Download 1020 KB 2017 Practical Strategies for Treatment

Leslie Walker MD
Case Western Reserve University Dept. of Psychiatry
April 2017
Objectives
Review prevalence of TRD and suicide
2. List appropriate stepwise strategies to treat TRD
3. Identify differential diagnoses of TRD
1.
Suicide in the US
 >41,000 completed (3:1 M:F) = 12.6/100,000 population
 >490,000 hospital visits (3:1 F:M)
Age & Suicide
(afsp.org)
Ethnicity & Suicide
(afsp.org)
Methods & Suicide
(afsp.org)
Risk Factors for Suicide
 Historical Factors
 FH of suicide
 FH of psychiatric illness
 Personal history of suicide attempts
 Experienced child abuse
 Environmental Factors
 Health Factors
Risk Factors for Suicide
 Historical Factors
 Environmental Factors
 Access to lethal means
 “Contagion” after exposure to suicide or media reports
 Prolonged stress
 Recent stress/loss
 Health Factors
Health Risk Factors for Suicide
 Psychiatric Illness
 Major Depression (80-90% of suicides)
 Bipolar Disorder
 Schizophrenia, other Psychotic Disorders, or psychotic
symptoms in any disorder
 Borderline or Antisocial Personality Disorder
 Conduct Disorder (age <18)
 Anxiety Disorders
 Substance Abuse
 Serious and/or Chronic Health Conditions & Pain
Treatment-Resistant Depression
 Failure to achieve
remission after two
well-established
antidepressant
treatment trials known
to have been of
evidence-based
acceptable dose and
duration
 Develops in about 30%
of patients with MDD
(Greden et al, 2011)
Most common mimics of TRD:
 Noncompliance
 Inadequate treatment
 Medical illness including




dementia
Substance abuse
Demoralization
Bereavement
Facilitating Factors:
sleep deprivation,
caregiver strain,
abusive relationship,
burnout or severe work
stress
Key Concepts in TRD
 Treat as early as possible (typical onset age 15-24).
 No medication has been shown to be superior.
 First, optimize the current regimen.
 If partial response, augment.
 Treat to remission.
 Openly address stigma to encourage med adherence.
 Prescribe exercise and nutrition for all.
(Greden et al, 2011)
Roadmap
for TRD
Greden et al, 2011
Initial Complementary Options
 Psychotherapy
 Cognitive Behavioral Therapy
 Interpersonal Therapy




Vitamin D at least >30
Folate 800+ mcg daily
B12 1 mg daily
Omega-3 Fatty Acids
 EPA & DHA ie fish oil caps
 1000 mg qd-BID
 Bright light therapy
 10,000 lux, 20-30’ q am
Effective AD Titration
(1) Target the minimum therapeutic dose.
(2) Increase at 2-week intervals if no significant
response, until either:
significant response
maximum dose tolerated by patient
maximum usual therapeutic dose
https://www.cms.gov/Medicare-Medicaid-Coordination/FraudPrevention/Medicaid-Integrity-Education/Pharmacy-EducationMaterials/Downloads/ad-adult-dosingchart.pdf (2013)
Therapeutic Doses of AD
 SSRIs
FDA-approved max
 Fluoxetine 20-80mg (to 120mg in OCD)
80mg
 Paroxetine 20-80mg qhs
60mg
 Paroxetine CR 25-75mg qhs
75mg
 Sertraline 100-200mg (300mg in OCD)
200mg
 Citalopram 20-80mg
40mg

