19 crisis is not yet fully appreciated, but it will be significant, with more than 

 and counting globally at the time of this writing.

The effects of COVID-19 are expected to last for a long time, with evidence for persistent and/or delayed 

 It has been observed that as many as three-fourths of patients hospitalized with COVID-19 had 

at least 1 ongoing symptom 6 months after 

 and 30% of patients, even those with mild illness, have reported 

persistent symptoms for as long as 9 months

 These long-term consequences include mental health issues, with 

 having persistent neurological and/or psychiatric consequences.

This recognized phase of prolonged illness, referred to by a variety of names including long COVID-19, long-haul COVID-19, and postacute COVID-19, has been recently designated by the National Institutes of Health as 

post-acute sequelae of SARS-CoV-2 infection

Although COVID-19 had initially been most notorious for causing respiratory pathology, with the most vulnerable patients progressing to 

 with an underlying etiology still to be determined but possibly involving dysregulated immune response, inflammation, microvascular thrombosis, and/or cellular damage from the virus.

 Although variable in presentation, PASC most commonly involves a constellation of symptoms (

 range from mild to disabling with significant effects on quality of life, even in patients whose acute course of illness was mild or who were previously healthy and active.

We have much to learn about PASC, due to the multiorgan system effects and the heterogeneity of symptoms in patients who 

. Beth Israel Deaconess Medical Center, a patient care, teaching, and research affiliate of Harvard Medical School in Boston, has recently launched the Critical Illness and COVID-19 Survivorship Program. The program aims to integrate care among pulmonary, critical care, sleep medicine, psychiatry, cognitive neurology, neurology, geriatrics, social work, and physical and occupational therapy clinicians. Although the cases differ, 3 deidentified vignettes demonstrate the core themes for patients presenting with PASC who are referred to psychiatry through the new program.

“Alma,” a woman aged 45 years, presents with a history of hypertension and a 4-week intensive care unit (ICU) stay due to acute respiratory failure, prolonged intubation, and paralysis after contracting COVID-19. Alma’s ICU stay was complicated by a course of delirium. She had been discharged home from a rehabilitation center more than 6 months prior to her appointment.

She has been referred for ongoing symptoms of 

 (PTSD) related to her ICU stay, significantly impaired sleep, and depressed mood. Additionally, Alma continues to struggle with ongoing memory and focus concerns, shortness of breath, and difficulty with weakness. Her cognitive and physical symptoms have improved, but they remain impairing.

The Mental Health Impacts of ICU Admissions

Prior to the COVID-19 pandemic, it had been increasingly recognized that survivors of ICU admissions commonly experience 

long-term physical, psychological, and cognitive impairments

 that adversely impact their quality of life.

 This group of multisystem impairments is referred to as post-intensive care syndrome (PICS). More than 50% of survivors of acute respiratory syndrome suffer from at least 1 feature of PICS a year after their ICU stay.

 are well characterized and persistent manifestations of PICS.

 The differences in characterization and etiologies between PICS and the independent influence of COVID-19 is not yet understood.

After contracting COVID-19, “John,” a man aged 70 years with a history of asthma, obstructive sleep apnea, diabetes, and major depression, was hospitalized for 4 days due to low oxygen levels, which required treatment with steroids.

John presents 3 months after hospitalization with worsening depression, insomnia, breathlessness, and related anxiety. His mood is also influenced by frustration with obstacles in restarting home health services. Due to a lack of assistance, it has been difficult for John to keep up with his many follow-up appointments or go to the pharmacy to pick up medications and other medical supplies. He reports being quite lonely and has not seen his out-of-state family for many months.

Identifying Predisposing Risk Factors for PASC

The outcomes for an individual after contracting COVID-19 will depend not only on the direct influence of the virus, but also on predisposing risk factors (ie, 

preexisting health conditions, socioeconomic factors

), the way their body responds to fighting off the virus (immune activation and/or dysregulation), and iatrogenic complications (ie, adverse effects of such medications as steroids and sedatives; hospital-acquired infections). Additionally, issues arise related to recovering from the virus, which include the onus of having been ill, concern about infecting loved ones, and obstacles in having day-to-day needs met. The 

 due to the pandemic, impacting ability to obtain care for health conditions or engage in preventative care, also are likely to play a role in health outcomes.

 are important risk factors and drive negative health outcomes, especially in older adults.

