psychiatrist

This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Educational Activity

Using Patient-Centered Assessment in Schizophrenia Care: Defining Recovery and Discussing Concerns and Preferences

Christoph U. Correll, MDa

Published: April 14, 2020

This CME activity is expired. For more CME activities, visit cme.psychiatrist.com.
Find more articles on this and other psychiatry and CNS topics:
The Journal of Clinical Psychiatry
The Primary Care Companion for CNS Disorders

Abstract

Syndromal recovery, satisfactory quality of life, and adequate functionality are relevant goals that define successful treatment of schizophrenia. Recovery requires effective symptom control in multiple clinical domains but also sufficient self-care and social and educational/vocational functionality. The finding that residual negative and cognitive symptoms have been related strongly to inadequate levels of functioning in people with schizophrenia is related to the fact that current pharmacologic agents tend to be most effective for the positive symptoms of the disease. Additional challenges include psychiatric comorbidities and adverse events related to medication that can lead to secondary negative and cognitive symptoms and nonadherence, all of which can worsen outcomes. Treatment modalities that target cognition and functional rehabilitation without introducing tolerability issues are needed. In general, pharmacologic interventions should be combined with evidence-based nonpharmacologic treatments, and patient-reported outcomes as well as measurement-based care should be employed, ideally in a coordinated specialty care framework. To facilitate positive treatment decisions, a combined shared decision and motivational interviewing approach should be implemented.

aDepartment of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York; Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany

J Clin Psychiatry 2020;81(3):MS19053BR2C

CME Background Information

Supported by educational grants from Alkermes, Inc.; Otsuka America Pharmaceutical, Inc. and Lundbeck.

Participants may receive credit by reading the activity, scoring 70% or higher on the posttest, and completing the evaluation.

Objectives

After completing this educational activity, you should be able to:

  • Use guidelines, clinical characteristics, and a patient-centered approach to select medication treatment for patients with schizophrenia who often relapse
  • Incorporate nonpharmacologic therapies to optimize patients’ potential for functional recovery

Financial Disclosure

The faculty for this CME activity and the CME Institute staff were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The Accreditation Council for Continuing Medical Education (ACCME) defines a commercial interest as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that create a conflict of interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute staff reported any relevant personal financial relationships. Faculty financial disclosure is as follows:

Dr Correll is a consultant for and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, ROVI, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva; has received grant/research support from Janssen and Takeda; is a member of the speakers/advisory boards for Alkermes, Allergan, Angelini, Gedeon Richter, IntraCellular Therapies, Janssen, LB Pharma, Lundbeck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva; is a stock option holder of LB Pharma; and has received other financial or material support for expert testimony from Bristol-Myers Squibb, Janssen, and Otsuka and royalties from UpToDate.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The American Academy of Physician Assistants (AAPA) accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit(s)™ from organizations accredited by the ACCME or a recognized state medical society. Physician assistants may receive a maximum of 1.0 hours of Category I credit for completing this program.

To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation.

MOC Approval Statement

Through the American Board of Medical Specialties (“ABMS”) ongoing commitment to increase access to practice relevant Continuing Certification Activities through the ABMS Continuing Certification DirectoryUsing Patient-Centered Assessment in Schizophrenia Care: Defining Recovery and Discussing Concerns and Preferences has met the requirements as a MOC Part II CME Activity (apply toward general CME requirement) for the following ABMS Member Boards:

MOC Part II CME Activity

Psychiatry and Neurology

Release, Review, and Expiration Dates

This brief report activity was published in March 2020 and is eligible for AMA PRA Category 1 Credit™ through March 31, 2022. The latest review of this material was in February 2020.

Statement of Need and Purpose

The goals of schizophrenia treatment are to control symptoms, prevent relapse, and improve functioning and quality of life. For many patients, these goals are not being met. Evidence demonstrates that long-acting injectable (LAI) antipsychotics are one of the most effective ways to prevent relapse in patients with schizophrenia, yet they remain underused. Health care providers infrequently discuss LAI antipsychotic options with their patients with schizophrenia. Clinicians also may overestimate adherence or not even assess it despite guideline recommendations. Patients with multiple relapses are often continued on oral medications, and few clinicians consider LAIs early in the course of illness. Health care providers need education on the efficacy, safety, and dosage/administration of LAIs, as well as on discussing LAIs with their patients. This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on schizophrenia.

Disclosure of Off-Label Usage

Dr Correll has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents or device therapies that is outside US Food and Drug Administration–approved labeling has been presented in this activity.

Review Process

The faculty members agreed to provide a balanced and evidence-based presentation and discussed the topics and CME objectives during the planning sessions. The faculty’s submitted content was validated by CME Institute staff, and the activity was evaluated for accuracy, use of evidence, and fair balance by a peer reviewer who is without conflict of interest.

