Module 11 Schizophrenia (PDF)

MODULE 11 Schizophrenia Overview of Module: ◦ History ◦ Prevalence and BoD ◦ ICD-11 ◦ Course ◦ Comorbidity – SUD ◦ Cannabis ◦ Models and Theories ◦ Neurodevelopmental and neurodegenerative aspects ◦ Treatment Reminder of the history… Mid 1800’s: Various psychiatrists describe symptoms of mental dete...

MODULE 11 Schizophrenia Overview of Module: ◦ History ◦ Prevalence and BoD ◦ ICD-11 ◦ Course ◦ Comorbidity – SUD ◦ Cannabis ◦ Models and Theories ◦ Neurodevelopmental and neurodegenerative aspects ◦ Treatment Reminder of the history… Mid 1800’s: Various psychiatrists describe symptoms of mental deterioration starting in adolescence ◦ Morel in France - démence précoce ◦ Clouston in Scotland - “adolescent insanity” ◦ Kahlbaum and Hecker in Germany – catatonia and hebephrenia Reminder of the history… In 1896, Emil Kraepelin documents dementia praecox ◦ biomedical approach; longitudinal method ◦ cognitive decline observed during adolescence ◦ followed years afterward by onset of psychosis ◦ argues cognitive decline is what differentiates dp from manic-depression ◦ i.e. degenerative illness vs remitting illness Reminder of the history… In 1911, Eugene Bleuler coins the alternative term “schizophrenia” ◦ Psychodynamic approach ◦ Proposes that a break in normal mental associations is more pathognomonic ◦ Leads to greater emphasis on psychotic symptoms and less on cognitive symptoms Bleuler’s influence continues to be seen… …in ICD and DSM classifications ◦ Schizophrenia is not included with the Neurodevelopmental Disorders, but is grouped with “Primary Psychotic Disorders” Prevalence National Comorbidity Survey Replication ◦US household-based survey using clinical diagnostic interviews ◦ Estimates for non-affective psychosis ◦ 0.5% lifetime prevalence ◦ 0.3% 12-month prevalence National Institutes of Mental Health https://www.nimh.nih.gov/health/statistics/schizophrenia 2019 Global Prevalence (12-month) per 100,000 5000 4500 Males 4000 Females 3500 3000 2500 2000 Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 DOI: https://doi.org/10.101 6/S2215-0366(21)00395-3 1500 1000 500 0 Anxiety Depression ADHD Conduct Disorder Bipolar ASD Schiz. Eating Disorder Canadian sample for comparison Bland, RC, Orn H, Newman SC (1988) Lifetime Prevalence of Psychiatric Disorders in Edmonton. Acta Psychiatrica Scandinavica, 77: 24-32 Relative impact exceeds prevalence Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 DOI: https://doi.org/10.1016/S22150366(21)00395-3 ICD-11 Schizophrenia in ICD-11 Schizophrenia or other primary psychotic disorders ◦ Schizophrenia ◦ Schizoaffective disorder ◦ Schizotypal disorder ◦ Acute and transient psychotic disorder ◦ Delusional disorder Schizophrenia in ICD-11 At least two of the following: Persistent delusions “Psychotic” symptoms: Persistent hallucinations At least 1 of these must be Disorganized thinking present Experiences of influence, passivity or control Negative symptoms Grossly disorganized behaviour that impedes goal-directed activity Psychomotor disturbances Most of the time, for at least 1 month NOT due to another medical condition, substance or medication Schizophrenia in ICD-11 Schizophrenia is characterized by a high degree of heterogeneity ◦presentation ◦course ◦response to treatment ◦prognosis Schizophrenia in ICD-11 ◦ Subtypes were previously used but have been removed due to paranoid ◦ Poor reliability ◦ Low heritability simple catatonic ◦ Poor utility ◦ Subtype made no difference to treatment, course, or prognosis ◦ Poor stability Valle, R (2020) Schizophrenia in ICD-11: Comparison of ICD-10 and DSM-5. Revista de Psiquiatría y Salud Mental (English Edition), 13 (12), 95-104. https://doi.org/10.1016/j.rpsmen.2020.01.002 hebephrenic ICD-11 Severe Moderate Mild None Symptom Specifiers Presence of symptoms rated across 6 domains: Positive Symptoms Negative Symptoms Depressive Mood Symptoms Manic Mood Symptoms Psychomotor Symptoms Cognitive Symptoms Symptoms Symptom Clusters Normal behaviour or experience which has become incoherent A behaviour or experience which healthy people do not have A normal behaviour or experience which is lacking Disorganized Positive Negative Disorganized Symptoms Disorganized speech ◦Loose associations ◦ A lack of connection between ideas ◦Neologisms ◦ A made-up word or expression ◦Tangential speech ◦ Digression to irrelevant topics