Antidepressants and Treatment of Mood Disorders: Antidepressants and Treatment of Mood Disorders Anita S. Kablinger M.D. Associate Professor Departments of Psychiatry and Pharmacology


Outline of Lecture: Outline of Lecture Definitions DSM-IV diagnoses and criteria Epidemiology Neurobiology Psychosocial theories Treatments


Definitions: Definitions Depression can refer to many things and mean different things to different people Symptom versus syndrome However, for a clinical depression consistent with DSM-IV, this must lead to functional impairment


DSM-IV Diagnostic Categories: DSM-IV Diagnostic Categories Major Depression Dysthymia Depressive Disorder NOS Bipolar Disorder, Type I or II Cyclothymia Bipolar Disorder NOS Mood Disorder secondary to GMC Substance-Induced Mood Disorder Adjustment Disorder (separate classification)


Epidemiology: Epidemiology Depression is the most common cause of disability in the world U.S. costs approximate 43$ billion per year for mood disorders Lifetime prevalence rates: (according to NCS), 21-24% for women and 12-15% for men


Major Depressive Disorder (MDD): Major Depressive Disorder (MDD) >2 week period of change in behavior with 5 of the following: *depressed mood *anhedonia appetite disturbance sleep disturbance psychomotor disturbance fatigue or loss of energy worthlessness or guilt impaired concentration suicidal thoughts * 1/5 symptoms must be these Rule out physical cause


Time Course of MDD: Time Course of MDD Often lasts for a year without treatment Chances increase by 50% for another episode after current episode (i.e. high relapse and recurrence rates) Many go on to experience chronic depression (but may be a result of inadequate treatment)


Heritability of Mood Disorders: Heritability of Mood Disorders Genetic factors very important RR of MDD is 2-5x greater in relatives of depressed patients than controls First degree relatives of Bipolar patients are 24x more likely to develop BAD than general population Twin and adoption studies help to understand and define this illness


Psychosocial Theories of Depression: Psychosocial Theories of Depression Risk factors include: recent stressors poor social support system history of early parental loss gender family history of depression negative cognitive style


Theories of Depression: Theories of Depression NE and DA broken down to variety of products through MAO and COMT 5HT is broken down by MAO to 5-HIAA Major mechanism for terminating signal is neuronal reuptake Monoaminergic Theories Reserpine (early antihypertensive) Iproniazid (used to treat TB) Imipramine (originally studied as an antipsychotic) Drugs enhancing noradrenergic functioning were antidepressants (eg. stimulants)


Indoleamine Hypothesis of Depression: Indoleamine Hypothesis of Depression Serotonin is functionally deficient in depression Decreased brain 5-HT and CSF 5-HIAA in many depressed patients Antidepressants tend to increase central serotonin transmission Depressed patients show reduction in 5-HT reuptake sites Blunted neuroendocrine challenges


Neurotransmitter Hypothesis of Mood Disorders: Neurotransmitter Hypothesis of Mood Disorders Led to catecholamine hypothesis NE ↓ in depression and  in mania 5-HT ↓ production or reuptake in depression Flaws: depression or mania not reliably produced and clinical response exceeds mechanism of action of drug


Neurobiology of Mood Disorders: Neurobiology of Mood Disorders Neuroendocrine abnormalities: reflect central neurotransmitter dysfunction hyperactivity of HPA: increased cortisol, nonsuppression of cortisol in DST blunting of TSH release following TRH infusion blunting of GH release with alpha-2 adrenergic agonism and serotonin-mediated increases in prolactin


Other Alterations in Depression: Other Alterations in Depression  CRH  acetylcholine activity  GABA levels Excessive glucocorticoid activity in psychotic depression Hippocampal volume loss


Neurobiology of Mood Disorders: Neurobiology of Mood Disorders Sleep abnormalities: usually found in endogenous depression prolonged sleep latency shortened REM latency and change in timing increased wakefulness decreased arousal threshold early morning awakening reduced stage 3 and 4 sleep


Kindling-Sensitization Hypothesis of Mood Disorders: Kindling-Sensitization Hypothesis of Mood Disorders Suggests that repeated exposure to stress and/or neurochemical changes during depressed episode sensitize brain regions responsible for affect Repeated episodes may permanently alter systems within the CNS Leads to shorter well periods, increased frequency and severity of illness


Treatments: Treatments Pharmacotherapy Psychotherapy Social interventions ECT TMS VNS


Which Medication?: Which Medication? Safety Tolerability Efficacy Payment Simplicity


Available Types of Pharmacotherapy: Available Types of Pharmacotherapy Tricyclic antidepressants (TCA) MAOI’s SSRI’s SNRI’s Atypical antidepressants Mood stabilizers Antipsychotics


General Treatment Rules: General Treatment Rules Often takes 4-6 weeks for response Monitor for response versus remission Vegetative symptoms tend to improve first, cognitive symptoms take longer SSRI’s are the first line of treatment for most MDD’s Address biopsychosocial needs and maintain meds for 6-12 months


Tricyclic Antidepressants: Tricyclic Antidepressants Available for more than 30 years Cheap but not clean Act by NE and/or 5 HT presynaptic reuptake inhibition Side effects include anticholinergic effects, orthostasis, slowing of cardiac conduction Secondary better than tertiary compounds


Selective Serotonin Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors Produce response rates close to 70% Safer and better tolerated than TCA’s Given once daily Starting and therapeutic doses often similar Most common side effects include GI symptoms, HA, insomnia, anxiety, and sexual dysfunction Five available in the U.S.


Novel or Atypical Antidepressants: Novel or Atypical Antidepressants Bupropion (NE and DA reuptake inhibition) Trazodone (5 HT2 alpha-ANT) Venlafaxine and Duloxetine (NE and 5 HT reuptake blockers – SNRI’s) Mirtazapine (presynaptic alpha 2 ANT and 5 HT2 and 5 HT3 ANT)


Psychotherapy in Depression: Psychotherapy in Depression Supportive Insight-oriented Interpersonal Cognitive-behavioral Psychodynamic Individual, group or family