Acknowledgment

This brief report is derived from the teleconference series “The Schizophrenia Remission Roller Coaster: Using Long-Acting Injectable Antipsychotics to Improve Adherence and Enhance Potential for Functional Recovery,” which was held in September and October 2019 and supported by educational grants from Alkermes, Inc.; Otsuka America Pharmaceutical, Inc. and Lundbeck.


Introduction

Treatment of schizophrenia is complicated by a host of challenges, including inconsistently defined clinical outcomes, failure to account for patient perspectives, adverse events contributing to medication nonadherence (which increases the likelihood of relapse), and a dearth of efficacious interventions targeting all of the disease’s symptom domains.1–3 This brief report addresses proposed definitions for response, remission, and recovery; the need for assessing patient-reported outcomes in the clinical setting; and the treatment challenges of negative, cognitive, and affective symptoms and adverse effects. (For more information, please see “Current Treatment Options and Emerging Agents for Schizophrenia” in this CME activity series.)

Definitions of Clinical Outcomes

Treatment outcomes in schizophrenia can be divided into categories, including response, remission, and recovery.

Response. Response is generally defined as a certain percentage decrease in symptoms compared to baseline, usually measured using the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS). Unfortunately, consensus has not been reached on what percentage of symptomatic decrease should indicate response, with a range of 20% to 60% reduction from baseline being used in the literature.4

Research5 comparing the BPRS with the Clinical Global Impressions (CGI) scale found that BPRS score reductions of 24%, 27%, and 30% at weeks 1, 2, and 4, respectively, corresponded to a CGI rating of “minimally improved.” BPRS score reductions of 44%, 53%, and 58% corresponded with a CGI rating of “much improved.” Similar research6 comparing the PANSS with the CGI scale found that PANSS score reductions of 19%, 23%, 26%, and 28% at weeks 1, 2, 4, and 6, respectively, corresponded to a CGI rating of “minimally improved.” PANSS score reductions of 40%, 45%, 51%, and 53% corresponded with a CGI rating of “much improved.”

With these findings in mind, the proposed definition for response is a 50% reduction in BPRS/PANSS score compared to baseline for acute or first-episode schizophrenia and a 25% reduction for chronic or treatment-resistant populations.4,6 However, response is a relative outcome and tells us only whether individuals are better relative to baseline but not whether they are well.

Remission. For patient wellness, clinicians need a defined absolute symptom threshold. In 2005, Andreasen et al7 proposed criteria for a consensus definition of remission in schizophrenia. The proposal identified specific symptom items that can be used to rate positive and negative symptoms on the following scales7:

  • Scale for the Assessment of Positive Symptoms (SAPS)—items 20 (delusions), 7 (hallucinations), 34 (positive formal thought disorder), and 25 (bizarre behavior)—and Scale for the Assessment of Negative Symptoms (SANS)—items 7 (affective flattening), 17 (avolition/apathy), 22 (anhedonia/asociality), and 13 (alogia)
  • BPRS—items 8 (grandiosity), 11 (suspiciousness), 15 (unusual thought content), 12 (hallucinatory behavior), 4 (conceptual disorganization), 7 (mannerisms/posturing), and 16 (blunted affect)—and the SANS
  • PANSS—items P1–3 (delusions, conceptual disorganization, hallucinatory behavior), G5 (mannerisms/posturing), G9 (unusual thought content), N1 (blunted affect), N4 (social withdrawal), and N6 (lack of spontaneity)

The PANSS option may be the most useful and accessible, as it covers both positive and negative symptoms using a single scale. Using any of the above methods, remission is defined as ratings of mild or less on all items sustained for at least 6 months.7

Recovery. The most desired treatment outcome is recovery. Liberman et al8 defined recovery as a period of at least 2 years in which the patient has maintained the following characteristics:

  • Symptom remission
  • Vocational functioning—working or attending school, or corresponding age-appropriate activities for individuals of retirement age
  • Independent living—successful, unsupervised living and self-care without being fully dependent on disability benefits and without dependence on a caregiver for reminders to engage in social or vocational activities; individuals can meet this criteria while living with family if age- or culture-appropriate
  • Peer relationships—having at least 1 interaction with someone outside the family per week

Patient-Centered Outcomes

A comprehensive assessment of the efficacy and impact of care in schizophrenia requires a patient-centered approach to treatment evaluation. In addition to clinical outcomes, clinicians should consider patient-centered treatment aims, including quality of life, health-related quality of life, and functioning.