Disorganized behaviour Positive Symptoms Hallucinations o most often auditory Delusions … of persecution … of grandeur … of control … of reference Positive Symptoms distinctively characteristic of a particular disease ◦Not pathognomonic of schizophrenia: ◦ All psychotic disorders share these features to varying degrees ◦ Can also occur as part of other disorders ◦ Migraine, delirium, dementia, bipolar disorder, delusional disorder... ◦ Can be induced via psychoactive substances Positive Symptoms distinctively characteristic of a particular disease ◦Not pathognomonic of schizophrenia: ◦ Roughly 3% of people experience voice-hearing at some point in their lives ◦ Positive symptoms must be evaluated in the context of cultural and religious norms and beliefs ◦ e.g. beliefs about ghosts, spirits, prophesying Positive Symptoms Are hallucinations unusual? ◦ The presence of an unseen “other” has been reported by many people in extreme distress: ◦ Antarctic explorer Ernest Shackleton wrote "It seemed to me often that we were four, not three," and his companions had the same "curious feeling." ◦ Sometimes referred to as “the fourth man” Positive Symptoms ◦Can be episodic (coming and going) and reactive to stress Negative Symptoms ◦Flattened affect: Muted expression of emotion ◦Alogia: “Poverty of speech” ◦Avolition: Diminished motivation and difficulty starting or sticking with normal activities ◦Asociality: Decreased interest in relationships and interactions ◦Anhedonia: Reduced anticipation of pleasure Negative Symptoms ◦Less dramatic, but often more problematic than positive symptoms ◦More persistent and less responsive to medication than positive symptoms ◦More negative symptoms → poorer function and worse outcome Course Course ◦Typical age at diagnosis: ◦ males: late teens – early twenties ◦ females: early twenties – early thirties ◦Is this the “onset”? Course In childhood: ◦ “Early-onset” = before 18 years of age ◦ “Childhood-onset” = before 13 years of age ◦Negative and disorganized symptoms tend to be more prominent Course In childhood: ◦ NIMH National Longitudinal Study ◦ Started in 1990 ◦ During the initial 5 years of recruiting, 350 children were referred as meeting DSM criteria based on files and phone interviews NIMH Longitudinal Study of Childhood-Onset Schizophrenia Diagnostic disposition of original 98 participants Primary diagnosis after in-person assessment n Schizophrenia 28 Multidimensionally impaired 21 Bipolar Disorder 8 Asperger’s / PDD 7 Schizotypal personality disorder 4 ADHD/CD/ODD 7 Dissociative Disorder / PTSD 4 Obsessive Compulsive Disorder 2 Schizoaffective Disorder 2 Organic Psychosis 3 Tourette syndrome 1 29% Course In childhood: ◦ NIMH National Longitudinal Study started in 1990 ◦ Findings confirm that pediatric schizophrenia is linked with adult-onset schizophrenia (i.e. they appear to be the same disorder) ◦ More severe illness; poorer prognosis ◦ Management is similar to adults ◦ Children are more susceptible to sedative and metabolic side-effects of medications ◦ Significant, rapid weight gain, diabetes, increased cardiovascular risk Course ◦Variable lifetime progression Recurring/remitting Gradual worsening of symptoms Complete remission Course ◦Symptom clusters can follow different trajectories, even in the same person ◦ Positive symptoms tend to diminish over time and are more responsive to medication ◦ Negative symptoms are more persistent / worsening and are closely tied to poorer prognosis Prodrome In general: ◦ the period between the appearance of initial symptoms and development of a full disorder or disease In relation to schizophrenia: ◦ the period from first noticeable symptoms to first prominent psychotic symptoms Beiser M, Erickson D, Fleming JAE, Iacono WG. (1993) Establishing the onset of psychotic illness. American journal of Psychiatry, 150:1349–1354. Prodrome Prodromal signs Increased anxiety Sleep disturbances Unusual fatigue Difficulties concentrating or focusing Feeling suspicious Disorganized thoughts or confusion Sensitivity to noise, lights, and other sensations Withdrawal from others Prodrome Typical progression (regardless of age): ◦ negative or nonspecific clinical symptoms ◦ depression, anxiety symptoms, social isolation and school/occupational failure ◦ subjective problems with attention, motivation, speech ◦ attenuated positive symptoms (APS) ◦ subpsychotic APS (too brief or infrequent to meet criteria); sometimes the person may have insight Larson, M. K., Walker, E. F., & Compton, M. T. (2010). Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders. Expert review of neurotherapeutics, 10(8), 1347–1359. https://doi.org/10.1586/ern.10.93 Prodrome Significance: ◦ Possibility that early identification and treatment could reduce or prevent more debilitating symptoms ◦ Retroactive studies suggest roughly 75% of people diagnosed with schizophrenia experienced an identifiable prodrome ◦ Suggesting this could yield a sensitive measure of risk the proportion of people with the disease who would be correctly identified by a given method Ultra-High Risk (UHR) Studies ◦Follow people who have prodromal signs plus indication of genetic risk for schizophrenia ◦Proactive studies: ◦ Roughly 1/4 UHR develop frank schizophrenia with 1-2 years ◦ Hence UHR criteria have had poor (but improving) specificity the proportion of people identified by a given method who actually have the disorder Ultra-High Risk (UHR) Studies Findings re preventative treatment ◦Looking at rate of conversion ◦ Cognitive training, CBT, antipsychotics have not yielded very promising results Change in status from at-risk” or prodromal, to exhibiting full disease or disorder Ultra-High Risk (UHR) Studies Findings re preventative treatment ◦ Several (but not all) studies point to the possible benefits of Omega3 supplements ◦ decreased conversion rates, decreased positive and negative symptoms, improved function ◦ maintained for multiple years after 12-week treatment in adolescents Comobidity in Schizophrenia 100 90 80 % Prevalence About half of those with schizophrenia also have another disorder 70 60 50 40 30 20 10 0 Panic Disorder PTSD OCD Depression SUD Cannabis Comorbidity Substance abuse disorder (SUD) ◦Co-morbid SUD is associated with longer duration of illness episodes, more frequent hospitalizations and poorer social and functional recovery ◦UHR may be especially vulnerable to substances ◦ smaller doses needed to cause harm Cannabis and Schizophrenia Strong evidence has accrued that ◦cannabis use is associated with later diagnosis of schizophrenia ◦cannabis use precedes onset of psychosis Arseneault L, Cannon M, Witton J, Murray RM (2004). Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry. 2004 Feb; 184:1107. doi: 10.1192/bjp.184.2.110. PMID: 14754822 Cannabis and Schizophrenia Potential confounds ruled out ◦ disturbed behaviour, low IQ, place of upbringing, cigarette smoking, poor social integration, gender, age, ethnic group, level of education, unemployment, single marital status and previous psychotic symptoms Arseneault L, Cannon M, Witton J, Murray RM (2004). Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry. 2004 Feb; 184:1107. doi: 10.1192/bjp.184.2.110. PMID: 14754822 Cannabis and Schizophrenia Relationship is… ◦dose dependent ◦specific to cannabis ◦specific to schizophrenia ◦strongest among young males Arseneault L, Cannon M, Witton J, Murray RM (2004). Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry. 2004 Feb; 184:110-7. doi: 10.1192/bjp.184.2.110. PMID: 14754822 C Hjorthøj, et al. (2023) Association between cannabis use disorder and schizophrenia stronger in young males than in females(link is external). Psychological Medicine. DOI: 10.1017/S0033291723000880. Cannabis and Schizophrenia “Overall, cannabis use appears to confer a twofold risk of later schizophrenia or schizophreniform disorder” Arseneault L, Cannon M, Witton J, Murray RM (2004). Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry. 2004 Feb; 184:1107. doi: 10.1192/bjp.184.2.110. PMID: 14754822 Cannabis and Schizophrenia Some evidence that the proportion of cases of schizophrenia associated with cannabis use has increased significantly since 2000 Theoretically linked to increased use and potency of cannabis Hjorthøj C, Posselt CM, Nordentoft M. (2021) Development Over Time of the PopulationAttributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark. JAMA Psychiatry 78(9):1013–1019. doi:10.1001/jamapsychiatry.2021.1471 Cannabis and Schizophrenia Unanswered question: Cannabis use precedes the onset of psychotic symptoms… …but does it precede the disease process? Models of Schizophrenia Models Diathesis-Stress Model predisposition or vulnerability ◦ ◦ Applied to schizophrenia in 1960s to explain the complexity of causal pathways NOT nature