“Susan” is a woman, aged 40 years, with a prior episode of major depression that had been in remission and mild attention-deficit symptoms that had been well controlled. She presents more than 7 months after contracting COVID-19.

During her acute course, she struggled with fever, cough, headache, shortness of breath, fatigue, and anosmia. Susan was evaluated in the emergency department due to the severity of her symptoms, but she did not require hospitalization. She has had persistent symptoms of breathlessness, profound fatigue, difficulty with concentration and memory, 

, and difficulty performing the duties of her job, which she has held for many years. She is referred for growing depression and feelings of hopelessness.

Symptoms of Lower Severity, but High Persistence

This clinical presentation—a patient who is younger, previously healthy, with milder acute COVID-19 symptoms and persistently impairing symptoms longitudinally—is often referred to as long COVID-19. Earlier in the pandemic, 

this clinical presentation was not fully recognized

 and, indeed, sometimes ignored or discounted.

Long COVID-19 challenges clinicians more than ever to listen to patients and break down the false dichotomy between mental and physical health. The experience of feeling trivialized and frustrated by an overemphasis on the psychological components of illness has been shared by 

 such as severe acute respiratory syndrome (SARS) in early 2000s and Middle East Respiratory Syndrome in 2012.

 It also has been a common experience in patients diagnosed with 

myalgic encephalomyelitis/chronic fatigue syndrome

 (ME/CFS), a complex and disabling illness with features that overlap those of long COVID-19.

The presentation of neuropsychiatric symptoms after COVID-19 are heterogeneous, and to some extent they may reflect variable and multifactorial causes. The 

 by patients, clinicians, and society alike of psychogenic vs organic, psychological vs physiological, functional vs neurological, are all overly simplified and represent 

antiquated views of the brain-body connection

 Breaking down long-standing silos in health care through the use of integrated multidisciplinary teams will be critical to finding more effective treatments. Bridging this divide is urgent, not only to understand and treat the consequences of this pandemic, but also to face the 

longstanding issue of mental health stigmatization

 that serves as an enduring barrier to patients seeking care for their mental health.

 Patients with PASC are at risk of mental health consequences, whether it be from the direct consequence of the virus, indirect consequences of quarantine and the pandemic, exacerbation of preexisting conditions, and/or ongoing challenges of coping with a new, poorly understood, chronic illness.

Issues to Consider in Treatment and Recovery

Many patients slowly recover with supportive measures and symptomatic treatment.

 Much of the initial recovery recommendations focus on physical rehabilitation and support. There are not yet formalized standards of care in treatment of depression and other mental health concerns in PASC. Notably, some patients with PASC may struggle with symptoms of dysautonomia such as persistent tachycardia and/or vulnerability to orthostasis, which may diminish tolerability to some psychotropic medications.

A number of patients with long COVID-19, similar to patients with ME/CFS, have 

 Therefore, pushing themselves to exercise beyond an identified energy envelope may be counterproductive and, in fact, propagate crash-and-burn cycles.

 For that reason, care must be taken in suggesting exercise, an otherwise recommended lifestyle intervention for improving stress, depression, cognition, and insomnia.

In addition to our standard treatments for depression, anxiety, and PTSD, there are some emerging areas of interest. Breathing exercises have been a recommendation of post–COVID-19 clinics and have benefited patients who have persistent feelings of breathlessness. 

, a breathing program, is available online and has been utilized by patients with long COVID-19.

 Respiratory rehabilitation has been suggested, especially when complemented by 

 (ie, tai chi, qigong) that combine conscious breathing in coordination with body movement.

