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Schizophrenia Treatment Principles PowerPoint Presentation

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This medical PowerPoint presentation talks about some key principles of schizophrenia treatment.
Schizophrenia is a complex and chronic mental illness that can severely impact a persons ability to function in daily life. While there is no known cure for schizophrenia, treatment can help manage symptoms and improve quality of life. Here are some key principles of schizophrenia treatment:
Medication: Antipsychotic medications are the cornerstone of schizophrenia treatment. These medications can help reduce hallucinations, delusions, and other symptoms associated with the disorder. Its important for individuals to work closely with their healthcare providers to find the right medication and dosage for them, as different people may respond differently to different medications.
Psychotherapy: Psychotherapy, also known as talk therapy, can be helpful for individuals with schizophrenia to better understand and manage their symptoms. Cognitive-behavioral therapy (CBT) can help individuals identify and challenge negative thought patterns and beliefs, while family therapy can help improve communication and relationships with loved ones.
Supportive services: Supportive services such as vocational rehabilitation, case management, and peer support can help individuals with schizophrenia manage their symptoms and improve their quality of life. These services can help individuals find employment, access healthcare, and develop a social support network.
Lifestyle changes: Making lifestyle changes such as getting regular exercise, eating a healthy diet, getting enough sleep, and avoiding drugs and alcohol can also be helpful for individuals with schizophrenia. These changes can help improve overall health and well-being and reduce the risk of exacerbating symptoms.
Ongoing monitoring: Schizophrenia is a chronic illness, and ongoing monitoring and treatment are important to manage symptoms and prevent relapses. Individuals with schizophrenia should work closely with their healthcare providers to develop a treatment plan that is tailored to their specific needs and to adjust the plan as necessary over time.

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Schizophrenia Treatment principles
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Treatment principles Schizophrenia
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Schizophrenia The progression of schizophrenia and functional decline Lieberman et al. Biol Psychiatry 2001;50(11):884–897 3 Healthy Worsening of severity of signs and symptoms Birth 10 20 30 40 50 60 Age (years) Chronic residual Progression/clinical deterioration Prodromal Premorbid Onset Number of relapses may be related to greater deterioration Illness-driven decline in functioning plateaus Clinical deterioration begins here and occurs throughout the 5–10 years before the first episode The longer the period of untreated psychosis, the worse the prognosis Patients may not recover from subsequent psychotic episodes as quickly or as fully as they did from previous episodes, and may experience greater degrees of residual symptomology and disability
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Schizophrenia Treatment should be optimised for each individual in order to improve the outcome Adapted from: Tandon et al. J Psychiatr Pract 2006;12(6):348–363 4 Reduces disease burden Adds to treatment burden Treatment (reduce symptoms and prevent relapse) Medications Psychosocial interventions (e.g. cognitive behavioural therapy) Rehabilitation (enhance adaptive skills) Social skills training Supports (environmental changes) Supported housing Supported employment Costs and unintended adverse consequences Adverse events Discrimination Direct and indirect costs Related health risks Treatment and other services Recovery Health and wellness Vocational and/or educational functioning Independent living Better physical health Instrumental competence Social integration Improved quality of life
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Schizophrenia Psychosocial interventions should be tailored to the goals, needs, abilities and circumstances of patients Canadian Psychiatric Association. Can J Psychiatry 2005;50(13 Suppl. 1):7S–57S 5 Patient Vocational training and support Integrated substance use programme Psychoeducation Family psychoeducation Peer support, self-help and recovery Cognitive behavioural therapy (CBT) Social skills training Medication treatment adherence and relapse prevention Consumer involvement (empowerment) in setting rehabilitation goals Social interaction skills Dysphoria and/or depression; stress and relapse prevention Patient needs help with Patient has Ability and interest in working Family members available; ongoing treatment, monitoring of recovery, and support Substance use issues