Quality of life. The World Health Organization defines quality of life as how people view their position in life in the context of their social environments and in relation to their goals, standards, and concerns.9

Health-related quality of life. Health-related quality of life is a concept describing individuals’ overall perception of how an illness and its treatment affect the physical, psychological, and social aspects of their lives.10

Functioning. Functioning is defined as a person’s ability to perform the normal daily activities that are required to meet basic needs, fulfill their roles, and maintain their health and wellbeing.11 A subset, social functionality, includes the following domains: education/occupation, living situation, role activities, relationships, behavioral functioning, and satisfaction with functioning.12,13

AV 1. Patient-Centered Model of Medication Adherence (00:39)

Reprinted from Kikkert and Dekker.14

Patient Decision-Making

Constructed by Kikkert and Decker14 and based on the Health Belief Model, a patient-centered framework provides a first-person perspective on key factors related to patient decision-making. This model suggests that, for patients, taking their medication—or not taking it—is a means to achieving the best possible outcome. As they assess the options of life with medication versus life without medication, they anticipate the consequences of each option based on their own experiences, their beliefs about medication, and information from others (AV 1).14

Patient Perspectives

In an interview between a representative from Schizophrenia and Related Disorders Alliance of America (SARDAA) and a patient with schizophrenia (oral communication, December 2019), the patient described his decision not to take his medication and then changing his mind.

 “A lot—a few times—I stopped taking my medication without telling any clinician because they would have put me in the psych ward and popped me with more pills, and I had had enough … so I started smoking pot and stuff like that and fully stopped taking the medicine, cancelled the doctor, moved away, and just became a mess. I came crawling back and finally, after years, I got treated.”

Positive treatment decisions are tied to patient-defined goals.15,16 To help patients make positive treatment decisions, using a combined shared decision-making and motivational interviewing technique is recommended.15,17 Shared decision-making refers to the recognition that the patient is an expert by experience but does not mean to leave the decision entirely up to the patient. Rather, the medical and clinical rationales need to be clearly presented so that patients can make decisions that increase the chance of positive outcomes, including functionality and autonomy. That the patient makes a decision does not automatically reflect exercised autonomy, as it is possible that inadequate illness insight or appreciation of the risks of stopping treatment or of using drugs leads to a reduction of autonomy due to illness exacerbation or severity. Motivational interviewing is a style of dialogue between two parties, which is intended to motivate one party into making positive changes by compassionately challenging the status quo and helping them explore alternatives. Principles of motivational interviewing include autonomy, collaboration, and evocation.

Information about risks and benefits needs to be presented in a fair and balanced way when discussing adherence-enhancing treatments, such as long-acting injectable (LAI) antipsychotics,18 which have shown superiority versus oral antipsychotics regarding treatment engagement, relapse and hospitalization, and mortality.19–22 Pros and cons should be laid out.23,24 However, a clinician bias against LAIs has been observed, in that doctors and nurses strongly overestimated concerns that they thought patients had against LAIs.25 This negative overestimation was present when compared with opinions of patients currently taking oral antipsychotics and, even more so, of patients currently taking LAIs.25 In another study,26 clinicians offering LAIs to their patients spent only 9% of speech time on positive aspects of this treatment modality; the remaining communication time was spent on perceived neutral or negative aspects of LAIs. After this type of discussion, only 33% of patients stated that they would be willing to take LAI treatment.26 After another clinician, who was trained in communication about LAIs, revisited the issue with patients, 96% of patients said that they might consider LAI treatment in the future26; an LAI initiation was not part of the study to verify this patient statement.

A cluster-randomized study27 at 39 sites compared an LAI treatment paradigm with usual care consisting predominantly of an oral antipsychotic paradigm. The sample comprised patients with first-episode and early-phase (≤ 5 years since diagnosis) schizophrenia, aged 18–35 years; 234 were treated at the 19 sites randomized to the LAI approach. As part of the study set-up, the entire treatment teams of these sites received specific training. This training involved education about the benefits of LAIs (which could be used in the shared decision and motivational interview approach), role play, answers to frequently asked questions, and solutions to logistic barriers, as well as treatment guidelines. Using this approach, 91% of patients who had agreed to participate in the study, which they knew would involve being offered an LAI as part of their care, had at least one LAI injection within the first 3 months of outpatient care engagement. Among the originally identified potential participants who met inclusion/exclusion criteria at the LAI sites, only 14% declined study participation specifically because they did not like being offered an LAI as part of their future treatment. This study suggests that many first-episode and early-phase patients would accept initiation of an LAI when a team approach and motivational interview plus shared decision making paradigm are used.

Patient-Reported Outcomes

Self-reporting can enhance a patient’s feeling of involvement in the treatment process, thereby improving self-esteem, while also providing the clinician with knowledge of the patient’s insight into the illness.4 A patient-reported outcome (PRO) is a measurement that is directly reported by the patient about his or her health, quality of life, or functional status that is not amended or interpreted by the clinician or anyone else. A PRO can be obtained by interview as long as the interviewer records only the patient’s response.10 These outcomes may be measured in absolute terms, such as a patient’s rating of the severity of depression.

