Treating Depression in Primary Care Strengths Weaknesses of

Treating Depression in Primary Care Strengths & Weaknesses of the NICE guideline David Goldberg Institute of Psychiatry King’s College, London

Evidence-based Medicine Ø How good is the evidence that, for the average person, medical treatment is better than a placebo?

Evidence-based Medicine Ø How good is the evidence that, for the average person, medical treatment is better than a placebo? If there are several treatments: Ø What is the most cost-effective treatment for a particular condition, for an average person?

Evidence-based Medicine Ø How good is the evidence that, for the average person, medical treatment is better than a placebo? If there are several treatments: Ø What is the most cost-effective treatment for a particular condition, for an average person? EBM is based upon meta-analyses of published RCTs

Patient-based Evidence What is the best treatment for me, with my particular characteristics and idiosyncrasies?

Patient-based Evidence What is the best treatment for me, with my particular characteristics and idiosyncrasies? To respond to this, the clinician needs to know the evidence from RCTs, but to be prepared to apply it to this particular individual

Problems with RCTs of depression Ø In the USA, investigators often advertise for “patients” in newspapers, and pay for their co-operation

Problems with RCTs of depression Ø In the USA, investigators often advertise for “patients” in newspapers, and pay for their co-operation Ø It is most unlikely that a clinician will ask a severely depressed patient to have a 50% chance of a placebo

Problems with RCTs of depression Ø In the USA, investigators often advertise for “patients” in newspapers, and pay for their co-operation Ø It is most unlikely that a clinician will ask a severely depressed patient to have a 50% chance of a placebo Ø although we may produce single severity scores using say, the Hamilton – how homogeneous are the patients?

Problems with RCTs of depression Ø In the USA, investigators often advertise for “patients” in newspapers, and pay for their cooperation Ø It is most unlikely that a clinician will ask a severely depressed patient to have a 50% chance of a placebo Ø although we may produce single severity scores using say, the Hamilton – how homogeneous are the patients? Ø If many negative studies have been suppressed, what does it mean to do metaanalyses on positively selected studies?

Emperor’s New Drugs Kirsch et al 2002 Relying on RCTs registered with the FDA: Ø Differences between AD and PBO only 2 symptoms on Ham-D Ø Such small differences can produce large “% responded “ differences Ø Argues that such small differences are due to side effects of ADs

Severity at baseline and response (-50%) after 4 weeks´ treatment: Angst placebo, moclobemide, imipramine

Irving Kirsch’s figure:

How homogeneous? Consider 2 young unmarried female patients; both aged 18; both with a Ham-D score of 24 How reasonable is it to try to say everything about severity with a single score on a depression scale?

Consider 2 young unmarried female patients; both aged 18; both with a Ham-D score of 24 Patient 1: is a lone mother Parents divorced Mother was depressed Sexual abuse since aet 11 Left home aet 14 Casual sex since Depressed for 2 years Recently worse since child taken into care

Consider 2 young unmarried female patients; both aged 18; both with a Ham-D score of 24 Patient 1: is a lone mother Parents divorced Mother was depressed Sexual abuse since aet 11 Left home aet 14 Casual sex since Patient 2: university student Supportive parents No FH of depression Many friends Affair with boyfriend last 2 years Depressed for 2 years He recently left with another girl Recently worse since child taken into care Depressed for 2 weeks since he left

Will these two young women respond in the same way to treatment? Should the treatment be the same?

NICE: The National Institute for Clinical Excellence A government provider of information based on Evidence Based Medicine (EBM) for the benefit of clinicians and their patients. Guidelines on schizophrenia, eating disorders, anxiety disorders, selfharm and now - depression

NICE: Terms of Reference Ø Clean meta-analyses to be performed Ø Exclusions: <16; puerperal; physical illness Ø Outcome: efficacy x 3, tolerability, toxicity Ø Economic considerations to be included Ø Outputs: long document on net, text & tables; short form; a very short form, User’s form

User Involvement Ø 3 Users on main group Ø 1 on each of 3 subgroups: services, drug treatments, psychological treatments Ø Gave their approval at every stage Ø Told us now big a change in symptoms was “worthwhile” Ø Thus: “Statistically but not clinically significant”

The NICE scale A = Systematic reviews, RCT ‘s B = 1+ Well conducted study C = Opinions of ‘respected experts’: but capable of empirical investigation GPP = Our opinions of good practice

“Stepped Care” Who needs treatment? Who should give it? When should patients be referred?