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Schizophrenia Disease phases in schizophrenia aIn antipsychotic discontinuation studies; bmedian (interquartile range)FES=first-episode schizophrenia Carbon & Correll. Dialogues Clin Neurosci 2014;16(4):505–524 6 13.5% [8–20%]b (FES: 16.6%)b 18–65% (FES: 40–87%) 10–45% (FES: ~10%) Any duration: 44%; 7–52% (FES: 17–81%) Illness severity Acute Stabilisation Maintenance Treatment phase Relapse Exacerbation Resistance Any duration:a 57.3% Remission Recovery Response
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Schizophrenia Different phases of schizophrenia have different treatment goals Adapted from: Lehman et al. Am J Psychiatry 2004;161(2 Suppl.):1–56 7 Sustain symptom remission or control (effectively treat increases in symptoms or relapses) Maintain or improve functioning and quality of life Continue to monitor adverse treatment effects Reduce stress/support and develop adaptation to life in the community Facilitate continued reduction in symptoms and consolidation of remission Reduce relapse risk and promote the process of recovery Prevent harm/control disturbed behaviour Reduce the severity of psychosis and symptoms/promote rapid return to the best level of functioning Determine and address causes Formulate short- and long-term treatment plans Engage, collaborate with family/connect to community services Stablephase Stabilisationphase Acutephase
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Schizophrenia Factors to consider when setting treatment goals Adapted from: 1. Lehman et al. Am J Psychiatry 2004;161(2 Suppl.):1–56; 2. Oh et al. Korean J Schizophr Res 2014;17(2):93–99 8 Relapse prevention1 by reducing or eliminating symptoms 3. Maximising treatment adherence1 so promoting and maintaining recovery from the debilitating effects of illness to the maximum extent possible Key considerations Assessing positive and negative symptoms2 Minimising medication adverse events2 Managing depressive symptoms2 2. Quality of life and subjective well-being2 by maximizing quality of life and adaptive functioning
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Schizophrenia The importance of relapse prevention HRQoL=Health-related quality of life 1. Birchwood et al. Adv Psychiatr Treat 2000;6(2):93–101;2. Shepherd et al. Psychol Med Monogr Suppl 1989;15:1–46; 3. Ascher-Svanum et al. BMC Psychiatry 2010;10:2; 4. Kane. J Clin Psychiatry 2007;68(Suppl. 14):27–30; 5. Lieberman et al. Psychiatr Serv 2008;59(5):487–496; 6. Briggs et al. Health Qual Life Outcomes 2008;6:105 9 Increased risk of suicide attempts3,4 Long-term symptoms and disability1,2 Decrease in treatment response4 Progressive decline in brain function5 Increased burden on family and caregivers4 Increased use of healthcare resources4 Negative impact on HRQoL6 Multiple relapses and subsequent exacerbations
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Schizophrenia Antipsychotic therapy significantly reduces relapse rates aWeighted by sample size of individual trials. In a meta-regression, antipsychotic drug–placebo advantages decreased with study length CI=confidence interval; NNT=number needed to treat Adapted from: Leucht et al. Lancet 2012;379(9831):2063–2071 10 Favours drug Favours placebo
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Survival analysis for clinical deteriorationa for patients receiving maintenance antipsychotic treatment versus intermittent treatment1 11 aIncrease from baseline in the sum of PANSS positive and negative scores ≥25%, or ≥10 points (if baseline value ≤40), or a CGI-C score ≥6;CGI-C=Clinical Global Impression – Change; PANSS=Positive and Negative Syndrome Scale 1. Gaebel et al. J Clin Psychiatry 2011;72(2):205–218 Continuous maintenance treatment may decrease deterioration in symptoms during the second year following diagnosis Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse1