Tools for measuring PROs. Patient-reported outcome measures (PROMs) are the tools or instruments used to measure PROs.28 PROMS can be general in nature or disease-specific and are usually self-completed questionnaires measuring functional status, health-related quality of life, symptom burden, personal experience of care, and health-related behaviors, such as anxiety and depression. Multiple PROMS can be used for patients to report on domains relevant to schizophrenia.4 Scales that can be completed in 10 minutes or less include the following: Brief Symptom InventoryDrug Attitude InventoryCamberwell Assessment of Need Short Appraisal ScheduleSubjective Wellbeing under Neuroleptic Treatment Scale–Short FormWorld Health Organization Quality of Life Assessment–BREF, and Sheehan Disability Scale.4

Challenges for Relapse Prevention

Treatment of schizophrenia in the modern era should focus on remission and recovery, health-related quality of life, and functioning.29 To achieve long-term improvement in quality of life and functionality, it is important to first achieve symptom remission.30,31 However, remission rates vary depending on population and pharmacotherapy. As few as 17% and as many as 81% of patients with first-episode schizophrenia attain symptom remission, although most studies report remission rates in a range of approximately 35%–50% for this population, depending on the intervention.32 Patients with chronic schizophrenia do not achieve remission as often or as quickly as those with a first episode.

Recovery remains an elusive goal for many people with schizophrenia.30,31 In a meta-analysis of 50 years of research, the median recovery rate was only 13.5%.33 Although patients experiencing a first-episode of schizophrenia had better remission rates than those with multiple episodes, no significant difference was found between the two groups in rates of recovery.33

Patient Perspectives

In an interview with a representative from SARDAA (oral communication, December 2019), a patient described his journey to recovery.

“I relapsed seven times. A few of the times I relapsed, I was taking my medicine. But it’s been maybe 7, 8 years since I’ve been to the hospital? I like my medication right now. I have an apartment. I’m on my own. I go to Narcotics Anonymous meetings. I go to the gym. I play basketball with my friends. I do some work.”

The major threat on the road to recovery is relapse. Many patients are not stable long enough to benefit from psychosocial, vocational, and functional rehabilitation, and with each relapse, their psychosocial environment and connectivity are disrupted, and the illness’s trajectory and biology are negatively affected. Relapse is commonly related to medication nonadherence.32,34 However, relapse can also occur during maintenance treatment, being associated with insufficient symptom stability and substance use.35,36 In the case of LAI treatment, relapse can also be related to inappropriate injection practices (eg, not deep intramuscular, systematically delayed injections due to rescheduled patients).37 Relapse needs to be prevented, as it is associated with gray matter decline38 and can lead to the development of secondary treatment resistance in previously treatment-responsive individuals.32,39–41

Relapse prevention and recovery require treatment that successfully targets ideally all of the clinical domains of schizophrenia and minimizes adverse effects.42

AV 2. Prevalence of Prominent Positive and Negative Symptoms in Schizophrenia (00:24)

Data from Rabinowitz et al.45

Positive symptoms. Schizophrenia is defined by positive symptoms—delusions, hallucinations, and disorganized thoughts and behavior.1 Antipsychotic medications indicated for the treatment of schizophrenia are generally effective at controlling positive symptoms but have limited efficacy against the remaining clinical domains.43

Negative symptoms. Negative symptoms—affective flattening, alogia, anhedonia, amotivation, and asociality1,43—are relatively common and impair functionality, particularly across social interactions.44 In an analysis of 1,447 antipsychotic-treated outpatients, approximately 1 in 5 had predominant negative symptoms (AV 2).45

Negative symptoms are relevant because patients who exhibit negative symptoms in their first episode of psychosis have lower rates of response, higher rates of delayed response, higher rates of nonresponse, and higher rates of relapse compared with patients exhibiting positive symptoms.46 To address negative symptoms, secondary negative symptoms need to be addressed,2,44 including the appropriate treatment of paranoia, anxiety, depression, and substance use disorders; avoidance of sedation and extrapyramidal side effects (EPS); management of chronic pain; minimization of stigma and self-stigma; and provision of psychosocial treatments.

To further address negative symptoms, nonpharmacologic strategies may be helpful; cognitive remediation has shown small to moderate benefits, indicating a link between negative and cognitive symptoms of schizophrenia.47,48 Additionally, aerobic exercise can reduce negative symptoms,49 and antidepressants have been shown to significantly reduce negative symptoms versus placebo.50,51

AV 3. Cognitive Impairment in Schizophrenia (00:52)

Based on Millan et al.52

Cognition. Cognitive dysfunction in schizophrenia affects all cognitive domains.52 Among measured cognitive domains in a review comparing psychiatric disorders (AV 3),52 only procedural memory received a ranking of “consistently present but not pronounced” in patients with schizophrenia, while other cognitive domains were more severely disturbed.

