Dr Claire Littlewood Consultant Old Age Psychiatrist

1. Anxiety and Depression: Management in Primary Care and appropriate referral to Secondary Care Services Dr Claire Littlewood Consultant Old Age Psychiatrist

2. Overview • GAD • Phobic anxiety disorder • Panic disorder • Depression – drug treatment

3. GAD • Overview • Symptoms • Diagnosis • Treatment • When to refer • Particular considerations

4. Overview of GAD • Most common anxiety disorder in primary care • Chronic, recurring and disabling condition • Low rates of remission • Linked to extensive use of primary care resources • Recognition in primary care is poor • Patients typically have their symptoms for 5–10 years before appropriate diagnosis and treatment

5. Overview of GAD • Affects women more often than men • Prevalence rates are high in mid-life: • lifetime prevalence in ≥45 year olds: 3.6% (men) vs. 10.3% (women) • People with generalised anxiety disorder often have co-occurring: • mental disorders • medical conditions

6. GAD has a lifetime prevalence of 5.7% and may occur at any point in life* *Based on a US survey with 9282 respondents. DSM–IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; WMH–CIDI, World Mental Health – Composite International Diagnostic Interview. Kessler RC, et al. Arch Gen Psychiatry. 2005; 62: 593–602.

7. Most don’t present with anxiety (Wittchen H-U, et al. J Clin Psychiatry 2002;63(Suppl 8):24–34) 60 47.8% 50 40 34.7% 32.5% Patients (%) 26.8% 30 20 15.5% 13.3% 10 0 Anxiety Physicalsymptoms Pain Depression Insomnia Follow-up consultation/prescription renewal

8. Generalised anxiety disorder often co-occurs with other anxiety and mood disorders: Any substance disorder 34.3% Dysthymia 37.7% Major depression 60.9% Any mood disorder 71.6% Panic disorder 21.8% Social phobia 34.0% Any other anxiety disorder 57.8% 0 10 20 30 40 50 60 70 80 90 100 % of population with generalised anxiety disorder Kessler R, et al. Psychol Med 2002;32:1213–25.

9. Symptoms of GAD are both somatic and psychological Buskey RH. JAAPA. 2004; 17: 19–24.

10. Overlap in symptoms between generalised anxiety disorder and depression Generalised anxietydisorder Depressed mood Apathy Withdrawal Loss of interest Worthlessness/guilt Weight loss Suicidality Anticipatory anxiety Uncontrollable worry Irritability Muscular tension Tension pains Physical symptoms Fatigue Poor concentration Sleep disturbances Restlessness Agitation Major depressivedisorder American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington DC: American Psychiatric Association; 2000.

11. GAD-7: patient self-reporting questionnaire Not at all Severaldays More thanhalf thedays Nearlyeveryday Over the last 2 weeks, how often have you been bothered by the following problems? Feeling nervous, anxious or on edge 1 0 1 2 3 2 0 1 2 3 Not being able to stop or control worrying 3 0 1 3 2 Worrying too much about different things 0 1 2 3 4 0 1 2 3 0 1 2 3 0 1 3 2 Trouble relaxing 5 Being so restless that it is hard to sit still 6 Becoming easily annoyed or irritable Total score = = Add columns + + 7 Feeling afraid as if something awful might happen If you checked off any problems, how difficult have these problems made it for you to do your work, take care of things at home or get along with other people? Not difficult at all Somewhat difficult Very difficult Extremely difficult Spitzer RL, et al. Arch Intern Med 2006;166:1092–7.

12. Interpreting the GAD-7 results • A cut-off score of 10 points demonstrates strong sensitivity (89%) and specificity (82%) for generalised anxiety disorder Spitzer RL, et al. Arch Intern Med 2006;166:1092–7.

13. GAD diagnosis using the ICD-10 criteria A period of at least 6 months with the primary symptoms of prominent tension, worry and feelings of apprehension, about everyday events and problems At least 4 of the following symptoms, of which at least one must be from items 1 to 4: • Autonomic arousal symptoms • 1. Palpitations, pounding heart or accelerated heart rate • 2. Sweating • 3. Trembling or shaking • 4. Dry mouth (not due to medication or dehydration) • General symptoms • 13. Hot flushes or cold chills • 14. Numbness or tingling • Symptoms of tension • 15. Muscle tension or aches and pains • 16. Restlessness and inability to relax • 17. Feeling keyed up/on edge/mental tension • 18. A sensation of a lump in the throat • Symptoms concerning chest and abdomen • 5. Difficulty breathing • 6. Feeling of choking • 7. Chest pain or discomfort • 8. Nausea or abdominal distress • Other non-specific symptoms • 19. Exaggerated response to minor surprises • 20. Difficulty in concentrating/mind going blank • 21. Persistent irritability • 22. Difficulty sleeping • Symptoms concerning brain and mind • 9. Feeling dizzy, unsteady, faint/light-headed • 10. Derealisation or depersonalisation • 11. Fear of losing control/going crazy/passing out • 12. Fear of dying ICD-10, International Classification of Diseases – 10th Revision. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research. World Health Organization. 1993.

