Download Ask the Expert: Depression Presenter: Kenneth J. Herrmann, MD

Ask the Expert: Depression
Presenter: Kenneth J. Herrmann,
MD
NAMI Conference
Spring 2014
Kenneth J Herrmann M.D.
 Medical School at Chicago Medical School
 Internship, residency in general psychiatry, fellowship in
child and adolescent psychiatry at the University of
Iowa
 Formerly, Medical Director of Youth Services at the
Mental Health Center of Dane Co.
 Psychiatric Consultant, Psychiatric Services SC,
www.psychsvcs.com/
 Past Vice-President, Board of Directors NAMI WI
 Principal, My World Defense, A Healthcare Security
Company, http://myworlddefense.com/
Diagnosis of Major Depressive Disorder
 Irritable/Depressed mood, diminished
pleasure/interest
 Weight changes of greater than 5% in one month
 Insomnia or hypersomnia
 Psychomotor agitation or retardation
 Fatigue or loss of energy, poor concentration
 Feelings of worthlessness, suicidal thoughts, guilt
Etiology of Depression
 Genetic factors
 Personality and environmental factors
 Biochemical abnormalities
Prognosis - Adolescence
Depression
-Duration average of 7 1/2 months
-44% in remission within 6 months of Dx
-92% recovered by 1 ½ years
-72% recurrence within five years
EPIDEMIOLOGY
 Depression:
-2% of children in general population
-7% depression in children admitted to
Hospital
-40% children in ped neuro clinics with
headaches=depression
-4.7% ages 14-16 (3.3% dysthymia)
(as age increases female rates increase)
-one in five adolescents by age 20
-Lifetime: Males 12% Females 25%
Trends for Affective Disorders
 Age at onset is decreasing
 Incidence is increasing
Risk Factors For Mood Disorders
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Substance Use
Prematurity
Family History
Head Injury
Limitations of Current Research
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Hard to recruit for certain disorders
FDA requirements for drug approval
Funding
Exclusion criteria
Dropout rates
Liability
Time from idea to publication
The Treatment for Adolescents with
Depression Study (TADS)
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Moderate to severe depression
Fluoxetine alone or in combo with CBT
13 academic and community sites in the US
12-17 yrs old
Combined > mono
42 week total study time
Study start 7/98, completed 3/04
Arch. Gen. Psychiatry 10/07
Thinking Outside the Box?
FDA warnings and the Antidepressants
 ? Adequate information
 ? Diagnosis
 Increase in antidep. use / decrease in suicides over 10
years prior to warning
CONCLUSIONS:
In both the United States and the Netherlands, SSRI
prescriptions for children and adolescents decreased
after U.S. and European regulatory agencies issued
warnings about a possible suicide risk with
antidepressant use in pediatric patients, and these
decreases were associated with increases in suicide rates
in children and adolescents.
Gibbons etal. Am J. Psychiatry 9/07
Diagnostic Accuracy is Most
Important
Mania/Bipolar Affective Disorder
(BPAD)
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Elevated, expansive or irritable mood
Inflated self-esteem or grandiosity
Decreased need for sleep
More talkative (distractible)
Flight of ideas or racing thoughts
Increase in activity
Foolish indulgencies
Characteristics of BPAD in Children
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Grandiosity
Inappropriate sexual interest
Psychotic symptoms
“Ultrarapid” cycling
Mood Disorder Questionnaire
Has there ever been a period of time when
you were not your usual self and…
… you felt so good or so hyper that other people thought you were not
your normal self or you were so hyper that you got into trouble?
… you were so irritable that you shouted at people or started fights or
arguments?
… you felt much more self-confident than usual?
… you got much less sleep than usual and found you didn’t really
miss it?
… you were much more talkative or spoke much faster than usual?
… thoughts raced through your head or you couldn’t slow
your mind down?
Hirschfeld et al. Am J Psychiatry. 2000;157:1873-1875.
Mood Disorder Questionnaire (cont’d)
… you were so easily distracted by things around you that you had
trouble concentrating or staying on track?