vs nurture, but nature + nurture Diathesis (Genetic Predisposition) Group Whole population Prevalence 0.5% Parent has Schizophrenia 9% DZ twin has Schizophrenia 12% MZ twin has Schizophrenia 44% Steel & Wykes (2013) Diathesis (Genetic Predisposition) Group Whole population Prevalence 0.5% Parent has Schizophrenia 9% DZ twin has Schizophrenia 12% MZ twin has Schizophrenia 44% Steel & Wykes (2013) Genetic Factors ◦Heritability estimated at 80% ◦Multiple genes identified thus far, each of which plays an incremental role ◦ Some rare variants and other common variants ◦ Suggests multiple genetic pathways and involvement of multiple structures and processes Evidence re Role of Stressors Increased incidence of ◦Being bullied ◦Out of home placement (foster care) ◦Serious physical illness ◦Assault ◦Sexual abuse (15x more likely than controls) Steel & Wykes (2013) Evidence re Role of Stressors Role of living environment Post-treatment, positive symptoms are more likely to recur when the individual lives in family environments which are hostile, critical, blaming, or overinvolved Steel & Wykes (2013) Dopamine Theory ◦Posits that symptoms result from altered dopamine production and/or sensitivity via some combination of : ◦ increased levels of dopamine ◦ increased number or sensitivity of dopamine receptors ◦ decreased number of presynaptic dopamine receptors Toda & Abi-Dargham (2007) Dopamine Theory ◦Supporting evidence ◦ All drugs which have anti-psychotic effects are known to act on dopamine in some way ◦ Hallucinations can be induced via administration of dopaminemimetics ◦ Antipsychotics block the action of dopamine-mimetics Dopamine Theory ◦HOWEVER… ◦ Not all antipsychotics act on dopamine in the same way or to the same extent ◦ Changes to dopamine levels following medication happen MUCH quicker than changes in symptoms ◦ None of the antipsychotics work on dopamine ALONE ◦ Studies have not demonstrated reliable differences in tissue concentrations of dopamine or in the density of pre-synaptic dopamine receptors in healthy vs schizophrenic brains Neurodevelopmental Theories ◦Neurodevelopmental disorders occur when the disease process starts early in development and stops the brain from developing normally. ◦Given that onset of psychosis doesn’t occur until late adolescence – early adulthood, why would think of schizophrenia as neurodevelopmental? Neurodevelopmental Theories Remember dementia paecox? ◦Schizophrenia is associated with reduced IQ and a wide range of cognitive (info processing) deficits ◦ speed of processing, executive functioning, sustained attention/vigilance, working memory, verbal learning and memory, reasoning and problem solving, verbal comprehension and social cognition Larson, M. K., Walker, E. F., & Compton, M. T. (2010). Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders. Expert review of neurotherapeutics, 10(8), 1347–1359. https://doi.org/10.1586/ern.10.93 Cognitive Deficits in Schizophrenia 50% of people are still in the average range Neurodevelopmental Theories ◦ ◦ Cognitive deficits are formally considered “additional features of schizophrenia” and they do not fall neatly into the positive/negative/disorganized constellation of symptoms However, some researcher posit these may be the core feature, giving rise to or linking the other symptoms Neurodevelopmental Theories Neuroanatomical differences are also associated with schizophrenia ◦enlarged lateral ventricles ◦reduced medial temporal and prefrontal lobe volumes ◦reduced gray matter in some areas of the brain Neurodevelopmental Theories ◦Cognitive symptoms and neuroanatomical changes have been found to emerge before positive symptoms and prior to starting antipsychotics Neurodevelopmental Theories ◦Other group differences are evident early in development: ◦ Higher rate of obstetric complications (not consistently replicated) ◦ Delayed milestones ◦ Poorer social functioning in childhood ◦ Higher incidence of peer rejection ◦ Greater incidence of speech problems Neurodevelopmental Theories Adolescence as phase shift ◦In adolescence, a fundamental reorganization of the brain takes place that continues into the beginning of the third decade of life Konrad, K., Firk, C., & Uhlhaas, P. J. (2013). Brain development during adolescence: neuroscientific insights into this developmental period. Deutsches Arzteblatt international, 110(25), 