|
Slide 59 -
|
Stanley Shyn, MD, PhD
UW Psychiatry and Behavioral Sciences
Harborview Medical Center Mood Disorders No disclosures / conflicts of interest Objectives
Mood, affect, mood disorders (mood D/O’s)
Nosology, epidemiology, treatment (tx) of:
Major depressive disorder (MDD)
Persistent depressive disorder
Premenstrual dysphoric disorder
Disruptive mood dysregulation disorder
Bipolar disorder (BD)
Cyclothymic disorder
Differential diagnosis (Ddx), including:
Depressive v. bipolar & related disorder due to another medical condition
Substance/medication-induced depressive v. bipolar & related disorder
Other specified depressive v. bipolar & related disorder
Unspecified depressive v. bipolar & related disorder Mood v. Affect
“mood”
a sustained emotional attitude
typically garnered through pt self-report
“affect”
the way a pt’s emotional state is conveyed
relates more to others’ perception of the pt’s emotional state, responsiveness Mood disorders
Ψ conditions where mood is primary, the predominant problem. Major Depressive Disorder Major Depressive D/O (MDD)
Diagnosis req’s ≥1 major depressive episode (MDE)
MDE = ≥2wks of
signif wt Δ (↓ or ↑)
insomnia or hypersomnia
Ψmotor agitation/retardation (PMA/PMR)
fatigue or anergia
guilt/worthlessness (G/W)
↓’d [ ]
recurrent thoughts of death or SI ↓’d mood
anhedonia Sleep
Interest
Guilt
Energy
Concentration
Appetite
Psychomotor
Suicide 5 symptoms (with ≥1 sx in blue) Epidemiology (Kendler et al, 1993; Schlesser & Altshuler, 1983)
leading cause of disability among adults under 45y of age
lifetime prevalence of 12% in ♂, 20% in ♀
relative risk (RR) of 2-3 in 1o relatives of probands; 41%:13% (monozygotic:
dizygotic) concordance
incidence peaks in 20s (but onset in late life not uncommon) Question:
When does a major depressive episode (MDE) ≠ Major Depressive Disorder? Major Depressive D/O (MDD)
EXCLUSIONS:
not attributable to a substance/medication or another medical condition
no prior [endogenous] episodes of mania or hypomania
Regarding bereavement:
no longer a formal exclusion in DSM-5 because:
the ‘2 month’ rule did not reflect reality
the depressive feelings associated with bereavement-related
depression respond to the same psychosocial and Rx txs
evidence does not support a different natural course once criteria
are met for an MDE…
use your clinical judgment, consider norms for the individual, his/her hx,
culture
consider: pangs of grief, preserved self-esteem (v. self-loathing), guilt of
failing the deceased (v. more general self-criticism), etc. Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern ≥2 of the following:
keyed-up/tense
unusually restless
can’t concentrate b/c of worry
fear something awful may happen
might lose control Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern ≥3 of the following nearly everyday during an MDE:
[drawn from list of sxs for a manic/hypomanic episode, minus distractibility;
this list includes elevated/expansive mood…] Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern ≥1 of the following during the most severe portion of the current episode:
absolute anhedonia or absolute mood non-reactivity
plus ≥3 of the following:
a distinct quality of depressed mood (e.g., worse than prior MDEs)
worse in the AM
early AM awakening (by at least 2h)
marked PMA or PMR
significant appetite or wt loss
excessive guilt Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern mood reactivity
plus ≥2 of the following:
significant appetite or wt increase
hypersomnia
leaden paralysis
long-standing interpersonal rejection sensitivity leading to social/work problems Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern delusions &/or hallucinations
examples of congruent delusions: personal inadequacy, guilt, death, nihilism,
deserved punishment Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern during most of the episode, ≥3 of the
following:
stupor
catalepsy (passive induction of a posture
held against gravity)
waxy flexibility
mutism
negativism
posturing (spontaneous, maintenance
against gravity)
mannerism (odd cariacture of a
normal action)
stereotypy
agitation (indep of external stimulus)
grimacing
echolalia or echopraxia Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern during pregnancy or in the 4wks after delivery Major depressive disorder w/ anxious distress w/ mixed features w/ atypical features w/ melancholic features w/ mood-[congruent, incongruent]
psychotic features w/ catatonia w/ peripartum onset w/ seasonal pattern relapses and remissions occur at characteristic times of the year
at least 2 seasonal MDE’s in the last 2y (and no non-seasonal MDEs during this
period)
seasonal episodes outnumber non-seasonal episodes (lifetime) If a patient always gets depressed with season unemployment (or the beginning
of the school year), would we call this ‘w/ seasonal pattern?’ No. Belmaker RH and Agam G, NEJM 2008, 358:55-68 iproniazid (1957)
imipramine (1959) The monoamine hypothesis (1965) Joseph Schildkraut Question:
Do antidepressants have additional actions besides inhibition of reuptake transporters? “…the Zoloft cartoon”
from: http://gifsoup.com/webroot/animatedgifs/50426_o.gif; chemical inbalance Chronic antidepressant treatment increases neurogenesis in adult rat
hippocampus.
