Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Treatment and Outcome of Refractory Depression
Document related concepts
Bipolar disorder wikipedia , lookup
History of psychiatry wikipedia , lookup
Mental status examination wikipedia , lookup
Dissociative identity disorder wikipedia , lookup
Antipsychotic wikipedia , lookup
Abnormal psychology wikipedia , lookup
Spectrum disorder wikipedia , lookup
Narcissistic personality disorder wikipedia , lookup
David J. Impastato wikipedia , lookup
History of psychiatric institutions wikipedia , lookup
History of mental disorders wikipedia , lookup
Moral treatment wikipedia , lookup
Emergency psychiatry wikipedia , lookup
Child psychopathology wikipedia , lookup
Controversy surrounding psychiatry wikipedia , lookup
Generalized anxiety disorder wikipedia , lookup
Bipolar II disorder wikipedia , lookup
Postpartum depression wikipedia , lookup
Biology of depression wikipedia , lookup
Behavioral theories of depression wikipedia , lookup
Major depressive disorder wikipedia , lookup
Evolutionary approaches to depression wikipedia , lookup
Transcript
Treatment and Outcome of Refractory Depression Dr Noel Kennedy St Edmundsbury & SPUH 11-March-17 Unipolar Depression Common Chronic Recurrent Disabling Expensive Undertreated Depressive disorders are the most common reason for admission to a psychiatric unit in Ireland Unipolar Depression Common Chronic Recurrent Disabling Expensive Undertreated 60-95% recurrence 8% unnatural death 50% time symptomatic (Lee & Murray 1988, Mueller et al 1999, Kennedy et al 2003) Unipolar Depression Common Chronic Recurrent More years with disability than any other medical/psychiatric disorder Disabling (Murray & Lopez 1996) Expensive Estimated economic cost of $50 billion p.a. Undertreated Unipolar Depression: Outcome • Recovery (O’Leary et al, 2000) - (50%-6months, 70-75%-1year, 80-85%-2 years) • Recurrence (Mueller et al, 1999) - (25%-1 year, 40%-2 years, 60+%-5 years) • Suicide (Osby et al, 1999) 7-9% hosp, 20+ OR • Psychosocial Impairment (Kennedy et al, 2007) - (25% work, 30-35% marital, 40-60% social) Long-Term Outcome Studies of Depression Recent long-term outcome studies No. subject (N) Years Subjects follow- followedup up (%) Non recovery (%) Recurred (%) Unnatural death follow-up (%) Lee & Murray (1988) 89 18 99 10 95 10 Kiloh et al (1988) 145 15 93 12 76 12 Surtees & Barkley (1994) 80 12 100 10 60 10 Kennedy et al (2003; 2004) 70 9-11 99 8 66 3 Toshiaki et al (2000) 90 Kanai et al (2003) Kolma et al (2008) 163 6 96 13 43 2 5 - 12 71 - NIMH CDS Judd et al (1998) 15 77 11.5b 85c N/Ad 442 Depression and subsyndromal symptoms over 10-year follow-up (Kennedy et al, 2004) 100% 90% 80% 70% 60% 50% 40% definite criteria residual minor symptoms asymptomatic 30% 20% 10% 0% Year 9 Year 8 Year 7 Year 6 Year 5 Year 4 Year 3 Year 2 Year 1 Residual Symptoms Predict Recurrence Subsyndromal depression • 50-60% of follow-up time spent with symptoms • Residual symptoms predict relapse • Residual symptoms impair social functioning) (Paykel et al, 1995; Judd et al, 1998, Kennedy et al, 2004) Recent Primary Care Outcome Studies • Outcome still relatively poor - Vantnaa 5-year Outcome Finland (Holma et al 2008) - 163 OPD, longitudinal, 88% remission, 70% recurred - PD, dysthymia, length of episode predicted outcome • Primary care/early in course still problematic - Japanese 6-year follow-up n=95, OPD mainly 1st episode 85% recovery, 