SESSION K2. When SSRIs Are Not Enough, What Then?

(1)

37th Annual Advanced Practice in Primary and Acute Care Conference: October 9-11, 2014

SESSION K2

When SSRIs Are Not Enough, What Then?

Scott MacHaffie, MN, ARNP

3:55

S

E

S

I

O

N

K2

Session Description:

Depression is the most common psychiatric condition seen in primary care

settings. With only about 1/3 of patients achieving remission with their

first antidepressant, partial or non-response are the rule rather than the

exception. Choosing what to do next is not straight forward. Evidence

based pharmacotherapy options for augmenting antidepressants and/or

switching treatments will be reviewed.

Learning Objectives:

Following my presentation, participants will be able to:

1. Identify clinically useful results of the STAR*D trials.

2. Discuss combinations of medications appropriate for antidepressant

augmentation.

3. Identify 2 nutritional supplements with evidence in antidepressant

augmentation.

(2)

10/15/2014

1

Treatment resistant depression defined

STAR*D results and implications for clinical practice

Review pharmacological strategies not addressed by

STAR*D

% Reduction in Depression Scores

Remission >75%

Response/ partial remission 50% - 74%

Partial Response 25% - 49% Non-response <25% Early Recovery/ Partial Remission 0-2 months Full remission/ Continuation phase 4-9 months Relapse Recurrence Full remission/ Maintenance phase 12 + months Recurrence Acute Treatment Phase

Treatment Resistant Depression (TRD)

Failure to achieve remissionwith two or more antidepressant trials, given adequate time, dose, and adherence

Treating to response(50% sx reduction) was once the acceptable target

Residual symptoms put patients at high risk of relapse and recurrence

Patients with residual symptoms (partial remission) are 3.5 times more likely to relapse compared to those fully recovered

This risk is greater than the risk associated with having ≥ 3 prior depressive episodes

Judd, L. L., Akiskal, H. S., Maser, J. D., Zeller, P. J., Endicott, J., Coryell, W., … Keller, M. B. (1998). Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. Journal of Affective Disorders, 50(2-3), 97–108. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9858069

Duration: 4-8 weeks

Dose: Minimum to moderate effectivedose

Nierenberg et al. (2000) - Fluoxetine 20 mg daily for 8 wks

o> 50% of eventual respondersat wk 8 - start to respond by wk 2

o> 75% of eventual respondersat wk 8 - start to respond by wk 4

oLack of some response by 4 – 6 is associated with a 73-88% chance of nothaving onset of responseby end of an 8 wk trial. Nierenberg, a a, Farabaugh, a H., Alpert, J. E., Gordon, J., Worthington, J. J., Rosenbaum, J. F., & Fava, M. (2000). Timing of onset of antidepressant response with fluoxetine treatment. The American Journal of Psychiatry, 157(9), 1423–8.

(3)

Remission, Relapse and Recurrence

Early

Recovery/

Partial

Remission

0-2 months

Full remission/

Continuation phase

4-9 months

Relapse

Recurrence

Full remission/

Maintenance phase

12 + months

Recurrence

Acute

Treatment

Phase

(4)

10/15/2014

2

Determine the effectiveness of different treatments

for patients who failed one SSRI

Duration: 7 years (October 1999 - September 2006)

Funding: National Institute of Mental Health

Level 1 – citalopram monotherapy

Level 2 – switch or augment citalopram

(w/ and w/o Psychotherapy)

Level 3 – switch or augment Level 2

Level 4 – switch to MAOI or an antidepressant

combination Citalopram Sertraline Venlafaxine XR Mirtazapine Nortriptyline Lithium T3 Bupropion SR Buspirone Tranylcypromine (MAOI)

Agents used

No atypical antipsychotics

Major depressive disorder

Nonpsychotic

Representative primary and specialty care practices

(nonacademic)

Self-declared patients

 Clinician deems antidepressant medication indicated.

 18-75 years of age.

 Baseline HRSD17 ≥14.

 Most concurrent Axis I, II, III disorders allowed.

Response (without remission)

50% decrease in baseline QIDS-SR16

Remission

HAMD₁₇ < 7

(5)

10/15/2014

3

Citalopram monotherapy up to 14 weeks

 Approx 33% remitted

Approx 15% more responded w/o remission Approx 50 % of remissions occurred by week 6 Approx 40 % of remissions occurred afterweek 8 Approx 20 % of remissions occurred from week 12+ Average time to remission : 7 weeks

Mean dose 41.8 mg (remitters and non-remitters) What does this say about “adequate duration”?