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Schizophrenia Only a small proportion of patients with schizophrenia achieve recovery CGI-SCH=Clinical Global Impression – Schizophrenia;EQ-5D VAS=EuroQoL5 dimensions visual analogue scale 1. Novick et al. Schizophr Res 2009;108(1–3):223–230 12 Employment, independent living, social activity, and medication adherence were important predictors of recovery1 A 3-year observational study of adults with schizophrenia (n=6,642)1 Long-lasting symptomatic remission Defined as CGI-SCH positive, negative, cognitive, and overall severity score <4, plus no inpatient admission for ≥24 months Long-lasting adequate quality of life Defined as ≥70 on the EQ-5D VAS for ≥24 months Long-lasting functional remission Defined as employed/student/housewife, plus independent living, plus active social interactions for ≥24 months Recovery, defined as all 3 of the above
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Selecting the most suitable treatment – minimal adverse events and maximum adherence Schizophrenia
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Environment Illness Medication Patient Schizophrenia Selecting suitable treatments for schizophrenia can pose a dilemma for psychiatrists An ‘ideal’ medication is one that can:2 Treat psychosis Lead to symptom resolution Lead to remission Overcome treatment resistance Effectively protect against relapse Have a benign adverse-event profile (with minimal sedation and akathisia) Have efficacy for symptoms of anxiety and depression 1. Kane et al. Dialogues Clin Neurosci 2010;12(3):345–357; 2. Correll. J Clin Psychiatry 2011;72(Suppl. 1):9–13; 3. Abidi et al. Can J Psychiatry 2003;48(11):749‒755; 4. Leucht et al. Lancet 2013;382(9896):951‒962; 5. Uçok et al. World Psychiatry 2008;7(1):58‒62; 6. Barnes et al. J Psychopharmacol 2011;25(2):567‒620 14 In selecting treatments for schizophrenia, physicians consider variables related to the:1,2 The long-term nature of adverse events, including metabolic, endocrine and cardiac complications, can pose a dilemma for physicians in providing effective treatment while avoiding adverse events3 Physicians have to consider how adverse events interact with the patient’s health and lifestyle (e.g., age, weight, cardiovascular health, co-prescribed medications, previously experienced adverse events)4-6
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Ongoing collaboration with patient in decision-making2 Careful assessment of possible adverse effects of treatment1,3 Schizophrenia Guidelines for good practice are measurement-based and individualised BPRS=Brief Psychiatric Rating Scale; PANSS=Positive and Negative Syndrome Scale 1. Canadian Psychiatric Association. Can J Psychiatry 2005;50(13 Suppl. 1):7S–57S [CPA Guidelines];2. Lehman et al. Am J Psychiatry 2004;161(Suppl. 2):1–56 [APA Practice Guidelines];3. Hasan et al. World J Biol Psychiatry 2013;14(1):2–44 [WFSBP guidelines] 15 Ongoing, careful monitoring is critical1-3 Reliable and repeated assessment of the efficacy of treatment using defined treatment targets is important1,2 Using standard rating scales such as BPRS and PANSS will facilitate this goal3 Standard protocols should be customised in response to individual vulnerabilities/needs and specific drug1
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Schizophrenia Treatment of schizophrenia needs a rational approach with minimal tolerability issues to optimise patient functioning APA=American Psychiatric Association; EPS=extrapyramidal symptoms; NICE=National Institute for Health and Care Excellence 1. Lehman et al. Am J Psychiatry 2004;161(Suppl. 2):1–56; 2. Kuipers et al. Psychosis and schizophrenia in adults. NICE clinical guideline 178. 2014 16 Antipsychotics that minimise EPS, cardiovascular risk, and activating and sedating adverse events may optimise the physical health and social functioning of patients with schizophrenia APA guidelines recommend choosing a medication that offers good clinical response without intolerable adverse events1 NICE guidelines recommend regular monitoring of adverse events systematically throughout treatment, and especially during the titration phase2 Patients who experience serious adverse events may decide that the adverse events outweigh the benefits of medication1 APA guidelines NICE guidelines
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1.3.4.1 For people with first episode psychosis offer: - Oral antipsychotic medication in conjunction with - Psychological interventions (family intervention and individual CBT)1.4.2.1 For people with an acute exacerbation or recurrence of psychosis or schizophrenia offer: - Oral antipsychotic medication - Psychological interventions (family intervention and individual CBT) CBT=cognitive behavioural therapy NICE. Psychosis and schizophrenia in adults: prevention and management. NICE clinical guideline 178. 2014 17
