(mostly)
Psychopharmacology
in Primary Care
Dr. Robert Granger, MD FRCPC
Thursday, September 4, 2014
S
Outline
S Common psych conditions in primary care
S Psychopharmacotherapy
S Non-medication therapy
S Resources in Calgary
S When to refer to psych
Ψ conditions
in primary care
S National Comorbidity Survey (Kessler and others 1994)
S DSM-III-R criteria
S Adult community sample (age 15-54)
Ψ conditions
in primary care
S NCS lifetime prevalence rates
S Anxiety: 24.9%
S Mood: 19.3%
S MDE: 17.1%
S Manic episode: 1.6%
S Substance: 26.6%
Ψ conditions
in primary care
S NCS comorbidity
S No disorder: 52%
S One disorder: 21%
S Two disorders: 13%
S Three disorders: 14%
Ψ conditions
in primary care
S NCS-Replication (Kessler and others 2005)
S DSM-IV criteria
S Adult community sample (age 18+)
Ψ conditions
in primary care
S NCS-R lifetime prevalence rates
S Anxiety: 28.8%
S Mood: 20.8%
S MDD: 16.6%
S Bipolar I-II: 3.9%
S Impulse control: 24.8%
S ADHD: 8.1%
S Substance: 14.6%
Ψ conditions
in primary care
S NCS-R comorbidity
S Any disorder: 46.4%
S Two or more disorders: 27.7%
S Three or more disorders: 17.3%
Ψ conditions
in primary care
S TAKE HOME:
S Anxiety, mood, and substance use disorders are common
S Comorbidity is common
Do antidepressants work?
S Psychiatric medications have similar effect sizes (ES) as
general medical medications (Leucht and others 2012)
S Meta-analysis of various medical and psychiatric conditions,
along with recommended therapies
S General medical median ES: 0.37 (95% CI: 0.37-0.53)
S Psychiatric median ES: 0.41 (95% CI: 0.41-0.57)
Do antidepressants work?
S SSRIs and SNRIs overall outperform placebo based on
response rates (Melander and others 2008)
S Active treatment response rate: 48%
S Placebo: response rate: 32%
S This applies to all severities of depression
Do antidepressants work?
S Reduce risk of depressive relapse by 70% (Geddes and others
2003)
S Results seemed similar for all classes of antidepressants
S Appear to reduce risk of suicide (Isacsson 2000)
S Swedish naturalistic study
S Antidepressant use increased 3.5 times from 1991-1996
S The suicide rate dropped 19% during this time
Do antidepressants work?
S TAKE HOME:
S Yes, antidepressants work
Before Rx: Ax
S Interview (Lam and others 2009)
S Suicidality
S Bipolarity
S Comorbidity
S Current medication use
S Features informing management (e.g., psychosis)
S Screening instruments
S PHQ-9 for all ages (can follow treatment course)
S GDS for elderly
When to use antidepressants
S CANMAT: Severity not explicitly stated
(Lam and others 2009)
S APA: For all severities, mild to severe
(Gelenberg and others 2010)
Which antidepressant to use:
CANMAT
S “Best” antidepressants vs. comparators (level 1 evidence):
sertraline, venlafaxine, escitalopram
S 1st Line: SSRI, SNRI, mirtazapine, bupropion (and others)
(Lam and others 2009)
Which antidepressant to use:
CANMAT
S Choice should be based on:
S Sx
S Comorbidity (e.g., bupropion poor choice for depression with
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anxiety)
Tolerability
Previous response
Drug-drug interactions
Patient preference
Cost
(Lam and others 2009)
Which antidepressant to use:
APA
S Anything goes (no 1st line/2nd line/etc.)