42% relapse, better psychosocial (Furukawa et al, 2000; Kanai et al, 2003) - Finnish 5-year 1ry care (Riihimaki et al, 2011) 70% remission, >1/3rd relapsed, 58% symptomatic Refractory Depression: Definitions • Failure to respond fully to >1 or several antidepressants (30++%) • Chronic duration <2 years (10%) - least likely to be effectively treated • Partial response also a problem (>40%) Levels of Treatment Resistance (Thase et al 2008) • Stage 1: Failure of one adequate trial of an antidepressant • Stage 2: Stage 1 and non response to alternative antidepressant • Stage 3: Stage 2 plus failure to respond to Lithium • Stage 4: Stage 3 plus failure to respond to a MAOI • Stage 5: Stage 4 plus failure to respond to ECT Assessment and Management of TRD • Thorough history, diagnosis, predictors and Tx (LIFE Chart, MSM, SAPAS) • Prescribed medications or medical illness may cause depression • Review precipitants of depression (e.g. bereavement, early life trauma, marital or family dysharmony, social factors) • Consider comorbidity (anxiety disorders, substance abuse, dementia) and personality disorder (cluster c) • Misdiagnosis (BPI >5%, BPII 10%+) • Chronicity/cognitive change Affective Spectrum Unipolar 5% Bipolar Bipolar <1% Spectrum Family Hx 3% Early onset Psychosis Bipolar Spectrum • BP II:- More like UP than BP - W>M - Clinical severity, rapid cycling, co-morbidity - Depressions with brief hypomanias • False Unipolar - 10-15% • Bipolar Spectrum Disorder Structural MRI: Unipolar Depression • white matter hyperintensities - late onset - DWML>>PVL - worse prognosis - poor treatment response - vascular depression Depression Comorbidity (NESARC) 45 40 35 30 25 20 15 10 5 0 Anxiety Alcohol Illicit Drug Personality Pharmacology of TRD TRD Management: Pharmacological • Antidepressants remission (30%) • Partial response a problem (40%) • Length of treatment important (4-8 weeks) • Not all antidepressants are equal (meta-analysis, % achieving full remission, TRD studies NNT high) • Consider symptoms • Length of continuation/maintenance treatment (Kennedy; Lam; Nutt & Thase, 2007) Consider Symptoms and Side Effects NE 5HT2c Attention Mood Obsessions Drive Sleep Anxiety Appetite Loss of pleasure Cognitions Consider Symptoms and Side Effects NE Mood Attention Sleep 5HT2c Obsessions Anxiety Drive Loss of pleasure Appetite DA Cognitions Consider Symptoms and Side Effects NE Venlafaxine (150+) Reboxetine Mirtazepine Bupropion Duloxetine SSRI TCA Olanzapine MAOI/RIMA Clomipramine Paroxetine Methylphenidate Venlafaxine (225+) Pramipexole D2/D3 DA 5HT2c Management of TRD: Options • Optimize length of treatment (6-8 weeks if partial response) • High dose treatment if linear dose response (especially TCA & venlafaxine) • Switch class of antidepressants • Augmentation of antidepressant • Consider antidepressant combinations or ECT STAR*D (Sequential Treatment Alternatives to Relieve Depression) • 6-year naturalistic study, 4000 enrolled, $35 m, NIMH - Step 1 Citalopram 60mgs, 3 months 27.5% remission - Step 2 switch (Sert, Ven, Bup) or augment (Bup>Bus) augment 30%>switch 25%, CBT - Step 3 >40% non-remitted after 2 trials (Nor>Mir) 13-25% remission (T3>Li) augment > switch - Step 4 Venlafaxine/Mirt 14% > Tranylcypromine 7% STAR*D (Sequential Treatment Alternatives to Relieve Depression) • Remission - female gender - employed - higher socioeconomic/income • Non-remission - medical/psychiatric co-morbidity - premorbid