The recognition of bipolar disorder in primary care


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Bipolar disorder and the complexities of screening and diagnosis in primary care. How more accurate detection and an integrated care pathway with secondary care can improve the diagnosis and outcome of the treatment of the disorder.

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The recognition of bipolar disorder in primary care

  1. 1. The recognition of bipolar disorder in primary care Dr. Nick Stafford, Consultant Psychiatrist LPT Nuffield Health Leicester, Sutton Coldfield Consulting & Clinical Partners Ltd, London Seminar to the GPs of De Monfort Surgery Leicester LE2 7HX Tuesday 19 November 2013
  2. 2. Disclosures Pharmaceuticals Astra Zeneca Ltd Otsuka Ltd Bristol Myers Squibb Ltd Glaxo Smith Kline Ltd Pfizer Ltd Eli Lilly Ltd Lundbeck Ltd Servier Laboratories Ltd GW Pharma Ltd Private Practice Clinical Partners Ltd Nuffield Health Sutton Coldfield Consulting My Mind Books
  3. 3. Small medical project in Wigston gets global media attention
  4. 4. Public Education/Professional Attitude Praised by the public for going public Criticized by psychiatrists for going public
  5. 5. Definition and prevalence of bipolar disorder • The spectrum of bipolar disorders includes: – – – – Bipolar I disorder Bipolar II disorder Cyclothymic disorder Bipolar disorder not otherwise specified (NOS) • Bipolar disorder has a lifetime prevalence of 4.4% overall1 – 1.0% bipolar I disorder – 1.1% bipolar II disorder – 2.4% for sub-threshold bipolar disorder 1Kessler et al. Annu Rev Clin Psychol 2007;3:137-158
  6. 6. Mood episodes: defining criteria Manic episode – A distinct period of >1 week (may be <1 week if hospitalised) during which patients experience abnormally and persistently raised, expansive or irritable mood Hypomanic episode – A distinct period of elevated, expansive or irritable mood, lasting ≥4 days, not sufficiently severe to cause pronounced impairment in social or occupational functioning Mixed episode – A period (1 week: DSM-IV; 2 weeks: ICD-10) in which the criteria are met for both manic and major depressive episodes Major depressive episode – A period of ≥2 weeks with either depressed mood or with a loss of interest or pleasure in almost all activities American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). American Psychiatric Press; 2000:382–401
  7. 7. Bipolar disorder: epidemiology • Highly prevalent psychiatric illness • Gender – Male = female in bipolar I disorder – Greater female representation in bipolar II disorder • Disease onset slightly later in females than males – Males: 48% onset <25 years; 80% onset <30 years – Females: 33% onset <25 years; 63% onset <35 years • Mean age at first hospitalization is 26 years
  8. 8. Aetiology of bipolar
  9. 9. Dopamine hypothesis of mania Mania is associated with hyperactivity of neurotransmission in the brain Hyperactivity in mesocortical pathway Activity in tuberoinfundibular pathway Hyperactivity in the mesolimbic pathway Hyperactivity in nigrostriatal pathway Adapted from: Stahl SM. Essential Psychopharmacology of antipsychotics and mood stabilizers. Cambridge University Press; 2009. SLIDE FROM LUNDBECK
  10. 10. Genetic epidemiology of bipolar • Children of affected parent(s) – One parent: 15-30% – Both parents: 50-75% • Siblings of affected sibling – One sibling: 15-25% – MZ concordance 60-70% • Additional genetic loading for depressive disorder, ADHD, OCD or Oppositional Defiant Disorder
  11. 11. Associati0n studies of candidate genes • BDNF gene (Vall66) • GAD1 gene (4s2241165) • Dopamine transporter gene (rs41084) • Serotonin transporter gene • Circadian / Clock genes – – – – ARNTL (BmaL1) TIMELESS PERIOD3 RORA & RORB
  12. 12. Candidate Genes • Bipolar I – DAO, GRM3, GRM4, GRIN2B, IL2RB, and TUBA8 • Overlapping with schizophrenia – DPYSL2, DTNBP1, G30/G72, GRID1, GRM4, and NOS1 • BDNF • Alpha subunit of the voltagedependent calcium channel • Glutamate signalling pathways
  13. 13. Genetic linkage studies • Strongest linkage on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12 • 6q25 (suicidal behaviour) • 7q21 (panic disorder) • 16p12 (psychosis) using phenotypic subtypes
  14. 14. Neuroendocrine factors
  15. 15. HPA Axis
  16. 16. HPT Axis • Elevated basal plasma concentrations of TSH • Exaggerated TSH response to TRH • Rapid cyclers higher rate of hypothyroidism • Blunted / absent evening surge of plasma TSH • Blunted TSH response to TRH • Presence of antithyroid microsomal and/or anti-thyroglobulin antibodies
  17. 17. Where bipolar is missed Each element is complex and requires its own solutions Public knowledge Primary care CAPTURE MISSED BIPOLAR PREVENT UNDERDIAGNOSIS Secondary psychiatric care Other specialist care IMPROVE DIAGNOSTIC ACCURACY PREVENT OVERDIAGNOSIS This isn’t possible by just focusing on one element or designed just by psychiatrists
  18. 18. The diagnosis of bipolar disorder COMPLEX DISORDER COMPLEX SERVICES
  19. 19. The goal in primary care “If a GP sees Depressive Disorder they should have a reflex consideration of bipolar disorder every time and ask relevant questions to probe for it” • How do we make this happen?