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Choice of antipsychotic medication1.3.5.1 The choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees. Provide information and discuss the likely benefits and possible side effects of each drug, including: - Metabolic (including weight gain and diabetes) - Extrapyramidal (including akathisia, dyskinesia, and dystonia) - Cardiovascular (including prolonging the QT interval) - Hormonal (including increasing plasma prolactin) - Other (including unpleasant subjective experiences) NICE. Psychosis and schizophrenia in adults: prevention and management. NICE clinical guideline 178. 2014 18
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Antipsychotics should be chosen individually, respecting the patient’s mental and somatic condition with special attention to side effectsThe selection of an antipsychotic medication should be guided by the patient’s previous experience of symptom response and side effects, intended route of administration, the patient’s preferences for a particular medication, the presence of comorbid medical conditions, and potential interactions with other prescribed medications. Special attention needs to be given to antipsychotic-related side effects Hasan et al. World J Biol Psychiatry 2012; 13 (5): 318–378 19
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Schizophrenia Shared decision-making and patient centered care lead to better health outcomes Shared decision-making is a process in which clinicians and patients work together to make decisions about care and treatment based on clinical evidence and the patient’s informed preferences1 A central part of shared decision-making is the recognition that patients and clinicians bring different, but equally important, knowledge and expertise to the process:1,2 1. Foot et al. People in control of their own health and care. The King’s Fund. 2014; 2. Coulter & Collins. Making shared decision-making a reality. The King’s Fund. 2011 20 When patients are involved in decisions about their health and care, the decisions are better, health and health outcomes improve, and resources are allocated more efficiently1
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31–40% of patients Schizophrenia Efficacy for positive and negative symptoms are higher priorities than tolerability for physicians when choosing a treatment n=6,523 EPS=extrapyramidal symptoms Lecrubier et al. Eur Psychiatry 2007;22(6):371–379 21 Common reasons for selecting an antipsychotic reported by 872 European and US physicians1 0–10% of patients Reduced risk of QTc irregularity 11–30% of patients Reduced risk of cognitive impairment Patient responded previously Tried and tested Reduced risk of weight gain Efficacy in refractory patients Avoidance of sedation Induction of sedation Improvement in cognitive function Complete symptom control Improved compliance Reduced risk of tardive dyskinesia Reduced aggression Familiarity with drug Effect on mood/ affective symptoms Reduced agitation 41–60% of patients 61–100% of patients Effect on positive symptoms (91%) Effect on negative symptoms (62%) Reduced risk of EPS/parkinsonism Patient acceptability Well tolerated
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Schizophrenia Negative symptoms and the treatment of schizophrenia Negative symptoms impact greatly on a person’s quality of life, and affect their ability to experience many life-fulfilling activities1 However, negative symptoms are unlikely to result in the person’s hospitalisation, or to the person coming into contact with the criminal justice system1 Negative symptoms have an economic cost to society:1 They prevent a large number of people with schizophrenia from working They result in a substantial economic cost added to the emotional and psychological burden on patients, carers, and healthcare professionals Diagnosing schizophrenia can be challenging for the healthcare professional, and complex for the patient to understand1 The identification and quantification of negative symptoms, in practice, can be a overwhelming task because:1,2 There is an inherent subjectivity to negative symptoms, and they can be mistaken for other mental illnesses There is an obvious discomfort for the healthcare professional when identifying the ‘lack’ of something 1. Living with schizophrenia website. https://www.livingwithschizophreniauk.org/information-sheets/negative-symptoms-understanding/;2. Mitra et al. Ind Psychiatry J 2016;25(2):135–144 22
