The pharmacological management of depression in primary careoxleas.nhs.uk/site-media/cms-downloads/Derek_Tracy_-_The... · 2015. 3. 24. · The pharmacological management of depression

The pharmacological management of

depression in primary care

Dr Derek Tracy

Consultant Psychiatrist Associate Clinical Director: crisis & inpatient services

18 March 2015

Overview

• A few slides on stats (not too many I promise)

• What to look for – History & mental state – Markers of risk

• What to do

– Pharmacological: the obvious and the more complex – Prescribing with physical co-morbidities

• When to refer

www.who.int/healthinfo/global_burden_disease

4 Ferrari, PLOS Medicine, 2013

Regions with statistically greater or lesser mean depression related disability

Aleman and Denys, Nature, 2014

Standardised suicide mortality per 100,000. QIPP NHS Atlas: http://www.library.nhs.uk/qipp/

Approximately 5,000 suicides p.a. in the UK Geographical & socio-economic variation Seven-fold variation between highest and lowest rates per PCT (Male medics 1.41, females 2.27 times more likely than general population)

What to look for in the history

• Depression is episodic – Can vary day by day, within days, but persistently low (cf Borderline PD) – However, people recover, it doesn’t last a lifetime (cf social misery)

• Pathological ‘highs’: very difficult, esp ‘Bipolar 2’ • Comorbid substance misuse, esp alcohol: can be difficult • Obvious perpetuating factors

– Relationships, family – (un)employment – Finances etc

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9

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Risk: the static & the dynamic

• The static: the factors that don’t readily change • Gender • Age • Socioeconomic: employment, debts, relationships etc • Co-morbid illness, esp chronic & with pain

• The dynamic: can vary rapidly

• Current mental state and mood • Degree of hopelessness • Sense of guilt & worthlessness • Drug and alcohol consumption, and impulsivity • Protective factors (may be dynamic or static)

• Predicting risk is very difficult:

• Past self-harm is the best predictor of future events • 16% repeat self-harm within a year (2% fatally), 7% dead within 9 years1

1Owens, 2002

Self-harm & predicting the future

• An escalation of ‘chasing the no’: – Wishing they weren’t here, not wake up – Wanting to die, to self-harm – Plans of self-harm: DETAIL DETAIL DETAIL – What stops them? Family, religion, guilt?

• Current self-harm: – Type: poisoning, cutting etc – Intent: some people draw relief, comfort (as with plans) – Context: alcohol? – Subjective vs objective risk (SSRIs vs insulin)

• Past self-harm: – Types of self-harm: poisoning, hanging, cutting – Suicidal intent (vs Para suicidal) – DETAIL DETAIL DETAIL

• Scales: no actuarial use. Self harm common, suicide rare

• For ≥ moderate severity depression1 • 20% respond without treatment • 30% respond with placebo • 50% respond with an antidepressant

• NNT of ~3 (cf statins) • The drugs work2

• Efficacy ∝ severity3

•

The most inefficacious drug is the one that isn’t taken

Demyttenaere, Int Clin Psychopharm, 1998

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Which drugs to start with? First line • SSRI1, only due to tolerability, not efficacy

• Not dogmatic: pharmacogenomics & what worked before?

• Any to recommend? Evidence2 for sertraline and escitalopram in

terms of efficacy & acceptability

• Mirtazapine, venlafaxine also show (minor but statistically significant) class differences2 in efficacy, but higher discontinuation rates

• Increasing evidence for lack of efficacy for reboxetine2, 3

1NICE guidelines, 2007 2Cipriani, Lancet, 2009 3Eyding, BMJ, 2010

Second line in Primary care

• It is reasonable to give another SSRI1, citalopram ≠ fluoxetine... • However evidence it’s better to change class2

• Class change options:

• SNRI (duloxetine3,4, venlafaxine5,6) • May also provide additional class benefits:

↑ cognition7

• No weight gain, effect on glycaemic control • Treatment of pain & somatic symptoms

• NaSSA (mirtazepine8,9): weight gain

• Balance of risks: ? secondary care

Specialist Training in Psychiatry, Tracy, OUP 2015

1Trivedi, NEJM, 2006

2Papakostas, Biol Psych, 2008 8Fava, Am J Psych, 2006 9Thase, NIMH, 2001 3Norman, Dr Des Dev Ther, 2010

4Girardi, Hum Psychopharmacol, 2009

5Rush, NEJM, 2006 6Brent, JAMA, 2008

7Herrera-Guzman, J Psych Res, 2009

Do SSRIs cause suicidality?

• Yes1 • Only in those

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Introduction of FDA regulation on the prescribing of ADs to adolescents. SMR rose from 7.23 to 8.14, or 213 additional deaths.

Center for disease control and prevention: www.cdc.gov./injury/wisqars/index.html

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If you’re feeling adventurous

• TCADs are still as efficacious1, help with neuropathic pain • ...just less well tolerated2,3......and lethal in overdose4

• Avoid MAOIs (though q ‘atypical’ depression5)

• Bupropion: good evidence from US, coming soon 150-300mg/d • Lamotrigine: to a minimum of 75mg BD (Stevens-Johnson synd) • Lithium • Atypical Antipsychotic: why do we do this/how do you feel about it?