  20. 20. Primary care red flags Presenting complaint: • Breast lump • Blood on toilet paper • Facial weakness • Depression Could it be: • Breast cancer? • Bowel cancer? • CVA? • Bipolar disorder?
  21. 21. Diagnostic challenges Bipolar disorder is frequently misdiagnosed or under-diagnosed • Most often misdiagnosed as major depressive disorder (MDD) – 31% of patients screening positive for bipolar disorder were misdiagnosed with MDD • 20% Misdiagnosis can lead to delays in recognition 31% – 34% of patients with bipolar disorder are symptomatic >10 years before accurate diagnosis • Misdiagnosed patients are more likely to receive inappropriate treatment than those correctly diagnosed 49% Correctly diagnosed Misdiagnosed Not diagnosed Patients screening positive for bipolar disorder on the Mood Disorder Questionnaire (n=85,358) MDD = Major Depressive Disorder National Depressive and Manic-Depressive Association (NDMDA). Hosp Community Psych 1993;44(8):800–801; Hirschfeld et al. J Clin Psychiatry 2003;64:53–59; Matza et al. J Clin Psychiatry 2005;66(11):1432–440. SLIDE FROM LUNDBECK
  22. 22. Misdiagnosis common SLIDE FROM LUNDBECK
  23. 23. Problems of misdiagnosis • Efficacious treatment with mood stabilisers and appropriate counselling specific to bipolar disorder is delayed as a result of misdiagnosis1 • When appropriate treatment for bipolar disorder is initiated for patients who have had several episodes of illness, treatment may be less effective2 • Inappropriate treatment with antidepressants can lead to an elevated risk of hypomania, mania, and cycling1
  24. 24. Considering Diagnosis Any mental health history Recurrent depressive disorder Any alcohol or substance misuse Repeated relationship problems Repeated occupational problems Family history
  25. 25. Common Difficulties in the Diagnosis of Bipolar • Functional mental illnesses Recurrent Depression, Anxiety • Emotionally unstable / borderline Personality disorder types Substance and alcohol misuse • Chronic or intermittent use Normal human emotion • Chronic stress & psychosocial problems
  26. 26. Psychiatric Comorbidities Anxiety disorders Panic disorder Simple phobia Alcohol misuse Personality disorders Childhood bipolar Cluster B Conduct disorder Substance misuse Childhood mental health Borderline ADHD Emotionally unstable Social phobia GAD OCD Sleep disorders PTSD Any substance misuse
  27. 27. ISBD Taskforce BD/UD
  28. 28. Practical solutions in primary care Education for everyone Screening tool – choice, is it used? Always be alert (as with cancer) Asking just a few questions can be effective Low level of suspicion Collateral history from someone close
  29. 29. Primary care screening options • Ask more questions – But which? (e.g. BRIDGE) • Collateral history encouraged • EMIS / Systm1 alerts – Surprisingly less popular with GPs • Formal screen HCL-32 – How useful is it in practice? – Frequency of use • MDQ preferable?