functioning - episode length Management of TRD: Augmentation • Level I: (Meta or RCT with Placebo) - low dose lithium (400-800 mgs, >0.6mmol/l) 50% response within 1 week - Second: low dose atypical antipsychotics (Olanzapine, (Level 1), Risper and Quet (level 2) • Level 2: (RCT Placebo or Active Comparison) - Bupropion, Triiodothronine (T3), Psychostimulants • Level 3: (Uncontrolled Trial (>10 subjects) - Modafanil, Methylphenidate, lamotrigine, pramipexole (level 3- BPAD!!) - Combinations (ven/mir, TCA/SSRI, MAOI/TCA • Negative data: (tryptophan, pindolol, buspirone) Novel Augmentation Approaches • Bupropion (Zyban 150) 200-400mgs/day - ↑Nad/Dop safe/alerting, ↑energy - Augmentation (SSRI or dual) or on own - Used in US to improve sexual s/e SSRIs - Side effects – agitation, tremor, insomnia - NB rare convulsions dose related - NB do not use with MAOI can be fatal - Not great for anxiety • Modafanil (Provigil) 200-800 mgs/day headache, ↑BP • Omega-3-fatty acids (EPA 1.5 gms/day ) • Dexamethasone 4 mgs/day X 4 days Psychotherapy for TRD • Cognitive Behavioural Therapy (Level 1) - Few RCTs 158 chronic patients randomized to CBT (26+ sessions) or TAU. Weakening benefit for 3.5 years (Paykel et al 1999; 2005) • CBASP (Cog Beh Analysis Sys Psych McCollough) - Chronic depression (20+ sessions) relationship prob solving, RCTs disappointing no better than pharm/BSP 2 recent trials (Kocsis et al, 2009; Schromm et al, 2009) • Interpersonal Therapy (Weissman) Level 2 + meds Physical Treatments • ECT (75% remission), less effect TRD, relapse • rTMS left dorsolateral prefrontal (level 2), very safe, little effect TRD or severe • VNS open label, 40% TRD increasing, hoarse • Surgery DBS, ant cing, subcaud tract • Light Therapy, 10,000 lux am, winter depression Chronic Depression • Episode lasts more than 2 years • Low grade “dysthymic like” state (Keller et al 1987) • Poor long-term social functioning (Kennedy et al, 2007) • 70+% risk of co-morbid personality disorder – dependant (Tyrer et al, 2004) Chronic Depression: Treatment • Agree goals with patient – slow gradual improvement over 1 year+, no magic cures • May need intensive multidisciplinary approach as an inpatient (OT, CBT, Ind + Gp Psy, FT, IPT) • LIFE , Episodes, Personality, Precip, Tx pharm + psych • Psychoeducation • Optimise pharmacological treatments 1. Treatment in Chronic TRD • All refractory depressives over 10-years Cambridge TRD (Kennedy & Paykel, 2004) • Mean episode length (41 months) • Best response - High dose TCAs and SNRIs - Combination antidepressants - Lithium augmentation - ECT - CBT • Over 80% response but few asymptomatic 2. Treatment in Chronic TRD • Tertiary refractory depressives Maudsley Unit less tertiary (Fedaku et al, BJPsych, 2012) • 118 (79%) prospective longitudinal follow-up mean 39 months) • • • • 60% remission (75% follow-up time symptomatic) 55% of those remitting relapsed Predictors - Severity, social support and education MAOIs and Duloxetine predicted remission Mood Disorders Units (MDU) • Given the morbidity associated with depression little data regarding operation or outcome of MDU • Gordon Parker, Sydney “Black Dog Institute” - detailed assessment and 3 month follow-up - access to online and group psychoeducation • Gene Paykel, Cambridge intensive inpatient (3 months) and daypatient treatment (3 months) • Tony Cleare, Maudsley intense inpatient treatment (6 months) Mood Disorders Units (MDU) • General