“Stepped Care” The strict EBM approach: Which patients merit active treatment? Which treatments for depression should be available in primary care, which in specialist care? Who should give them? - assumes a severity score gives comparable information about depression

“Stepped Care” Patient-based evidence: Which individuals merit active treatments? Which particular treatments will suit this individual? When should this person be referred? Evidence from EBM should be obeyed in perhaps only 70% of cases

Who is responsible for care? What do they do? Why do they do it? Acute Wards CMHT, OPD, crisis team, Day Hospital PCMHW, GP, Counsellor, social worker, psychologist GP, Practice nurse, Practice counsellor Risk to Life Treatment resistance frequent recurrences Moderate or Severe Depression Mild Depression Recognition Medication, ECT nursing care Medication, complex Psychological i. v’s Medication, Brief psych. interventions, support groups Active Review: Self Help, Computerised CBT, Exercise

Step 1: Recognition in Primary care & general hospital care Screening with 2 routine questions in high risk groups [B] OR Ø past history of depression Ø significant physical illness causing disability Ø other mental health problems e. g. dementia

Use two screening questions. . - During the past month, have you been feeling down, depressed or hopeless? - During the last month, have you often been bothered by having little interest or pleasure in doing things

Consider psychological, social & physical of the patient, and the quality of interpersonal characteristics, & assess impact on: Ø Depression Ø Choice of treatment [consider alternatives, respect patient preference] Ø Monitoring

RISK ü always ask directly about suicidal ideas & intent, advise patients & carers to be vigilant GPP ü patients under 30 prescribed SSRIs must be warned of suicidal ideas, and seen again a week later C ü ensure that suicidal patients have adequate social support GPP

Information ü provide appropriate information on nature, course and treatment of depression GPP ü avoid use of clinical language & provide information in language understood by the patient GPP ü make contact with those who do not attend follow-up C

RECOGNISED, MILD DEPRESSION Ø Patients may improve spontaneously Ø where intervention is not wanted, arrange further consultation within 2 weeks Ø contact patients who do not attend Ø consider advice about sleep hygiene and physical exercise [3+ sessions /week; >45 mins for 12 weeks] Ø consider guided self help or written support materials Ø computerised treatments may also help

Step 2: Recognised mild depression The following are all recommended: • physical exercise [B] • problem solving [B] • guided self-help [A] • Computerised CBT [A] • “watchful waiting” [GPP] • St. John’s Wort (with reservations!) [B] • AD’s not recommended for initial Rx of mild or sub-threshold depression [C]

So, is the criterion for “Major Depression” too low? PROBABLY NOT: Ø Clinicians should take account of time course, family & previous history, availability of social support as well as “severity” on a symptom scale Ø they should offer alternative treatments as well as, and sometimes instead of, drugs Ø Some ADs have other effects than mood elevation, including anxiolytic & hypnotic effects, which can be extremely useful Ø Anything that encourages a “clinical management” approach is desirable Ø it is the clinician who must appear in the Coroner’s Court!

Self-help vs. waiting list Mead et al Psych Med 2005, 35, 1633 114 patients with anxious depression randomised to self-help (home-made) and waiting list. No diagnostic measure, but Beck DI = 26 at onset 3 month FU – no differences in outcome in either depression or anxiety; BDI = 17 -20

Step 3: Moderate & severe depression Ø Active treatment recommended in all cases Ø Offer anti-depressants in all cases, but discuss fears about addiction Ø Monitor patients for side effects & suicidal ideas regularly Ø continue AD’s for 6/12+ after remission

Psychological treatments Problem solving by PC staff [B] If psychological treatment preferred, CBT is Rx of choice [16 -20 sessions over 6 -9 months + consider boosters] [A]

Antidepressants compared Ø In general practice, they all have equal efficacy Ø Some are better tolerated than others Ø Some are more toxic in over-dose Ø females tolerate tricyclics poorly Ø They have very different costs!