14. Treatment GAD • NICE: CG113 – Jan 2011 ‘GAD and panic disorder (with or without agoraphobia) • GAD and panic disorder (with or without agoraphobia) in adults • First line: low intensity psychological intervention, e.g. education, self help • Second line: high IPI (CBT or applied relaxation) or drug Rx according to pt. preference (efficacy same)

15. Drug treatment GAD (NICE) • First line: SSRI • Second line: alternative SSRI or SNRI • Third line: Pregabalin • Benzos short term only • Antipsychotics to be avoided in primary care • High risk relapse so advise to continue effective drug at least 1 year

16. WFSBP Treatment guidelines: Generalised anxiety disorder 2008 Continue Yes FIRST-LINE Pregabalin SSRIs* SNRIs** 4–6 weeks Further 4–6 weeks Response? Partial Change dose or switch No • Benzodiazepines† (2nd line because of abuse potential) • Treatment-resistant patients with no history of dependence • Add-on to SSRIs/SNRIs in first few weeks until onset of efficacy of antidepressant • TCAs • Imipramine† effective, but lethal in overdose and tolerability less than first-line SECOND LINE *SSRIs: escitalopram, paroxetine, sertraline† **SNRIs: venlafaxine, duloxetine † Not licensed for the treatment of GAD in the UK SSRI, selective serotonin reuptake inhibitor SNRI, selective serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressantWFSBP, World Federation of Societies of Biological Psychiatry Bandelow B, et al. World J Biol Psychiatry 2008;9:248–312. Please note that not all treatments mentioned are approved for GAD/anxiety in all EU countries. Please refer to local Summary of Product Characteristics before prescribing

17. Refer to secondary care if: • Inadequate response to treatment thus far (trial of 2 drugs reasonable) • Risk DSH • Significant co-morbidity / complexity

18. Particular considerations • Citalopram and latest safety data - dose dependent QTc prolongation • Pts under 30: SSRI or SNRI assoc. with increased risk suicidal thoughts / DSH. See within 1 week of Rxing and monitor DSH weekly for first month

19. SSRIs and GI bleeding • Similar relative risk to those on NSAIDs • Absolute risk low – 3 cases GI bleed needing hospitalisation per 1000 years pt treatment • Higher risk in over 80s, history GI bleed or concomitant use NSAID – NICE advise avoid SSRI if possible, or use PPI also

20. Pregnancy • No evidence for Pregabalin • SSRIs: no evidence congenital malformations except Paroxetine • SNRIs: no evidence congenital malformations but watch BP in third trimester

21. Elderly and GAD • Affects cognitive function • Benzos used most worldwide • Limited studies – but essentially the same as adult anxiety • Evidence also for citalopram, quetiapine (?mech of act) but not VXL • Evidence for Imipramine and Clomipramine

22. Phobic anxiety disorders • Anxiety provoked only / mainly in certain situations • Coexists often with depression / GAD – ALWAYS GEAR TREATMENT TO PRIMARY DIAGNOSIS • Licensed: clomipramine. Also escitalopram and paroxetine for social phobia

23. Panic Disorder • Recurrent attacks severe anxiety (panic) • Not restricted to particular situations • Unpredictable • Often coexists with depression +/or GAD • Licensed: Citalopram, Paroxetine, Sertraline

24. Depression CG90 Oct 09 • First line –SSRI • Elderly / physical health problems – consider Citalopram or Sertraline • NB Recent MHRA safety guidance re Citalopram and QTc • Second line – diff SSRI or newer generation e.g. Mirtazapine • Third line, VXL, TCA (Not dosulepin) or MAOI

25. Cipriani study • Lancet 2009 • Meta-analysis of 117 RCTs • Best efficacy and tolerability for Sertraline and Escitalopram

26. When to refer • NICE vague! • Reasonable to refer after adequate trial 2 antidepressants, unless concerns re risk DSH, other co-morbidities etc

27. Duration of treatment • At least 6/12 • 2 yrs if high risk relapse / recurrent depression • In elderly – trials indicate long term treatment effective up to 3 yrs • Depression more likely to relapse with age, therefore consider lifelong treatment

28. Hyponatraemia • Can occur with all anti-depressants • Worse with SSRIs • Duloxetine less problematic • Agomelatine causes least, but contraindicated in dementia, and avoid in hepatic impairment

29. Summary GAD • Overview • Symptoms • Diagnosis • Treatment • When to refer • Particular considerations Phobic anxiety disorder Panic disorder Depression – drug treatment

30. Thank you • Questions?