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Schizophrenia Depressive symptoms and the treatment of schizophrenia Individuals living with schizophrenia are commonly affected by depression:1 Some experience episodic major depression Some experience mild depression symptoms on a chronic basis In schizophrenia, depression may impact the motivation to perform potentially reinforcing acts, possibly through the induction of anhedonia1 Depression has a major adverse impact on everyday functioning1 1. Harvey. Innov Clin Neurosci 2011;8(10):14–18 23 Improving the recognition and management of depressive symptoms may reduce the adverse impact of severe mental illness on everyday functioning1
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Schizophrenia Negative feelings towards medication are associated with lower scores in both affect and self-esteem quality of life subscales General life satisfaction Work, p<0.01 Cognitive symptoms (PANSS), p<0.001 Affect Work, p<0.001 General life satisfaction Depression/anxiety (PANSS), p<0.05 Parkinsonism, p<0.05 Affect Negative feelings and effects (DAI), p<0.01 Self-esteem Depression/anxiety (PANSS), p<0.01 Parkinsonism, p<0.001 Negative feelings and effects (DAI), p<0.05 Lancashire QoL profile subscales: General life satisfaction, Affect, Self-esteem DAI=Drug Attitude Inventory; PANSS=Positive and Negative Syndrome Scale; QoL=quality of life 1. Hofer et al. J Clin Psychiatry 2004;65(7):932–939 24 Positive correlation of variable with QoL subscale Negative correlation of variable with QoL subscale Effects of sociodemographic variables, psychopathology, antipsychotic-induced adverse events, and attitude toward medication on QoL (multiple linear regression analysis)1
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Schizophrenia Adverse events are associated with lower adherence In a survey of patients with schizophrenia (n=876), the adjusted odds ratios for the impact of each adverse event on complete adherence were significant for the following variables: Adherence defined as a score of zero on the Morisky Medication Adherence Scale DiBonaventura et al. BMC Psychiatry 2012;12:20 25 Agitation Decreased interest in sex Difficult or painful menstrual periods Insomnia Nausea/vomiting Restlessness/feeling jittery Constipation Dizziness Increase in blood glucose levels Male breast enlargement or secretions Sedation Sexual dysfunction Sleepiness Tremors Weight gain Odds ratio 0.51–1.00 Odds ratio 0.00–0.50 Experiencing adverse events of medication increases the risk of non-adherence
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Schizophrenia Adherence to antipsychotic therapy Individual studies have reported that a majority of patients become non-adherent within 1–2 years of discharge from hospital1 Mean rates of adherence ranging from 47–95% have been reported in a systematic review of studies of antipsychotic medication1 1. Sendt et al. Psychiatry Res 2015;225(1–2):14–30; 2. Tiihonen et al. Am J Psychiatry 2011;168(6):603–609; 3. Ascher-Svanum et al. J Clin Psychiatry 2006;67(7):1114–1123 26 Ensuring continuous delivery of antipsychotic medication in schizophrenia constitutes a significant challenge1-3
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Schizophrenia The risks and consequences of non-adherence In one study of antipsychotic discontinuation in a cohort of 2,588 patients in Finland, only 58% of patients collected a prescription for an antipsychotic therapy within 30 days of being discharged from hospital1 Adherence rates in a large nationwide cohort study in Finland1 Systematic review of the rate of recurrence following a remission from a first episode of non-affective psychosis2 1. Tiihonen et al. Am J Psychiatry 2011;168(6):603–609; 2. Zipursky et al. Schizophr Res 2014;152(2–3):408–414 27 The risk of symptom recurrence in remitted patients following discontinuation of antipsychotic therapy is high2 Collected an antipsychotic prescription during the first 30 days after hospital discharge Continued their initial treatment for 30 days or longer following discharge from hospital
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Schizophrenia Improving adherence with LAIs can lead to improved outcomes CI=confidence interval; LAI=long-acting injectable; RCT=randomised controlled trial 1. Adapted from: Leucht et al. Lancet 2012;379(9831):2063–2071;2. Kishimoto et al. J Clin Psychiatry 2013;74(10):957–965; 3. Kishimoto et al. Schizophr Bull 2018;44(3):603–619 28 Favours drug Favours placebo A meta-analysis of mirror-image studies showed that LAIs were superior to oral antipsychotics in:2 Preventing hospitalisation (16 studies, n=4,066):risk ratio: 0.43 (95% CI: 0.35, 0.53); p<0.001 Reducing the number of hospitalisations(15 studies, 6,342 person-years):rate ratio: 0.38 (95% CI: 0.28, 0.51); p<0.001 Meta-analysis of 116 publications of LAI versus oral formulations of antipsychotic therapy1 A meta-analysis of prospective and retrospective cohort studies showed that LAIs were superior to oral antipsychotics in:3 Decreasing hospitalisation rates (15 studies, 68,009 person-years): rate ratio: 0.85 (95% CI: 0.78–0.93); p<0.001 Improving discontinuation rates (10 studies, n=37,293):risk ratio: 0.78 (95% CI: 0.67–0.91); p=0.001 Mirror image studies Cohort studies
