The recognition of bipolar disorder in primary care

Dr. Nick Stafford, Consultant Psychiatrist LPTNuffield Health Leicester, Sutton Coldfield Consulting

& Clinical Partners Ltd, London

Seminar to the GPs of De Monfort SurgeryLeicester LE2 7HX

Tuesday 19 November 2013

DisclosuresPharmaceuticalsAstra Zeneca LtdOtsuka LtdBristol Myers Squibb LtdGlaxo Smith Kline LtdPfizer LtdEli Lilly LtdLundbeck LtdServier Laboratories LtdGW Pharma Ltd

Private PracticeClinical Partners LtdNuffield HealthSutton Coldfield ConsultingMy Mind Books

Small medical project inWigston gets global media attention

nstafford@doctors.org.uk

Public Education/Professional Attitude

Praised by the public for going public Criticized by psychiatrists for going public

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

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

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

Aetiology of bipolar

Bipolar DisorderStress

Genetics

Neuro-transmitters

Neuro-endocrine

Medical

Dopamine hypothesis of maniaMania is associated with hyperactivity of neurotransmission in the brain

Hyperactivity in mesocortical pathway Hyperactivity in the mesolimbic pathway

Hyperactivity in nigrostriatal pathway

Activity in tuberoinfundibular pathway

Adapted from: Stahl SM. Essential Psychopharmacology of antipsychotics and mood stabilizers. Cambridge University Press; 2009. SLIDE FROM LUNDBECK

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

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

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 voltage-

dependent calcium channel• Glutamate signalling pathways

Genetic linkage studies

• Strongest linkage on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12

• 6q25 (suicidal behaviour)• 7q21 (panic disorder)• 16p12 (psychosis) using

phenotypic subtypes

Neuroendocrine factors

Mood Thermo

stat

Stress

HPA axis

HPT axis

HPA Axis

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

Where bipolar is missed

Public knowledge

Primary care

Secondary psychiatric

care

Other specialist

care

Each element is complex and requires its own solutions

CAPTURE MISSED BIPOLARPREVENT UNDERDIAGNOSIS

IMPROVE DIAGNOSTIC ACCURACYPREVENT OVERDIAGNOSIS

This isn’t possible by just focusing on one elementor designed just by psychiatrists

The diagnosis of bipolar disorder

Whole systems problems

Whole systems solutions

COMPLEXDISORDER

COMPLEXSERVICES

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?

Primary care red flags

Presenting complaint: Could it be:• Breast lump

• Blood on toilet paper

• Facial weakness

• Depression

• Breast cancer?• Bowel cancer?• CVA?• Bipolar

disorder?

Diagnostic challenges

• Most often misdiagnosed as major depressive disorder (MDD)

– 31% of patients screening positive for bipolar disorder were misdiagnosed with MDD

• Misdiagnosis can lead to delays in recognition

– 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

MDD = Major Depressive DisorderNational 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

Correctly diagnosed

Misdiagnosed

Not diagnosed

Patients screening positive for bipolar disorder on the Mood Disorder

Questionnaire (n=85,358)

Bipolar disorder is frequently misdiagnosed or under-diagnosed

20%

31%

49%

Misdiagnosis common

SLIDE FROM LUNDBECK

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

Considering Diagnosis

Any mental health history

Recurrent depressive disorder

Any alcohol or substance misuse

Repeated relationship problems

Repeated occupational problems

Family history

Common Difficulties in the Diagnosis of Bipolar

• Functional mental illnessesRecurrent Depression, Anxiety

• Emotionally unstable / borderline typesPersonality disorder

• Chronic or intermittent useSubstance and alcohol misuse

• Chronic stress & psychosocial problems

Normal human emotion

Psychiatric Comorbidities

Anxiety disorders

Panic disorder

Simple phobia

Social phobia

GAD

OCD

Sleep disorders

PTSD

Substance misuse

Alcohol misuse

Any substance misuse

Childhood mental health

Childhood bipolar

Conduct disorder

ADHD

Personality disorders

Cluster B

Borderline

Emotionally unstable

ISBD Taskforce BD/UD

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

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?