Female gender Being employed Caucasian (vs. African-American) Being married or co-habitating

Being more educated

Having private insurance

Having less medical

problems

Having less psychiatric

co-morbidities

Lower baseline severity

Better baseline physical

and mental function

Greater life satisfaction

Shorter current episode

Sertraline Bupropion SR Venlafaxine XR Cognitive Therapy Citalopram + Bupropion SR Citalopram + Buspirone Citalopram + Cognitive Therapy

Switch

Augment

Citalopram intolerant or non-remitters _

Switching

NO significant difference between In class switch (citalopram -> sertraline)

Change to dual action antidepressant (venlafaxine XR)

Out of class switch (bupropion SR)

Psychotherapy (absent an antidepressant)

Remission rates - approx 25% in each arm No difference in time to response No difference in time to remission

Augmenting citalopram partial response

NO significant difference between Remission rates - approx 33% in each arm

Time to response

Time to remission (drug augmentation)

Tolerability

Bupropion SR + citalopram > buspirone + citalopram

Dropout rate 12.5% vs 20%

Cognitive therapy augmentation

About 2 weeks longer to achieve remission than drug augmentation (with no additional side effects)

Mirtazapine Nortriptyline

Level 2 + Lithium

Switch

Augment

Intolerant or non-remitters at level 2

Level 2 + Liothyronine

(6)

Sertraline Bupropion SR

Venlafaxine

XR

Cognitive

Therapy

Citalopram

+

Bupropion SR

Citalopram

+

Buspirone

Citalopram

+

Cognitive

Therapy

Level 2

Switch

Augment

(7)

Mirtazapine

Nortriptyline

Level 2

+

Lithium

Level 3

Switch

Augment

Level 2

+

Liothyronine

(T3)

(8)

10/15/2014

4

Augmenting Level 2 agent with Li or T3

No significant difference between Li or T3 augmentation in …

Remission rates – (13% and 24% respectively)

Time to response

Time to remission

No significant difference in remission rates for the different Level 2 drugs when augmented at Level 3. Tolerability

T3 augmentation > Lithium augmentation

Switching from Level 2 agents

No significant difference between mirtazapine vs. nortriptyline in…

Remission rates – ( approx 10% and 15% respectively)

Time to response Time to remission MAOI Venlafaxine XR + Mirtazapine

Switch

Switching from Level 3 agents

No significant difference between tranylcypromine vs. venlafaxine XR + mirtazapine

Remission rates – ( approx 10% and 15% respectively)

Time to response

Time to remission

The MAOI had significantly more dropouts d/t

washout time and intolerability.

Cumulative remission rate after four acute

treatment steps was 67%.

Level 1—33% By level 2—57% By Level 3—63% By Level 4—67%

Remission was more likely during the first two

levels.

Rate of remission drops off steeply after level 2

Almost 50% of those who achieved remission w/ citalopram alone did so at week 8 or later!

 Are we waiting long enough?

Switch at level 2 (in class and out) – equally effective Augment at level 2 – equally effective

Switch at level 3 – equally effective Augment at level 3 – equally effective Switch at level 4 – equally effective (sort of)

(9)

MAOI

Venlafaxine

XR

+

Mirtazapine

Level 4

Switch

(10)

10/15/2014

5

Remission can take longer than 8 weeks.

Dosing should be more aggressive than timid

It is more important to keep trying than picking the right

drug or combination of drugs.

Tolerability improves the chance of achieving remission by avoiding dropouts.

Cognitive therapy is a viable switch or augmenting option, though many chose not to use it

Since STAR*D

Several new antidepressants and classes Atypical antipsychotic augmentation studies Anticonvulsants

Medical foods and supplements

SSRI SNRI DNRI SARI SPARI NaSSA Multimodal

fluoxetine venlafaxine bupropion nefazodone vilazodone mirtazapine vortioxetine sertraline duloxetine trazodone

paroxetine desvenlafaxine citalopram L-milnacipran escitalopram

SSRI – selective serotonin reuptake inhibitor SNRI – serotonin norepinephrine reuptake inhibitor DNRI – dopamine norepinephrine reuptake inhibitor SARI – serotonin 2A, 2C antagonist, serotonin reuptake inhibitor

SPARI – serotonin partial agonist reuptake inhibitor (SSRI + 5HT1A partial agonism) NaSSA – noradrenergic and specific serotonergic agent (α2 blocker)

Multimodal – various receptor interactions and potential mechanisms of action.