Malberg JE, Eisch AJ, Nestler EJ, Duman RS.
J Neurosci. 2000 Dec 15;20(24):9104-10
Requirement of hippocampal neurogenesis for the behavioral effects of
antidepressants.
Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S,
Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R.
Science. 2003 Aug 8;301(5634):805-9.
Depression and antidepressants: insights from knockout of dopamine,
serotonin or noradrenaline re-uptake transporters.
Haenisch B, Bönisch H.
Pharmacol Ther. 2011 Mar;129(3):352-68. Epub 2010 Dec 13. Review.
Nicotinic acetylcholine receptor antagonistic activity of monoamine
uptake blockers in rat hippocampal slices.
Hennings EC, Kiss JP, De Oliveira K, Toth PT, Vizi ES.
J Neurochem. 1999 Sep;73(3):1043-50.
Block of an ether-a-go-go-like K(+) channel by imipramine rescues egl-2
excitation defects in Caenorhabditis elegans.
Weinshenker D, Wei A, Salkoff L, Thomas JH.
J Neurosci. 1999 Nov 15;19(22):9831-40. photo from: http://www.sciencedaily.com/releases/2006/11/061121082449.htm Subsequent hypotheses about MDD
altered glutamatergic transmission
↓’d GABAergic transmission
monoamine-Ach imbalance
disruption of endogenous opioid signalling
neurosteroid deficiencies
thyroxine abnormalities
cytokine-mediated x-talk betw immune system & CNS
circadian abnormalities
(specific brain structure/circuit dysfxns…) as summarized in Belmaker RH and Agam G, NEJM 2008, 358:55-68 MDD tx options
selective serotonin reuptake
inhibitors (SSRIs)
fluoxetine (PROZAC), 20-80 mg/d
citalopram (CELEXA), 20-40 mg/d
escitalopram (LEXAPRO), 10-20 mg/d
sertraline (ZOLOFT), 50-200 mg/d
paroxetine (PAXIL), 20-50 mg/d
serotonin-norepinephrine reuptake
inhibitors (SNRIs)
venlafaxine XR (EFFEXOR XR),
37.5-225 mg/d
desvenlafaxine (PRISTIQ)
duloxetine (CYMBALTA), 30-120 mg/d
others
bupropion SR, XL (WELLBUTRIN)
100-200 mg BID (SR)
150-450 mg/d (XL)
mirtazapine (REMERON), 15-45 mg/d
trazodone, 50-200mg/noc (for sleep)
nefazodone tricyclic antidepressants (TCADs)
amitriptyline nortriptyline
imipramine desipramine
monoamine oxidase inhibitors (MAO-Is)
typically, non-selective & irreversible
MAO-A (NE, EPI, 5HT, DA)
MAO-B (trace amines, DA)
why we “wash-out”
5HT syndrome
HTNsive crisis
selegiline (EMSAM)
[additional] augmenting agents
Li+
T3, 25 mcg/d
buspirone (BuSPAR), 5-30 mg BID
atypical antipsychotics Sequenced Treatment Alternatives for the Relief of Depression
(STAR*D)
major NIMH-funded study (PI: A. John Rush) w/ 14 regional centers & 41 clinical
sites
initial enrollment of 4,041 patients
aim: which tx algorithms work best after an initial failure to remit non-psychotic
depression w/ an antidepressant? http://www.clinicaltrials.gov/ct/show/NCT00021528?order=1 Trivedi MH et al, Am J Psychiatry. 2006 Jan;163(1):28-40 47% response rate
on citalopram
(by *QIDS-SR, 50% ↓
in sxs) Sequenced Treatment Alternatives for the Relief of Depression
(STAR*D), n = 2,876 (qualifying pts) 33% remission rate
on citalopram
(by QIDS-SR, score <5) Rx choice:
according to side effects (SE’s), comorbid condn’s / risks (GMC & Ψ), ?FmRxHx
6-8wk trials each (preferable)
augmentation v. switch?