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

Bipolar patients symptomatic for almost half of their lives

Judd et al. Arch Gen Psychiatry 2002;59:530–537; Judd et al. Arch Gen Psychiatry 2003;60:261–269 SLIDE FROM LUNDBECK

• n=146 (Bipolar I)• 12.8-year follow-up

Weeks asymptomatic Weeks depressed Weeks manic / hypomanic Weeks cycling / mixed

• Similarly, patients with bipolar II disorder were symptomatic for 54% of the time over 13.4 years

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

Bipolar kindling: progression of recurrence

Kessing et al. (1998) Br J Psychiat, 172: 23-28 SLIDE FROM LUNDBECK

Episode number

Leng

th o

f int

er-e

piso

de

inte

rval

(yea

rs)

n=2,902

n=2,029

n=1,429n=1,034 n=756

n=172 n=34

1 2 3 4 5 10 15

Bipolar: burden of illness

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

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

Bipolar I: comorbidities

Bipolardisorder

Impulsecontrol

ADHD

Personalitydisorders

Migraine

Anxietydisorders

Eatingdisorders

Substanceabuse

Obesity

Cardio-vascular

Diabetesmellitus

Paindisorders

McIntyre, et al. Hum Psychopharmacol 2004;19(6):369-386SLIDE FROM LUNDBECK

Disease and treatment are complicated by frequent psychiatric and physical comorbidities

ADHD=Attention deficit hyperactivity disorder

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 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;58:844-850; 4Tondo, et al. CNS Drugs 2003;17:491-511

SLIDE ADAPTED FROM LUNDBECK

Adherence issues insevere 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):1209-

1223; 5Fleischhacker, et al. Acta Psychiatr Scand Suppl 1994;382:11-15; SLIDE ADAPTED FROM LUNDBECK

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

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– Being unmarried– Multiple medication regimens

1. Colom F, et al. J Clin Psychiatry 2000;61:549–555.2. Sajatovic M, et al. Bipolar Disorders 2006;8:232–241.

• First year of lithium treatment

• History of manic episodes

• Comorbid psychiatric illness

• Substance abuseSLIDE ADAPTED FROM LUNDBECK

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

Allan YoungTony HaleHeinz GrunzeDaniel SmithFrancesc ColomNick Stafford

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

Time to hospital readmission for patients treatedin the mood disorder clinic v. standard out-patient care.

Kessing L V et al. BJP 2013;202:212-219

©2013 by The Royal College of Psychiatrists

N=158Single manic episodeAfter 1st, 2nd or 3rd IP admissPOM = time to readmission

HR = 0.6095%CI = 0.37 – 0.97P=0.034

Kessing L V et al. BJP 2013;202:212-219

Economic analysis

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

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

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%

Staff (bipolar clinic)

• Consultant psychiatrist• ST4 Trainee psychiatrist• GP trainee• 3 non-medical prescribers• Visiting clinicians• Occupational therapist• Administrative staff

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

The philosophy of the pathway design

Apply what is known Nothing new

Engineer the parts Feedback to clinicians

Don’t be cleverA model that can be

applied anywhere

Simple appliance of science

Specialised Bipolar Clinic Model

New assessments Follow ups

Tertiary service Group and individual BPE

MDT

Integration in South Leicestershire outpatient clinic services

CMHT Outpatient

Clinic Services

Generic OPC & wellbeing

services

NMP & CPN assessment

clinic

Bipolar specialised

clinic

Integrated depression

clinic

Elements of the Clinic 1st Assessment

Pre-Interview Questionnaire• Lengthy (up to 3 hrs.)• Patients enjoy

completing• Structure similar to

semi-structured interview

• Question based around DSM-IV criteria

Semi-Structured Interview• 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

Specialised bipolar clinic model essential to make this work

Soon to commence a parallel specialised depression clinic

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

Assessment elements

Comprehensive reportCopied to patient

Holistic management planTx - Medical, Psychological

Health advice, Quality information

Multi-dimensionalCo-morbidities managedDetailed risk assessment

Health & Wellbeing groupMetabolic screening

Managed with GP

THANK YOU