Affective Disorders Brian E. Wood, D.O. Department Chair, Psychiatry Edward Via Virginia College of Osteopathic Medicine Assistant Professor of Clinical.

Affective Disorders

Brian E. Wood, D.O.

Department Chair, Psychiatry

Edward Via Virginia College of Osteopathic Medicine

Assistant Professor of Clinical Psychiatric Medicine

University of Virginia, School of Medicine

Mood Disorders

• Major Depressive disorder

• Bipolar disorder

• Dysthymic disorder

• Cyclothymic disorder

• Mood Disorder due to secondary sources– General medical conditions– Substance use/abuse

Major Depressive Episode

Mood

Time

Mood

Manic Episode

Time

Epidemiology

• Major Depressive Disorder– Prevalence 2-3/100 men, 5-10/100 women– Lifetime expectancy 10% in men, 20% in women.– Risk increases throughout life for men, peaks in 40’s

then decreases in women

• Bipolar Disorder– Prevalence 1/100 in men and women– Lifetime expectancy 1% in men and women– Usually occurs in the mid 20’s and 30’s perhaps

slightly later in women

Epidemiology

• Dysthymic Disorder– Much less studied– More common in females– Onset frequently in 20’s to 30’s– More common among first degree relatives with MDD.

• Cyclothymic Disorder– Essentially occurs more frequently in the same groups

and age ranges as Bipolar Disorder– More common among first degree relatives with MDD

or Bipolar Disorder.

Etiology

• Major Depressive Disorder– Heritability 10-13% in first degree relatives– Mz concordance rate higher than Dz rate– Increased risk in lower socioeconomic classes– Increased risk with family history of ETOH,

depression or early parental loss.

Etiology

• Bipolar Disorder– Heritability 20-25% in first degree relatives

• Child with 1 Bipolar parent 25% risk

• Child with both parents bipolar 50-75% risk

– Slightly increased risk in higher socioeconomic groups

– Mz concordance rate 40-70%, Dz concordance rate 20%.

Etiology

• Dysthymic Disorder– Occurs more frequently in first degree relatives

with MDD but rate essentially unknown

• Cyclothymic Disorder– Thought to be a less severe form of Bipolar

Disoder

DSM IV – TRMDD

• One or more major depressive episodes for at least 2 wks. Duration

• Five or more symptoms of depression (wt. Loss, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or innappropriate guilt, diminished concentration, recurrent thoughts of death or suicide) including either depressed mood or loss of interest or pleasure.

• Rule outs for bereavement, substance induced, etc.

DSM IV –TRBipolar Disorder

• One or more manic or mixed episodes usually accompanied by MDE

• Manic episode characterized by at least 1 wk of elevated, expansive, or irritable mood with at least three symptoms including grandiosity, insomnia, talkativeness, flight of ideas or racing thoughts, distractibility, increased activity, excessive involvement in pleasurable activity.

• Rule outs for substances, medical conditions, etc.• Occupational or social dysfunction

Differential Diagnosis

• MDD– Mood disorder due to general medical

condition or substance induced– Manic or mixed episodes with irritable mood– Adjustment Disorder– Simple or complicated Bereavement– Dementia with prominent apathy

Differential Diagnosis

• Bipolar Disorder– Mood disorder due to general medical

condition or substance induced– Hypomanic episode– MDE with prominent irritability– Attention Deficit/Hyperactivity Disorder

Pharmacologic TreatmentMDD

• Pharmacologic Treatment (monotherapy)– Antidepressants

• TCA’s

• MAOI’s

• SSRI (generally first line treatment)- steady state from 6 - 15 days.

• Other antidepressants (Venlafaxine, Mirtazapine)

– Psychostimulants

Tricyclic Antidepressants

• Primary action on NE, SE.• Also have alpha 1 blocking, histamine blocking

and anticholinergic effects• AV nodal block• Lethal in overdose• Infrequently used today for treatment of

depression but some resurgence in use due to tx. Resistance and off label uses (ex. Pain control)

Monoamine Oxidase Inhibitors

• Primary action on MAO that breaks down NE

• Significant alpha 1 and histaminergic effects but little antcholinergic or AV node effects.

• Risk of hypertensive crisis with Tyramine containing foods or with noradrenergic agents (ex. Pseudoephedrine)

SSRI’s

• Primary action at 5HT2 receptor.• Most widely prescribed psychotropic medication

in use today and generally first line treatment for depression.

• Generally very well tolerated with minimal incidence of side effects.

• Not lethal in overdose.• Do have significant drug-drug interactions due to

CP450 metabolism.

Cytochrome Polymorphism Inhibitors Potentially significant Interactions

1A2 Possible Fluvoxamine Haloperidol

Phenytoin

Theophylline

Caffeine

2C9 Yes; 2-3%of whites; 15-20%of Asians Fluoxetine

Fluvoxamine

Sertraline

Phenytoin

Diazepam

Tolbuamide

2D6 Yes; 5-8% of whites; lower in Asians and African Americans

Fluoxetine

Fluvoxamine

Paroxetine

Sertraline

Citalpram

TCA’s

Haloperidol

Perphenazine

Thioridazine

Clozapine

Risperidone

B-Blockers

Type 1C antiarrhythmics

3A Possible Fluoxetine

Fluvoxamine

Sertraline

Citalpram

TCA’s

Carbamazepine

Alprazolam

Triazolam

Terfenadine

Astemizole

Effects of SSRI’s on Cytochrome P450 Enzymes

Adapted from DeVane (1994)

ECT

• Application of brief electrical pulse to induce controlled generalized seizure.

• Mechanism of action unknown but correlates with “surge” of neurotransmitters in the CNS and changes in permeability in the blood-brain barrier.

• Modern ECT applied with general anaesthesia and neuromuscular blockade.

• Probably the highest efficacy of any single agent used to treat affective disorders.

Other Treatments

• Interpersonal psychotherapy

• Cognitive-behavioral therapy

• Psychodynamic psychotherapy

Pharmacologic Treatmentof Bipolar Disorder

• Li compounds – primary effect at voltage gated Na channel of the neuron

• Anticonvulsants – effect at the voltage gated Na channel and membrane stabilization effects.– Valproic acid– Carbamazepine– Other anticonvulsants

Summary

• Affective disorders are disorders of mood regulation and include both hyper-excitable and hypo-excitable states defined by episodes.

• They are generally recurrent diseases but occasionally occur in single episodes.

• They are familial with probable genetic inheritance but with significant environmental factors affecting expression.

• Affective disorders are treatable diseases requiring careful evaluation, initiation of appropriate treatment, and follow up in order to improve condition, quality of life and minimize risks.