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Schizophrenia Take home points A key challenge for physicians is to choose an antipsychotic that effectively controls symptoms, while minimising adverse events – however, physicians typically prioritise efficacy for positive and negative symptoms Adverse events are associated with lower adherence to treatment Non-adherence to antipsychotic therapy is common, and increases the risk of psychotic relapse LAI formulations increase adherence rates, and reduce the risk of relapse LAI=Long-acting injectable 29
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How do adverse events impact a patient’s functioning? …are these adverse events a necessary compromise for continued symptom control? Schizophrenia
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Schizophrenia Adverse events can impose a significant burden on patients Adverse events impair a patient’s functional ability, reducing quality of life1,2 If not addressed, antipsychotic adverse events can cause long-term distress and contribute to chronic health complications3 A small shift in functional status may have marked effects on an individual’s quality of life2 1. Morgan et al. Aust N Z J Psychiatry 2012;46(8):735–752;2. Awad et al. Acta Psychiatr Scand Suppl 1994;380:27–32;3. Barnes et al. J Psychopharmacol 2011;25(5):567–620 31 Reported medication adverse events Reported impairment intheir daily life as a result of medication adverse events Reported moderate or severe impairment In a study of 1,825 participants with psychosis1
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Schizophrenia Adverse events can be classified into different groups 1. UpToDate website. https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects. Accessed April 2019; 2. Lehman et al. Am J Psychiatry 2004;161(Suppl. 2):1–56; 3. Lieberman et al. N Engl J Med 2005;353(12):1209–1223; 4. Kane et al. Schizophr Res 2016;174(1–3):93–98;5. Cheng-Shannon et al. J Child Adolesc Psychopharmacol 2004;14(3):372–394; 6. Citrome. J Clin Psychopharmacol 2017;37(2):138–147 32 Metabolic Hyperglycaemia Weight gain Hyperlipidaemia Diabetes mellitus Metabolic syndrome Sedating Somnolence Hypersomnia Sedation Cardiovascular QT interval prolongation Cardiac arrhythmias Sexual/endocrine Sexual dysfunction Hyperprolactinaemia Extrapyramidal symptoms Dyskinesia Dystonia Parkinsonism Activating Akathisia Agitation Insomnia Anxiety Restlessness Fatigue Antipsychotic-induced adverse events1-5
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Note: All antipsychotic drugs carry a significant risk for extrapyramidal symptoms for which active management is recommended. While antipsychotics have been shown to contribute to the these adverse events, each drug has its own specific risk profile Schizophrenia There are multiple clinical benefits of a low risk of extrapyramidal symptoms Tandon & Jibson. Ann Clin Psychiatry 2002;14(2):123–129 33 Enhanced compliance Lower tardive dyskinesia risk Fewer motor adverse events Less dysphoria Less impaired cognition Reduced negative symptoms Reduced extrapyramidal symptoms
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Cognitive impairment Emotional symptoms Schizophrenia Akathisia is associated with emotional symptoms and cognitive impairment 1. Hofer et al. J Clin Psychiatry 2004;65(7):932–939; 2. Kim & Byun. J Clin Pharm Ther 2007;32:461–467; 3. Kim et al. Compr Psychiatry 2002;43(6):456–462 34 Depression3 Anxiety2 Somatization3 Obsessive–compulsive3 Paranoid ideation3 Reduced self-esteem1 Severe subjective distress3 Mental control3 Associate learning3 Discrimination2 Perception2 Coping responses2 Selective attention2
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Schizophrenia Gastrointestinal adverse events can occur with antipsychotics Gastrointestinal adverse events that can occur with antipsychotics include:1 Dyspepsia Vomiting Nausea Oesophageal dysmotility Hypersalivation Dry mouth Constipation In a retrospective study of 273 patients with schizophrenia, over a period of 22 months:2 1. MHRA Antipsychotics learning module 2015. Available at: http://www.mhra.gov.uk/antipsychotics-learning-module/con155606?useSecondary=&showpage=8, Accessed April 2019; 2. De Hert et al. BMC Gastroenterol 2011;11:17 35 36.3% had at least 1 pharmacological intervention for constipation
