1. (mostly)Psychopharmacologyin Primary Care Dr. Robert Granger, MD FRCPC Thursday, September 4, 2014

2. Outline • Common psych conditions in primary care • Psychopharmacotherapy • Non-medication therapy • Resources in Calgary • When to refer to psych

3. Ψ conditionsin primary care • National Comorbidity Survey (Kessler and others 1994) • DSM-III-R criteria • Adult community sample (age 15-54)

4. Ψ conditionsin primary care • NCS lifetime prevalence rates • Anxiety: 24.9% • Mood: 19.3% • MDE: 17.1% • Manic episode: 1.6% • Substance: 26.6%

5. Ψ conditionsin primary care • NCS comorbidity • No disorder: 52% • One disorder: 21% • Two disorders: 13% • Three disorders: 14%

6. Ψ conditionsin primary care • NCS-Replication (Kessler and others 2005) • DSM-IV criteria • Adult community sample (age 18+)

7. Ψ conditionsin primary care • NCS-R lifetime prevalence rates • Anxiety: 28.8% • Mood: 20.8% • MDD: 16.6% • Bipolar I-II: 3.9% • Impulse control: 24.8% • ADHD: 8.1% • Substance: 14.6%

8. Ψ conditionsin primary care • NCS-R comorbidity • Any disorder: 46.4% • Two or more disorders: 27.7% • Three or more disorders: 17.3%

9. Ψ conditionsin primary care • TAKE HOME: • Anxiety, mood, and substance use disorders are common • Comorbidity is common

10. Do antidepressants work? • Psychiatric medications have similar effect sizes (ES) as general medical medications (Leuchtand others 2012) • Meta-analysis of various medical and psychiatric conditions, along with recommended therapies • General medical median ES: 0.37 (95% CI: 0.37-0.53) • Psychiatric median ES: 0.41 (95% CI: 0.41-0.57)

11. Do antidepressants work? • SSRIs and SNRIs overall outperform placebo based on response rates (Melanderand others 2008) • Active treatment response rate: 48% • Placebo: response rate: 32% • This applies to all severities of depression

12. Do antidepressants work? • Reduce risk of depressive relapse by 70% (Geddes and others 2003) • Results seemed similar for all classes of antidepressants • Appear to reduce risk of suicide (Isacsson 2000) • Swedish naturalistic study • Antidepressant use increased 3.5 times from 1991-1996 • The suicide rate dropped 19% during this time

13. Do antidepressants work? • TAKE HOME: • Yes, antidepressants work

14. Before Rx: Ax • Interview (Lam and others 2009) • Suicidality • Bipolarity • Comorbidity • Current medication use • Features informing management (e.g., psychosis) • Screening instruments • PHQ-9 for all ages (can follow treatment course) • GDS for elderly

15. When to use antidepressants • CANMAT: Severity not explicitly stated (Lam and others 2009) • APA: For all severities, mild to severe (Gelenbergand others 2010)

16. Which antidepressant to use: CANMAT • “Best” antidepressants vs. comparators (level 1 evidence): sertraline, venlafaxine, escitalopram • 1st Line: SSRI, SNRI, mirtazapine, bupropion (and others) (Lam and others 2009)

17. Which antidepressant to use: CANMAT • Choice should be based on: • Sx • Comorbidity (e.g., bupropion poor choice for depression with anxiety) • Tolerability • Previous response • Drug-drug interactions • Patient preference • Cost (Lam and others 2009)

18. Which antidepressant to use: APA • Anything goes (no 1st line/2ndline/etc.) • Choice of antidepressant based on • Patient factors (e.g., FHx, medical conditions) • Pharmacokinetic factors (body to drug; e.g., CYP450)

19. Which antidepressant to use: SSRI • For depression and/or anxiety • Fluoxetine (Prozac): good evidence children and adolescents • Avoid in elderly due to long half-life • Paroxetine (Paxil): good evidence in adults • Avoid in patients taking numerous other medications (drug-drug interactions) • Consider avoiding in patients who may not tolerate discontinuation syndrome