Dysfunction in the various cognitive domains has an impact on real-world functioning.53–55 Although currently no medications are approved for the treatment of cognitive deficits in schizophrenia, clinicians can address secondary cognitive symptoms to improve patients’ functioning and quality of life. Similar to secondary negative symptoms (see above), secondary cognitive dysfunction can be due to comorbid psychiatric conditions, medication side effects, physical conditions, or environmental conditions.2 Patients with schizophrenia should be screened for comorbidities including mental retardation, dementia, depression, anxiety disorders, substance abuse, and paranoia, all of which can impair cognition. Adverse events (eg, EPS, sedation), medical or physical conditions (eg, sleep apnea, chronic pain, being overweight or obese), and environmental factors (eg, deprivation, stigma) can all impair cognition.2,44

Some cognitive benefits may be found with cognitive-behavioral therapy, cognitive remediation, social skills training, and computer-assisted training programs, in conjunction with antipsychotic treatment.2,56

Affective symptoms. Patients with schizophrenia commonly experience affective symptoms, including depression, anxiety, and suicidality, although it can be difficult for clinicians to differentiate negative symptoms from depressive symptoms. An analysis57 of patients presenting with symptoms that could be categorized as depressive or negative found that certain symptoms indicated the likelihood of either depression or negative symptoms. Symptoms with more specificity for depression were low mood, pessimism, and suicidal ideation, all of which should be inquired about during the clinical interview. Alogia and blunted affect had more specificity for negative symptoms; these symptoms can be observed by clinicians in the patient’s behavior.

Depression in people with schizophrenia is relevant because low mood is a strong predictor of low quality of life58 and suicidality.27,28 Interestingly, greater illness insight in the first episode or early-phase schizophrenia is associated with an increased likelihood of depression and suicidality.58,61 Depression comorbid with schizophrenia should be treated by using an antipsychotic with antidepressant activity, or, after having addressed positive symptoms, by adding an antidepressant agent.62 Cognitive-behavioral therapy may also be useful.62

Adverse events. Side effects impact adherence levels,63 poor adherence is associated with increased rates of relapse,34,64 and relapse prevents recovery.32 Therefore, medication tolerability is the link between effective symptom control, recovery, quality of life, and functional capacity.65

Patient Perspectives

A patient with schizophrenia described in an interview with a SARDAA representative (oral communication, December 2019) his satisfaction with his physician assessing him for adverse effects:

”We’re cool; I like my doctor. At this point, I see him once a month. Checks my weight. Checks my heart. Checks my blood pressure. Checks my sugar. You know, checks my medicine levels.”

The clinician’s objective assessment and the patient’s subjective perspective are both important when assessing side effects. From the clinical perspective, certain side effects might convey relevant clinical and medical risk, but the patient’s subjective distress and impacted life quality due to side effects may determine adherence. In a large, nationwide study63 of adults with a self-reported diagnosis of schizophrenia, approximately 86% of participants reported experiencing at least one side effect. Most side effects were associated with significantly reduced adherence, and participants who reported complete adherence were approximately half as likely to report a hospitalization for mental health reasons or other reasons compared with participants reporting poor adherence.63

Specific side effects were found to be associated with reduced adherence; EPS or agitation reduced adherence by approximately 43%.63 Weight gain and metabolic side effects reduced adherence by 36%. Prolactin elevation, endocrine dysfunction, and sexual side effects each reduced adherence by 31%. Sedation and cognitive impairment reduced adherence by 30%, and gastrointestinal side effects reduced adherence by 21%.63

When surveyed, family members of people with schizophrenia reported that sedation, weight gain, and EPS most reduced the quality of life of their loved ones with schizophrenia.66 When patients with schizophrenia were asked what impaired their quality of life the most, they ranked the following side effects from most to least impairing: weight gain, somnolence or insomnia, and concentration difficulties, memory loss, or disordered thoughts.67 The potential for these side effects should be kept in mind when choosing medication, especially early in the illness, and clinicians should always employ a “first do no harm” approach. Moreover, using patient-reported adverse effect reporting may improve adherence and minimize adverse effects via more appropriate medication selection and adjustment.68

Finally, improved quality of life, remission, and recovery are more likely when patients receive antipsychotic treatment combined with psychosocial interventions, ideally in a coordinated specialty care framework.69,70

Conclusion

To improve outcomes in people with schizophrenia, symptom control in the clinical domains beyond positive symptoms is needed. Patient-reported outcomes are important for assessing the impact of the illness and the success of its treatment. Recovery, satisfactory quality of life, and adequate functionality can be achieved only when treatment addresses the various domains of schizophrenia without causing impairing adverse events that are associated with nonadherence. Pharmacotherapy in combination with psychosocial interventions that target cognition, family environment, social skills, and vocational rehabilitation is likely to have the best outcome. Novel agents are needed to better address the multidimensional syndrome of schizophrenia.