FDA warning on QT prolongation
 Escitalopram 10-30mg
 Fluvoxamine 100-300mg qhs
 Low dose venlafaxine ER 75-150mg
20mg
300mg
375mg
Therapeutic Doses of AD
 SSRI+ 5HT receptor
FDA-approved max
 Viibryd 10-40mg
40mg
 Trintellix 5-30mg
20mg
 SNRIs
 Venlafaxine ER 150-450mg
375mg
 Pristiq (desvenlafaxine) 50-150mg
100mg
 Duloxetine 60-180mg
120mg
 Fetzima 40-120mg
120mg
Therapeutic Doses of AD
 Other mechanism
FDA-approved max
 Trazodone 150-600mg qhs
400/600mg
 Nefazodone 300-600mg
600mg
 Mirtazapine 30-60mg qhs
45mg
 Buproprion SR/XL 300-450mg
450mg
Therapeutic Doses of AD
 TCAs
FDA-approved max
 Nortriptyline 75-200mg qhs
150mg

Dose that gives 12-hour serum level 75-150 ng/mL
 Amitriptyline 100-300mg qhs
 Vivactil (protriptyline) 15-60mg
 Doxepin 100-300mg qhs
 MAOIs
 EMSAM patch (selegiline) 6-12mg
 Nardil (phenelzine) 15-30mg TID
 Parnate (tranylcypromine) 30-60mg
150/300mg
60mg
300mg
12mg
90mg
60mg
Effective AD Titration
(1) Target starting dose to minimum therapeutic dose as a
planned titration based on patient factors.
i.e. sertraline in an anxious patient with major depression:
Target therapeutic dose: 100mg
Start 25mg each morning.
Increase by 25mg every 5-7 days til you reach 100mg daily.
Call me if you have bothersome side effects, or if any of your
symptoms get worse (like insomnia or anxiety), or if you have
thoughts of death or suicide.
Effective AD Titration
(2) Increase at 2-week intervals if no significant
response, until significant response, maximum dose
tolerated by patient, or maximum usual therapeutic dose
is reached.
i.e. After 2 weeks at sertraline 100mg, patient feels a little
better, more energy, more hopeful, but not dramatically
better.
Increase to 125 or 150mg daily depending on whether
patient tolerated the initial titration easily.
After 2 weeks at 150mg, patient feels much better, able to
enjoy hobbies, more productive at work. Stay at 150mg.
Effective AD Titration
(1) Target a minimum therapeutic dose.
(2) Then increase at 2-week intervals if no significant
response, until significant response, maximum dose
tolerated by patient, or maximum usual therapeutic dose
is reached.
(3) If patient has no clinical response at max dose, taper
off the medication and try a new medication.
(4) If there is a significant improvement, hold at that
dose and watch over next 4-12 weeks.
Partial Response (“Plateau”)
 When patients have clearly improved on an
antidepressant at maximum dose tolerated, but are not
in remission (<5 DSM-5 criteria met over past 2 weeks,
or HAM-D <9)
 Keep the baseline antidepressant and begin an
augmentation strategy.
Roadmap
for TRD
Greden et al, 2011
Augmentation Strategies for SSRIs
 Buproprion SR or XL 150-450mg daily
 L-methyl-folate (Deplin) 15mg daily
 Very low energy? TSH >2.5? OSA on CPAP?
 Liothyronine (T3) 25-50 mcg daily
 Modafinil 100-400mg daily
 Still can’t sleep?
 Mirtazapine 7.5-60mg qhs
 Nortriptyline to a 12-hour serum level of 75-150
Augmentation Strategies for SSRIs
 lithium carbonate ER qhs or BID
 target 12-hr serum level of 0.6-1.0
 follow lithium level, thyroid and renal functions
 Atypical antipsychotics (aripiprazole, quetiapine,
olanzapine, brexiprazole)
 warn re EPS (extrapyramidal symptoms), TD (tardive
dyskinesia, weight gain and increased lipids
 follow AIMS, weight, waist circumference, labs
Less evidence for augmentation
 5-HT 1A Agonists
 Buspirone (BuSpar) 15-60mg daily in BID-TID dosing
 Pindolol
 SAM-e (s-adenosylmethionine)
rd
3
Line Options
 MAOIs – must washout from 5HT medicines first
