Introduction to Major Depression

1
Introduction to Major Depression
2
Course of Depression
Adapted from Kupfer DA. J Clin Psychiat 1991 52
(5) 28-34
3
Depression. Not only a state of mind.
Reference Adapted from American Psychiatric
Association. Diagnostic and Statistical Manual of
Mental Disorders. Fourth Edition,Text Revision.
Washington, DC American Psychiatric Association.
2000345-356,489.
4
The Connection Between Stress and Depression

• STRESS
• Activation of the HPA axis
• CORTISOL
• Blunting of the 5-HT and NA induced responses
• DEPRESSION

Negative Feedback
Deakin, JFW. 1996 J Psychopharm 10(1), 31-38
5
Response and Remission
6
Residual Symptoms After Partial Remission
p lt 0.001
Paykel ES et al. Psychological Medicine 1995 25
1171-1180
7
ANTIDEPRESSANTS
Enzyme inhibitors MAOI Phenelzine Isocarboxazid Tr
anylcypromine RIMA Moclobemide
Monoamine re-uptake inhibitors
NaSSA Mirtazapine
SNRI Venlafaxine Duloxetine
TCAs related antidepressants Amitriptyline Mapro
tiline Amoxapine Mianserin Clomipramine Trazodone
Dosulepin Doxepin Imipramine Lofepramine Nortript
yline Trimipramine
SSRI (S-)Citalopram Fluoxetine Fluvoxamine Paroxet
ine Sertraline
NARI Reboxetine
TCAtricyclic antidepressant MAOImonoamine-oxida
se inhibitor RIMAreversible inhibitor of
monoamine-oxidase A NARInoradrenaline re-uptake
inhibitor SSRIselective serotonin re-uptake
inhibitor SNRIserotonin noradrenaline
re-uptake inhibitor NaSSA noradrenaline
specific serotonergic antidepressant
8
Neurotransmitters and Functioning
Norepinephrine
Serotonin
Anxiety Irritability
Impulse
Vigilance
Mood Emotion Cognitive function
Appetite Sex Aggression
Energy Motivation
Drive Euphoria Pleasure
Dopamine
Adapted from Healy D McMonagle T. J
Psychopharmacol 199711(4)S25-31.
9
Neurotransmission
Synaptic Cleft
MAO
Presynaptic Neurone
Postsynaptic Neurone
Reuptake pump
10
Neurone
Stahl S. Essential Psychopharmacology
Neuroscientific Basis and Practical Applications
2nd Ed CUP p273-279
11
ANTIDEPRESSANTS
Enzyme inhibitors MAOI Phenelzine Isocarboxazid Tr
anylcypromine RIMA Moclobemide
Monoamine re-uptake inhibitors
NaSSA Mirtazapine
SNRI Venlafaxine Duloxetine
TCAs related antidepressants Amitriptyline Mapro
tiline Amoxapine Mianserin Clomipramine Trazodone
Dosulepin Doxepin Imipramine Lofepramine Nortript
yline Trimipramine
SSRI (S-)Citalopram Fluoxetine Fluvoxamine Paroxet
ine Sertraline
NARI Reboxetine
TCAtricyclic antidepressant MAOImonoamine-oxida
se inhibitor RIMAreversible inhibitor of
monoamine-oxidase A NARInoradrenaline re-uptake
inhibitor SSRIselective serotonin re-uptake
inhibitor SNRIserotonin noradrenaline
re-uptake inhibitor NaSSA noradrenaline
specific serotonergic antidepressant
12
Case Fatality Rates
Source UK Yellow Card Data
13
Ethnicity and Depression

• Pharmacokinetic, dynamic and genetic differences
  do appear to exist across ethnic groups
• Activity of CYP2C19 is reduced in 20 Asians, 5
  Hispanics and 3 whites
• Dexamethasone suppression test (DST) results
  suggest that depressed non-white patients have
  different patterns of HPA axis activity compared
  with white MDD patients
• African American patients had a relatively low
  rate of DST non-suppression compared with white
  patients (25 vs 58 non suppression
  respectively)
• Polymorphism of the 5HTT may differ across ethnic
  groups
• Environmental and dietary factors are likely to
  be involved

Yann MW and Cohen LJ. Drug Metab Drug
Interactions 2000 16 1 39-67 Lin K-M. J Clin
Psych 2001 62 13 13-19
14
Genetic x Environment

• Childhood maltreatment predicted adult depression
  only among individuals carrying an s allele but
  not among l/l homozygotes (p0.05)

Probability of major depression episode
No Probable
Severe Maltreatment Maltreatment
Maltreatment
Caspi A et al Science 2003 301 386-389
15
Genetic x Environment

• Effect of life events on self-reports of
  depression symptoms at age 26 significantly
  stronger among s/s subjects vs l/l subjects
  (p0.02)

• Stressful life events predicted suicide ideation
  or attempt among individuals carrying an s allele
  but not among l/l homozygotes (p0.05)

Caspi A et al Science 2003 301 386-389
16
Discuss choice of drug with the patient.
Include Therapeutic effects Adverse
effects Discontinuation effects
Maudsley Prescribing Guidelines 2005-2006
Start antidepressant Titrate to recognised
therapeutic dose. Assess efficacy over 4-6 weeks
No effect
Poorly tolerated
Effective
Continue for 4-6 months at full treatment
dose Consider longer-term treatment in recurrent
depression
Give an antidepressant from a different
class Titrate to therapeutic dose. Assess over
4-6 weeks
Increase dose Assess over a further 2 weeks
Effective
Effective
No effect
Give an antidepressant from a different
class Titrate to therapeutic dose. Assess over
4-6 weeks, increase dose as necessary
Effective
Poorly tolerated or No effect
Refer to suggested treatments for refractory
depression
No effect
Adapted from Maudsley Prescribing Guidelines
2005-2006. (Martin Dunitz 8th Ed)