425–431. https://doi.org/10.3238/arztebl.2013.0425 Neurodevelopmental Theories Adolescence as phase shift ◦Anatomical changes: ◦ elimination of unused synapses (pruning) ◦ increase in white matter ◦ changes in neurotransmitter systems Konrad, K., Firk, C., & Uhlhaas, P. J. (2013). Brain development during adolescence: neuroscientific insights into this developmental period. Deutsches Arzteblatt international, 110(25), 425–431. https://doi.org/10.3238/arztebl.2013.0425 Neurodevelopmental Theories Adolescence as phase shift ◦Functional changes: ◦ decreased in delta wave ◦ decreased prefrontal metabolism ◦Structural and functional changes appear to be exaggerated among those with schizophrenia Konrad, K., Firk, C., & Uhlhaas, P. J. (2013). Brain development during adolescence: neuroscientific insights into this developmental period. Deutsches Arzteblatt international, 110(25), 425–431. https://doi.org/10.3238/arztebl.2013.0425 Neurodevelopmental Theories ◦DUP (duration of untreated psychosis) ◦ a prognostic indicator ◦ Longer DUP is associated with greater cognitive decline, more negative and positive symptoms, and poorer global functioning after first episode schizophrenia G.P. Amminger, GP, Edwards, J, Brewer, WJ, Harrigan, S, McGorry, PD (2002). Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia. Schizophrenia Research, 54(3): 223-230 https://doi.org/10.1016/S0920-9964(01)00278-X Tor K. Larsen, Moe, LC , Vibe-Hansen, L, Johannessen, JO (2000). Premorbid functioning versus duration of untreated psychosis in 1 year outcome in first-episode psychosis, Schizophrenia Research, 45(1-2):1-9. https://doi.org/10.1016/S0920-9964(99)00169-3. Neurodevelopmental Theories ◦One example: PUFA Model ◦ Proposes PUFA deficiency as one of multiple causal pathways ◦ Genetic factors create poor intake and/ or poor uptake of PUFA ◦ PUFA deficiency then results in neuroanatomic abnormalities ◦ Neuroanatomic abnormalities then lead to cognitive deficits ◦ Impact may be reversible to a certain point in development Hsu, M. C., Huang, Y. S., & Ouyang, W. C. (2020). Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms. Lipids in health and disease, 19(1), 159. https://doi.org/10.1186/s12944-020-01337-0 Adolescence: CNS reorganization leads to emergence of pos/neg symptoms PUFA Model GENETIC PROFILE STRUCTURAL ABNORMALITIES PUFA COGNITIVE DEFICITS NEUROTOXICITY Neurodevelopmental Theories ◦One example: PUFA Model ◦ Explains several findings ◦ Early developmental findings ◦ Anatomical differences ◦ cognitive deficits ◦ Late diagnosis ◦ Involvement of dopamine ◦ Preventative action of PUFA among UHR ◦ Relationship between DUP and functional deterioration Neurodevelopmental Theories ◦One example: PUFA Model a progressive neurodevelopmental disease Assessment Mental Status Exam A semi-structured, brief interaction Typically completed toward the beginning of an episode of psychiatric care ◦Emergency visit ◦Intake assessment Mental Status Exam Provides a “snapshot” into how the client is functioning in the moment of the assessment ◦Appearance ◦Affect ◦Behaviour ◦Consciousness / attention ◦Thought processes Mental Status Exam What’s NOT assessed: ◦Client’s history ◦History of presenting problem ◦Psychosocial stressors and resources ◦Physical processes (e.g., hormonal or neurological function) ◦Environmental contingencies ◦Cultural / religious influences and implications ◦Client’s readiness for treatment History Changes in behavior Onset of presenting symptoms Previous level of functioning Academic and occupational function Social function and relationships Family history of mental illness Past medical and psychiatric problems Current and past drug use Medical exam Both positive and negative symptoms can have other organic causes which should be ruled out ◦ Infection ◦ Brain injury ◦ Epilepsy Structured Diagnostic Interview SCID-5 (Structured Clinical Interview for DSM-5 ) ◦Takes 1-2 hours to administer ◦Maps directly on to DSM-5 diagnostic criteria ◦Requires extensive training ◦Used for research and clinical purposes Structured Diagnstic Interview MINI (Mini International Neuropsychiatric Interview) ◦Can be used within both DSM and ICD structures ◦Takes 15-30 minutes to administer ◦Requires expertise re psychopathology, knowledge of DSM/ICD, and specific training ◦Used for research and clinical purposes Rating scales PANSS Positive and Negative Symptom Scale (PANSS) ◦ Clinician