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Physical activity as an adjunct treatment for schizophrenia and related psychotic disorders: A systematic… Holowachuk, Brad; Hvidston, Erin; Mitchell, Andrea; Richards, Rachel; Richmond, Melissa 2008-08-21

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Physical activity as an adjunct treatment for schizophrenia and related psychotic disorders: A systematic review Brad Holowachuk Erin Hvidston Andrea Mitchell Rachel Richards Melissa Richmond Supervisor: Dr. Darlene Redenbach Outline • Introduction • Methods • Results & Discussion • Conclusion Introduction • Schizophrenia: − severe psychiatric illness −median incidence 15.2 per 100, 000; male>female (McGrath et al., 2004) − onset adolescence (Andreasen, 1995) − features: • cognitive, sensori-perceptual, motor, and emotional disturbances; reality distortion Psychiatric Profile of Schizophrenia • Positive and negative symptoms (Andreasen, 1995) • Depression and anxiety also prevalent (Goodwin et al., 2003; Siris et al., 2001) • Variability in clinical presentation(Andreasen, 1995) • Decline in psychosocial, behavioural, and occupational functioning Positive Negative delusions hallucinations thought disorganization catatonia affective flattening loss of pleasure/interest de-motivation social withdrawal psychomotor dysfunction Treatment of Schizophrenia • primarily anti-psychotic medication (Brenner et al., 1992) • side-effects: − sedation − weight-gain/obesity − metabolic and cardiovascular disorders − motor disturbances (Freedman, 2003; Schultz et al., 2007) • 5 - 25% respond poorly requiring alternate therapies (Brenner et al., 1992; Patterson and Leeuwenkamp, 2008) Complications of Treatment 1) Comorbidity • Medication and lifestyle factors 2) Psychiatric Relapse • poor therapeutic response (Brenner et al., 1992) • factors influencing non-adherence (Robinson et al., 2002; Stanniland and Taylor, 2000; Valenstein et al., 2004) • substance abuse (Addington and Addington, 1997; Cantor- Graae et al., 2001;Hambrecht and Hafner, 1996; Schultz et al., 2007) • stress (Gispen-de Wied, 2000; Schultz et al., 2007) Social and Economic Sequelae • Comorbidity and relapses experienced by patients lead to: ↓ patient participation in society ↑ economical and social costs for families and the health care system (Lauber et al., 2005; Wong and Van Tol, 2003) • Need to identify adjunct treatments to mitigate such complications Exercise as Adjunct Treatment • reduces stress levels in healthy adults (Wijndaele et al., 2007) • helps reduce symptoms of clinical depression     (Babyak et al., 2000; Lawlor and Hopker, 2001) −effect equivalent to cognitive therapy −decreases relapse rates • helps reduce symptoms of clinical anxiety (Petruzzello et al., 1991) • reduces medical comorbidity in persons with schizophrenia (Skinar et al., 2005; Faulkner et al., 2003) Exercise as Adjunct Treatment • Insufficient evidence concerning the effects of exercise on psychiatric and psychological outcomes in schizophrenia Exercise as Adjunct Treatment •Systematic reviews on this topic: −Contain only physiological outcomes (Faulkner et al., 2003) −Contain few and methodologically weak studies (Bradshaw et al., 2005) −Embed exercise within a broader category of treatments (Crawford-Walker et al., 2005) −Current protocol includes only RCTs (Campbell and Foxcroft, 2003); a significant limitation since majority of research is quasi-experimental (Faulkner & Biddle, 1999) Overall Impression • Need to determine whether exercise can influence psychiatric and psychological outcomes in schizophrenia as demonstrated for other clinical populations (Babyak et al., 2000; Lawlor and Hopker, 2001; Petruzzello et al., 1991) • Evidence to support exercise as an adjunct treatment may produce: − more comprehensive therapy − better adherence Æ reducing relapse − ↑ therapeutic effectiveness Systematic Review Statement • To systematically assess the effects of physical activity on psychological and psychiatric outcomes in persons with schizophrenia and related psychotic disorders Definitions and Format • Physical activity is inclusive of exercise, and is defined as, “bodily movement that is produced by the contraction of skeletal muscle and that substantially increases energy expenditure” (Whaley, 2006) • This review was conducted in accordance with the National Health Service Centre for Reviews and Dissemination (2001) CRD Report 4. Methods Methods • Eligibility Criteria • Search Strategy • Study Selection • Quality Assessment • Data Extraction • Data Synthesis Eligibility Criteria • Subject Characteristics – Persons with schizophrenia or related psychotic disorders (schizoaffective, schizophreniform, and bipolar disorder with psychotic features) – Subjects with concurrent brain pathology, major depression and psychoses were excluded Eligibility Criteria • Intervention − Physical activity in isolation or concurrent with other interventions (e.g. cognitive therapy) −All other regular maintenance treatment included (e.g. medications) Eligibility Criteria • Outcomes – Psychiatric and psychological outcome measures – Studies reporting only physical/physiological outcomes were excluded –Outcome measures with no reliability/validity were excluded Eligibility Criteria • Study characteristics − Peer reviewed, quantitative studies − 1960 to present day − Published and grey literature − French and English and foreign language abstracts with sufficient data Search Strategy • Four fold strategy − Electronic database search − Hand search − Reference search − Author contact Study Selection • Independently conducted by two reviewers • Reviewers were blinded to authors’ names • Level of agreement was recorded • Disagreements mediated by a third reviewer • Inter-rater agreement at full text stage was ‘excellent’ (Landis and Koch, 1977) − κ =0.93 Quality Assessment • Two measures used to assess methodological quality − Bradshaw et al. (2005) adaptation − Jadad et al. (1996) • Pilot tested by three reviewers on literature concerning exercise and depression • QA of included studies conducted by two independent reviewers • Protocol for agreement/disagreement followed as described in study selection Data Extraction • Forms created and pilot tested by two reviewers • Data extracted independently then compared and compiled Data Synthesis • Descriptive synthesis planned due to expected heterogeneity of included studies Description of Studies Description of Studies • Subjects • Study Design • Interventions • Outcome Measures • Other Description of Studies • Description of studies − 271 abstracts consistent with eligibility criteria − 67 full text articles − 59 available in French or English (5 in foreign languages, 3 unavailable in print) − 15 met eligibility criteria for review Description of Studies • Subjects – 400 subjects • 209 males • 113 females • 78 unknown –Mean age of 35.7 years (2 studies did not provide age data) – 9 of 15 studies used standardized diagnostic criteria – 9 studies in USA; 1 in each of Canada, Scotland, Israel, India and Spain Description of Studies • Study Design – 4 RCTs, 9 quasi experimental designs, 1 case series, 1 case study – 4 completed in an inpatient hospital setting, 8 in an outpatient setting, 1 took place in the community, 1 occurred in a mixed inpatient/outpatient setting – Duration of studies ranged from 4 weeks to 10 years with follow up phases as long as 2 years Description of Interventions • RCTs (n=4) − Treadmill walking vs. non-exercise (Beebe et al., 2005) − Physical exercise vs. relaxation (Canarvis, 1996) − Yoga therapy vs. physical exercise therapy (Duraiswamy et al., 2007) −Holistic treatment vs. social skills treatment (Lukoff et al., 2007) Description of Interventions • Quasi experimental studies (n=9) − Walking vs. treatment as usual (Ball et al., 2001) − Recreational games and skills (Bergman et al., 1993) − Fitness training (Centorrino et al., 2006) − Aerobic exercise (Fuller, 1990; Jorgensen, 1986) − Outdoor adventure vs. treatment as usual (Kelley et al., 1997) − Running vs. waiting to run, random activities, meditation, new meditation (Levin, 1983) − Active vs. passive therapeutic recreation (Morris et al., 1999) − Exercise vs. standard care (Torres-Carbajo et al., 2005) Description of Interventions • Case series (n=1) −Aerobic exercise on a stationary bike (Pelham and Campagna, 1991) • Case study (n=1) −Weight training (Adams, 1995) Description of Studies • Outcome Measures − 36 outcome measures identified • Psychiatric (anxiety, depression, clinical severity, psychomotor symptoms, relapse rate) • Psychological (behavioural scales, self concept, self efficacy, self image, quality of life, and functioning) −Outcome measures divided into 12 categories based on criteria assessed Description of Studies • Other −Attrition −Adverse events −Health screen −Compensation Results • Methodological Quality • Bradshaw et al. (2005): • mean = 56% (range of 35-82%) • n=4 < 50%, n=9 50-75%, n=2 > 75% • Items with low scores presented in