Case Practice Question

Jack, a 26-year-old patient with schizophrenia, has been stabilized with a long-acting injectable antipsychotic. At follow-up, Jack’s positive symptoms are still in remission, but he displays low mood and pessimism about his future. Which of the following is the best next step?

A. Screen for adverse events
B. Screen for depression and suicidality; if found, add an antidepressant
C. Add an oral antipsychotic to Jack’s prescription regimen
D. Switch to a first-line oral antipsychotic

Discussion of the Case Practice Question

Preferred response: B. Screen for depression and suicidality; if found, add an antidepressant.
Low mood and pessimism may indicate the presence of comorbid depression.57  Jack is susceptible to suicidality because it is early in the course of his illness, and he may feel that his future is limited by his illness.61 If depressive symptoms are present, concomitant antidepressant pharmacotherapy is appropriate, according to guidelines.62

Clinical Points

  • Use measurement-based assessment of treatment outcomes.
  • Collect patient-reported outcomes to assess quality of care.
  • Assess and address all symptom domains, with a focus on negative symptoms and cognition for functional outcome and depression for prevention of suicidality.
  • Employ pharmacotherapy in combination with psychosocial interventions for functional rehabilitation.

References

  1. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1(1):15067. Pubmed CrossRef
  2. Carbon M, Correll CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr. 2014;19(suppl 1):38–52, quiz 35–37, 53. Pubmed CrossRef
  3. Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757–777. Pubmed CrossRef
  4. Correll CU, Kishimoto T, Nielsen J, et al. Quantifying clinical relevance in the treatment of schizophrenia. Clin Ther. 2011;33(12):B16–B39. Pubmed CrossRef
  5. Leucht S, Kane JM, Kissling W, et al. Clinical implications of Brief Psychiatric Rating Scale scores. Br J Psychiatry. 2005;187(4):366–371. Pubmed CrossRef
  6. Leucht S, Kane JM, Kissling W, et al. What does the PANSS mean? Schizophr Res. 2005;79(2–3):231–238. Pubmed CrossRef
  7. Andreasen NC, Carpenter WT Jr, Kane JM, et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–449. Pubmed CrossRef
  8. Liberman RP, Kopelowicz A, Ventura J, et al. Operational criteria and factors related to recovery from schizophrenia. Int Rev Psychiatry. 2002;14(4):256–272. CrossRef
  9. Division of Mental Health and Prevention of Substance Abuse, World Health Organization. Programme on Mental Health: WHOQOL User Manual. Geneva, Switzerland: WHO website. https://www.who.int/mental_health/evidence/who_qol_user_manual_98.pdf. 1998.
  10. US Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH). Guidance for Industry—Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Silver Spring, MD. FDA website. https://www.fda.gov/media/77832/download. 2009.
  11. Leidy NK. Functional status and the forward progress of merry-go-rounds: toward a coherent analytical framework. Nurs Res. 1994;43(4):196–202. Pubmed CrossRef
  12. De Silva MJ, Cooper S, Li HL, et al. Effect of psychosocial interventions on social functioning in depression and schizophrenia: meta-analysis. Br J Psychiatry. 2013;202(4):253–260. Pubmed CrossRef
  13. Brissos S, Molodynski A, Dias VV, et al. The importance of measuring psychosocial functioning in schizophrenia. Ann Gen Psychiatry. 2011;10(1):18. Pubmed CrossRef
  14. Kikkert MJ, Dekker J. Medication adherence decisions in patients with schizophrenia. Prim Care Companion CNS Disord. 2017;19(6):17n02182. Pubmed CrossRef
  15. Lasser RA, Schooler NR, Kujawa M, et al. A new psychosocial tool for gaining patient understanding and acceptance of long-acting injectable antipsychotic therapy. Psychiatry (Edgmont). 2009;6(4):22–27. Pubmed
  16. Magill M, Gaume J, Apodaca TR, et al. The technical hypothesis of motivational interviewing: a meta-analysis of MI’s key causal model. J Consult Clin Psychol. 2014;82(6):973–983. Pubmed CrossRef
  17. Stovell D, Morrison AP, Panayiotou M, et al. Shared treatment decision-making and empowerment-related outcomes in psychosis: systematic review and meta-analysis. Br J Psychiatry. 2016;209(1):23–28. Pubmed CrossRef
  18. Potkin S, Bera R, Zubek D, et al. Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia. BMC Psychiatry. 2013;13(1):261. Pubmed CrossRef
  19. Taipale H, Mittendorfer-Rutz E, Alexanderson K, et al. Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia. Schizophr Res. 2018;197:274–280. Pubmed CrossRef