, a form of yoga that combines breathing with humming, has also been recommended, not only because it can be calming, but because it may enhance nitric oxide expression.

 have long been compelling for patients with ME/CFS, but heterogeneity in studies and small sample sizes limit our evidence base.

 There are not yet systematic studies of mind-body interventions in PASC. Of note, 

 provided some relief for survivors of SARS when they did not find adequate support from standard health care.

 has been an important element in the fight against COVID-19.

 The COVID Symptom Study captures and analyzes daily symptom tracking in millions of app users in the United States and United Kingdom.

 It recently provided insight into long COVID-19, identifying the strongest predictor for ongoing illness as having

apps are likely to play an important role in complementing mental health treatment

, allowing for real-time measurement-based care, shared decision-making, and enhanced therapeutic alliances.

We are only just beginning to understand COVID-19 and its consequences. It will take multiyear studies to elucidate long-term sequelae and to understand how to best help patients. Also, this virus has further elucidated the 

inequities in our society and in health care

 Although this has been a time of tribulation, it is also a time that presents an opportunity to understand the trajectory of biological, psychological, and socioeconomic outcomes that will allow us to move toward eroding the stagnancy of mind-body dualism and breaking down siloed care. It also presents the opportunity to find more satisfying outcomes and improved quality of life for those with chronic illnesses.

is a geriatric psychiatrist at Beth Israel Deaconess Medical Center (BIDMC) and an instructor at Harvard Medical School. She is the consulting psychiatrist for the BIDMC Critical Illness and COVID-19 Survivorship Program.

 is Stanley Cobb Professor and Academic Head of Psychiatry at Beth Israel Medical Center and Harvard Medical School.

1. Global statistics. HIV.gov. Updated November 25, 2020. Accessed May 24, 2021. 

https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics

2. Yehia BR, Stephens-Shield AJ, Momplaisir F, et al. 

Health outcomes of HIV-infected people with mental illness

An interactive web-based dashboard to track COVID-19 in real time

4. Nalbandian A, Sehgal K, Gupta A, et al. 

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

6. Logue JK, Franko NM, McCulloch DJ, et al. 

Sequelae in adults at 6 months after COVID-19 infection

7. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

8. Collins FS. NIH launches new initiative to study ‘long COVID.’ National Institutes of Health. February 23, 2021. Accessed May 24, 2021. 

https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

10. Gupta A, Madhavan MV, Sehgal K, et al. 

Extrapulmonary manifestations of COVID-19

11. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. 

Management of post-acute Covid-19 in primary care

12. Marra A, Pandharipande PP, Girard TD, et al. 

Co-occurrence of post-intensive care syndrome problems among 406 survivors of critical illness

Aging and post-intensive care syndrome: a critical need for geriatric psychiatry

14. Wright A, Salazar A, Mirica M, et al. 

The invisible epidemic: neglected chronic disease management during COVID-19

Social isolation and loneliness in older adults: review and commentary of a national academies report

16. Ladds E, Rushforth A, Wieringa S, et al. 

Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services

17. Rogers JP, Chesney E, Oliver D, et al. 

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

18. McManimen S, McClellan D, Stoothoff J, et al. 

Dismissing chronic illness: a qualitative analysis of negative health care experiences

19. Perez DL, Keshavan MS, Scharf JM, et al. 

Bridging the great divide: what can neurology learn from psychiatry?

The convergence of neurology and psychiatry: the importance of cross-disciplinary education

The health crisis of mental health stigma

22. Myalgic encephalomyelitis/chronic fatigue syndrome: treatment of ME/CFS. CDC. January 28, 2021. Accessed May 24, 2021. 

https://www.cdc.gov/me-cfs/treatment/index.html

23. O’Rourke M. Unlocking the mysteries of long COVID. The Atlantic. March 8, 2021. Accessed May 24, 2021. 

https://www.theatlantic.com/magazine/archive/2021/04/unlocking-the-mysteries-of-long-covid/618076/

Chinese Association of Rehabilitation Medicine; Respiratory Rehabilitation Committee of Chinese Association of Rehabilitation Medicine; Cardiopulmonary Rehabilitation Group of Chinese Society of Physical Medicine and Rehabilitation

. Recommendations for respiratory rehabilitation in adults with coronavirus disease 2019. 

