OVERVIEW OF MOOD DISORDERS

OVERVIEW OF MOOD DISORDERS

Dr. H. Gandy, MD, FRCPCChildren’s Hospital of Eastern

OntarioApril 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 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 overviewEpidemiology of depression 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 overviewEpidemiology of bipolar disorder 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 overviewEpidemiology of Dysthymia 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 overviewMajor depression-clinical symptoms 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 S leep I nterest G uilt E nergy C oncentration A ppetite P sychomotor S uicide


Major depression-DSM-IV diagnosis 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 overviewBipolar Affective Disorder classification-DSM-IV 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 One or more major depressive episodes accompanied by at least

one hypomanic episode. No evidence of psychotic features Cyclothymic disorder 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 overviewBipolar affective disorder-clinical symptoms-mania 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 overviewBipolar affective disorder – DSM-IV criteriaManic episode: 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 overviewDysthymia-clinical symptoms 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 overviewDysthymia-DSM-IV criteria 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 overviewEtiology of mood disorders - Biological factorsBiogenic amines Norepinephrine - down regulation of beta adrenergic receptors and drug response Serotonin – decrease in serotonin receptors after long-term exposure to drugs Dopamine – activity may be reduced in depression and increased in maniaOther neurochemical factors GABA - amino acid neurotransmitter implicated in depression Adrenal axis – correlation between hypersecretion of cortisol and depression Thyroid axis – blunted release of TSH to infusion of TRH seen in depression Growth hormone – blunted sleep induced stimulation of GH release in depressionSleep abnormalities – delayed sleep onset, shortened REM latency in depressionKindling – in temporal lobes involved in pathophysiology of bipolar disorderCircadian rhythms – sleep deprivation and transient clinical improvement in depression.

Light level changes in seasonal affective disorderNeuroimmune regulation – cortisol axis disruption may affect immune statusBrain imaging – enlarged cerebral ventricles in BAD, smaller caudate nuclei in depression.

Mood disorders overviewEtiology continuedNeuroanatomical considerations – limbic system, basal ganglia, hypothalamusGenetic factors 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. Adoption studies – biological children of affected parents remain at increased

risk even if reared in non-affected adoptive families. Twin studies – concordance rate for BAD in monozygotic twins is up to 90% Linkage studies – chromosomes 5, 11 and X have been implicated particularly in

BADPsychosocial factors Life events and environmental stress – stress, family functioning, early loss Premorbid personality factors – dependent, obsessional, hysterical personalities

at greater risk for depression Psychodynamic factors – object loss, depressive position, aggression turned

inwards, incompleteness and despair Learned helplessness Cognitive theory – cognitive distortions

Mood disorders overviewMedical causes of depressive

symptomsNeurological Cerebrovascular disease Dementia Epilepsy Infections Multiple sclerosis Neoplasms Parkinson’s disease Wilson’s disease hydrocephalus

Mood disorders overviewMedical causes of depressive symptomsEndocrine Adrenal Menses related Postpartum Thyroid disordersInfectious and inflammatory AIDS Chronic fatigue syndrome Mononucleosis Pneumonia Lupus tuberculosis

Mood disorders overviewMedical causes of depressive symptomsMiscellaneous medical Cancer Cardiopulmonary disease Porphyria Vitamin deficiencies


Pharmacological causes of depressive symptoms 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 overviewSeasonal affective disorder 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.


Postpartum depression Major depressive, manic or makes

episode or brief psychotic disorder associated with postpartum onset.

Onset of episode is within four weeks postpartum


TreatmentsPsychosocial therapiesPsychodynamic 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) 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.


Cognitive distortions All or nothing thinking Overgeneralization Mental filter Disqualifying the positive Jumping to conclusions


Cognitive distortions Magnification and minimization Emotional reasoning “Should” statements Labeling Personalization

Mood disorders overview Psychosocial therapies cont’d Interpersonal psychotherapy (Meyer, Sullivan,

Klerman, 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 overviewTreatmentPharmacotherapy – depression antidepressants SSRI’s – Prozac, Paxil, Zoloft, Celexa, Luvox, Cipralex SNRI’s – Effexor, Remeron TCAs – amitriptyline, desipramine, Clomipramine RIMA’s - Moclobemide MAOI’’s – Phenelzine, TranylcyprominePharmacotherapy – bipolar disorder Lithium carbonate Epival/valproic acid Carbamazepine Olanzapine,Quetiapine, risperidone Lamotrigine Topiramate

Mood disorders overviewSSRIs 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 medicationBut… 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 overviewSSRIs/SNRIsCommon 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 overviewTricyclic antidepressants 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 overviewRIMAs 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 overviewMAOIsBlock enzymatic degradation of monoamines including tyramine Increased levels of tyramine can cause sudden increases in blood

pressure leading to hypertension, strokes and MIsThis is prevented by restricting dietary tyramineFoods to be avoided: 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 overviewLithium Carbonate 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 production of cyclic AMP. In humans, lithium alters the excitability of the CNS as

measured by cortical evoked potentials Can be used in combination with other antimanic drugs. Narrow therapeutic window thus plasma concentration

monitoring is essential

Mood disorders overviewLithium Carbonate Initial workup includes CBC, lytes, BUN, Cr, (sometimes 24 hr

creatinine clearance) glucose, ECG, TSH Therapeutic range 0.5 to 1.5 mmol/L. Serum concentrations

over 2 mmol/L are considered toxicCommon side effects include: Anorexia, nausea, vomiting,diarrhea,thirst, tremor, ataxia,

weakness, restlessness, polyuria, rash and acne Worsening of sluggishness, drowsiness, lethargy, coarse hand

tremor or muscle twitchings, loss of appetite, vomiting, and

diarrhea suggest onset of toxicity.

Mood disorders overviewAnticonvulsants 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 overviewAtypical antipsychotics 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


Physical treatments ECT – treatment resistant depression catatonia,

psychotic depression 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


Hospitalization 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


Questions?

OVERVIEW OF MOOD DISORDERS

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