(mostly) psychopharmacology in primary care dr. robert granger, md frcpc thursday, september 4, 2014
TRANSCRIPT
S
(mostly)
Psychopharmacology
in Primary Care
Dr. Robert Granger, MD FRCPC
Thursday, September 4, 2014
Outline
Common psych conditions in primary care
Psychopharmacotherapy
Non-medication therapy
Resources in Calgary
When to refer to psych
Ψ conditionsin primary care
National Comorbidity Survey (Kessler and others 1994)
DSM-III-R criteria
Adult community sample (age 15-54)
Ψ conditionsin primary care
NCS lifetime prevalence rates
Anxiety: 24.9%
Mood: 19.3% MDE: 17.1% Manic episode: 1.6%
Substance: 26.6%
Ψ conditionsin primary care
NCS comorbidity
No disorder: 52%
One disorder: 21%
Two disorders: 13%
Three disorders: 14%
Ψ conditionsin primary care
NCS-Replication (Kessler and others 2005)
DSM-IV criteria
Adult community sample (age 18+)
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%
Ψ conditionsin primary care
NCS-R comorbidity
Any disorder: 46.4%
Two or more disorders: 27.7%
Three or more disorders: 17.3%
Ψ conditionsin primary care
TAKE HOME:
Anxiety, mood, and substance use disorders are common
Comorbidity is common
Do antidepressants work?
Psychiatric medications have similar effect sizes (ES) as general medical medications (Leucht and 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)
Do antidepressants work?
SSRIs and SNRIs overall outperform placebo based on response rates (Melander and others 2008) Active treatment response rate: 48% Placebo: response rate: 32%
This applies to all severities of depression
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
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
When to use antidepressants
CANMAT: Severity not explicitly stated(Lam and others 2009)
APA: For all severities, mild to severe(Gelenberg and others
2010)
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)
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)
Which antidepressant to use: APA
Anything goes (no 1st line/2nd line/etc.)
Choice of antidepressant based on Patient factors (e.g., FHx, medical conditions) Pharmacokinetic factors (body to drug; e.g., CYP450)
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
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 favour escitalopram 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
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
Which antidepressant to use: bupropion (Wellbutrin)
Primarily for depression
May aggravate anxiety
“Unfairly” blacklisted for contraindication in patients with seizures or eating disorder
“Activating”
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
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
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)
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
(Gelenberg and others 2010)
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)
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: Trivedi and others 2006)
Remission rates, STAR*D: Level 1 (citalopram) ~30% Level 2 (switch or augment) ~50% After all levels (more switch and augment) ~70%
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
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
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)
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)
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)
Bipolar disorder
CANMAT guidelines (Yatham and others 2013)
Acute mania
Acute bipolar depression
Maintenance
Bipolar d/o: Depression
Lithium
Lamotrigine
Quetiapine
Olanzapine + SSRI
Lithium/VPA + SSRI/bupropion
Bipolar d/o: Maintenance
Lithium
Lamotrigine
VPA
Olanzapine
Quetiapine
Aripiprazole
Risperidone long-acting injection
Ziprasidone (with lithium or VPA)
Non-medication: Psychotherapy
Types Cognitive-Behavioural Therapy (CBT): depression
and anxiety Interpersonal Therapy (IPT): depression Dialectical Behaviour Therapy (DBT): borderline PD
When to use psychotherapy
CANMAT Severity not explicitly stated Unlikely to be useful in cases of severe depression
and depression with psychotic features
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)
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
(Gelenberg and others 2010)
Non-medication: Social
Social Primary determinants of health (e.g., Mosaic PCN) Support groups Lifestyle modifications
Resources in andoutside Calgary
Access Mental Health
Regional clinics
PCN-specific resources
Canadian Mental Health Association
For rural practitioners
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
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
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 teens programs
List of PCNs: http://www.albertapci.ca/ABOUTPCNS/PCNSINALBERTA/Pages/ProvincialPCNSummary.aspx
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)
Resources for rural practitioners
Psychiatrists in local area
Rural Mental Health clinics
Telemental Health (through Ponoka)
When to refer to psych
Diagnostic uncertainty or complexity (e.g., comorbidity)
Suboptimal response to two or more trials after possible contributing factors are addressed
Acuity (may require telephone consultation or referral to Emergency Department)
References
Geddes, J., Carney, S., Davies, C., Furukawa, T., Kupfer, D., Frank, E., Goodwin, G. (2003). Relapse prevention with antidepressant drug treatment in depressive disorders: a review. The Lancet. Volume 361(9358)653-661.
Gelenberg, A., Freeman, M., Markowitz, J., Rosenbaum, J., Thase, M., Trivedi, M., Van Rhoads, R. (2010). Practice Guideline for the Treatment of Patients with Major Depressive Disorder. Third Edition. American Psychiatric Assocation.
Isacsson G. (2000). Suicide prevention—a medical breakthrough? Acta Psychiatrica Scandinavica. 102(2):113-117. Kessler, R., McGonagle, K., Zhao, S., Nelson, C., Hughes, M., Eshleman, S., Wittchen, H., and Kendler, K. (1994). Lifetime and 12-
Month Prevalence of DSM-III-R Psychiatric Disorders in the United States. Archives of General Psychiatry. Volume 51(1):8-19. Kessler, R., Berglund P., Demler, O., Jin, R., Merikangas, K., Walters, E. (2005). Lifetime Prevalence and Age-of-Onset Distributions
of DSM-IV Disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry. Volume 62(6):593-602.
Lam, R., Kennedy, S., Grigoriadis, S., McIntyre, R., Milev, R., Ramasubbu, R., Parikh, S., Patten, S. and Ravindran, A. (2009). Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. Journal of Affective Disorders. Volume 117 (Supplement 1):S26-S43.
Leucht, S., Hierl, S., Kissling, W., Dold, M., Davis, J. (2012). Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. British Journal of Psychiatry. Volume 200(2):97-106.
Melander, H., Salmonson, T., Abadie, E., van Zweiten-Boot, B., (2008). A regulatory Apologia—A review of placebo-contolled studies in regulatory submissions of new-generation antidepressants. European Neuropsychopharmacology. Volume 18(9):623-627.
Parikh, S., Segal, Z., Grigoriadis, S., Ravindran, A., Kennedy, S., Lam, R., Patten, S. (2009). Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. Journal of Affective Disorders. Volume 117 (Supplement 1):S15-25.
Trivedi, M., Rush, A., Wisniewski, S., Nierenberg, A., Warden, D., Ritz, L., Norquist, G., Howland, R., Lebowitz, B., McGrath, P., Shores-Wilson, K., Biggs, M., Balasubramani, G., Fava., M. (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. American Journal of Psychiatry. Volume 163(1):28-40.
Yatham, L., Kennedy, S., Parikh, S., Schaffer, A., Beaulieu, S., Alda, M., O’Donovan, C., MacQueen, G., McIntyre, R., Sharma, V., Ravindran, A., Young, L., Milev, R., Bond, D., Frey, B., Goldstein, B., Lafer, B., Birmaher, B., Ha, K., Nolen, W., Berk, M. (2013). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disorders. Volume 15(1):1-44.