Most familiar – for better and worse

All generic and still very reasonable first line

In primary care these drugs can be

Started too high Under-dosed too long Switched too quick Augmented too late Monitored too infrequently

Best augmented by

drugs with complimentary mechanisms Bupropion buspirone mirtazapine atypical antipsychotics T3 Lithium Trazodone Modafinil

Best NOTaugmented by

drugs also using 5HT reuptake inhibition such as :

SNRIs Vilazodone Vortioxetine

drugs with complimentary mechanisms Buspirone Mirtazapine Atypical antipsychotics T3 Lithium Trazodone Modafinil

drugs also using 5HT reuptake inhibition such as :

SSRIs / SNRIs Vilazodone Vortioxetine

Drugs also using NE

reuptake inhibition such as:

(11)

Antidepressant Spectrum

SSRI

SNRI

DNRI

SARI

SPARI

NaSSA

Multimodal

fluoxetine

venlafaxine

bupropion

nefazodone

vilazodone

mirtazapine

vortioxetine

sertraline

duloxetine

Trazodone

paroxetine

desvenlafaxine

citalopram

L-milnacipran

escitalopram

SSRI – selective serotonin reuptake inhibitor

SNRI – serotonin norepinephrine reuptake inhibitor

DNRI – dopamine norepinephrine reuptake inhibitor

SARI – serotonin 2A, 2C antagonist, serotonin reuptake inhibitor

SPARI – serotonin partial agonist reuptake inhibitor (SSRI + 5HT1A partial agonism)

NaSSA – noradrenergic and specific serotonergic agent (

α

blocker)

(12)

10/15/2014

6

Compliments serotonergic

mechanisms

SR (BID or TID dosing) XL (Once daily dosing) Wt neutral

Sometimes reverses SSRI/SNRI sexual side effects or emotional blunting

SR 100-150 mg QD. May ↑

to BID after 7 days XL 150 mg QD. May ↑to 300 mg daily after 7 days If not tolerated, ↓ dose Partial response and

tolerable by wk 6-8?, ↑ to 450 mg daily

drugs with complimentary mechanisms SSRIs Buspirone Mirtazapine Atypical Antipsychotics T3 Lithium

drugs also using NE reuptake inhibition such as:

SNRIs

Or strongly adrenergic /dopaminergic agents

Stimulants

Or drugs that are otherwise stimulating

 Modafinil

SSRI effect plus 5HT 2A, 2C antagonism. This minimizes common SSRI side effects such as…

 Sexual dysfunction  Insomnia  Anxiety

Antidepressant at > 150 mg daily, divided (very sedating). At < 150 mg, hypnotic effect only

ER more tolerable and once daily dosing Priapism 1/1000 – 1/10,000

Sedation limits use ≥ 150 mg

At < 150 mg it may improve tolerability of SSRIs ER version more likely to

be a successful augmenter d/t tolerability at antidepressant doses As hypnotic: initial 50 mg ½ tab hs , ↑to effect as tolerated. As antidepressant: initial 150 mg ½ BID. May ↑to effect as tolerated weekly. MAX 400 mg divided ER version (scored): start

150 mg QD. May ↑by 75 mg weekly. Target 150 - 300 mg. MAX 375mg

drugs with complimentary mechanisms SNRI Buspirone Atypical antipsychotics T3 Lithium Modafinil

Drugs that are also sedating

Dual serotonin and norepinephrine agent

Does not block reuptake of either

α2 antagonist

Blocking the autoreceptor on NE neurons enhances release of NE

Blocking the heterorecepter on 5HT neurons enhances 5HT release

5HT 2C and 5HT3 antagonism enhances NE and

(13)

10/15/2014

7

Compliments or amplifies effects of 5HT and NE reuptake inhibition by promoting 5HT, NE and dopamine release Unlikely to cause side

effects like SSRI or SNRI and may actually blunt them

 Low to no nausea  Low to no sexual side effect  Low to no insomnia

Initial 15 mg HS x 7 days then 30 mg HS Partial response and

tolerable by wk 6, ↑ to 45 mg HS

High risk of wt gain, High risk of sedation, dry mouth, constipation

drugs with complimentary mechanisms SSRI SNRI* Buspirone Atypical antipsychotics T3 Lithium Modafinil