S Choice of antidepressant based on
S Patient factors (e.g., FHx, medical conditions)
S Pharmacokinetic factors (body to drug; e.g., CYP450)
Which antidepressant to use:
SSRI
S For depression and/or anxiety
S Fluoxetine (Prozac): good evidence children and
adolescents
S Avoid in elderly due to long half-life
S Paroxetine (Paxil): good evidence in adults
S Avoid in patients taking numerous other medications (drugdrug interactions)
S Consider avoiding in patients who may not tolerate
discontinuation syndrome
Which antidepressant to use:
SSRI
S Sertraline (Zoloft): good evidence in adults and elderly; few
drug-drug interactions and side effects
S 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
S Fluvoxamine (Luvox): particularly good evidence in OCD;
sedating; prone to more frequent drug-drug interactions
Which antidepressant to use:
SNRI
S For depression and/or anxiety
S Venlafaxine (Effexor): good evidence in adults and elderly;
more noradrenergic at higher doses, which can cause
increased blood pressure
S Duloxetine (Cymbalta): same as above; also has indication
for fibromyalgia pain and neuropathic pain
Which antidepressant to use:
bupropion (Wellbutrin)
S Primarily for depression
S May aggravate anxiety
S “Unfairly” blacklisted for contraindication in patients with
seizures or eating disorder
S “Activating”
Which antidepressant to use:
mirtazapine (Remeron)
S Primarily for depression
S Has limited benefit in terms of treating anxiety
S Sedative
S May have more rapid onset of action than other
antidepressants
How to use antidepressants
S Start low, go slow, aim high (especially with anxiety)
S Monitor every 1-2 weeks at first due to high risk of suicide,
then Q2-4 weeks (Lam and others 2009)
S Monitor response
S Clinical Global Impression
S PHQ-9 for depression
S HAM-D, BDI
How to use antidepressants
S Conduct an adequate trial: Duration and Dose
S CANMAT: Wait 4-6 weeks
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If more than minimal improvement, wait another 2-4 weeks “before
considering additional strategies” (Lam and others 2009)
How to use antidepressants
S APA: 4-8 weeks on “maximally tolerated dose”
S If less than moderate improvement, reassess Dx, assess side
effects, review complicating conditions and psychosocial
factors, and adjust treatment plan
S Then wait another 4-8 weeks before deciding on further
adjustments
(Gelenberg and others 2010)
When antidepressants
don’t work
S Assess compliance
S Assess adequacy of dose and duration
S Reassess Dx
S Could psych Sx be due to medical disorder, substances, or
another psych disorder? (e.g., sleep apnea causing Sx of
depression)
S Assess psychosocial factors (e.g., affordability of
medication, supports)
When antidepressants
don’t work
S Not everyone will respond to first choice of antidepressant
S Up to 2/3 of patients will not achieve full remission with the
first antidepressant trial (STAR*D: Trivedi and others 2006)
S Remission rates, STAR*D:
S Level 1 (citalopram) ~30%
S Level 2 (switch or augment) ~50%
S After all levels (more switch and augment) ~70%
STAR*D
When antidepressants
don’t work: increase or switch
S Increase: if medication is tolerated and dose is modest
S Switch: if response remains minimal after dose optimization
S Within family (SSRI to SSRI)
S Outside family (SSRI to SNRI or other)
S ECT or TMS
When antidepressants
don’t work: add-on
S Add-on: if response is partial but incomplete after dose
optimization
S Other antidepressant (regular dose of bupropion, mirtazapine)
S Atypical antipsychotic (low dose of OLZ/RIS/QUE/ARI)
S Other agent
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Lithium: 0.5-0.8 mEq/L (600-1200 mg daily dose)
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T3: 25-50 mcg daily dose
S Psychotherapy
Lam and others 2009
When antidepressants
don’t work: algorithm
Lam and others 2009
How long to use antidepressants
S Treat to remission for 6-24 months
S Consider treating long-term (2 years to lifetime) if:
S Patient is older
S Episodes are recurrent, chronic, severe, or psychotic
(Lam and others 2009)
Antidepressant side effects