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Schizophrenia Weight gain can occur with antipsychotics Weight gain has been ranked among the most bothersome of the antipsychotic adverse events – by patients with schizophrenia, and by physicians1 Weight gain has been associated with drug affinity for the H1 receptor; affinity for the D2, 5-HT1A, 5-HT2C, and adrenergic α2 receptors have also been implicated2 A meta-analysis identified 257 publications of clinical trials reporting weight change3 The majority of the publications were trials where patients were switched between different antipsychotics3 All but 3 specific antipsychotics showed a degree of weight gain after prolonged use, however, switching to one of these 3 antipsychotics did not result in weight loss3 1. Llorca et al. BMC Psychiatry 2017;17(1):67; 2. Nasrallah. Mol Psychiatry 2008;13(1):27–35; 3. Bak et al. PLOS One 2014;9(4):e94112 36 Virtually all antipsychotics cause weight gain, which is a bothersome adverse event1,3
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Medication non-adherence2 Concerns over the safety of dependants,4 particularly as women are more sensitive to sedative effects5 Risk of unintentional injury3 Reduced cognitive performance and functional capacity1 Schizophrenia Some antipsychotics are associated with high rates of sedating adverse events, which can worsen outcomes 1. Loebel et al. CNS Spectr 2014;19(2):197–205; 2. DiBonaventura et al. BMC Psychiatry 2012;12:20; 3. Said et al. Pharmacoepidemiol Drug Saf 2008;17(4):354–364; 4. Seeman. Psychiatr Q 2012;83(1):83–89; 5. Lindberg et al. Int Clin Psychopharmacol 2002;17(4):177–184; 6. Miller. Curr Psychiatr 2007;6(8):38–51; 7. Miller et al. Prim Care Companion J Clin Psychiatry 2004;6(Suppl. 2):3–7 37 For agitated patients, sedating adverse events and true antipsychotic effects are sometimes incorrectly thought to be the same6 Sedation may be considered necessary for controlling positive symptoms; however, selecting a less sedating antipsychotic for patients who experience excessive sleeping can improve outcomes7 Antipsychotic-induced sedating adverse events have been associated with:
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Patient discontinues treatment, or becomes non-adherent1 Dissatisfaction with medication1 Schizophrenia Sedation impacts patient functioning and caregiver burden 1. Kane & Sharif. J Clin Psychiatry 2008;69(Suppl. 1):18–31; 2. Hofstetter et al. BMC Psychiatry 2005;5:13 38 “They do not want to get out of bed or participate in activities” Caregiver Effects of patient sedation can increase caregiver burden “Constantly feel tired” “No energy” “Cannot think clearly” Patient Patients may also have impaired cognitive and motor performance and increased risk of injury Functional impairments in vocational, academic, social and recreational activities1 Persistent sedation or somnolence1 Impacts on patient’s quality of life1,2
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EPS/activating*** Metabolic** Schizophrenia Activating and sedating effects are among the most ‘bothersome’ antipsychotic adverse events *p<0.05, **p<0.01, ***p<0.001 for the association with a lower likelihood of adherenceEPS=extrapyramidal symptoms; GI=gastrointestinal DiBonaventura et al. BMC Psychiatry 2012;12:20 39 In this cross-sectional study (n=876), 86.2% of patients with schizophrenia reported the presence of any medication adverse event Sedating/cognition* Prolactin/endocrine* GI
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Schizophrenia Medication adverse events can impair workplace performance and act as a barrier to entering or returning to work 1. Novak & Švab. Psychiatr Danub 2009;21(1):99–102;2. Steadman. Working with schizophrenia: employment, recovery and inclusion in Germany. The Work Foundation. 2015 40 In a focus group of patients with schizophrenia, stigma of adverse events was most felt in employment and occupation; adverse events led to some individuals reducing their dose or skipping regular medication1 The onset of schizophrenia during the teens and early twenties can interrupt:2 Education Early career Transition to independent living Employers and colleagues may be cautious of working with someone with schizophrenia due to negative misconceptions of their ability and/or nature2 Treatment adverse events, symptoms and risk of relapse may make entering or returning to work difficult2 ‘Lazy’ ‘Pretending’ ‘Addiction problems’ Flight of ideas Lack of concentration Tiredness Muscle rigidity and clumsiness ‘Ridiculous’ Consequence of schizophrenia Perception by others