 Tranylcypromine (Parnate) 30-60mg daily
 Phenelzine (Nardil) 45-90mg daily
 Selegiline (Emsam patch) 6-12mg/24 hrs
 ECT (electroconvulsive therapy)
 rTMS (repetitive transcranial magnetic stimulation)
 ? IV ketamine – available at CCF if criteria met
 VNS (vagal nerve stimulation)
 ? DBS (deep brain stimulation)
Permanent Antidepressant Rx
 3+ previous episodes of MDD.
 2 episodes plus FH or >120 days spent depressed in lifetime.
 1 episode plus FH or >12o days spent depressed in lifetime or
 Early age of onset
 TRD
 Psychosis
 Prompt relapse following previous discontinuation
 Previous SA or prominent SI during current episode
 Current severity (i.e. PHQ >9, HAM-D >18)
 Comorbid medical condition or occupation that makes relapse
hazardous
 Abnormal labs: elev cortisol, abnl HPA axis measures
 MRI evidence of hippocampal or amygdala atrophy
(Greden et al, 2011)
Recurrent episode?
(1) Re-evaluate to confirm major depressive episode.
(2) If current medication is not at max dose, increase
current medication dose every 2 weeks until
response, intolerant, or max dose.
(3) If 3+ episodes or FH of bipolar disorder, consider
including a mood stabilizer (i.e. lithium,
lamotrigine, atypicals) in your maintenance therapy.
Differential Diagnosis of TRD
 Bipolar (Type I or II) Depression
 PTSD or other anxiety disorder
 ADHD or ADD-I
 MCI or dementia
 Comorbid alcohol, MJ, or other drug abuse
 Depression as part of or presenting symptom of a new
medical diagnosis
 Chronic pain
 Personality disorder
Depression in Medical Illness
 Endocrine
 Hypothyroidism (and watch for hyperthyroidism)
 Diabetes mellitus
 Low testosterone
 PMDD, pregnancy, postpartum, perimenopause
 Neurology
 Sleep apnea and other sleep disorders
 Parkinson disease and other dementias
 Multiple sclerosis
 Epilepsy
 Oncology
 Pancreatic CA
Depression as a Side Effect
 Interferon-alpha
 Accutane
 Chantix
 FDA warning on all antidepressants (2004) and
anticonvulsants (2009) regarding possible risk of
suicidal thoughts/behaviors in ages 15-24 after
initiation of treatment (first 1-2 months) has been
associated with decreased diagnosis and treatment
and increased suicide rates
History, physical exam, then …
 MOCA if over 60
 CBC – r/o anemia
 TSH, fT4 – r/o hypothyroidism or hyperthyroidism
 B12, folate, D
 CMP – r/o hepatic or renal dysfunction
 Consider HCG, testosterone
 Consider gene testing if multiple antidepressants have
failed or not been tolerated (ie Genomind, Genesight)
Genetic testing
 Some genes coding for 5HT or DA transport proteins,
receptors, etc.
 Some genes coding for some of the hepatic enzymes
involved in the metabolism of psychoactive drugs,
which can guide your dosing strategy if patient is a fast
or slow metabolizer at a particular enzyme.
 Genetic testing can tell you if your patient MAY be
more likely to have side effects or non-response to a
particular drug or class of drugs.
 Genetic testing cannot tell you EFFICACY – whether
your patient will respond to a particular medication.
Print Resources
Greden JF, Riba MB, McInnis MG. Treatment-Resistant
Depression: A Roadmap for Effective Care. APPI, 2011.
Jamison, KR. Night Falls Fast: Understanding Suicide.
Random House, 1999.
MacKinnon DF. Still Down: What to Do When
Antidepressants Fail. JHU Press, 2016.
Solomon, A. The Noonday Demon: An Atlas of
Depression. Scribner, 2001; new edition 2015.
Organizations
 AFSP (American
Foundation for Suicide
Prevention)
afsp.org/chapter/afspnorthern-ohio/
 NAMI (National Alliance
on Mental Illness
namigreatercleveland.org