20. Which antidepressant to use: SSRI • Sertraline (Zoloft): good evidence in adults and elderly; few drug-drug interactions and side effects • Citalopram (Celexa) and escitalopram (Cipralex): good evidence in adults in elderly; clinicians favourescitalopram due to warning about QT prolongation at higher doses of citalopram; few drug-drug interactions and side effects • Fluvoxamine (Luvox): particularly good evidence in OCD; sedating; prone to more frequent drug-drug interactions

21. Which antidepressant to use: SNRI • For depression and/or anxiety • Venlafaxine (Effexor): good evidence in adults and elderly; more noradrenergic at higher doses, which can cause increased blood pressure • Duloxetine (Cymbalta): same as above; also has indication for fibromyalgia pain and neuropathic pain

22. Which antidepressant to use: bupropion (Wellbutrin) • Primarily for depression • May aggravate anxiety • “Unfairly” blacklisted for contraindication in patients with seizures or eating disorder • “Activating”

23. Which antidepressant to use: mirtazapine (Remeron) • Primarily for depression • Has limited benefit in terms of treating anxiety • Sedative • May have more rapid onset of action than other antidepressants

24. How to use antidepressants • Start low, go slow, aim high (especially with anxiety) • Monitor every 1-2 weeks at first due to high risk of suicide, then Q2-4 weeks (Lam and others 2009) • Monitor response • Clinical Global Impression • PHQ-9 for depression • HAM-D, BDI

25. How to use antidepressants • Conduct an adequate trial: Duration and Dose • CANMAT: Wait 4-6 weeks • If more than minimal improvement, wait another 2-4 weeks “before considering additional strategies” (Lam and others 2009)

26. How to use antidepressants • APA: 4-8 weeks on “maximally tolerated dose” • If less than moderate improvement, reassess Dx, assess side effects, review complicating conditions and psychosocial factors, and adjust treatment plan • Then wait another 4-8 weeks before deciding on further adjustments (Gelenbergand others 2010)

27. When antidepressantsdon’t work • Assess compliance • Assess adequacy of dose and duration • Reassess Dx • Could psych Sx be due to medical disorder, substances, or another psych disorder? (e.g., sleep apnea causing Sx of depression) • Assess psychosocial factors (e.g., affordability of medication, supports)

28. When antidepressantsdon’t work • Not everyone will respond to first choice of antidepressant • Up to 2/3 of patients will not achieve full remission with the first antidepressant trial (STAR*D: Trivediand others 2006) • Remission rates, STAR*D: • Level 1 (citalopram) ~30% • Level 2 (switch or augment) ~50% • After all levels (more switch and augment) ~70%

29. STAR*D

30. When antidepressantsdon’t work: increase or switch • Increase: if medication is tolerated and dose is modest • Switch: if response remains minimal after dose optimization • Within family (SSRI to SSRI) • Outside family (SSRI to SNRI or other) • ECT or TMS

31. When antidepressantsdon’t work: add-on • Add-on: if response is partial but incomplete after dose optimization • Other antidepressant (regular dose of bupropion, mirtazapine) • Atypical antipsychotic (low dose of OLZ/RIS/QUE/ARI) • Other agent • Lithium: 0.5-0.8 mEq/L (600-1200 mg daily dose) • T3: 25-50 mcg daily dose • Psychotherapy Lam and others 2009

32. When antidepressantsdon’t work: algorithm Lam and others 2009

33. How long to use antidepressants • Treat to remission for 6-24 months • Consider treating long-term (2 years to lifetime) if: • Patient is older • Episodes are recurrent, chronic, severe, or psychotic (Lam and others 2009)