*QIDS-SR = Quick Inventory of Depressive Symptomatology, Self-Report (range 0-27)
http://www.ids-qids.org/ MDD tx options
Ψtherapy
cognitive bx therapy (CBT)
interpersonal therapy (IPT)
psychodynamic therapy
interventional Ψ
electroconvulsive therapy (ECT)
transcranial magnetic stimulation (TMS)
vagal nerve stimulation (VNS)
deep brain stimulation (DBS)
other
lightbox therapy (mostly for MDD w/ seasonal features) Major Depressive D/O (MDD)
NATURAL HISTORY (Frank E and Thase ME, 1999 & DSM-5)
recovery usually begins:
w/in 3mos for two in five indivs
w/in 1y for four in five indivs
risk of subsequent episodes (w/in 3y) increases w/ n:
≥50% if n=1
≥70% if n=2
≥90% if n=3
dz course does not typically change as one ages
5-10% will eventually be dx’d w/ bipolar disorder (BD)
more likely w/:
onset of ‘MDD’ in adolescence
a family history of BD
‘mixed features’
6% lifetime SUI risk (Davies S et al, 2001); up to 15% w/ severe MDD Persistent depressive disorder (dysthymia)
2y of depressed mood (1y in children/adolescents) most of the day, more days than
not, plus 2 of the following:
appetite disturbance (↓ or ↑) veg
sleep disturbance (↓ or ↑) veg
↓energy E
↓esteem E
poor [ ] C
hopeless H
never sx-free for more than 2mos at a time
overlapping dx of MDD is now allowed
there has never been mania, hypomania, or cyclothymia
MDD specifiers can also be used for dysthymia
additionally:
early onset (before age 21)
late onset (at age 21 or older)
w/ pure dysthymic syndrome from DSM-5 w/ persistent MDE
w/ intermittent MDE’s, w/ current episode
w/ intermittent MDE’s, w/o current episode --these last 3 are essentially a co-dx of MDD, but
captured within the specifier… Persistent depressive disorder (dysthymia)
may be more treatment-resistant (TxR) than straightforward MDD
EPIDEMIOLOGY
lifetime prevalence = 6%
12-mo prevalence = 0.5%, compared w/ 1.5% for MDD
high comorbidity w/ personality d/o’s (particularly clusters B, C) From Sadock & Sadock & DSM-5 Case 1.
36yo F presenting w/ 3mos of ↓mood. She reports getting only ~4h of sleep/noc b/c
of regular early AM awakenings. She feels drained everyday, all day long. She’s
gained about 10 lbs in the last 2mos.
What else would you like to ask?
How would you work-up this patient?
In the meantime, what would you dx and what would be your tentative tx plan? She returns 1mo later and reports that her mood continues to spiral downward. Now,
she adds that she’s starting to think more morbid thoughts and that maybe it wouldn’t
be such a bad thing if she weren’t around anymore.
What would you ask now?
How would you revise your tx plan? The pt’s sxs are finally stabilized and she returns at a later date w/ her sxs in remission
x 1mo. “Doctor, I’m feeling so much better now. Do you think I can stop my psych
Rxs?”
