Download Mood Disorder (Child)

OVERVIEW OF MOOD
DISORDERS
Dr. H. Gandy, MD, FRCPC
Children’s Hospital of Eastern Ontario
April 24, 2007
Mood Disorders
Review
 Types of Mood Disorders
 Epidemiology
 Clinical Symptoms and DSM-IV diagnoses
 Etiology of Mood Disorders
 Treatments
 Questions
Mood disorders overview
Types of mood disorders
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Major Depression
Bipolar affective disorder (BAD I, BAD II,
Cyclothymic Disorder
Dysthymic Disorder
Seasonal affective disorder
Substance induced affective disorder
Mood disorder secondary to general medical
condition
Mood disorders overview
Epidemiology of depression
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Major depression typical onset is the mid-20s.the peak annual
prevalence occurred in ages 15 to 25 years.
NIMH research indicates depression onset is occurring earlier than in
past decades.
Depression in youth may predict more severe illness in adulthood.
Lifetime prevalence of major depressive episode is 12.2%
Approximately 8% of adults will experience major depression at some
time in their lives.
Major depression is more common in women than men.
Prevalence of major depression can be related to having a chronic
medical condition or unemployment.
Married people have the lowest prevalence of depression.
Worldwide, major depression is the leading cause of years lived with
disability and the fourth leading cause of disability adjusted life years.
Mood disorders overview
Epidemiology of bipolar disorder
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Weighted lifetime prevalence rate is 2.2%
Younger age, low income, lifetime anxiety disorder and presence of
substance use disorder in the past 12 months were significantly
associated with the presence of a bipolar disorder diagnosis.
A lifetime history of anxiety disorder was reported by 52% of those
diagnosed with bipolar disorder.
Both panic disorder and agoraphobia were more frequent among
women compared with men diagnosed with BAD.
The mean age of onset of illness was 22.5 years the standard deviation
of 12 years
It is estimated over 500,000 Canadians likely suffer from bipolar
disorder
Mood disorders overview
Epidemiology of Dysthymia
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Prevalence in general practice setting 5.1%.
90% of those diagnosed had at least one co-morbid psychiatric
disorder.
Patients with dysthymia are more likely to have worse health status,
worry more about their health, report levels of pain that impair their
function, have higher depression scores, lower social role function
scores, lower social adjustment scores and lower coping ability.
More children of people with dysthymia meet criteria for one or more
childhood psychiatric disorders.
People with dysthymia used a greater proportion of health and social
services, had higher per person annual health-care costs.
Mood disorders overview
Major depression-clinical symptoms
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Sad or empty mood
Feelings of hopelessness, pessimism
Feelings of guilt, worthlessness, helplessness
Loss of interest or pleasure in activities that were once enjoyed
Decreased energy, fatigue, being “slowed down”
difficulty concentrating, remembering, making decisions
Insomnia, early-morning awakening or oversleeping
Appetite and/or weight loss or overheating and weight gain
Thoughts of death or suicide; suicide attempts
Restlessness, irritability
Persistent physical symptoms that do not respond to treatment such as
headaches, digestive disorders and chronic pain
Mood disorders overview
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S leep
I nterest
G uilt
E nergy
C oncentration
A ppetite
P sychomotor
S uicide
Mood disorders overview
Major depression-DSM-IV diagnosis
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Depressed mood or loss of interest or pleasure in daily activities
for at least a two week period
Mood must represent a change from persons normal mood
Major depression cannot be diagnosed if depressed mood is
caused by substances or a general medical condition.
At least five of the following symptoms must be present for a
two-week period:
Abnormal depressed mood
Abnormal loss of interest and pleasure
Appetite or weak disturbance
Sleep disturbance
Activity disturbance
Abnormal fatigue or loss of energy
Abnormal self reproach or guilt
Abnormal concentration or indecisiveness
Abnormal morbid thoughts of death or suicide
Mood disorders overview
Bipolar Affective Disorder classification-DSM-IV
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Bipolar I disorder
One or more manic or mixed episodes, usually accompanied by major
depressive episodes
Major manic episode may include delusional ideation and
hallucinations. (Bipolar with psychotic features)
Bipolar II disorder
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One or more major depressive episodes accompanied by at least one
hypomanic episode.
No evidence of psychotic features
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Cyclothymic disorder
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Chronic, fluctuating mood disturbance involving numerous periods of
hypomanic symptoms and numerous periods of depressive symptoms.