S Common: headache, GI upset, sexual dysfunction
(SSRI/SNRI), sedation, weight gain
S Less common: anxiety, depersonalization
S Rare but serious: SIADH, UGI bleed (SSRI), serotonin
syndrome (SSRI/SNRI), seizure
(Lam and others 2009)
Antidepressants and Suicidality
S Antidepressants are NOT associated with increased
suicidality (thinking or behaviour) or completed suicide in
young adults or older adults
S Young children may experience a slight increase in
suicidality, but NOT completed suicide)
(Lam and others, 2009)
Bipolar disorder
S CANMAT guidelines (Yatham and others 2013)
S Acute mania
S Acute bipolar depression
S Maintenance
Bipolar d/o: Acute mania
S Lithium
S Valproic acid (VPA)
S Atypical antipsychotics
Bipolar d/o: Depression
S Lithium
S Lamotrigine
S Quetiapine
S Olanzapine + SSRI
S Lithium/VPA + SSRI/bupropion
Bipolar d/o: Maintenance
S Lithium
S Lamotrigine
S VPA
S Olanzapine
S Quetiapine
S Aripiprazole
S Risperidone long-acting injection
S Ziprasidone (with lithium or VPA)
Non-medication: Psychotherapy
S Types
S Cognitive-Behavioural Therapy (CBT): depression and anxiety
S Interpersonal Therapy (IPT): depression
S Dialectical Behaviour Therapy (DBT): borderline PD
When to use psychotherapy
S CANMAT
S Severity not explicitly stated
S Unlikely to be useful in cases of severe depression and
depression with psychotic features
When to use psychotherapy
S CANMAT
S Concurrent combination Tx with meds
S
Superior to either modality alone
S Sequential combination Tx
S I.e., addition of CBT or IPT to partial responders to medication
S Crossover Tx
S I.e., d/c successful medication treatment and crossover to
psychotherapy
S Evidence for use in acute (CBT and IPT) and maintenance (CBT)
phases
(Parikh and others 2009)
When to use psychotherapy
S APA
S Can be sole treatment modality in mild to moderate severity
S Might be particularly useful in patients with Axis II or those
who wish to avoid medications (e.g., expectant mothers)
S Psychotherapy and medication can be combined in all
severities of depression
(Gelenberg and others 2010)
Non-medication: Social
S Social
S Primary determinants of health (e.g., Mosaic PCN)
S Support groups
S Lifestyle modifications
Resources in and
outside Calgary
S Access Mental Health
S Regional clinics
S PCN-specific resources
S Canadian Mental Health Association
S For rural practitioners
Resources:
Access Mental Health
S 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…”
S Phone: (403) 943-1500
S Anyone can phone for information
Resources: regional clinics
S Distributed throughout Calgary and Alberta
S NW: Northwest Community Mental Health Centre (Foothills
Professional Building)
S NE: Northeast Calgary Mental Health Clinic (Sunridge)
S Central: Central Community Mental Health Centre (Sheldon
Chumir)
S Southern Alberta: Airdrie, Banff, Canmore, Chestermere,
Claresholm, Cochrane, Didsbury, High River, Nanton, Black
Diamond, Okotoks
Resources: PCN-specific
S Calgary Foothills, Calgary West Central, South Calgary,
and Highland (Airdrie) PCNs: BHC model
S Mosaic PCN: Chronic disease management, fitness, cardiac
rehab
S Calgary Rural (Okotoks): Seniors and teens programs
S List of PCNs:
http://www.albertapci.ca/ABOUTPCNS/PCNSINALBER
TA/Pages/ProvincialPCNSummary.aspx
Resources: Canadian Mental
Health Association
S Phone: 403.297.1700
S Main website: calgary.cmha.ca
S Community resources (Calgary Association of Self Help)
S Programs (Family Support, ILS, Leisure and Recreation)
S Educational resources (Your Mental Health, Understanding
Mental Illness)
Resources for rural practitioners
S Psychiatrists in local area
S Rural Mental Health clinics
S Telemental Health (through Ponoka)
When to refer to psych
S Diagnostic uncertainty or complexity (e.g., comorbidity)
S Suboptimal response to two or more trials after possible
contributing factors are addressed
S Acuity (may require telephone consultation or referral to
Emergency Department)
Questions
S robert.granger@albertahealthservices.ca
References
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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.