1. Depression Key slides

2. What is depression? NICE Full guideline CG90. October 2009

3. Wide range of mental health problems characterised by absence of a positive affect (lack of interest and anhedonia), low mood, and a range of associated emotional, cognitive, physical and behavioural symptoms What is ‘normal’? Major depressive illnesses identified by severity, persistence of other symptoms and the degree of functional and social impairment Consider duration, stage of illness and treatment history

4. What are the burdens of depression? NICE Full guideline CG90. October 2009

5. Mental and physical suffering Social impairments –Inability to communicate –Disturbed relationships –Changes in social functioning Martial relationships and neglect of children Stigma Reduced self esteem / confidence Reduced working ability Exacerbation of pain and distress associated with physical illness Economic burdens

6. What causes depression? Shah PJ. Hosp Pharm 2002; 9: 219-22; Thompson C. Medicine 2000; 28: 1-5

7. Multifactorial and largely unknown Genetic predisposition –60% concurrence in twins Early childhood environment –Lack of parental care or loss of mother? Social stress and life events –Severe life events increase risk 6x in following 6 months Neuroendocrine changes –eg HPA axis Neurochemical changes –No single pathway Other diseases Drugs

8. What are some of the possible triggers for depression? WHO 1998

9. Psychological –Recent bereavement –Relationship problems –Unemployment –Moving house –Stress at work –Financial problems Medications –Antihypertensives –H2 blockers –Oral contraceptives –Steroids Illness –Infectious disease –Chronic medical problems –Alcohol abuse –Substance abuse Other –Family history –Childbirth –Menopause –Seasonal changes

10. How common is depression in the UK? NICE Full guideline 90 CKS Depression Nov 2007. www.cks.nhs.uk

11. 5-10% consulting have major depression 130 per 1000 people 80 per 1000 (62%) consult their GP 49 out of 80 (61%) are subsequently not recognised 1 in 4 or 5 are referred to secondary care Dysthymia occurs in 1-4% of adults

12. Identification and assessment NICE CG 90. Oct 2009 Be alert to possible depression (particularly in those with a past history of depression or a chronic physical health problem with associated functional impairment) and consider asking people who may have depression: 1.During the last month, have you often been bothered by feeling down, depressed or hopeless? 2.During the last month, have you often been bothered by little interest or pleasure in doing things? –If “yes” to either: follow-up (Whooley and Simon. New Engl J Med 2000;343:1942–50)

13. Identification and assessment NICE CG 90. Oct 2009 NICE Full Guideline 90. Oct 2009 Confirmation requires more detailed clinical assessment; consider using a validated measure e.g. PHQ-9, HDRS, BDI Comprehensive assessment should not rely solely on symptom count. Consider: –Degree of impairment and/or disability –Duration of episode Always ask a person with depression directly about suicidal ideas and intent. PHQ = Patient Health Questionnaire HDRS = Hamilton Depression Rating Scale BDI = Beck Depression Inventory

14. Depressed mood Loss of interest or pleasure (anhedonia) Insomnia or hypoinsomnia Appetite or weight change Fatigue or loss of energy Increased/decreased psychomotor activity Guilt or feelings of worthlessness Suicidal ideation Diagnosis of major depression by DSM-IV Williams, et al. JAMA 2002;287:1160–70; NICE CG 90. Oct 2009; Gruenberg AM, et al. 2005  2 weeks At least 1 of X should be present Major depression (  5 symptoms) Minor depression (2–4 symptoms) X

15. Categories of severity from DSM-IV NICE CG 90. October 2009 Subthreshold –< 5 symptoms Mild –Few if any symptoms in excess of the 5 required and resulting in only mild functional impairment Moderate –Symptoms or functional impairment between mild and severe Severe –Most symptoms and they significantly interfere with functioning

16. Management of depression The stepped care model NICE CG 90. Quick Reference Guide Oct 2009 Antidepressants for duration of illness + at least 6 months

17. NICE Step 2: persistent subthreshold depressive symptoms or mild to moderate depression (1) NICE CG 90. Oct 2009 Consider offering low intensity psychosocial interventions: –Individual guided self-help based on cognitive behavioural therapy (CBT) principles –Computerised cognitive behavioural therapy (CCBT) –A structured physical activity programme Choice of intervention should be guided by the patient’s preference Group CBT may be offered for those who decline low-intensity treatments Offer advice on sleep hygiene, if needed Monitor –those judged to recover without a formal intervention –those with subthreshold depressive symptoms who request an intervention.