… you had much more energy than usual?
… you were much more active or did many more things
than usual?
… you were much more social or outgoing than usual; for example,
you telephoned friends in the middle of the night?
… you were much more interested in sex than usual?
… you did things that were unusual for you or that other people might
have thought were excessive, foolish, or risky?
… spending money got you or your family into trouble?
Hirschfeld et al. Am J Psychiatry. 2000;157:1873-1875.
Depression
 Adolescents
30% BPAD switch
Irritability
 Adults
10% switch
Sadness
Long-term Frequency of Depressive
Symptoms
(Percent of Follow-up Weeks)
Patients with bipolar I disorder experienced mood symptoms
nearly half of the time during a 12.8-year follow-up period.
Depressive symptoms were predominant
• Over the long term, patients with bipolar I
disorder spent nearly half of their time
symptomatically ill
• Depression accounted for 31.9% of the time
• Patients experienced manic symptoms 9.3%
of the time
• Depression (but not mania) predicted greater
future illness burden
Judd et al. Arch Gen Psychiatry. 2002;59:530-537.
Age of Onset
(Pooled Data N=1,304)
500
400
300
# of Pts
200
100
0
Under
10
10-19
20-29
30-39
40-49
50-59
60-69
70 and
Over
Age of Onset
Goodwin F, Jamison K. Manic Depression. New York: Oxford University Press; 1990.
Predictors of BPAD Outcome
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Acute onset
Hypersomnic retarded depression
Psychosis
Postpartum onset
Family history
Antidepressant Hypersomnia
Treatment for Depression
Non-Medical Txment of Depression
 Cognitive Behavioral Therapy (CBT)
 Dialectical behavior therapy (DBT)
 Mindfulness
NEUROTRANSMITTER EFFECTS OF
ANTIDEPRESSANTS
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NE
 Bupropion SR
5-HT
DA
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 SSRIs
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 Venlafaxine 
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 Nefazodone
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 Mirtazapine
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 Desipramine
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Richelson. J Clin Psychiatry. 1994
The role of BDNF and its receptors in depression and
antidepressant drug action: Reactivation of developmental
plasticity
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Recent evidence suggests that neuronal plasticity plays an important role in the recovery from
depression. Antidepressant drugs and electroconvulsive shock treatment increase the
expression of several molecules, which are associated with neuronal plasticity, in particular the
neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis
and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is
associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some
cases these neurodegenerative signs can be attenuated by successful treatment. Such
observations suggest a central role for neuronal plasticity in depression and the antidepressant
effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant
fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which,
under appropriate environmental guidance, leads to the rewiring of a developmentally
dysfunctional neural network. These observations suggest that the simple form of the
neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support
underlies mood disorders and increases in these neurotrophic factors to normal levels brings
about mood recovery, may not sufficiently explain the complex process of recovery from
depression. This review discusses recent data on the role of BDNF and its receptors in depression
and the antidepressant response and suggests a model whereby the effects of antidepressant
treatments could be explained by a reactivation of activity-dependent and BDNF-mediated
cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to
environmental challenges. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010
Somatic Depression Treatment
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Bupropion
Serotonin (re)-uptake inhibitors
TCA’s (Tricyclic Antidepressant)
Others: Nefazodone, Trazadone, Mirtazapine,
Venlafaxine, duloxetine MAOI’s (including Selegiline
(Emsam patch))
 ECT
 Trancranial Magnetic Stimulation (TMS)
Newer Antidepressants
 Vilazodone (Viibryd): diarrhea, nausea or vomiting,
and trouble sleeping, increases serotonin.
 Vortioxetine (Brintellix): nausea, constipation, and
vomiting, increases serotonin
 Levomilnacacipran (Fetzima): nausea or vomiting,
constipation, sweating, increased heart rate, erectile
dysfunction, and palpitations, increases serotonin and
norepinephrine.
Things to consider with meds
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Comorbidities: anxiety, subst. abuse,
Compliance
Formulary (preferred drug list)
Medical legal
Indication (“Off Label?”)