  20. Correll CU, Citrome L, Haddad PM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. Pubmed CrossRef
  21. Kishimoto T, Nitta M, Borenstein M, et al. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013;74(10):957–965. Pubmed CrossRef
  22. Kishimoto T, Hagi K, Nitta M, et al. Effectiveness of long-acting injectable vs oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies. Schizophr Bull. 2018;44(3):603–619. Pubmed CrossRef
  23. Correll CU. Addressing barriers to using long-acting injectable antipsychotics and appropriately monitoring antipsychotic adverse effects. J Clin Psychiatry. 2013;74(8):e16. CrossRef
  24. Correll CU. The role of the extended health care team in successful LAI therapy: education to overcome barriers. J Clin Psychiatry. 2014;75(9):e25. CrossRef
  25. Cahling L, Berntsson A, Bröms G, et al. Perceptions and knowledge of antipsychotics among mental health professionals and patients. BJPsych Bull. 2017;41(5):254–259. Pubmed CrossRef
  26. Weiden PJ, Roma RS, Velligan DI, et al. The challenge of offering long-acting antipsychotic therapies: a preliminary discourse analysis of psychiatrist recommendations for injectable therapy to patients with schizophrenia. J Clin Psychiatry. 2015;76(6):684–690. Pubmed CrossRef
  27. Kane JM, Schooler NR, Marcy P, et al. Patients with early-phase schizophrenia will accept treatment with sustained-release medication (long-acting injectable antipsychotics): results from the recruitment phase of the PRELAPSE trial. J Clin Psychiatry. 2019;80(3):18m12546. Pubmed CrossRef
  28. Weldring T, Smith SMS. Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). Health Serv Insights. 2013;6:61–68. Pubmed CrossRef
  29. Juckel G, Morosini PL. The new approach: psychosocial functioning as a necessary outcome criterion for therapeutic success in schizophrenia. Curr Opin Psychiatry. 2008;21(6):630–639. Pubmed CrossRef
  30. Lambert M, Naber D, Schacht A, et al. Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia. Acta Psychiatr Scand. 2008;118(3):220–229. Pubmed CrossRef
  31. Phahladira L, Luckhoff HK, Asmal L, et al. Early recovery in the first 24 months of treatment in first-episode schizophrenia-spectrum disorders. NPJ Schizophr. 2020;6(1):2. Pubmed CrossRef
  32. Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014;16(4):505–524. Pubmed
  33. Jääskeläinen E, Juola P, Hirvonen N, et al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. 2013;39(6):1296–1306. Pubmed CrossRef
  34. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12(3):216–226. Pubmed CrossRef
  35. Rubio JM, Taipale H, Correll CU, et al. Psychosis breakthrough on antipsychotic maintenance: results from a nationwide study [published online ahead of print June 13, 2019]. Psychol MedPubmed CrossRef
  36. Emsley R, Asmal L, Rubio JM, et al. Predictors of psychosis breakthrough during 24 months of long-acting antipsychotic maintenance treatment in first episode schizophrenia [published online ahead of print November 22, 2019]. Schizophr ResPubmed CrossRef
  37. Correll CU, Sliwa JK, Najarian DM, et al. Practical considerations for managing breakthrough psychosis and symptomatic worsening in patients with schizophrenia on long-acting injectable antipsychotics [published online ahead of print December 27, 2019]. CNS Spectr. 2018;(December):1–17. Pubmed CrossRef
  38. Andreasen NC, Liu D, Ziebell S, et al. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry. 2013;170(6):609–615. Pubmed CrossRef
  39. Wiersma D, Nienhuis FJ, Slooff CJ, et al. Natural course of schizophrenic disorders: a 15-year follow-up of a Dutch incidence cohort. Schizophr Bull. 1998;24(1):75–85. Pubmed CrossRef
  40. Emsley R, Nuamah I, Hough D, et al. Treatment response after relapse in a placebo-controlled maintenance trial in schizophrenia. Schizophr Res. 2012;138(1):29–34. Pubmed CrossRef
  41. Takeuchi H, Siu C, Remington G, et al. Does relapse contribute to treatment resistance? antipsychotic response in first- vs second-episode schizophrenia. Neuropsychopharmacology. 2019;44(6):1036–1042. Pubmed CrossRef
  42. Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry. 2018;17(2):149–160. Pubmed CrossRef
  43. Millan MJ, Fone K, Steckler T, et al. Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014;24(5):645–692. Pubmed CrossRef
  44. Correll CU, Schooler NR. Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr Dis Treat. 2020;16:519–534. Pubmed CrossRef
  45. Rabinowitz J, Berardo CG, Bugarski-Kirola D, et al. Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis. Schizophr Res. 2013;150(2–3):339–342. Pubmed CrossRef