Drugs that are also sedating

SSRI plus 5HT1A partial agonism

Mischaracterized as SSRI + buspirone = vilazodone

 Vilazodone is far more potent at 5HT1A receptors than buspirone

Desensitizes 5HT autoreceptors -> enhanced 5HT neuron firing -> direct increase in 5HT activity and indirect Dopamine activity

10 mg x 7 days, 20 mg x 7 days, then 40 mg a day. Titration may need to be longer for sensitive patients

Less wt gain and sexual side effects than SSRIs, More activating than many antidepressants Common side effects

 GI - nausea, cramping, loose stool  Dizziness

 Insomnia  Vivid dreams

No clear role as an augmenter of other drugs as yet

drugs with complimentary mechanisms Bupropion Mirtazapine Trazodone Atypical antipsychotics T3 Lithium

drugs also using 5HT reuptake inhibition such as : SNRIs SSRIs Vortioxetine or 5HT1A agonism Buspirone Vortioxetine

SSRI + action at these other serotonin receptors

 1A agonist  1B partial agonist  1D antagonist  7 antagonist  3 antagonist

In animal models it enhances serotonin, norepinephrine, dopamine, acetylcholine and histamine

Nausea, loose stool, dry mouth, constipation, sexual dysfunction (maybe less than SSRIs)

(14)

10/15/2014

8

Wt neutral, CV neutral

CYP 2D6 substrate – cut dose in half when combined w/ inhibitors such as bupropion

Half life – 66 hrs

Initial 10 mg QD. May progress to 15 or max of 20 mg daily No clear role as an augmenter of other drugs as yet

drugs with complimentary mechanisms Bupropion* Mirtazapine Trazodone Atypical antipsychotics T3 Lithium

drugs also using 5HT reuptake inhibition such as : SNRIs SSRIs Vilazodone or 5HT1A agonism Buspirone Vilazodone

 Frequently under-dosed leading to poor confidence in efficacy in anxiety prophylaxis

 Desensitizes 5HT autoreceptors -> enhanced 5HT neuron firing -> direct increase in 5HT activity and indirect Dopamine activity

 Sometimes reverses SSRI/SNRI sexual side effects

 Evidence for antidepressant efficacy in the minorityof studies

 Initial 7.5 to 15 mg BID.

 Target should be 30 mg BID if tolerated

 Increase incrementally once a week as the patient’s tolerability permits.

 Dizziness, nausea, overstimulation

Chang, C. M., Sato, S., & Han, C. (2013). Evidence for the benefits of nonantipsychotic pharmacological augmentation in the treatment of depression. CNS Drugs, 27(SUPPL.1), S21–7. doi:10.1007/s40263-012-0030-1

 13 augmentation studies from 1970 to 2013 – most with tryciclics

 About 1/3 were double blind  Generally positive  Some methodological limitations  No long term studies

 Risk of decreased bone density if used long term, especially in post-menopausal women

 25 mcg daily

 May ↑to 50 mcg daily if no response after 2-4 weeks.

 DC if no response by 8-12 weeks

 Weigh risk/benefit if continuing

 Other potential side effects  palpitations, arrhythmias  sweating

 nervousness  tremor

Long h/o successful use as augmentation

….of tricyclics

Supported by 10 double blind, placebo controlled RCTs

Fewer studies for augmenting newer

antidepressants

Results generally positive but not as robust as w/ tricyclics

Designs were limiting

 Narrow therapeutic index 0.5 – 1.1 mEq/L – requires monitoring  Common side effects

 GI – nausea, loose stool  Tremor

 Polyuria, polydipsia  Wt gain  Acne

 Serious potential side effects  Renal impairment  Hypothyroidism  Arrhythmias, ECG changes  Monitoring

 ECG if over 50  Renal function  Thyroid function

 150 mg BID. ↑to target of 600-900 mg daily, divided to achieve a serum level of about 0.5 mEq/L

 Serum levels on the low end of range may be effective enough and far more tolerable than levels typical for managing bipolar disorder.

 Patients may respond by two weeks

(15)

10/15/2014

9

• Modafinil (C-IV)

oStimulating but not a true stimulant . Works in the histamine system

oVery helpful for residual fatigue but not so much mood or anhedonia

• Stimulants (C-II)

oHelpful for residual fatigue and lassitude that amplify depression

oHelpful for depression that is comorbid with ADHD

oVarious limitations common to stimulants

oAbuse

oDependence

Atypical antipsychotic augmentation (AAA?) is recommended in most guidelines (including the APA) for partial or non-responders, at the same stage as switching or combination strategies.

Equivalent to level 2 and 3 of STAR*D

Recommended doses are typically lower than for bipolar disorder or schizophrenia.