Modified Bhramari pranayama in Covid 19 infection

Effectiveness of body awareness interventions in fibromyalgia and chronic fatigue syndrome: a systematic review and meta-analysis

Coping with future epidemics: tai chi practice as an overcoming strategy used by survivors of severe acute respiratory syndrome (SARS) in post-SARS Hong Kong

28. Collins F. Predicting ‘long COVID syndrome’ with help of a smartphone app. NIH Director’s Blog. March 23, 2021. 

https://directorsblog.nih.gov/2021/03/23/predicting-long-covid-syndrome-with-help-of-a-smartphone-app/

29. Sudre CH, Murray B, Varsavsky T, et al. 

30. Rodriguez-Villa E, Rauseo-Ricupero N, Camacho E, et al. 

The digital clinic: implementing technology and augmenting care for mental health

The COVID pandemic and the endemic disparities in care across race for psychotic disorders

Articles

1 in 3 COVID-19 survivors experience persistent consequences. What can psychiatry do to help?  

Developing a Collaborative Approach to Post-Acute Sequelae of SARS-CoV-2 Infection

Dr Torous is a Clinical Fellow in Psychiatry at Harvard Medical School and Senior Resident at the Harvard Longwood Psychiatry Residency Training Program in Boston. He is the Digital Psychiatry Editor for Psychiatric Times. Twitter: 

. Dr. Keshavan is Stanley Cobb Professor of Psychiatry at Beth Israel Deaconess Medical Center in Boston.

 a new formulation of aripiprazole that includes an ingestible digital sensor that can record when the medication was taken by sending a signal to a wearable patch.

 This medication, Abilify MyCite, is now approved for use in schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder, and as an add-on treatment for depression in adults.

Some have questioned whether an ingestible medication that sends digital signals regarding adherence is appropriate for use in disorders like schizophrenia. Concerns that Abilify MyCite may increase paranoia and delusions have been raised. However, while concern for patient welfare is well intentioned, it may be more appropriate to consider what the evidence reveals about technology use and schizophrenia.

 (NAMI) to conduct a survey of over 400 individuals with schizophrenia and their use of digital technologies. We found that these patients were not only open to using technology but using it 

 on smartphones and monitoring for schizophrenia last year and did not identify a single case of harm.

Coincidently, we worked with a patient with schizophrenia who 

 to track how aripiprazole reduced the number of auditory hallucinations he experienced.

 This individual used a digital tally counter to record real-time hallucinations and discovered that tracking was useful for keeping him engaged with treatment. While only a single case, it does demonstrate that some patients with schizophrenia are extremely interested in innovative approaches to their medications and want to try new tools. It would be wrong to deny them this opportunity because others have concerns that may or may not apply.

Rather, it is encouraging to see the introduction of new tools and innovations for psychiatric disorders. Schizophrenia and related disorders impact ~1.5% of the population, and in the US, the 

 of schizophrenia is greater than $60 billion per year.

 While antipsychotic medications (eg, aripiprazole), can be effective for reducing symptoms and helping patients recover, adverse effects can be difficult for some to tolerate. Stopping antipsychotic medications is the leading cause of relapse in schizophrenia, and while Abilify MyCite is not FDA-approved 

For the appropriate patients, it is possible to imagine how this digital pill could help them with medication, monitor progress, and share results their family and psychiatrists. And if the Abilify MyCite system detects when a patient has stopped taking the medication, that may be a window to have a conversation about adverse effects or other issues. A quick discussion here could prevent a relapse that can be stressful to patients and their families as well as expensive to the health care system. Of course, some patients may not want to use such a system and could easily take off the wearable patch.