Side Effects
Treatment: Lamotrigine (Lamictal)
 Positives:
Once a day dosing possible
No Blood tests
Few complaints of SE’s
 Negatives
Long time to get up to good
dose
Rash ?
Neuroleptics (antipsychotics)
Mood Disorders (primarily BD)
Schizophrenia/Schizoaffective
Some Sxs of PTSD
Clozapine
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WBC monitoring
Constipation
Dizziness
Sedation
Miracle
Aripiprazole (Abilify)
 Wgt neutral?, EPS, Nonsedating, Agitation
 FDA approved ABILIFY® (aripiprazole) for the
acute treatment of manic and mixed episodes,
maintenance treatment of manic or mixed
episodes, and as add-on treatment to lithium or
valproate, associated with Bipolar I Disorder, with
or without psychotic features, and schizophrenia
in pediatric patients (10 to 17 years old). Refractoy
Depression
Treatment: Risperidone (Risperdal)
 Positives:
No blood tests
Once a day dosing
Fast
Shotgun
FDA approved Risperdal
(risperidone) for the treatment
of schizophrenia in adolescents,
ages 13 to 17, and for the shortterm treatment of manic or
mixed episodes of bipolar I
disorder in children and
adolescents ages 10 to 17.
 Negatives:
Prolactin
Some reports of mania induction
Weight gain
Sedation
NMS
Tardive dyskinesia
Diabetes risk
Treatment: Olanzapine (Zyprexa)
 Positives:
No blood tests
Once a day dosing
Data
FDA indication
Fast
Shotgun
 Negatives:
Sedation
Weight gain
Diabetes risk
Ziprasidone (Geodon)
 Wgt neutral
 Sedating vs activating
 Efficacy?
Quetiapine (Seroquel)
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Midrange sedation
Midrange wgt gain
Diabetes risk
Refractory Depression
Bipolar Depression
Treatment: Lithium
 Positives:
Low suicide rates
FDA approved 12yrs and older
Long history of use
Once a day dosing
Cheap
Negatives:
Narrow therapeutic window
Fluid balance issues
Monitoring (thyroid & kidney)
Acne
Weight
The 3 Newest
 Lurasidone (Latuda): (Bipolar Depression)Once a day,
with food, sedation and EPS
 Asenapine (Saphris): Once a day, disolves in mouthsome find unpleasant taste
 Iloperidone (Fanapt) Twice a day
Buproprion For Prevention of Depressive
sx’s
 SADS
 Hospice family members
Combined therapy: symptoms/ cooccurring conditions
 ADHD: stimulants, bupropion, ?modafinil
 Anxiety: (OCD too) gabapentine, tiagabine, SSRI,
TCA
 Depression: ECT, additional mood stabilizer
(lamotrigine), antidepressant if we must
 Fatigue: modafinil, stimulants
 Insomnia: benzodiazepines, neuroleptics,
mirtazepine, trazadone
 Mania: mood stabilizer, neuroleptic
The Good News
Neurotrophic Effects of Mood Stabilizers?
MRI studies “…revealed that chronic lithium
significantly
increases total grey mattervolume
in the human brain of
patients with manicdepressive illness.
Neuroprotective?
“…lithium and valproate have recently been
demonstrated to robustly increase the expression of
the cytoprotective protein bcl-2 in the central nervous
system.”
Husseini et. al.
From a Mouth Swab
 “Your doctor may use cytochrome P450 tests
(CYP450 tests) to help determine how your body
processes (metabolizes) a drug. Our bodies
contain numerous P450 enzymes to process
medications. Because of inherited (genetic) traits
which cause variations in these enzymes,
medications affect each person differently.”
Genetic Testing
Future Trends Summary
 Earlier Identification and Aggressive Txmnt
 Increase focus on primary and especially
secondary Prevention
 Neurotransmitter and enzyme specific treatment.
 More delineation of “Normal” behavior and it’s
relationship to our genes.
 More Exploration of Combined Therapy
 Remission not just response