18. Using antidepressants for persistent subthreshold depressive symptoms or mild to moderate depression NICE CG 90. Oct 2009 Antidepressants Not recommended for the routine treatment of persistent subthreshold depressive symptoms or mild depression because the risk-benefit ratio is poor Consider them for people with –Past history of moderate or severe depression –Initial presentation of subthreshold depression that has been present for a long period (typically >2 years) –Subthreshold depressive symptoms or mild depression that persists after other interventions.

19. Options Antidepressant (normally SSRI), or High intensity psychological intervention –CBT (group or mindfulness-based) –Interpersonal Therapy (IPT) –Behavioural activation –Behavioural couples therapy, or A combination of antidepressants and high-intensity psychological intervention (CBT or interpersonal therapy) if moderate or severe depression Choice depends on patient’s preference, duration of episode, trajectory of symptoms, previous illness course and treatment response, likelihood of adherence to treatment, likely side effects. NICE Step 3: persistent subthreshold depressive symptoms or mild to moderate depression with initial inadequate response; or moderate and severe depression NICE CG 90. Oct 2009

20. Which antidepressant? NICE CG 90. October 2009

21. SSRIs –Equally effective as other antidepressants –Have a favourable risk-benefit ratio Note: –Increased risk of GI bleeding –Higher risk of drug interactions with fluoxetine, fluvoxamine and paroxetine –Higher risk of discontinuation symptoms with paroxetine Consider toxicity in OD for those with significant suicide risk –Venlafaxine associated with greater risk of death in OD –TCAs (except lofeapramine) associated with greatest OD risk Discuss drug choice with patient Do not prescribe dosulepin

22. Drugs other than SSRIs NICE CG 90. October 2009 Need to consider….. Likelihood of discontinuation due to side effects with venlafaxine, duloxetine and TCAs Cautions, contraindications and monitoring required –Duloxetine and venlafaxine exacerbate hypertension –Higher doses of venlafaxine may exacerbate arrhythmias and need to monitor BP –TCAs may cause postural hypotension / arrhythmias –Mianserin needs haematological monitoring in elderly Non-revesible MAOIs eg phenelzine normally only prescribed in secondary care Do not prescribe dosulepin

23. What should you discuss with the patient? NICE CG 90. October 2009

24. Explore their concerns and give a full explanation including: –Gradual delay in onset of full effect –Take as prescribed and continue for 6 months after remission –Information on potential side effects –Potential for interaction with other medicines –The risk and nature of discontinuation symptoms (especially if drug has a shorter half-life eg paroxetine and venlafaxine –Addiction does not occur

25. During the initial treatment stages there is a potential for: –Agitation –Anxiety –Suicidal ideation Be vigilant of mood changes, negativity or hopelessness especially during high-risk periods When the illness is severe or persistent information and support should be offered to the carer

26. What about St John’s wort?

27. May be of benefit in mild to moderate depression, but do not prescribe because of: –Uncertainty about appropriate dose and persistence of effect –Variation in the nature of the preparation –Potential serious interactions with other drugs (eg OCP, anticoagulants and anticonvulsants) Inform patients of these issues and the different potencies available

28. How should you follow up patients? NICE CG 90. October 2009

29. If no increased risk of suicide –See after 2 weeks –Then regularly (eg every 2-4 weeks for 1 st 3 months) –Longer intervals thereafter if good response If <30 years or increased risk of suicide –See after 1 week –See frequently until risk not considered significant

30. If no improvements after 2-4 weeks on 1 st drug check adherence After 3-4 weeks if response is absent / minimal consider: –Increasing dose –Switching antidepressant If some improvement by 4 weeks, continue for another 2-4 weeks –If response inadequate consider switching drugs

31. How long should you continue medication? NICE CG 90. October 2009

32. At least 6 months after remission Explain: –This greatly reduces the risk of relapse –Antidepressants aren’t associated with addiction Review with patient need to continue longer than 6 months. Consider: –Number of previous episodes –Presence of residual symptoms –Other health problems –Psychosocial difficulties For patients at risk of relapse, continue for at least 2 years

33. How should you stop or reduce dose of antidepressants? NICE CG 90. October 2009

34. Slowly over a 4 week period (some may need longer) Due to long half-life no need with fluoxetine

35. What should you do if patients do not respond to initial treatment? NICE CG 90. October 2009

36. Check adherence and any side effects Increase frequency or appointments and assessments Options –Reintroduce previous treatments that have been inadequately delivered or adhered to –Increase the dose –Switch to an alternative antidepressant –Combine drugs (consult with a psychiatrist)