Some relative costs…. For drugs, assume 4 sessions, 10 mins Amitryptiline 100 mg……. . £ 67. 10 Fluoxetin 20 mg…………………. . £ 114. 00 Venlafaxine 75 mg…………… £ 159. 50 Ø Problem solving, 6 x 30 mins Ø By GP …………… £ 273. 00 Ø By nurse………. . …………… £ 183. 00

Drug treatments in PC First line treatment Ø SSRI’s are 1 st line AD’s, more so for women [A] Ø Continue treatment for 6/12 [A] Ø Fluoxetine & citalopram cheap, fewest discontinuation symptoms of SSRIs [C] Ø sertraline is best in heart disease [GPP] Ø Do not use venlafaxine as 1 st line Rx [B] Ø Avoid paroxetine, short ½ life [C] Ø Avoid dothiepin in isch. ht. disease [C]

Drug treatments in PC The patient fails to respond… Ø check drug taken regularly & in prescribed dose Ø increase dose within permitted range, only modest, incremental increases Ø if poorly tolerated switch to another drug Ø switch to 2 nd AD if no response in 1/12

Drug treatments in PC Second line treatments Ø Try another SSRI [C] Ø Mirtazepine acceptable (but sedation & weight gain) [A] Ø Moclobemide acceptable (but wash out previous AD) [A] Ø Lofepramine, mirtazepine & reboxetine are safer in o/d [GPP] Ø Combined treatments, lithium augmentation, phenelzine, and venlafaxine, should not be initiated in PC

Chronic anxious depression (mainly seen in primary care) Remember social & I-P causes [GPP] Combined AD and CBT [A] Consider befriending [C] Telephone support [B] Enhanced care [C]

Enhanced care Vonkorff & Goldberg BMJ 2001, 323, 948 Intensive follow up, by nurse, producing better outcomes at moderate cost

Enhanced care Vonkorff & Goldberg BMJ 2001, 323, 948 Intensive follow up, by nurse, producing better outcomes at moderate cost Vergouwen et al, Psychol Med 2005, 35, 25: Randomised 211 depressed PC pts of 30 GPs to “depression care programme DCP + SSRI” or just SSRI. Results: Adherence high (87% in both groups at 10/52), all symptom measures = at all FU points. Both groups had systematic follow-up; DCP had “patient education, self help, active participation of Dr & pt in treatment”

How to decide in each case? (Patient-based Evidence) What is time course of the disorder? Is there a family history of depression? Is there a past history of depression? Is there social support? How severe is the depression now? Is severity increasing?

How to decide in each case? (Patient-based Evidence) What is time course of the disorder? Less than 2 weeks, or Symptoms intermittent - general advice, watch & wait

How to decide in each case? What is time course of the disorder? Is there a family history of depression? If YES, favours active treatment

How to decide in each case? What is time course of the disorder? Is there a family history of depression? Is there a past history of depression? If YES, favours active treatment

How to decide in each case? What is time course of the disorder? Is there a family history of depression? Is there a past history of depression? Is there good social support? NO – active treatment YES, and MILD: favours advice, watch & wait

How to decide in each case? What is time course of the disorder? Is there a family history of depression? Is there a past history of depression? Is there social support? How severe is the depression now? Is severity increasing? ≥ 7 symptoms or ≤ 6 deteriorating: treat ≤ 6, improving - advice, watch & wait

Who is responsible for care? What do they do? Why do they do it? Acute Wards CMHT, OPD, crisis team, Day Hospital PCMHW, GP, Counsellor, social worker, psychologist GP, Practice nurse, Practice counsellor Risk to Life Treatment resistance frequent recurrences Moderate or Severe Depression Mild Depression Recognition Medication, ECT nursing care Medication, complex Psychological i. v’s Medication, Brief psych. interventions, support groups Active Review: Self Help, Computerised CBT, Exercise

