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

Do antidepressants work?

TAKE HOME:

Yes, antidepressants work

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%

STAR*D

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

When antidepressantsdon’t work: algorithm

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: Acute mania

Lithium

Valproic acid (VPA)

Atypical antipsychotics

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)

Questions

robert.granger@albertahealthservices.ca

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.