interview/rating scale used to rate SEVERITY of symptoms ◦ Yields separate scores for positive symptoms, negative symptoms, and symptoms of general psychopathlogy ◦ Well-established, gold standard for measuring changes in symptoms over time ◦ 30 likert-scale items (1-7) ◦ takes 45 minutes in addition to information gathering Treatment Antipsychotics ◦Front line treatment Antipsychotics ◦Typical (first generation antipsychotics) ◦ e.g., chlorpromazine, haloperidol, thioridazine, loxapine ◦ reduce dopaminergic neurotransmission in the four dopamine pathways Antipsychotics ◦Typical (first generation) ◦ associated with a range of side effects Severity of Side Effects Frequency (%) Mild 55.0 Moderate 42.3 Severe 2.7 Wubeshet, Y.S., Mohammed, O.S. & Desse, T.A. (2019) Prevalence and management practice of first generation antipsychotics induced side effects among schizophrenic patients at Amanuel Mental Specialized Hospital, central Ethiopia: cross-sectional study. BMC Psychiatry 19, 32 (2019). https://doi.org/10.1186/s12888-018-1999x Antipsychotics ◦Extrapyramidal Side Effects ◦ result from lack of dopamine ◦ Akathisia ◦ Subjective restlessness that makes it hard to sit down or hold still. ◦ Incidence: 5% to 36% of people who take antipsychotics Antipsychotics ◦Extrapyramidal Side Effects ◦ Dystonia ◦ involuntarily contraction of muscles which can lead to painful movements ◦ usually starts within 48 hours of taking an antipsychotic ◦ incidence: 2% - 90% depending on risk factors ◦ Male, young, previous dystonia, cocaine use Antipsychotics ◦Extrapyramidal Side Effects ◦ Parkinsonism ◦ tremors, slower thought processes, slower movements, rigid muscles, difficulty speaking, and facial stiffness Antipsychotics ◦Extrapyramidal Side Effects ◦ Tardive Dyskinesia ◦ uncontrollable facial movements such as sucking, chewing, lip-smacking, sticking the tongue out, or blinking repeatedly ◦ appear after long-term use ◦ symptoms may continue even after treatment ◦ Incidence 15-20% Antipsychotics ◦Extrapyramidal Side Effects ◦ Neuroleptic Malignant Syndrome ◦ potentially life-threatening response ◦ very high fever, fast and irregular heartbeat, excessive sweating, muscle rigidity, altered mental state, altered blood pressure ◦ treated with benzodiazepines ◦ Incidence: < 0.1% Antipsychotics ◦Atypical (second-generation) e.g., aripiprazole, olanzapine, risperidone, quetiapine ◦ block dopamine and also affect serotonin levels ◦ have milder movement-related side-effects than the first generation drugs Antipsychotics ◦Atypical (second-generation) ◦ Still have significant side effects ◦ Blurred vision, dizziness, sexual dysfunction, weight gain increased risk of diabetes, motor problems ◦ Require close medical monitoring Treatment Recommendations 1. Treatment with secondgeneration antipsychotics 2. Monitor for side-effects 3. Switch to clozapine if SGA ineffective 4. Add adjunctive therapies Antipsychotics – key points ◦ Help to manage positive symptoms ◦ Have a minor impact on negative symptoms ◦ May take several weeks to have a significant impact ◦ Not sufficient to address psychosocial impact of illness ◦ About ½ of people stop taking their antipsychotics after about a year Adjunctive Therapy ◦Cognitive-Behavioural Therapy ◦ Supports readiness /compliance to treatment ◦ Helps reduce impact of positive symptoms by changing the way the client thinks about and responds to them Impact of CBT on Psychotic Symptoms Randomized control trial with wait list control Lincoln et al (2012) Adjunctive Therapy ◦Family-Based Interventions ◦ Different from “Family Therapy” ◦ Typically combine several elements: ◦ Education about the disorder ◦ Helping the family support the client’s adaptive function and health behaviours ◦ Support navigating systems ◦ Crisis management ◦ Reduce risk of relapse and re-hospitalization and improve function Adjunctive Therapy ◦Cognitive Training / Remediation ◦ Intended to reduce disorganized symptoms ◦ Repeated administration of specific cognitive tasks to build cognitive skills ◦ e.g., goal-focused behaviour, problemsolving, attention, etc Adjunctive Therapy ◦Cognitive Training / Remediation ◦ mixed results in terms of outcomes ◦ are there specific client characteristics which predict benefit? ◦ intervention likely will require close tailoring to specific clients Reser et al. (2019) Key Take-Aways ◦Symptoms ◦Causes ◦Models ◦Treatments