Who should be referred to mental health care? ü all those who ask to be referred ü all new cases of psychosis, and all who relapse on treatment ü cases of severe eating disorders ü all those whose depression fails to respond to two different treatments, or who relapse frequently ü all cases where risk of suicide is high, or there is a risk to others ü others who require a specialist treatment not available in primary care: eg CBT, or sexual counselling, ECT

The UK Model New problems that fail to respond to treatment, old patients in relapse PRIMARY CARE COMMUNITY MENTAL HEALTH TEAM CMHC staff visit chronic patients, liaise with GP; stable patients in remission sent back to primary care SHARED CARE PLANS HERE

Who should be referred back for MH to primary care? “Shared Care” ü all those who have stabilised on treatment – for example schizophrenics and bipolar illnesses. ü all those chronic depressives for whom a management programme has been agreed.

SHARED CARE: Shared care refers to improving the relationship between primary and secondary services, with Ø shared care plans, mutually agreed Ø a dedicated linkworker Ø mild cases may only see psychiatrist, more severe cases also have nursing care

A Shared Care Plan ü ü ü ü name, address, next of kin name of key worker, phone diagnosis, treatment plan main symptoms in relapse main symptoms in remission current treatment, who gives best alternative treatment how to admit in emergency, phone number!

Joe Neary (GP): In “Primary Solutions” Sainsbury 2003 “…joint working needs to be agreed between the community mental health team and the primary care team, but such practice is uncommon…. both services are overloaded, and both have daunting quality and development agendas”

Step 4: ROLE OF SPECIALIST MENTAL HEALTH SERVICES Separate advice on Ø “acute phase non-responders” Ø treatment resistant cases Ø relapse prevention Ø atypical cases

Acute Phase non-responders Ø Augment with another class AD (but not [B] Ø Move to CBT or IPT [B] Ø If severe, drug + CBT [B] Ø venlafaxine may help, but toxicity in overdose [B] Ø Augmenting with lithium “could” help [C] Ø Cardiac disease: sertraline, not prothiaden [B] carbamazepine, lamotrigine or buspirone)

Treatment Resistant [failed to respond to 2+ AD’s] Ø Moderate+, no response to AD’s -> CBT [B] Ø Partial response to AD’s, add CBT [B] Ø Augmentation strategy: AD + AD [B] Ø Go on to venlafaxine [C] Ø Adding Lithium “should” help

Relapse prevention Ø Multiple episodes, good response continue treatment for 2+ yrs [B] Ø Augment AD with lithium [B] Ø If lithium augmentation effective, maintain for 6/12+ [B] Ø If unable or unwilling to continue an effective drug -> IPT [B] Ø Crisis resolution and home treatment teams [C]

Atypical Cases Ø Atypical depression in females: MAOI’s if SSRIs fail [B] Ø Psychotic depression: augment with anti- psychotic [C]

Cognitive behaviour therapy v for those who fail medical treatments v with history of relapse / limited response to other measures v those at risk of relapse who do not wish to continue drugs v those with 2+ previous episodes of moderate or severe depression

Step 5: In-patient care Admit if significant risk of suicide or self harm [C] Consider crisis resolution and home treatment teams for those who can be discharged early [C] ECT if rapid or short-term improvement is called for in severe depression [NICE]

Conclusion - 1 We need to know about EBM, for the average patient But we have to have some way of applying it to the patient consulting us

Conclusion - 2 Drugs working on different pharmacological systems are equally effective Psychotherapies working on quite different principles are almost equally effective Caring treatment and a placebo is fairly effective But ALL patients need to have hope, and an expectancy of improvement

Conclusion - 3 We all have our own ways of achieving this end!

Download our Report from the Internet: www. nice. org. uk/pdf/word/CG 023 NICEguideline. doc (All appendices can also be downloaded from the NICE site) Obtain hard copy: National Collaborating Centre for Mental Health (2004) “Depression: Management of depression in primary and secondary care” London: Gaskell, or from NICE