Symptoms may be severe but no suicidal ideation or incapacitation
Mood disorders overview
Bipolar affective disorder-clinical symptoms-mania
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Abnormal or excessive elation
unusual irritability
Decreased need for sleep
Grandiose ideation
Increased talking
racing thoughts
Increased sexual desire
Markedly increased energy
Poor judgment
Inappropriate social behavior
Mood disorders overview
Bipolar affective disorder – DSM-IV criteria
Manic episode:
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A distinct period of abnormally and persistently elevated, expansive or
irritable mood lasting at least one week
During this period of mood disturbance three or more of the following
symptoms have persisted:
Inflated self-esteem or grandiosity
Decreased need for sleep
More talkative than usual
insomnia or hypersomnia nearly every day
psychomotor agitation
Flight of ideas or subjective experience that thoughts are racing
Distractability
Increased goal directed activity and/or excessive involvement in pleasurable
activities that have a high potential for negative consequences
Mood disorders overview
Dysthymia-clinical symptoms
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A chronically depressed mood that occurs most of the day or days for
at least two years.
No major depressive episode has been present during the first two
years of the disturbance.
The disturbance is not better accounted for by chronic major
depression or major depressive disorder in partial remission.
There has never been a manic episode.
The disturbance does not occur exclusively during the course of a
chronic psychotic disorder
The symptoms are not due to the direct effects of a substance or a
general medical condition
The symptoms cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
Mood disorders overview
Dysthymia-DSM-IV criteria
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A depressed mood for most of the day, for more days than not, as
indicated either by subjective account or observation by others, for at
least two years. In children and adolescents the duration must be at
least one year.
The presence of two or more of the following:
Poor appetite or overeating
insomnia or hypersomnia
Low-energy or fatigue
low self-esteem
poor concentration /difficulty making decisions
feelings of hopelessness
During the two-year period the person has never been without the
symptoms for more than two months at a time.
Mood disorders overview
Etiology of mood disorders - Biological factors
Biogenic amines
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Norepinephrine - down regulation of beta adrenergic receptors and drug
response
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Serotonin – decrease in serotonin receptors after long-term exposure to drugs
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Dopamine – activity may be reduced in depression and increased in mania
Other neurochemical factors
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GABA - amino acid neurotransmitter implicated in depression
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Adrenal axis – correlation between hypersecretion of cortisol and depression
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Thyroid axis – blunted release of TSH to infusion of TRH seen in depression
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Growth hormone – blunted sleep induced stimulation of GH release in depression
Sleep abnormalities – delayed sleep onset, shortened REM latency in depression
Kindling – in temporal lobes involved in pathophysiology of bipolar disorder
Circadian rhythms – sleep deprivation and transient clinical improvement in
depression. Light level changes in seasonal affective disorder
Neuroimmune regulation – cortisol axis disruption may affect immune status
Brain imaging – enlarged cerebral ventricles in BAD, smaller caudate nuclei in
depression.
Mood disorders overview
Etiology continued
Neuroanatomical considerations – limbic system, basal ganglia, hypothalamus
Genetic factors
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Family studies – 1st degree relatives are 8 to 18 times more likely than controls
to have BAD, 2 to 10 times more likely in depression.
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Adoption studies – biological children of affected parents remain at increased
risk even if reared in non-affected adoptive families.