Patkar, A. a., & Pae, C. U. (2013). Atypical antipsychotic augmentation strategies in the context of guideline-based care for the treatment of major depressive disorder. CNS Drugs, 27(SUPPL.1), S29–37. doi:10.1007/s40263-012-0031-0

2009 meta-analysis of 16 randomized placebo controlled trials:

 Atypical antipsychotics as augmentation are collectively superior to placebo for response and remission

 No significant differences in efficacy between agents Aripiprazole (Abilify)

Olanzapine (Zyprexa)

Quetiapine (Seroquel, Seroquel XR)

Risperidone (Risperdal)

Nelson, J. C., & Papakostas, G. I. (2009). Atypical Antipsychotic Augmentation in Major Depressive Disorder : A Meta-Analysis of

Placebo-Controlled Randomized Trials, (September), 980–991. Wright, B. M., Eiland, E. H., & Lorenz, R. (2013). Augmentation with atypical antipsychotics for depression: A review of evidence-based support from the medical literature. Pharmacotherapy, 33(3), 344–359.

Evidence comparison

2013 Literature review of 35 studies including RCTs and open label

Most Evidence Modest Evidence Lacking Evidence Aripiprazole (Abilify) X Quetiapine (Seroquel, XR) X Olanzapine (Zyprexa) X Risperidone (Risperdal) X Ziprasidone (Geodon) X Common limitations

Metabolic (Not all atypicals are equal in this regard)

Wt gain Elevated glucose Elevated lipids

Tardive Dyskinesia (TD)

Neuroleptic malignant syndrome (NMS) (0.05 – 2%) Serotonin syndrome

Elevated prolactin Restlessness / Akathisia

No guideline for maintenance or stopping in depression

Correll, C. U., & Schenk, E. M. (2008). Tardive dyskinesia and new antipsychotics. Current Opinion in Psychiatry, 21(2), 151–6. doi:10.1097/YCO.0b013e3282f53132 Risk factors Duration Dose Gender (F>M) Age

Annualized incidence in non-elderly adults

Atypicals 1-3% “Typicals” 4-7%

Annualized incidence in elderly adults

Atypicals 5.2% “Typicals” 5.2%

(16)

10/15/2014

10

Generic (Brand) Weight _Gain Diabetes _Risk _lipidemiaDys- QTc CYP 3A4 CYP 2D6 Sedation Prolactin

*Aripiprazole (Abilify)

Low to

none Low to none Low to none -1 to -4 _substrateMajor _substrateMajor Low Low Asenapine

(Saphris) Low to

none Low to none Low to none 2-5 substrateMajor Weak

inhibitor Mod Low Lurasidone

(Latuda) Low to none Low to none Low to none None _substrateMajor none Low Low to _mod

*Olanzapine

(Zyprexa

High High High 2 to 6.5 None _substrateMinor High Mod

*Quetiapine

(Seroquel

Mod Mod Mod 6 to 15 _substrateMajor _substrateMinor High Low

*Risperidone

(Risperdal)

Mod Mod Low 3.5 to 10 substrateMajor substrateMajor Low Mod to High

Ziprasidone

(Geodon Low or

none Low to none Low to none 16 to 21 Major

substrate None Low Low

PL Detail-Document, Comparison of Atypical Antipsychotics. Pharmacist’s Letter/Prescriber’s Letter. October 2012.

Kato, M., & Chang, C. M. (2013). Augmentation treatments with second-generation antipsychotics to antidepressants in treatment-resistant depression. CNS Drugs, 27(SUPPL.1), S11–9. doi:10.1007/s40263-012-0029-7

Positive comparisons w/ TCAs in several studies before 2010

Sam-e augmentation of SSRI/SNRI – a 2010 Double blind, placebo controlled RCT x 6 weeks

 HAM-D ≥ 16 after 6 weeks at a minimally effective dose of antidepressant

 Sam-e 400 mg BID x 2 wks then 800 mg BID x 4 wks  Response Sam-e 36% vs placebo 17.6%

 Remission Sam-e 26% vs placebo 11.7%  Small elevated BP

Papakostas, G. I., Mischoulon, D., Shyu, I., Alpert, J. E., & Fava, M. (2010). S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. The American Journal of Psychiatry, 167(8), 942–8. doi:10.1176/appi.ajp.2009.09081198

Nahas, R., & Sheikh, O. (2011). Complementary and alternative medicine for the treatment of major depressive disorder. Canadian Family Physician, 57, 659–663. Retrieved from http://www.cfp.ca/content/57/6/659.short

Folic acid supplement for documented folic acid deficiency Some solid evidence for prescription L-methylfolate 15 mg

daily in those not technically deficient

 More beneficial still in select patients poor converters (MTHFR gene variant)

obese patients (BMI ≥ 30).