34. Antidepressant side effects • Common: headache, GI upset, sexual dysfunction (SSRI/SNRI), sedation, weight gain • Less common: anxiety, depersonalization • Rare but serious: SIADH, UGI bleed (SSRI), serotonin syndrome (SSRI/SNRI), seizure (Lam and others 2009)

35. Antidepressants and Suicidality • Antidepressants are NOT associated with increased suicidality (thinking or behaviour) or completed suicide in young adults or older adults • Young children may experience a slight increase in suicidality, but NOT completed suicide) (Lam and others, 2009)

36. Bipolar disorder • CANMAT guidelines (Yathamand others 2013) • Acute mania • Acute bipolar depression • Maintenance

37. Bipolar d/o: Acute mania • Lithium • Valproic acid (VPA) • Atypical antipsychotics

38. Bipolar d/o: Depression • Lithium • Lamotrigine • Quetiapine • Olanzapine + SSRI • Lithium/VPA + SSRI/bupropion

39. Bipolar d/o: Maintenance • Lithium • Lamotrigine • VPA • Olanzapine • Quetiapine • Aripiprazole • Risperidone long-acting injection • Ziprasidone (with lithium or VPA)

40. Non-medication: Psychotherapy • Types • Cognitive-Behavioural Therapy (CBT): depression and anxiety • Interpersonal Therapy (IPT): depression • Dialectical Behaviour Therapy (DBT): borderline PD

41. When to use psychotherapy • CANMAT • Severity not explicitly stated • Unlikely to be useful in cases of severe depression and depression with psychotic features

42. When to use psychotherapy • CANMAT • Concurrent combination Tx with meds • Superior to either modality alone • Sequential combination Tx • I.e., addition of CBT or IPT to partial responders to medication • Crossover Tx • I.e., d/c successful medication treatment and crossover to psychotherapy • Evidence for use in acute (CBT and IPT) and maintenance (CBT) phases (Parikh and others 2009)

43. When to use psychotherapy • APA • Can be sole treatment modality in mild to moderate severity • Might be particularly useful in patients with Axis II or those who wish to avoid medications (e.g., expectant mothers) • Psychotherapy and medication can be combined in all severities of depression (Gelenbergand others 2010)

44. Non-medication: Social • Social • Primary determinants of health (e.g., Mosaic PCN) • Support groups • Lifestyle modifications

45. Resources in andoutside Calgary • Access Mental Health • Regional clinics • PCN-specific resources • Canadian Mental Health Association • For rural practitioners

46. Resources:Access Mental Health • From the website: “Clinicians help people navigate the addiction and mental health system. They are familiar with both Alberta Health Services and community based programs…” • Phone: (403) 943-1500 • Anyone can phone for information

47. Resources: regional clinics • Distributed throughout Calgary and Alberta • NW: Northwest Community Mental Health Centre (Foothills Professional Building) • NE: Northeast Calgary Mental Health Clinic (Sunridge) • Central: Central Community Mental Health Centre (Sheldon Chumir) • Southern Alberta: Airdrie, Banff, Canmore, Chestermere, Claresholm, Cochrane, Didsbury, High River, Nanton, Black Diamond, Okotoks

48. Resources: PCN-specific • Calgary Foothills, Calgary West Central, South Calgary, and Highland (Airdrie) PCNs: BHC model • Mosaic PCN: Chronic disease management, fitness, cardiac rehab • Calgary Rural (Okotoks): Seniors and teensprograms • List of PCNs: http://www.albertapci.ca/ABOUTPCNS/PCNSINALBERTA/Pages/ProvincialPCNSummary.aspx

49. Resources: Canadian Mental Health Association • Phone: 403.297.1700 • Main website: calgary.cmha.ca • Community resources (Calgary Association of Self Help) • Programs (Family Support, ILS, Leisure and Recreation) • Educational resources (Your Mental Health, Understanding Mental Illness)

50. Resources for rural practitioners • Psychiatrists in local area • Rural Mental Health clinics • Telemental Health (through Ponoka)