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Twin studies – concordance rate for BAD in monozygotic twins is up to 90%
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Linkage studies – chromosomes 5, 11 and X have been implicated particularly in
BAD
Psychosocial factors
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Life events and environmental stress – stress, family functioning, early loss
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Premorbid personality factors – dependent, obsessional, hysterical personalities
at greater risk for depression
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Psychodynamic factors – object loss, depressive position, aggression turned
inwards, incompleteness and despair
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Learned helplessness
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Cognitive theory – cognitive distortions
Mood disorders overview
Medical causes of depressive symptoms
Neurological
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Cerebrovascular disease
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Dementia
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Epilepsy
 Infections
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Multiple sclerosis
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Neoplasms
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Parkinson’s disease
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Wilson’s disease
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hydrocephalus
Mood disorders overview
Medical causes of depressive symptoms
Endocrine
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Adrenal
Menses related
Postpartum
Thyroid disorders
Infectious and inflammatory
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AIDS
Chronic fatigue syndrome
Mononucleosis
Pneumonia
Lupus
tuberculosis
Mood disorders overview
Medical causes of depressive symptoms
Miscellaneous medical
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Cancer
Cardiopulmonary disease
Porphyria
Vitamin deficiencies
Mood disorders overview
Pharmacological causes of depressive symptoms
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Analgesics and anti-inflammatories - ibuprofen
Antibacterial’s – ampicillin, metronidazole
Antihypertensive’s – beta blockers, clonidine, reserpine
Antineoplastics – bleomycin, vincristine
Neurological and psychiatric – amantadine, carbamazepine, Ritalin
Steroids and hormones – corticosteroids, oral contraceptives,
prednisone
Mood disorders overview
Seasonal affective disorder
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A seasonal pattern which can be applied to major depressive
episodes and bipolar I, bipolar II disorders
A regular temporal relationship between the onset of depressive
episodes and a particular time of year (not seasonal related
psychosocial stressors)
Full remissions also occur at a characteristic time of year
In the last two to four years major depressive episodes have
occurred that demonstrate the temporal seasonal relationship to
findings above
Episodes substantially outnumber non-seasonal depressive
episodes that may have occurred over a lifetime.
Mood disorders overview
Postpartum depression
 Major depressive, manic or makes
episode or brief psychotic disorder
associated with postpartum onset.
 Onset of episode is within four weeks
postpartum
Mood disorders overview
Treatments
Psychosocial therapies
Psychodynamic psychotherapy (Freud, Kohut)
Involves ego regression in the service of promoting personality change
through understanding of past conflicts and achieving insight into
various psychological defenses. Involves confronting defenses and full
or partial analysis of transference and resistance.
Cognitive behavioral therapy (Adler, Beck)
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Involves analysis of distorted thinking leading to dysphoria due to
learned negative views of self, others and world. Provides symptomatic
relief through alteration of target thoughts, identifying self-destructive
cognitions. Involves recording and monitoring cognitions, correcting
distorted schemas with logic and experimental testing including
homework.
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Mood disorders overview
Cognitive distortions
 All or nothing thinking
 Overgeneralization
 Mental filter
 Disqualifying the positive
 Jumping to conclusions
Mood disorders overview
Cognitive distortions
 Magnification and minimization
 Emotional reasoning
 “Should” statements
 Labeling
 Personalization
Mood disorders overview
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Psychosocial therapies cont’d
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Interpersonal psychotherapy (Meyer, Sullivan, Klerman,
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Weissman)
Depression is a result of impaired interpersonal relations
involving absent or unsatisfactory social bonds.
Provide symptomatic relief through resolution of current
interpersonal problems improving interpersonal communication
skills.
Therapy involves clarifying and managing maladaptive
relationships and learning new ones through communication
and social skills training.
Mood disorders overview
Treatment
Pharmacotherapy – depression
antidepressants
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SSRI’s – Prozac, Paxil, Zoloft, Celexa, Luvox, Cipralex
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SNRI’s – Effexor, Remeron
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TCAs – amitriptyline, desipramine, Clomipramine
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RIMA’s - Moclobemide
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MAOI’’s – Phenelzine, Tranylcypromine
Pharmacotherapy – bipolar disorder
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Lithium carbonate
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Epival/valproic acid
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Carbamazepine
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Olanzapine,Quetiapine, risperidone
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Lamotrigine
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Topiramate
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Mood disorders overview
SSRIs
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Best evidence of efficacy in the pharmacological treatment of
depression
First-line treatment in moderate to severe depression
3 to 8 weeks required until full therapeutic effect
One year maintenance therapy typically recommended
Well tolerated, safe in overdose, simple prescribing regimens
Few drug interactions – can be used in combination with other classes
of medications with some exceptions.
Up to 80% of adults will respond to first medication
But…
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Significant side effects frequently underreported
Withdrawal syndromes reported
May contribute to or worsen suicidal ideation in first four weeks of
treatment
Only 40 to 50% response rate in children and adolescents(? Safety)
Mood disorders overview
SSRIs/SNRIs
Common side effects include:
 Fatigue, headache, dry mouth, blurred vision,
nausea, diarrhea, urinary hesitancy, tremor,
sweating, vivid dreams, sexual dysfunction
 Rare side effects include serotonin syndrome,
akathesia,? Suicidal ideation/behavior,
extrapyramidal symptoms
Mood disorders overview
Tricyclic antidepressants
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Second or third line drug treatment for depression
Good evidence of efficacy in adults. No evidence of
efficacy in children and adolescents.