That said, we all must be careful in this new world of digital psychiatry. Looking at the mobile app space, the lack of consumer privacy protections for apps that record personal health information like medications and even sensor data (such as real-time location) is 

 By carefully claiming not to be medical devices, companies that produces these apps live outside of FDA and federal privacy protections, and thus are able to engage in questionable data collection practices. Outside the scope of health care, there may be a literal need for paternalism (and materialism) after the 

 in summer 2017 of numerous cyber security risks that included recording children’s conversations and selling families’ personal data.

There are real privacy risks today-right now Abilify MyCite is taking the right steps to mitigate potential harm through regulation and research. Like any new medication, Abilify MyCite will only become well adopted if it can demonstrate that it is effective in the real world. While its ability to track ingestion is novel and raises concerns, it also presents an opportunity to improve outcomes for patients with schizophrenia and related disorders.

. Dr. Keshavan is Stanley Cobb Professor of Psychiatry, Beth Israel Deaconess Medical Center in Boston.

1. US Food and Drug Administration. FDA approves pill with sensor that digitally tracks if patients have ingested their medication. November 13, 2017. 

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm584933.htm.

2. Gay K, Torous J, Joseph A, Pandya A, Duckworth K. 

Digital Technology Use Among Individuals with Schizophrenia: Results of an Online Survey

3. Torous J, Firth J, Mueller N, Onnela JP, Baker JT. 

Methodology and Reporting of Mobile Heath and Smartphone Application Studies for Schizophrenia

Patient-Driven Innovation for Mobile Mental Health Technology: Case Report of Symptom Tracking in Schizophrenia

Outpatient antipsychotic treatment and inpatient costs of schizophrenia

6. FBI. Consumer Notice: Internet-Connected Toys Could Present Privacy and Contact Concerns for Children. July 17, 2017. 

https://www.ic3.gov/media/2017/170717.aspx.

7. Torous J, Roberts LW. Needed innovation in digital health and smartphone applications for mental health: transparency and trust. 

What does the evidence tell us about digital sensors for treatment adherence in patients with schizophrenia and other psychiatric disorders?

Digitally Tracking Patients With Schizophrenia: The Future Is Here

It was not too long ago that the management of schizophrenia was generally viewed as pessimistic, and focused primarily on symptom relief. Over the past two decades, there has been a paradigm shift in our approach to the overall management of schizophrenia, toward preventive and early interventions. These approaches are being increasingly guided by recent pathophysiological models. In particular, it has become clear that neurobiological alterations are seen before onset of the illness (the premorbid phase) (Johnstone et al., 2002) and may progress during the early stages of the illness (the prodromal phase).

Further deterioration in brain structure and function may appear in some cases after characteristic symptoms of the illness begin (the psychotic phase), especially during the initial years. These observations suggest a critical window of opportunity, early in the illness, to effect lasting modifications in overall illness course (Keshavan et al., 2005a).

The three key questions for the field are:

Can schizophrenia be prevented in those at risk for the disorder (primary prevention)?

Can the first episode of psychosis be prevented in patients experiencing the prodromal phase of the illness (secondary prevention)?

Can we prevent relapses and further functional decline in patients who have already experienced the first episode of psychosis (tertiary prevention)?

Recent work, outlined below, suggests that considerable progress has been achieved in these areas over the years.

Primary prevention is best realized by removing a cause before the illness develops (e.g., preventing dental cavities by adding fluoride to the water). In schizophrenia, this remains speculative at best for now. The widely reported risk factors for schizophrenia include genetic factors, season and place of birth, pregnancy and birth complications, and antenatal exposure to viruses. Possible interventions for the families of genetically at-risk individuals include genetic counseling, prevention of viral infections during pregnancy and adequate prenatal care for women with schizophrenia.

In the future, it hopefully will be possible to design interventions that are specific to those individuals genetically at risk who display neurobehavioral and neurobiological precursors found by ongoing prospective studies to be accurate predictors of later illness (Keshavan et al., 2005b). For example, a program for an adolescent at genetic risk for schizophrenia who also displays cognitive and social deficits might include improvement of the home environment, prevention of abuse and neglect, a structured school environment combined with cognitive remediation, and possibly social skills training.