 Benefits of various OTC formulations of L-methylfolate are unknown

Jain, R., Papakostas, G. I., Shelton, R. C., Zajecka, j. M., Clain, A., Baer, L., Penchina, M., & Meisner, A., Fava, M. (2012, April). Personalized therapy of adjunctive L-methylfolate to selective serotonin reuptake inhibitor-resistant major depressive disorder. Poster presented at the College of Psychaitric and Neurological Pharmacists Annual Meeting, Tampa, FL.

Papakostas, G. I., Shelton, R. C., Zajecka, J. M., Etemad, B., Rickels, K., Clain, A., … Fava, M. (2012). L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. The American Journal of Psychiatry, 169(12), 1267–74. doi:10.1176/appi.ajp.2012.11071114

• Lamotrigine

Appealing for its tolerability (other than the higher than average risk of non-benign rash)

Limited and conflicting evidence in TRD.

• Omega-3

Conflicting meta-analyses

One meta-analysis did show benefit for depression if the EPA was > 60%

Treat to remission, not just response

Monotherapy first if not already tried and failed

Adequate dose for adequate trial (4-8 wks)

Partial response by weeks 4-6 - consider a dose increase or wait

Partial response at weeks 6-8 – consider dose increase or augmentation

No response by week 6-8 consider augment or switch

Gelenberg, A. J., Freeman, M. P., Markowitz, J. C., Rosenbaum, J. F., Thase, M. E., Trivedi, M. H., … Silbersweig, D. A. (2010). Treatment of Patients With Major Depressive Disorder.

Base drug choices on pt factors, side effect profile and potential drug interactions

 Tolerability improves the chance of achieving remission by avoiding dropouts

Optimize dose(s) of what the patient is already taking

Remission can take longer than 8 weeks

It is more important to keep trying than picking the right

(17)

Atypical Antipsychotic Comparisons

PL Detail-Document, Comparison of Atypical Antipsychotics. Pharmacist’s Letter/Prescriber’s Letter. October 2012.

Kato, M., & Chang, C. M. (2013). Augmentation treatments with second-generation antipsychotics to antidepressants in

treatment-resistant depression.

CNS Drugs

,

27

(SUPPL.1), S11–9. doi:10.1007/s40263-012-0029-7

Generic (Brand)

Weight

Gain

Diabetes

Risk

lipidemia

Dys-

QTc

CYP 3A4

CYP 2D6

Sedation

Prolactin

*

Aripiprazole

(

Abilify

)

Low to

none

Low to

none

Low to

none

-1 to -4

Major

substrate

Major

substrate

Low

Asenapine

(

Saphris

)

Low to

none

Low to

none

Low to

none

2-5

Major

substrate

Weak

inhibitor

Mod

Low

Lurasidone

(

Latuda

)

Low to

none

Low to

none

Low to

none

None

Major

substrate

none

Low

Low to

mod

*

Olanzapine

(

Zyprexa

High

2 to 6.5

None

Minor

substrate

High

Mod

*

Quetiapine

(

Seroquel

Mod

6 to 15

Major

substrate

Minor

substrate

HIgh

Low

*

Risperidone

(

Risperdal)

Mod

Low

3.5 to 10

Major

substrate

Major

substrate

Low

Mod to

High

Ziprasidone

(

Geodon

Low or

none

Low to

none

Low to

none

16 to 21

Major

(18)

10/15/2014

11

Augmentation is usually more time efficient than

switching

When using two or more drugs try not to duplicate mechanisms of action (use drugs from complimentary classes)

In class switching can work just as well as out of class switching

Augment with another antidepressant agent before using more complex options (Li, T3, AA)

Always recommend lifestyle modifications

The 4 “S”s Sleep

Structure

Stress reduction/stress management

“Sweat” – regular physical activity that breaks a sweat

Always recommend psychotherapy early

As a “switch” or as an augmentation to medication

Visits

Monthly until remitted Then quarterly

Continuation

Continue the drug(s) that produced remission, at the dose(s) that produced remission

4-9 months for a first episode

12-24 months for a second episode

Indefinitely for 3 or more episodes

Thank You.