37. Switching drugs NICE CG 90. October 2009 The evidence for the relative advantage of switching either within class or between classes is weak Reasonable choices for 2 nd antidepressant –Initially a different SSRI or better tolerated newer generation SSRI –Subsequently switching to an antidepressants that may be less well tolerated eg venlafaxine, a TCA or an MAOI Caution with switching –From fluoxetine to other antidepressants –From fluoxetine or paroxetine to a TCA –To a new serotonergic antidepressant or MAOI –From a non-reversible MAOI

38. Combining drugs NICE CG 90. October 2009 Only start in primary care in consultation with a psychiatrist Consider adding: –Lithium –An antipsychotic (eg aripiprazole, olanzapine, quetiapine or risperidone none licensed for depression in the UK –Another antidepressant (eg mianserin or mirtazapine in augmenting)

39. ‘Augmentation treatment’ NICE CG 90. October 2009 Not recommended routinely Antidepressant + benzodiazepine >2 weeks –Risk of dependence Antidepressant + busiprone / carbamazepine / lamotrigine / valproate / pinodol / thyroid hormones (none licensed in UK for depression) –Insufficient evidence

40. How might you ensure safety in prescribing? NICE CG 90. October 2009

41. Monitor symptoms and side effects eg anxiety, agitation, mood changes and suicide risk (especially if <30 years), particularly when initiating treatment and warn of possibility If high suicide risk: –Limit prescription quantity –Consider additional support (primary care staff or telephone contact) Monitor for relapse and discontinuation / withdrawal symptoms when reducing or stopping medication If not at risk of suicide see after 2 weeks, thereafter every 2-4 weeks in the 1 st 3 months

42. Continue for at least 6 months after remission Consider interactions with other drugs Consider specific cautions, contraindications and monitoring requirements Non-reversible MAOI normal prescribed by specialist Dosulepin not recommended Do not initiate 2 drugs together in primary care unless advised by a consultant

43. When should you refer? NICE CG 90. October 2009

44. Severe depression Moderate depression and complex disorders Significant risk of self-harm Psychotic symptoms Those requiring complex multiprofessional care When depression fails to respond to various strategies for augmentation and combination treatments Where an expert opinion on treatment and management required

45. Which non-drug treatments are recommended? NICE CG 90. October 2009

46. Low intensity psychosocial interventions Individual guided self-help based on cognitive behavioural therapy (CBT) principles Computerised cognitive behavioural therapy (CCBT) Beating the Blues www.beatingtheblues.co.uk and MoodGYM www.moodgym.anu.edu.auwww.beatingtheblues.co.uk www.moodgym.anu.edu.au A structured physical activity programme

47. High intensity psychological interventions CBT (group or mindfulness-based) Interpersonal Therapy (IPT) Behavioural activation Behavioural couples therapy

48. Others Counselling Short-term psychodynamic psychotherapy Group-based peer support programmes is a low-intensity option for those with chronic physical health problems

49. Case study 1

50. Working through this case study will help you to: Review your practice relating to the identification and assessment of people with possible depression Prioritise treatment for people who present with mild depression Advise patients who start treatment with an antidepressant

51. Mrs C is a 53-year-old woman presenting with symptoms of irritability, low mood and feeling that she cannot cope. She has been experiencing these symptoms for the past month, but has been reluctant to bother you about them She has been experiencing family problems with her husband and children for the last several months. She has asthma, but she denies that this is problematic at the moment. She has previously smoked 20 cigarettes per day and managed to stop six months ago. Now she feels so low that she has started smoking again, although she says she can't really afford to

52. She accepts that she hasn't been getting out of the house much recently when her family have asked her to go out with them, but adds that she is less active during the winter months anyway; she often prefers to stay in and watch television. Her husband has commented that she is drinking more alcohol than normal A friend had recommended that she takes St John's wort for her mood and she has been for the last few weeks. She says that she hasn't noticed any significant change, but feels more anxious about her life and wants to know what can be done to help

53. List the possible triggers for Mrs C's symptoms of depression?

54. Recent bereavement Relationship problems Unemployment Moving house Stress at work Financial problems Family history of depression Menopause Seasonal changes Over use of alcohol and / or corticosteroids

55. At her last appointment, which was over one year ago for treatment of her asthma, it was noted that Mrs C had not been using her inhalers in the correct manner and the clinical records show that the she was less communicative than normal What two questions could have been asked at the time to help identify depression?

57. During the last month, have you often been bothered by feeling down, depressed or hopeless? During the last month, have you often been bothered by little interest or pleasure in doing things?