Secondary prevention strategies seek to prevent conversion to the full-blown psychotic illness in people experiencing the prodromal phase of the illness. The view that the attenuated psychotic-like symptoms characterizing the prodrome might be mediated by phasic dopaminergic excess has encouraged early treatment with low doses of dopamine-blocking drugs.

In a single-blind design, McGorry et al. (2002) compared low-dose risperidone (Risperdal) plus cognitive-behavioral therapy (CBT) with a needs-based intervention (i.e., counseling and case management) for six months. This was followed by a six-month observation period of all patients on needs-based therapy only. The combined specific intervention led to a significant preventive treatment effect in a modest sized population of 59 participants. Using a double-blind, randomized approach, Woods et al. (2003) compared the efficacy of olanzapine (Zyprexa) versus placebo. At eight weeks, a modest improvement was seen in symptoms associated with olanzapine treatment, though significant weight gain was also seen.

The German Research Network on Schizophrenia (Bechdolf et al., 2005; Ruhrmann et al., 2005 ) reported promising but very preliminary results in a randomized, open-label design, comparing amisulspride to psychological management for prodromal symptoms. Using a naturalistic treatment strategy Cornblatt et al. (2002) observed that for individuals in the earlier prodromal stages with moderate positive symptoms, antidepressants may be an effective alternative to antipsychotics.

Other, more experimental approaches are being investigated as well. Researchers in Melbourne, Australia, have been conducting a one-year trial with low-dose lithium (Eskalith, Lithobid), the definitive results of which are expected soon. Using predictions derived from the membrane model of schizophrenia, Woods et al. (2002) conducted a three-month study with ethyl-eicosapentaenoic acid, an omega-3 fatty acid. The results are awaited.

Some studies suggest that psychological treatments such as CBT may have advantages over standard treatments for psychosis in terms of reducing the transition from pre-psychotic states to full-blown psychosis (Haddock and Lewis, 2005). Morrison et al. (2002) randomized prodromal patients into those receiving CBT versus monitoring only. At one-year followup, 6% of the CBT arm versus 22% of the control arm had developed psychosis (Haddock and Lewis, 2005).

Tertiary prevention seeks to prevent disability and relapse in patients who have already developed psychosis. First-episode patients show higher response rates to treatment (46% to 96%) compared to multi-episode patients but also show high rates of relapse due to noncompliance (Robinson et al., 2005). There is increasing evidence that relapse rates are reduced by early introduction of family intervention to reduce levels of expressed emotion, CBT to address cognitive distortions and individual psychotherapy aimed at restoring a sense of self and achieving mastery over the illness (for a review, see Haddock and Lewis, 2005).

Comprehensive early psychosis treatment packages involving pharmacologic and psychosocial treatments as outlined above are more cost-effective than treatment as usual in improving long term recovery, as shown by recent controlled trials. Petersen et al. (2005) randomized 547 patients to either integrated treatment over two years, consisting of assertive community treatment with family involvement and social skills training or standard treatment offering contact with a community mental health center. Patients in the integrated treatment limb had significantly better recovery of positive and negative symptoms, less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment. Investing in early and comprehensive intervention can therefore improve our patients' lives in the longer term as well as reduce overall costs of treatment.

First-episode patients with schizophrenia also have high rates of comorbid substance abuse, depression, noncompliance, and impairments in cognition and social skills. Dual diagnosis patients with psychosis and substance abuse are more likely to relapse. A recent controlled trial has shown that, compared to standard care, such patients are likely to benefit from combined psychosocial treatment packages including motivational enhancement (Barrowclough et al., 2001).

Patients with the first episode of psychosis are also likely to experience a high likelihood of depression and suicidal behavior during the early course of their illness. Controlled trials are underway showing initial promising results (Power et al., 2003). Noncompliance rates are high in the first episode of psychosis, perhaps related to high rates of poor insight. Motivational enhancement therapies may help improve compliance as shown in controlled trials in patients with psychotic disorders (Kemp et al., 1998). An uncontrolled study showed a lack of efficacy of this treatment in patients with schizophrenia or schizoaffective disorder (Byerly et al., 2005). Results from controlled studies in early schizophrenia are awaited. Finally, cognitive remediation studies have also begun to provide encouraging results in regard to improvements in functional outcome when introduced early in the course of schizophrenia (Hogarty et al., 2004).