Same side effect profile as SSRIs plus:
Cardiac arrhythmias and conduction issues
(prolonged QT interval)
Lowers seizure threshold
Significantly more intense side effects than SSRIs
Dangerous/lethal in overdose
Several significant drug-drug interactions
Mood disorders overview
RIMAs
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Selective blocker of MAOI A (80%) found mostly in
the brain thus dietary restrictions not required
Reversible in that they inhibit the enzyme for a time,
but eventually detach, allowing the enzyme to
function once more
Only one drug in this class available in Canada
Limited evidence of efficacy in treatment of
depression.
Some evidence of efficacy in treatment of anxiety
disorder
May has some advantages in the treatment of
atypical depression
Not considered first line treatment
Mood disorders overview
MAOIs
Block enzymatic degradation of monoamines including tyramine
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Increased levels of tyramine can cause sudden increases in blood pressure
leading to hypertension, strokes and MIs
This is prevented by restricting dietary tyramine
Foods to be avoided:
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aged foods
alcoholic beverages (especially chianti, sherry, liqueurs, and beer)
alcohol-free or reduced-alcohol beer or wine
anchovies
bologna, pepperoni, salami, summer sausage, or any fermented sausage
caviar
cheeses (especially strong or aged varieties), except for cottage and cream cheese
chicken livers
fermented foods
figs (canned)
fruit: raisins, bananas (or any overripe fruit)
meat prepared with tenderizers; unfresh meat; meat extracts
smoked or pickled meat, poultry, or fish
soy sauce
Mood disorders overview
Lithium Carbonate
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Considered gold standard in treatment of mania and maintenance
therapy for BAD
Lithium enhances the uptake of norepinephrine and serotonin into the
synaptosomes, thus reducing their action.
It reduces release of norepinephrine from synaptic vesicles and inhibits
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production of cyclic AMP.
In humans, lithium alters the excitability of the CNS as measured by
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cortical evoked potentials
Can be used in combination with other antimanic drugs.
Narrow therapeutic window thus plasma concentration monitoring is
essential
Mood disorders overview
Lithium Carbonate
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Initial workup includes CBC, lytes, BUN, Cr, (sometimes 24 hr creatinine
clearance) glucose, ECG, TSH
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Therapeutic range 0.5 to 1.5 mmol/L. Serum concentrations over 2
mmol/L are considered toxic
Common side effects include:
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Anorexia, nausea, vomiting,diarrhea,thirst, tremor, ataxia, weakness,
restlessness, polyuria, rash and acne
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Worsening of sluggishness, drowsiness, lethargy, coarse hand tremor
or muscle twitchings, loss of appetite, vomiting, and diarrhea suggest
onset of toxicity.
Mood disorders overview
Anticonvulsants
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Epival, Valproic Acid, carbamazepine
May be used in combination with lithium
Some require blood level monitoring
Evidence for effectiveness as a first line agents
Less value in maintenance therapy
Thrombocytopenia, leukopenia must be monitored
With Epival: growing concerns about polycystic ovarian disease
Lamotrigine showing promise particularly for preventing
depression in BAD
Lamotrigine carries risk for Stevens-Johnson syndrome
Topirmate is weight neutral or causes some weight loss
Mood disorders overview
Atypical antipsychotics
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Olanzapine showing promise as first-line agent for both acute
episodes of mania and in maintenance therapy
May be used in combination with lithium or anticonvulsants
Low incidence of EPS but other side effects significant including:
Weight gain
Glucose metabolism abnormalities including DKA
Dyslipidemias
Hyperprolactinemia
Unknown if tardive dyskinesia represents a significant long-term
side effect
Mood disorders overview
Physical treatments
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ECT – treatment resistant depression catatonia, psychotic
depression
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Repetitive transcranial magnetic stimulation – efficacy
similar to ECT – no GA required and fewer post procedure side
effects
Vagal nerve stimulation – deep brain stimulation for
treatment refractory cases
Direct Deep Brain Stimulation
Light therapy – for SAD, specific wavelengths shown to be
most effective
Mood disorders overview
Hospitalization
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Form 1 criteria – harm to self, harm to others, severe
psychosis, mania or catatonia, unable to care for self
in the community
Treatment resistant cases
Poor psychosocial supports
Complex cases and/or complex treatment regimens
Delivery of ECT
Medically compromised cases
Mood disorders overview
Questions?