1Barbui, Br J Psych, 2001

2Furukawa, BMJ, 2008

3Anderson, J Psychopharmacol, 2008

4Flanagan, Hum psychopharm, 2008

5Parker, Acta Psychiatr Scand, 2009

Special populations I*

• Pregnancy • Choices led by the mother, but 2/3 baby blues, ~10% develop depression1 • Discontinuation/past history might be a rationale for 2⁰ care monitoring • No drug is “safe” in pregnancy, but huge variation (e.g. ADs vs. mood stabilisers) • Risks of untreated depression: not bonding/neglect/intentional harm • I generally avoid change in a stable patient: 65% relapse with discontinuation (vs 25%)2 • Most evidence for amitriptyline and fluoxetine3, avoid paroxetine4

• Post MI • ADs can block cardiac Na+ channels, prolong PR, QRS, QTc, induce arrhythmias, esp TCADs • Sertraline generally recommended5 post MI, but other SSRIs likely to be safe

• Post CVA • Depression occurs in 30-40%: ADs have proven role in aiding recovery • Issues: interactions, esp with warfarin; SSRIs can increase bleeds but not linked to recurrence6 • Post CVA mirtazapine and SSRIs recommended

*I can’t cover all permutations of illness or degree of illness. Always a balance of risks of treatment vs non-treatment.

2Cohen, JAMA, 2006

1Munk-Olsen, JAMA, 2006 3Nulman, Am J Psych, 2002 4Thormahlen, Ann Pharmacother, 2006

5Glassman, JAMA, 2002 6Bak, Stroke, 2002

Special populations II: diabetes

• SSRIs (fluoxetine, paroxetine, citalopram, sertraline etc.) - first line • Evidence for favourable effects on diabetic parameters in type II • Most data for fluoxetine1, associated with improvements in HbA1c, weight loss,

enhanced insulin sensitivity & reduced insulin requirement

• SNRIs (duloxetine2, venlafaxine) • No evidence for disrupting glycaemic control or causing weight gain • Duloxetine has a good evidence base for diabetic neuropathy

• NaSSA (mirtazapine): little data, strong association with weight gain3 • TCADs: appetite, weight gain, hyperglycaemia: avoid4

1Briscoe, Diabetes, 2008

2Crucitti, Curr Med Res Opin, 2010

3Himmerich, Diabetes Care, 2006

4Kivimaki, Diabetes Care, 2010

• Partially dependent on attitude, adherence, but chronic illness model • Plan/negotiate discontinuation, do slowly (min 2/52)1 • Minimum 6/12 from when well in 1st episode2 • Minimum 2 years if >1 episode3, as

• >50% have a 2nd episode • >80% of whom have a 3rd episode4,5

• If stopped on recovery, 50% relapse within 6/126 • Greatest risk on discontinuation, however long the depression7 • Continuing ADs ↓ odds relapse rate by ~ 2/38 • Benefits persist at 36 months after recovery8

Staying on antidepressant treatment

1Baldessarini, EBMH, 2010

2Reimherr, Am J Psychiatry, 1998

3NICE, 2007

4Forshall, Psychiatr Bull, 1999

5Kupfer, RCPsych, 1996

6Anderson, J Psychopharmacol, 2008

7Keller, J Clin Psychiatry, 2007

8Geddes, Lancet, 2003

Anxiety disorders: biggest meta-analysis to date

25 Bandelow, 2014

The social: leading horses to water, the hardest bit

• For me there are two major problems here • A huge amount of what we see is social: drug use, unemployment,

physical violence, lack of education…and we feel the inadequacy of drugs, therapy

• These factors often conspire to produce the patient who won’t/cannot/doesn’t understand how to help themselves

• MIND is a wonderful resource

• Adult education

Passing to secondary care

• The urgent – Perinatal, though not all perinatal: risk call (past hx, meds, supports…) – Risky: to self, to others, of neglect. – For me: the more info you can supply the better, even to identify areas you

can’t explore (Donald Rumsfeld’s unknown unknowns) • The unresponsive

– First/second/third line have failed – You need a fresh set of eyes – For me: as much info on doses, duration, s/e, best guess adherence, degree of

interference with life/functioning • The complex

– Co-morbid anxiety, psychosis, PD: likely to need MDT work – The very vulnerable, for similar reasons – The “diagnostically different”

Questions

[email protected]

mailto:[email protected]:[email protected]

The pharmacological management of depression in primary careOverviewSlide Number 3Slide Number 4Slide Number 5�What to look for in the historySlide Number 8Slide Number 9Slide Number 10Risk: the static & the dynamicSelf-harm & predicting the futureThe pharmacological: the drugs don’t work?The most inefficacious drug is the one that isn’t takenSlide Number 15Which drugs to start with? First lineSecond line in Primary careDo SSRIs cause suicidality?Slide Number 19Slide Number 20If you’re feeling adventurous Special populations I*Special populations II: diabetesStaying on antidepressant treatmentAnxiety disorders: biggest meta-analysis to dateThe social: leading horses to water, the hardest bitPassing to secondary careQuestions