discussion • ‘substantial’ agreement (κ=0.71) (Landis and Koch, 1977) • Jadad et al. (1996): • mean= 0.80  (range of  0 - 2) • lack of double blinding and random assignment • attrition underreported • ‘substantial’ agreement (κ =0.73) (Landis and Koch, 1977) Grading of Evidence • Cochrane Musculoskeletal Group (2006) method of grading − Silver • Small sample sizes • Limited blinding of assessors • No blinding of subjects to intervention Results & Discussion Results & Discussion Outline • 1 – Results & Discussion of Outcomes • 2 – Limitations • 3 – Recommendations Results of Outcomes • Anxiety and Depression • Behaviour • Global Psychiatric Symptom Severity • Locus of Control • Pain • Psychomotor • Quality of Life and Functioning • Relapse Rate • Self Concept and Self Efficacy • Self Image • Symptoms of Schizophrenia • Trust and Cooperation Outcome: Anxiety & Depression • 7 studies • RCTs - Anxiety −Holistic health vs. social skills training found no significant differences between groups (Lukoff et al., 1986) − Physical activity vs. relaxation found no between group differences but significant within group reductions (Canarvis, 1996) Outcome: Anxiety & Depression • Quasi Experimental −adventure group had significant decreases in anxiety and depression compared with controls (Kelley et al., 1997) −aerobic exercise group had significant decreases in anxiety and depression compared with controls (Levin, 1983) − 2 additional studies using aerobic interventions reported improvements, but not significant between-group differences (Jorgensen, 1986; Ball et al., 2001) Outcome: Anxiety & Depression • Case series −general trend of a reduction in depression (Pelham and Campagana, 1991) Outcome: Anxiety & Depression • Most studies demonstrated decreases in symptoms • Underlying cause may be due to co-existing condition and not symptoms of schizophrenia • Future research should consider focusing on symptoms specific to schizophrenia Outcomes: Global Symptom Severity − 8 studies − RCTs • no between, but significant within- group improvements in overall psychiatric status for both holistic and social skills groups (Lukoff et al., 1986) Outcomes: Global Symptom Severity • Quasi experimental studies − significant between-group difference showing decreases in Somatization and Hostility for aerobic exercise condition (Jorgensen, 1986) − significant between-group difference with reduced Interpersonal sensitivity and Hostility in outdoor adventure condition (Kelley et al., 1997) − no significant between-group differences; significant within-group reductions in Obsession/Compulsion, and Phobic Anxiety for aerobic exercise condition (Levin, 1983) − no significant differences (Ball et al., 2001; Bergman et al., 1993; Centorrino et al., 2006) Outcomes: Global Symptom Severity • Case Series −general trend of increasing improvements over time with structured exercise (Pelham and Campagna, 1991) Outcomes: Global Symptom Severity • Few significant between-group differences • Significant change within groups • Results may indicate clinical significance Outcomes: Relapse Rate • 2 studies • 1 RCT found no significant differences between holistic health and social skills intervention (Lukoff et al., 1986) • 1 quasi experimental study found significantly fewer relapses for the exercise group compared to the control group (Torres-Carbajo et al., 2005) Outcomes: Relapse Rate • Not often examined • Economic / social impact on family and health care system indicates this measure should be addressed in future studies Outcomes: Quality of Life & Functioning • 2 studies • Yoga therapy (YT) had significant improvement in QOL and functioning compared with physical training (PT) (Duraiswamy et al., 2007) • Within-group differences were found for functional measures in both YT and PT • 1 study found no effect of exercise on QOL (Centorrino et al., 2006) Outcomes: Quality of Life & Functioning • Yoga shown to increase QOL and functioning • Due to self-reflective nature of yoga? Outcomes: Symptoms of Schizophrenia • 7 studies − 1 RCT found significant reduction in symptoms for yoga group as compared with physical training; and significant within- group reductions for both (Duraiswamy et al., 2007) − 1 RCT demonstrated significant within-group reductions for both holistic health and social skills groups (Lukoff et al., 1986) − 1 RCT found clinical significance (Beebe et al., 2005) − 3 quasi experimental studies showed no change (Ball et al., 2001; Centorrino et al., 2006; Fuller, 1990), and 1 case