  30. 30. If GP refers to the Clinic • Standard GP letter (no forms to fill in) • HCL-32 if appropriate, not mandatory – MDQ if preferred • • • • Option to use the Mental Health Facilitator Patient educated about possible bipolar Leaflets given (pre- and post-diagnosis) Mood diary before OPC appointment
  31. 31. Bipolar patients symptomatic for almost half of their lives Weeks asymptomatic 9% Weeks depressed 6% • n=146 (Bipolar I) • 12.8-year follow-up Weeks manic / hypomanic Weeks cycling / mixed 32% 53% • Similarly, patients with bipolar II disorder were symptomatic for 54% of the time over 13.4 years Judd et al. Arch Gen Psychiatry 2002;59:530–537; Judd et al. Arch Gen Psychiatry 2003;60:261–269 SLIDE FROM LUNDBECK
  32. 32. Bipolar: chronic and recurrent • The risk of recurrence in the 12 months after a mood episode is especially high in patients with BPD compared with other psychiatric disorders1 – 50% in 1 year – 75% at 4 years – Afterwards 10% per year • STEP-BD – Systematic Treatment Enhancement Program for Bipolar Disorder2 – Represents the largest prospective examination of outcomes to date – In 2-year follow-up of 1,469 patients, 48.5% experienced a recurrence
  33. 33. Bipolar kindling: progression of recurrence Length of inter-episode interval (years) 5 4 n=2,902 3 n=2,029 n=1,429 2 n=1,034 n=756 n=172 1 0 1 2 3 4 5 10 n=34 15 Episode number Kessing et al. (1998) Br J Psychiat, 172: 23-28 SLIDE FROM LUNDBECK
  34. 34. Bipolar: burden of illness Healthy life Reduced by 12 years Working life Reduced by 14 years Life expectancy Reduced by 9 years Employment problems Twice as common Divorce/separation Twice as common Coryell W et al. Am J Psychiatry. 1993;150(5):720-727; Scott J. Br J Psychiatry. 1995;167(5):581-588; SLIDE FROM LUNDBECK
  35. 35. Bipolar I: comorbidities Disease and treatment are complicated by frequent psychiatric and physical comorbidities Pain disorders Diabetes mellitus Cardiovascular Obesity Migraine Personality disorders Bipolar disorder Substance abuse Eating disorders ADHD Impulse control ADHD=Attention deficit hyperactivity disorder Anxiety disorders McIntyre, et al. Hum Psychopharmacol 2004;19(6):369-386 SLIDE FROM LUNDBECK
  36. 36. Bipolar I: mortality • Life expectancy for patients with mental illness is substantially shorter than that of the general population1 • Bipolar disorder – Patients with untreated illness have >4-fold higher SMR2 – Cardiovascular disease is one of the leading causes of premature mortality in this population3 – More than 20-fold increased risk for death by suicide4 SLIDE ADAPTED FROM LUNDBECK 1Fagiolini & Goracci. J Clin Psychiatry 2009;70(Suppl 3):22-29; 2Angst, et al. J Affect Disord 2002;68:167-181; 3Ösby, et al. Arch Gen Psychiatry 2001;58:844850; 4Tondo, et al. CNS Drugs 2003;17:491-511
  37. 37. Adherence issues in severe mental illness • Non-adherence rates for antipsychotic medications are generally reported to be between 40% and 60%1 • Side effects are a main reason for non-adherence and were the reason for discontinuation in 6–61% of patients2-3 – Specific AEs related to discontinuation included EPS, weight gain, metabolic effects, and sedation4,5 • Other reasons for non-adherence include lack of insight into illness and lack of social support1 1Patel, et al. J Clin Psychiatry 2008;69:1548-1556; 2Fleck, et al. J Clin Psychiatry 2005;66:646-652; 3Stroup, et al. Schizophr Res 2009;107(1):1-12; 4Lieberman, et al. N Engl J Med 2005;353(12):12091223; 5Fleischhacker, et al. Acta Psychiatr Scand Suppl 1994;382:11-15; SLIDE ADAPTED FROM LUNDBECK
  38. 38. Impact of adverse effects of medication on non-adherence • Adverse effects of medication can contribute to non-adherence • The occurrence of and reaction to side effects will vary enormously from patient to patient • Impact of adverse effects on physical health negatively impacts adherence • Side effects that are most distressing to patients are: – Weight gain – Anticholinergic side effects – Sexual dysfunction – Akinesia – Muscle rigidity – Akathisia Greening J. Psychiatr Bull 2005;29:210–2. SLIDE ADAPTED FROM LUNDBECK
  39. 39. Impact of treatment discontinuation on the course of bipolar disorder • One of the most important predictors of relapse1 • Other consequences include2 – Worsening symptoms – Psychosocial deterioration – Increased risk of suicide • Non-adherence is frequent – rates of up to 64% have been reported1 • Factors frequently associated with non-adherence include:1 – Young age – Male gender First year of lithium treatment – Being unmarried History of manic episodes – Multiple medication regimens Comorbid psychiatric illness SLIDE ADAPTED FROM LUNDBECK 1. Colom F, et al. J Clin Psychiatry 2000;61:549–555. 2. Sajatovic M, et al. Bipolar Disorders 2006;8:232–241. • • • • Substance abuse