How would you answer? Premenstrual dysphoric d/o
Criterion A. In most menstrual cycles, ≥5 sxs in the final week before onset of menses,
w/ improvement w/in a few days after onset of menses, and near-absent in the week
post-menses
Criterion B. ≥1 (or more) sx of marked:
1. lability (e.g., mood swings, suddenly sad, increased rejection sensitivity)
2. irritability /anger / increase in interpersonal conflicts
3. anxiety / tension / keyed-up feeling/edginess
Criterion C. ≥1 (or more) sx to reach a total of 5 in combation w/ previous list:
1. anhedonia
2. [ ] impairment
3. anergia
4. significant appetite change (including specific food cravings)
5. sleep disturbance (↑ or ↓)
6. feeling overwhelmed or out of control
7. px sxs (e.g., breast tenderness/swelling, arthralgias/myalgias, bloating, wt gain)
Special notes. Can’t just be menstrual exacerbation of MDD or other Axis I or II dx;
must have confirmation by prospective daily rating scales during at least 2 sx-ic
cycles (provisional dx allowed beforehand) Premenstrual dysphoric d/o
(M)ood (labile &/or irritable &/or anxious)
Sleep
Interest
Body
Energy
Concentration
Appetite
Out of control Treatment:
SSRI
daily
luteal phase only (i.e., day 14 of cycle menses)
some data suggest successful in tx’ing mixed episodes, BD indivs w/ comorbid
substance issues
Areas of concern:
Li+ ↔ renal; interaction w/ NSAIDs
VPA ↔ liver; VPA in young ♀ polycystic ovarian syndrome (PCOS)
Teratogenicity
Li+ Ebstein’s anomaly (1st trimester)
hazard ratio 10-20, but AR still 1:1000
VPA neural tube defects
AR 10%
OTHER NOTES:
CBZ: auto-induction, agranulocytosis
Lamictal: Stevens-Johnson syndrome (SJS), interaxn w/ oral contraceptives (OCPs),
interaxn w/ VPA Bipolar Disorder (BD) – treatment (cont’d)
How many agents to use?
combination tx often helpful in acute stabilization
antipsychotics REQ’D when there are psychotic features to mood episode
Adjuncts
benzos
--Don’t forget about ECT… Manic switch w/…
reuptake blockers
Lamictal, too! (van der Loos ML et al, 2009) Bipolar Disorder (BD) – natural history
60% of manic episodes immediately precede an MDE
MDE’s usually significantly outnumber hypomanic and manic episodes
~10% of BD II’s BD I
episodes tend to increase in frequency/duration w/ age
re: suicide…
35% lifetime prevalence of at least one SUI attempt in bipolar
15% suicide completion rate (may be an overestimate)
15x the risk of the general population (for completions)
perhaps ¼ of all suicides in the population
>lethality of SUI attempts in BD II (than BD I) adapated, in part,from DSM-5 Cyclothymic D/O
2y of fluctuating mood (1y in children, adolescents)
hypomanic symptoms (but NOT episodes)
dysthymic symptoms (but no MDEs)
≥ half the time & (no more than 2mos sx-free)
EXCLUSIONS
no manic/hypomanic episodes
no depressive episodes Differential diagnosis Phenocopies and gray areas…
Anxiety D/O’s (esp. GAD, PTSD)
Schizoaffective D/O
Delirium
Dementia
Personality D/O’s
Substance/Medication-induced Depressive D/O
Depressive D/O d/t Another Medical Condition
Other Specified Depressive D/O
Unspecified Depressive D/O
Substance/Medication-induced Bipolar and Related D/O
Bipolar and Related D/O d/t Another Medical Condition
Other Specified Bipolar and Related D/O
Unspecified Bipolar and Related D/O Depressive, Bipolar & Related D/O d/t a Another Medical Condition
Endocrine (e.g., thyroid, hypothalamic-pituitary-adrenal/HPA)
Neurologic (e.g., multiple sclerosis, CVA, brain tumor, Parkinson’s, Alzheimer’s/other
dementia, Huntington’s, seizure d/o)
Neoplastic (e.g., pancreas)
TBI
Autoimmune (e.g., neuropsychiatric systemic lupus erythematosus / NPSLE)
Hematologic (e.g., acute intermittent porphyria / AIP)
typically: anx/depr >> s/t Ψosis, mania (rare)
acute abdominal pain, muscle weakness
port wine-colored urine (porphobilinogen)
transient damage to nerve cells
Nutritional (e.g., B12)
Infectious (e.g., HIV, Syphilis) Substance/Medication-induced Depressive, Bipolar & Related D/O
ILLICITS
can be from intoxication or withdrawal phases
EtOH – typically depressive
stimulants – typically manic/hypomanic
--good to ask about sxs during windows of sobriety (ideally, ≥6mos)
high substance comorbidity rates w/ endogenous Axis I Ψ d/o’s, though (esp. BD I)
Prescription Rxs
steroids
IFN-α2b, RBV (HCV tx)
β-blockers
antidepressants
α-TB drugs Other Specified / Unspecified v. Adjustment D/O (e.g., w/ depressed
mood, w/ mixed anxiety & depressed mood)
What is Adjustment D/O?