study found an increase in symptoms (Adams, 1995) Outcomes: Symptoms of Schizophrenia • Between-group and within-group significance • Results may indicate clinical significance • Subtype analyses concerning diagnosis may allow increased sensitivity of findings Outcomes: Other • Outcomes not as readily addressed: − Self-efficacy / concept − Self-image − Locus of control − Pain − Psychomotor − Behavioural − Trust and co-operation • Should be considered as future studies emphasize a more holistic treatment approach Results & Discussion Outline • 1 – Results &Discussion of Outcomes • 2 – Limitations • 3 – Recommendations Limitations: Breadth of Literature • Main focus is on physiological outcomes −Cardiovascular fitness −Weight loss • Literature on psychological outcomes is generally lacking Limitations: Heterogeneity • Study design − Ranged from RCTs to case study −Majority quasi-experimental • Population characteristics − Research setting, diagnosis, sample size, medications • Intervention − Standardization: design and supervision − Follow up Limitations: Methodological Quality • Generally poor • Highlighted in “Recommendations” section Limitations: Summary • Further limitations imposed by inclusion criteria • Limitations compounded to create bias • Attempts to mitigate bias: − Standardized guideline for review − Inclusion of various forms of literature Discussion Outline • 1 – Results & Discussion of Outcomes • 2 – Limitations • 3 – Recommendations −Diagnostic Criteria − Sample Size − Physical Activity Criteria − Follow Up −Other Methodological Issue: Diagnostic Criteria • Methodological Issues: −Standardized diagnostic criteria not used / reported by many studies −Subtypes often not classified −Lack of criteria weakens credibility of the study Recommendations: Diagnostic Criteria • Recommendations: −Utilize standardized diagnostic criteria (e.g. DSM) − Include subtype diagnoses to account for various presentations Strengthens causal relationship between physical activity and symptoms of schizophrenia Methodological Issue: Sample Size Methodological Issues: −Consistently small sample sizes −No power calculations Recommendations: − Perform power calculations when appropriate − Increase sample size when possible Improves ability to detect change Methodological Issue: Physical Activity Criteria Methodological Issue: − Few studies included interventions designed and supervised by qualified personnel Recommendations: − Follow standardized criteria (e.g. ACSM) and ensure supervision Allows for comparison between physical activity interventions and increases the credibility of the results Methodological Issue: Follow Up Methodological Issue: − Few studies demonstrated appropriate follow up Recommendation: Perform follow up within a time frame in which physical activity effects are maintained Methodological Issue: Other • Subject selection − Randomization vs. convenience sampling • Baseline comparison − Undetected between subject variability • Medication standardization − Chlorpromazine equivalents as covariate • Attrition − Underreported and misreported • Adverse effects / events − Underreported Summary of Recommendations • Standardized diagnostic criteria • Adequate sample size • Standardized physical activity interventions • Design / supervision for physical activity interventions • Subtype analyses by diagnostic category • Appropriate follow up • Consider sampling methods, baseline data collection, medication standardization, attrition reporting and adverse events. Conclusion • Results not sufficient to indicate that physical activity can produce a significant change in outcomes • There is, however, suggested clinical relevance for many of the findings Conclusion • Given that physical activity is beneficial to overall health and mental well being, it may be considered a useful adjunct treatment. • Using improved methodological standards, future research may result in a higher level of evidence and thus may more clearly demonstrate the role of physical activity as an adjunct to psychological and psychiatric treatment. • This review provides a compendium upon which future research can be based. Acknowledgements Special thanks to: • Dr. Darlene Redenbach • Dr. Angela Busch • Charlotte Beck • Melissa Canarvis, Kathi Fuller, Dr. Cathy Jorgensen, and Dr. Stephen Levin • Physiotherapist Inge Kreuzer and recreational therapist Donna Beniusis of Riverview Hospital in Coquitlam B.C. References Adams, L., 1995. 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