  40. 40. The need for improvement in treatment options • Almost 50% of patients experience a recurrence despite adequate treatment for bipolar disorder – Residual symptoms increase the risk of a recurrence • Few patients (26%) achieve full symptom resolution – Remission should be the goal of treatment • Many patients who show signs of symptom improvement continue to experience psychosocial and vocational impairments that affect normal daily living – Over a 1-year period, functional recovery occurred in only 24% of patients • Long-term medication compliance is poor Keck et al. Am J Psychiatry 1998;155:646–652; Perlis et al. Am J Psychiatry 2006;163:217–224; Keller. J Clin Psychiatry 2006;67(Suppl 1):5–7 SLIDE ADAPTED FROM LUNDBECK
  41. 41. Allan Young Tony Hale Heinz Grunze Daniel Smith Francesc Colom Nick Stafford
  42. 42. The Leicester Model • • • • • • • • A model easily replicated in generic adult services Within a CMHT Following NWW in South Leicestershire Locality Not (specialist) commissioned Within existing time and financial resources No changes to job plan needed Not academic No research or service development grants
  43. 43. Time to hospital readmission for patients treated in the mood disorder clinic v. standard out-patient care. N=158 Single manic episode After 1st, 2nd or 3rd IP admiss POM = time to readmission HR = 0.60 95%CI = 0.37 – 0.97 P=0.034 Kessing L V et al. BJP 2013;202:212-219 ©2013 by The Royal College of Psychiatrists
  44. 44. Economic analysis Kessing L V et al. BJP 2013;202:212-219
  45. 45. Why? • Specialist clinics work • They make working life interesting • Patient satisfaction is high • Complex phenotype with high external validity • Requires broad knowledge of – Psychopathology, Neuropsychology – (Poly) Psychopharmacology, Psychotherapy • Better continuity of care • Improved education and research in the team • Develop the use of non-medical prescribers
  46. 46. Preparing the clinic setting • Reducing the outpatient clinic load • 720 caseload to 250 • Caseload percentages – New referrals – Existing mood disorders – 30% total caseload managed in specialised clinic • Initially half day/week (first 18 months) • Now one day a week • Preparing additional specialist depression clinic
  47. 47. Utilizing existing resources • There are enough cases of bipolar in a CMHT caseload to stream them through a single weekly clinic – Bipolar = 25% • We are now beginning to do the same with more difficult to treat depression cases – Depression = 30-40%
  48. 48. Staff (bipolar clinic) • • • • • • • Consultant psychiatrist ST4 Trainee psychiatrist GP trainee 3 non-medical prescribers Visiting clinicians Occupational therapist Administrative staff
  49. 49. Non-medical prescribers • • • • • • • Supplementary prescribers MDT model in service 1 hour MDT supervision end of clinic Focus on BAP & WFSBP guidelines Regular teaching Developing 6/12 Mood Disorders Magazine Advice from Professor Hale’s Kent clinic
  50. 50. The philosophy of the pathway design Apply what is known Nothing new Simple appliance of science Don’t be clever A model that can be applied anywhere Engineer the parts Feedback to clinicians
  51. 51. Specialised Bipolar Clinic Model New assessments Follow ups MDT Tertiary service Group and individual BPE
  52. 52. Integration in South Leicestershire outpatient clinic services NMP & CPN assessment clinic Generic OPC & wellbeing services Bipolar specialised clinic CMHT Outpatient Clinic Services Integrated depression clinic
  53. 53. Elements of the Clinic 1st Assessment Specialised bipolar clinic model essential to make this work Pre-Interview Questionnaire Semi-Structured Interview • Lengthy (up to 3 hrs.) • Patients enjoy completing • Structure similar to semi-structured interview • Question based around DSM-IV criteria • Detailed focus on moods • Predominant Polarity • Bipolarity Index • Detailed medication history • Comorbidities examined • PD screening (IPDE) • Multi-axial DSM-IV diagnosis (DSM-5 July) MDT • Consultant • ST4 • Non-medical prescriber • Visiting clinicians • CPN • OT (BPE) • Social Worker • Adequate time built in for assessments and follow ups Soon to commence a parallel specialised depression clinic
  54. 54. Semi structured assessment • Face to face interview: – – – – – – – Questionnaire structure maintained Clarify pre-interview questionnaire Extra detail were needed Are diagnostic criteria met? Listed in conclusion. Bipolar I, II etc… Predominant Polarity & Polarity Index Review of comorbidity • Axis I + addictions • Axis II – IPDE
  55. 55. Assessment elements Comprehensive report Copied to patient Multi-dimensional Co-morbidities managed Detailed risk assessment Holistic management plan Tx - Medical, Psychological Health advice, Quality information Health & Wellbeing group Metabolic screening Managed with GP
  56. 56. THANK YOU