principles - detailed initial assessment (semi-structured interview) - psychoeducational programmes - access to psychotherapy (individual and group) - High dose pharmacotherapy (augmentation) - continuity of care (6-12 months) - link clinical care and research “ Finding the right balance of treatment whether lithium, antipsychotics, SSRIs or other kinds of treatment can be a very hit and miss heuristic process requiring great patience and careful, classy, caring doctoring” Stephen Fry St Edmundsbury Mood Disorder Programme • Inpatient 4-6 weeks:NB Avoids Institutationalism - Assess episodic LIFE, SAPAS, Tx, precip/perp - Agree care plan - Programme generic + specialized (GP CBT, IPT, Mind, RO, BA) - Individual work (OT, IPT, FT, CBT, DP, Pharmacist 60%+) • Daypatient 3-6 months (>1 prog):- RO, CFT, BAD, CBT, ACT, Mind, HSE, RTPD also SPUH progs • Outpatient care (>1 year) - Continuity (88% 1st episode >1 year follow-up) Integrated Service Inpatient Unit (52 Beds) Day-Patient Unit (40 places) Dean Clinic (3 Days per week) Integrated Service Subspecialization Dr Prasad MDT Mood/BPAD Dr Morgan MDT Mood/Dual Dx Dr Kennedy MDT Mood/Refractory Depression SEH Inpatient MDU Programme Monday Tuesday Wednesday Thursday Friday 10 Anxiety L All 10 Depress L All 10 Managing Change L All 10 Psychol GP All 10 Goal Setting All 11 Healthy Eat All 11.30 Stress Man Ref 11 Relaxation All 11 Info Centre All 11 Exercise All 12 CBT GP Ref 11.30 Induction All New 12 Roles in Tran 12 Inpatient GP All Psychotherapy GP Ref 11 Art/Music Class All 2 BADep GP All 2 Pilates All 4 Exercise All 2.30 Social GP All 3.15 Relaxation All 2 Healthy Self Esteem All 3 Mindfulness GP All 6 Twilight All 2.30 Relaxation + Mindfulness All 2 CBT L All 3 Pilates All 4 Relaxation All St Edmundsbury MDU: Operation and Outcome • 18-month longitudinal follow-up:- All first-episode depression admissions (2009-2010) (n=137) - Semi-structured interview (SCID, SAPAS, LIFE) - LIFE weekly 18-month follow-up of outcome (100%) • Baseline (MSM):- 75% treatment resistant, 42% MSM resistant - 33% chronic (>2 years) - 56% PD, 40% psychiatric co-morbidity - 40% tertiary referrals Inpatient MDU Individual Treatment n (137) % Family/Couple/IPT 66 48 Occupational Therapy 65 47 CBT 46 34 Psychotherapy 40 29 Social Worker 9 7 Intervention Inpatient Pharmacological Treatment Pharmacological Agent SSRI SNRI TCA Augmentation Lithium Bupropion Antipsychotic Combination ECT Baseline % Discharge % 56 39 4 32 12 4 16 12 1 21 64 15 74 25 10 22 33 11 St Edmundsbury MDU: Outcome • Remission and Relapse:- 95% remission overall 73% within 6 months 88% within 1 year - 33% of those remitted had a full relapse • Predictors:- remission = male gender, length of episode, resistance - relapse = personality disorder, length of episode Symptomatic Outcome after First Episode Depression (NIMH CDS, Kanai et al 2005) Symptomatic Outcome after MDU First Episode Depression Treatment Conclusions • Despite high levels of morbidity little data exists about treatment of refractory depression • Refractory depression is likely to need intensive and lengthy psychoeducational, psychological and pharmacological treatments • Good continuity of care leads to a more consistent response in depression • Intensive specialized treatment appears to impact on percentage remitting over time and symptomatology but less or relapse risk. • Need for further approaches given co-morbidity (eg schema therapy)