58. If Mrs C answers "yes" to either question, she may be depressed and further assessment is needed Adding in the question "Is this something with which you would like help?" to the two screening questions for depression, improves the specificity of the two question approach in general practice, i.e. it helps to rule IN the diagnosis of depression and is less likely to give a false positive result If Mrs C answers "no" to both questions, this does not necessarily always exclude depression; further assessment is necessary if depression is still suspected

59. Mrs C answers "yes" to both of these two questions

60. What further three questions do NICE recommend asking to improve the accuracy of the assessment of depression in people who have chronic physical health problems

61. During the last month, have you often been bothered by feelings of worthlessness? During the last month, have you often been bothered by poor concentration? During the last month, have you often been bothered by thoughts of death?

62. How should Mrs C be assessed further?

63. Assessment should not rely simply on a symptom count, but it should take into account both the degree of functional impairment and/or disability associated with the possible depression and the duration of the episode The Patient Health Questionnaire, the Hamilton Depression Rating Score or the Beck Depression Inventory should be considered NICE recommends that patients with depression are always asked directly about suicidal ideas and intent, and that help is arranged that is appropriate to their level of risk The updated 2009 NICE guidelines (CG90 and CG91) decided to adopt DSM-IV for diagnosis of depression in adults rather than ICD-10, which was used in the previous guideline

64. Using a validated measure of severity, Mrs C appears to have mild depression. She hasn't previously been diagnosed with depression

65. What treatment options you would recommend?

66. People with mild depression should usually be offered one or more low-intensity psychosocial interventions initially These include: –Individual guided self-help based on the principles of cognitive behavioural therapy (CBT) –Computerised CBT (CCBT) –Structured physical activity programme The effectiveness of counselling in managing depression is uncertain and so it is now only recommended as an option for Mrs C, if she declines other more established treatments Antidepressants aren't recommended for the routine treatment of mild depression because the risk-benefit ratio is poor. However, they may be considered where mild depression persists after other interventions

67. Although there is evidence that St John's wort may be of benefit in mild or moderate depression NICE recommends that practitioners should not prescribe or advise its use by people with depression There is uncertainty about the appropriate dose and persistence of effect, variation in the nature of the preparations available and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)

68. What would you do if Mrs C refused any psychosocial treatment for her depression?

69. NICE recommends that people with mild depression who do not want an intervention should be assessed again, normally within two weeks If they do not attend follow-up appointments, contact should be made with them In addition, Mrs C should be given information about the nature and course of her depression and the presenting problems, and any concerns she may have about them should be discussed. This is also recommended for patients who are judged by the practitioner to recover without a formal intervention

70. Mrs C mentions that she has had difficulty sleeping recently. How would you advise her?

71. Practical advice on sleep hygiene for Mrs C could include: –Establishing regular sleep and wake times –Creating a proper environment for sleep –Taking part in regular physical activity In addition she has been drinking more alcohol than normal and has started smoking again She should be advised to avoid drinking alcohol and smoking (along with excess eating, if relevant) before sleep It would be helpful to reassure Mrs MC that insomnia is a common symptom of depression, and this might improve with treatment

72. Mrs MC chooses to try computerised CBT and regular physical activity You follow her up regularly, but her depression symptoms have not improved and after 6 weeks she returns to you asking if she can try an antidepressant?

73. What other options could you offer her at this stage?

74. NICE recommends that patients with mild depression and an inadequate response to initial treatments may be offered either an antidepressant or a high-intensity psychological therapy High-intensity psychological therapies include: –CBT –Interpersonal therapy (IPT) –Behavioural activation –Behavioural couples therapy

75. After explaining, and offering, a high-intensity non-drug option to Mrs MC, she decides that she would still prefer to try an antidepressant. What factors should influence the choice of drug?

76. Antidepressants have largely equal efficacy and so the choice of drug should be largely dependent on: –Side-effect profile –Patient preference –Previous experience of treatments –Propensity to cause discontinuation symptoms –Safety in overdose –Interaction potential Normally an SSRI in generic form should be chosen as SSRIs have a favourable risk-benefit ratio

77. When prescribing an antidepressant, what advice would you give to the patient to help with concordance?

78. Good practice would be to explore any concerns the patient may have about taking medication and give a full explanation of the reasons for prescribing. Information to provide about taking antidepressants includes: –The gradual delay in obtaining the full antidepressant effect –The importance of taking medication as prescribed and the need to continue treatment for at least 6 months after remission –Information on potential side effects –Potential for interactions with other medicines –The risk and nature of discontinuation reactions (e.g. with shorter half-life drugs such as paroxetine and venlafaxine) and how to minimise them –Addiction doesn't occur with antidepressants It is also worth advising the patient of the potential for increased agitation, anxiety and suicidal ideation in the initial phases of treatment