  46. Austin SF, Mors O, Budtz-Jørgensen E, et al. Long-term trajectories of positive and negative symptoms in first episode psychosis: a 10 year follow-up study in the OPUS cohort. Schizophr Res. 2015;168(1–2):84–91. Pubmed CrossRef
  47. Cella M, Preti A, Edwards C, et al. Cognitive remediation for negative symptoms of schizophrenia: a network meta-analysis. Clin Psychol Rev. 2017;52:43–51. Pubmed CrossRef
  48. De Mare A, Cantarella M, Galeoto G. Effectiveness of integrated neurocognitive therapy on cognitive impairment and functional outcome for schizophrenia outpatients. Schizophr Res Treatment. 2018;2018:2360697. Pubmed CrossRef
  49. Stubbs B, Vancampfort D, Hallgren M, et al. EPA guidance on physical activity as a treatment for severe mental illness: a meta-review of the evidence and Position Statement from the European Psychiatric Association (EPA), supported by the International Organization of Physical Therapists in Mental Health (IOPTMH). Eur Psychiatry. 2018;54:124–144. Pubmed CrossRef
  50. Helfer B, Samara MT, Huhn M, et al. Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. Am J Psychiatry. 2016;173(9):876–886. Pubmed CrossRef
  51. Galling B, Vernon JA, Pagsberg AK, et al. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia. Acta Psychiatr Scand. 2018;137(3):187–205. Pubmed CrossRef
  52. Millan MJ, Agid Y, Brüne M, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11(2):141–168. Pubmed CrossRef
  53. Green MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry. 2006;67(suppl 9):3–8, discussion 36–42. Pubmed CrossRef
  54. Palmer BW, Dawes SE, Heaton RK. What do we know about neuropsychological aspects of schizophrenia? Neuropsychol Rev. 2009;19(3):365–384. Pubmed CrossRef
  55. Bowie CR, Leung WW, Reichenberg A, et al. Predicting schizophrenia patients’ real-world behavior with specific neuropsychological and functional capacity measures. Biol Psychiatry. 2008;63(5):505–511. Pubmed CrossRef
  56. Keefe RSE, Haig GM, Marder SR, et al. Report on ISCTM consensus meeting on clinical assessment of response to treatment of cognitive impairment in schizophrenia. Schizophr Bull. 2016;42(1):19–33. Pubmed. 10.1093/schbul/sbv111
  57. Krynicki CR, Upthegrove R, Deakin JFW, et al. The relationship between negative symptoms and depression in schizophrenia: a systematic review. Acta Psychiatr Scand. 2018;137(5):380–390. Pubmed CrossRef
  58. Siu CO, Harvey PD, Agid O, et al. Insight and subjective measures of quality of life in chronic schizophrenia. Schizophr Res Cogn. 2015;2(3):127–132. Pubmed CrossRef
  59. Sanchez-Gistau V, Baeza I, Arango C, et al. Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study. J Clin Psychiatry. 2013;74(1):59–66. Pubmed CrossRef
  60. Sanchez-Gistau V, Baeza I, Arango C, et al. The affective dimension of early-onset psychosis and its relationship with suicide. J Child Psychol Psychiatry. 2015;56(7):747–755. Pubmed CrossRef
  61. Ventriglio A, Gentile A, Bonfitto I, et al. Suicide in the early stage of schizophrenia. Front Psychiatry. 2016;7:116. Pubmed CrossRef
  62. Dondé C, Vignaud P, Poulet E, et al. Management of depression in patients with schizophrenia spectrum disorders: a critical review of international guidelines. Acta Psychiatr Scand. 2018;138(4):289–299. Pubmed CrossRef
  63. Dibonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012;12(1):20. Pubmed CrossRef
  64. Sun SX, Liu GG, Christensen DB, et al. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;23(10):2305–2312. Pubmed CrossRef
  65. Correll CU. What are we looking for in new antipsychotics? J Clin Psychiatry. 2011;72(suppl 1):9–13. Pubmed CrossRef
  66. Angermeyer MC, Matschinger H. Attitude of family to neuroleptics [in German]. Psychiatr Prax. 1999;26(4):171–174. Pubmed
  67. McIntyre RS. Understanding needs, interactions, treatment, and expectations among individuals affected by bipolar disorder or schizophrenia: the UNITE global survey. J Clin Psychiatry. 2009;70(suppl 3):5–11. Pubmed CrossRef
  68. Robinson DG, Schooler NR, Correll CU, et al. Psychopharmacological treatment in the RAISE-ETP study: outcomes of a manual and computer decision support system based intervention. Am J Psychiatry. 2018;175(2):169–179. Pubmed CrossRef
  69. Correll CU, Galling B, Pawar A, et al. Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. JAMA Psychiatry. 2018;75(6):555–565. Pubmed CrossRef
  70. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiatry. 2016;173(4):362–372. Pubmed CrossRef

Volume: 81

Quick Links:

References