develops in response to a stressor (w/in 3mos)
terminates w/in 6mos of the end of the original precipitating stressor
clinically significant b/c:
there is marked distress out of proportion to the severity of the stressor
or there is significant impairment
Intended, in DSM-5, to be < of a residual dx and to be thought of as more in the
same spectrum as Acute Stress D/O (ASD) and PTSD, but:
not necessarily w/ as severe a stressor as in ASD or PTSD
not necessarily w/ as severe a sx response as in ASD or PTSD Mood D/O’s lab w/u
CBC
Chem panel
TSH
B12
U-tox
U-preg (dep on demographics)
RPR
HIV-1,2 ELISA (lower threshold for BD patients…) Summary – cont’d
Diagnostic building blocks (not counting mixed feature possibilities…) Summary – cont’d
Mood D/O’s are Ψ conditions where emotional dysregulation is the primary issue.
Mood d/o’s can be endogenous, due to substances/medication, or due to another
medical condition. There are additional phenocopies which should always be in
your Ddx, including Anxiety D/O’s, Schizoaffective D/O, Personality D/O’s, Delirium,
and Mild/Major Neurocognitive D/O’s.
The monoamine hypothesis of depression is only a preliminary framework for
conceptualizing Mood d/o’s and their tx, and requires significant theoretical
revision.
Mood D/O’s, like other Ψ conditions in the DSM, are best conceived as syndromes
rather than as unitary or homogeneous medical conditions.
A little less than ½ of tx-naïve pts will respond to their first antidepressant; only 1/3
will remit without further intervention.
Non-pharmacologic approaches to treating Mood D/O’s include psychotherapy and
interventional procedures (e.g., ECT). Additional case presentations Case 2.
18yo M high school student who was BIB his parents to the ER after ingesting a bottle
of 50 Tylenol pills. Recently, he has been isolating himself to his room more, sitting-
out dinners with the family, and has been overheard at home talking about what a
horrible “sinner” he is. He has shown increasing despondence and mood lability.
He is well-connected with friends at school, outgoing—and the above changes have
occurred more in a matter of weeks than they have months/years.
On interview, the pt appears dysphoric, tearful, and internally preoccupied.
What else would you like to know?
How would you work-up this patient?
In the meantime, what would you dx and what would be your tentative tx plan? Case 3.
50yo F, under-employed and barely hanging-on with temp agency work, comes in for
her first office visit to see you about “mood swings” that haven’t responded well to
venlafaxine XR. She is dysphoric on presentation—but also quite irritable with your
Q’s. This has been a lifelong issue for her, but she has managed to stay out of IP
hospitalization through it all.
What would you like to ask her?
W/u and provisional dx & tx plan? A U-tox comes back (+)for methamphetamine. A week later, you get an angry call
from the pt’s E. Coast-based sister—who complains that you have the pt on the ‘wrong
Rxs.’ She shares additional hx (in her voicemail) that the pt has had past episodes of
elevated mood, sexual and financial indiscretions, and demands to know how you are
going to modify the tx plan.
What would you tell the pt’s sister?
How does this change your working dx and tx plan?
|