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e.g., further attempts to find employment are more difficult Schizophrenia Emotional and practical burdens of schizophrenia on families are intertwined Tsang et al. Int J Rehabil Res 2003;26(2):123–130 41 The subjective burden of social stigma for relatives of patients includes feelings of frustration, anxiety, low self-esteem and helplessness e.g., financial burden e.g., frustration e.g., anxiety Difficulties in meeting practical demands Patient symptoms aggravated Negative emotional response
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Schizophrenia Take home points Treatment adverse events – including activating, sedating, cardiovascular, metabolic, sexual, and endocrine effects, and extrapyramidal symptoms – are burdensome for patients, reducing functioning and quality of life Some antipsychotics are associated with sedation, which worsens outcomes and increases caregiver burden The adverse-event burden of antipsychotics reduces patient functioning, and can act as a barrier to entering or returning to work EPS=extrapyramidal symptoms 42
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The importance of early intervention for patients with schizophrenia Schizophrenia
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Schizophrenia Association between DUP and symptom severity at first treatment contact DUP=duration of untreated psychosis Adapted from: Perkins et al. Am J Psychiatry 2005;162(10):1785–1804 44 In this meta-analysis of 43 studies, DUP was associated only with the severity of negative symptoms – not severity of global psychopathology, positive symptoms, or neurocognitive functioning 3 studies 5 studies 6 studies 2 studies 2 studies 1 study 1 study 1 study Studies with positive effect size (Hedge’s gu >0.0) Studies with negative effect size (Hedge’s gu ≤0.0)
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Schizophrenia Association between DUP and treatment response DUP=duration of untreated psychosis Adapted from: Perkins et al. Am J Psychiatry 2005;162(10):1785–1804 45 In this meta-analysis of 43 studies, a shorter DUP was associated with greater response to antipsychotic treatment, as measured by severity of global psychopathology, positive symptoms, negative symptoms, and functional outcomes 4 studies 5 studies 7 studies 4 studies Studies with positive effect size (Hedge’s gu >0.0) Studies with negative effect size (Hedge’s gu ≤0.0)
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Schizophrenia Patients with long DUP were less likely to achieve remission CI=confidence interval; DUP=duration of untreated psychosis; GAF=Global Assessment of Functioning; PANSS=Positive and Negative Syndrome Scale; SAPS=Scale for the Assessment of Positive Symptoms; WHO=World Health Organization Marshall et al. Arch Gen Psychiatry 2005;62(9):975–983 46 Favours short DUP In this systematic review of patient outcomes, short DUP was associated with greater chance of remission Odds of no remission in the long versus short DUP groups
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Schizophrenia Shorter DUP leads to improved outcomes in patients with first-episode schizophrenia aUnfavourable course defined as ‘continuous’ plus ‘episodic with intercritical residual symptoms’ according to DSM-IV-TR; favourable course defined as ‘episodic without intercritical residual symptoms’, plus ‘single episodes in partial remission’, and ‘single episode in full remission’ DSM-IV-TR=Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision; DUP=duration of untreated psychosis 1. Owens et al. Br J Psychiatry 2010;196(4):296–301; 2. Primavera et al. Ann Gen Psychiatry 2012;11(1):21 47 Patients relapsed within 1 year1 Patients with a favourablea illness course2 Shorter duration of untreated illness was associated with lower relapse rates Shorter DUP was associated with favourable course of illness
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Schizophrenia Early intervention services versus treatment as usual In 10 studies among 2,105 patients, the risk of ≥1 psychiatric hospitalisation was significantly lower with early intervention studies than treatment as usual: This equates to a number needed to treat (NNT) of 10.1 (95% CI: 6.4, 23.9), p=0.001 Adapted from: Correll et al. JAMA Psychiatry 2018;75(6):555–565 48 32.3% 42.4% versus Risk ratio: 0.74 (95% CI: 0.61, 0.90), p=0.003 Early intervention Treatment as usual Risk of ≥1 psychiatric hospitalisation
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Summary Schizophrenia
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Schizophrenia Summary For references, please see slide notes 50