In summary, the evidence base of early interventions in schizophrenia is rapidly gaining acceptance in the field. However, as the field matures, it will be necessary to more extensively replicate the findings of the handful of early prevention studies, more conclusively validate the criteria currently defining the prodrome, further extend the range of potential interventions to include treatments other than antipsychotics, and to target specific prodromal and possibly premorbid phases of illness. Evidence-based demonstrations of cost-effectiveness of such interventions are critically needed if this field of research is to sustain and solidify this paradigm shift.

 Barrowclough C, Haddock G, Tarrier N et al. (2001), Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. Am J Psychiatry 158(10):1706-1713.
 

 Bechdolf A, Ruhrmann S, Wagner M et al. (2005), Interventions in the initial prodromal states of psychosis in Germany: concept and recruitment. Br J Psychiatry 48(suppl):45-48.
 

 Byerly MJ, Fisher R, Carmody T, Rush AJ (2005), A trial of compliance therapy in outpatients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 66(8):997-1001.
 

 Cornblatt B, Lencz T, Correll C et al. (2002), Treating the prodrome: naturalistic findings from the RAP Program. Acta Psychiatr Scand 106(suppl 1):44.
 

 Haddock G, Lewis S (2005), Psychological interventions in early psychosis. Schizophr Bull 31(3):697-704.
 

 Hogarty GE, Flesher S, Ulrich R et al. (2004), Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry 61(9):866-876.
 

 Johnstone EC, Lawrie SM, Cosway R (2002), What does the Edinburgh high-risk study tell us about schizophrenia? Am J Med Genet 114(8):906-912.
 

 Kemp R, Kirov G, Everitt B et al. (1998), Randomised controlled trial of compliance therapy. 18-month follow-up. Br J Psychiatry 172:413-419 [see comment].
 

 Keshavan MS, Berger G, Zipursky RB et al. (2005a), Neurobiology of early psychosis. Br J Psychiatry 48(suppl):8-18.
 

 Keshavan MS, Diwadkar VA, Montrose DM et al. (2005b), Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr Res 79(1):45-57.
 

 McGorry PD, Yung AR, Phillips LJ et al. (2002), Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 59(10):921-928.
 

 Morrison AP, Bentall RP, French P et al. (2002), Randomised controlled trial of early detection and cognitive therapy for preventing transition to psychosis in high-risk individuals. Study design and interim analysis of transition rate and psychological risk factors. Br J Psychiatry 43(suppl):78-84.
 

 Petersen L, Jeppesen P, Thorup A et al. (2005), A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness.[Published erratum BMJ 331(7524):1065.] BMJ 331(7517):602 [see comment].
 

 Power PJ, Bell RJ, Mills R et al. (2003), Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis. Aust N Z J Psychiatry 37(4):414-420.
 

 Robinson DG, Woerner MG, Delman HM, Kane JM (2005), Pharmacological treatments for first-episode schizophrenia. Schizophr Bull 31(3):705-722.
 

 Ruhrmann S, Schultze-Lutter F, Maier W, Klosterkotter J (2005), Pharmacological intervention in the initial prodromal phase of psychosis. Eur Psychiatry 20(1):1-6.
 

It was not too long ago that the management of schizophrenia focused primarily on symptom relief in inpatient and outpatient settings. Over the past two decades, there has been a paradigm shift in our approach in the overall management of schizophrenia, toward preventive and early interventions. What are some of these management techniques, and how well do they work?

Matcheri S. Keshavan, MD

Articles

Developing a Collaborative Approach to Post-Acute Sequelae of SARS-CoV-2 Infection

Digitally Tracking Patients With Schizophrenia: The Future Is Here

Prevention and Early Interventions