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Year 2 Medicine > Affective Disorders: Neurobiology and Treatment > Flashcards

Affective Disorders: Neurobiology and Treatment Flashcards

1
Q

Neurobiology of depression

A
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2
Q

Aetiology of depression

  • …factorial
  • … understood
  • Interactions of … factors, childhood …, past hx of … disorders, … predisposition (neuroticism)
  • Often precipitated by … … events
A
  • Multifactorial
  • Incompletely understood
  • Interactions of genetic factors, childhood adversities, past hx of mood disorders, psychological predisposition (neuroticism)
  • Often precipitated by stressful life events
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3
Q

Neurobiology of depression

  • 1.Disruption of … transmission
  • 2.Gaba and …
  • 3…. Axis and Glucocorticoids
  • 4.Neuroplasticity and Neuronal …
  • 5…. dysfunction
A
  • 1.Disruption of monoamine transmission
  • 2.Gaba and Glutamate
  • 3.HPA Axis and Glucocorticoids
  • 4.Neuroplasticity and Neuronal Atrophy
  • 5.Immune dysfunction
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4
Q

Neurobiology of depression

  • 1.Disruption of monoamine …
  • 2…. and Glutamate
  • 3.HPA Axis and …
  • 4.Neuro… and Neuronal Atrophy
  • 5.Immune dysfunction
A
  • 1.Disruption of monoamine transmission
  • 2.Gaba and Glutamate
  • 3.HPA Axis and Glucocorticoids
  • 4.Neuroplasticity and Neuronal Atrophy
  • 5.Immune dysfunction
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5
Q

Neurobiology of depression

  • 1…. of monoamine transmission
  • 2.Gaba and Glutamate
  • 3.HPA Axis and Glucocorticoids
  • 4.Neuroplasticity and … Atrophy
  • 5.Immune …
A
  • 1.Disruption of monoamine transmission
  • 2.Gaba and Glutamate
  • 3.HPA Axis and Glucocorticoids
  • 4.Neuroplasticity and Neuronal Atrophy
  • 5.Immune dysfunction
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6
Q

Neural systems involved in depression

A
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7
Q

Monoamines and depressive symptoms

A
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8
Q

Serotonin dysfunction in Depression

  • All traditional antidepressants affect 5HT/NA systems
    • lowered 5-HT concentrations (acute … depletion) studies
    • Reduced 5-HT Transporter in post-mortem … studies
A
  • All traditional antidepressants affect 5HT/NA systems
    • lowered 5-HT concentrations (acute tryptohan depletion) studies
    • Reduced 5-HT Transporter in post-mortem suicide studies
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9
Q

Antidepressants - History

Most act on what?

A
  • In bold those acting on Serotonin
  • 1950s Monoamine oxidase inhibitors (MAOIs)
  • Tricyclics (TCAs)
  • 1982 Trazodone
  • 1988 Fluoxetine (Prozac)
  • 1989 Bupropion
  • 1994 Venlafaxine
  • 1996 Mirtazapine
  • 2004 Duloxetine
  • 2008 Agomelatine
  • 2016 Vortioxetine
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10
Q

Reduced 5-HT Transporter in Depression
PET/SPECT studies

A
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11
Q

Serotonin (5-HT) and Noradrenaline (NA) Pathways in the Human Brain

  • Both serotonin (5-HT) and noadrenaline (NA) are neurotransmitters that have … tracts to the cerebral cortex and limbic area, as well as … tracts to the spinal cord
  • The cell bodies for these tracts originate in major nuclei of the …brain. For the central nervous system, the 5-HT cell bodies are located in the raphe nuclei and the largest cluster of NA cells are located in the locus …
  • Each of these midbrain nuclei has ascending tracts, which project to brain regions thought to be involved in depressive symptoms, as well as ascending and descending tracts involved in pain suppression
  • The monoamine theory of depression suggests that a relative deficiency in synaptic levels of serotonin and noradrenaline in key central nervous system pathways underlies depressive illness (CNS = brain + spinal cord)
  • 5-HT- and NA -secreting neurons project upward from their respective nuclei in the brainstem, directly stimulating many areas of the brain
  • Brain areas stimulated include the prefrontal cortex, which is involved in executive functions, and the limbic system which include anatomical structures involved in behaviour, motivation, and emotion, such as the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala
A
  • Both serotonin (5-HT) and noadrenaline (NA) are neurotransmitters that have ascending tracts to the cerebral cortex and limbic area, as well as descending tracts to the spinal cord
  • The cell bodies for these tracts originate in major nuclei of the midbrain. For the central nervous system, the 5-HT cell bodies are located in the raphe nuclei and the largest cluster of NA cells are located in the locus coeruleus
  • Each of these midbrain nuclei has ascending tracts, which project to brain regions thought to be involved in depressive symptoms, as well as ascending and descending tracts involved in pain suppression
  • The monoamine theory of depression suggests that a relative deficiency in synaptic levels of serotonin and noradrenaline in key central nervous system pathways underlies depressive illness (CNS = brain + spinal cord)
  • 5-HT- and NA -secreting neurons project upward from their respective nuclei in the brainstem, directly stimulating many areas of the brain
  • Brain areas stimulated include the prefrontal cortex, which is involved in executive functions, and the limbic system which include anatomical structures involved in behaviour, motivation, and emotion, such as the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala
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12
Q

Serotonin (5-HT) and Noradrenaline (NA) Pathways in the Human Brain

  • Both serotonin (5-HT) and noadrenaline (NA) are neurotransmitters that have ascending tracts to the cerebral cortex and limbic area, as well as descending tracts to the spinal cord
  • The cell bodies for these tracts originate in major nuclei of the midbrain. For the central nervous system, the 5-HT cell bodies are located in the raphe nuclei and the largest cluster of NA cells are located in the locus coeruleus
  • Each of these midbrain nuclei has ascending tracts, which project to brain regions thought to be involved in … symptoms, as well as ascending and descending tracts involved in … …
  • The … theory of depression suggests that a relative deficiency in synaptic levels of serotonin and noradrenaline in key central nervous system pathways underlies depressive illness (CNS = brain + spinal cord)
  • 5-HT- and NA -secreting neurons project upward from their respective nuclei in the brainstem, directly stimulating many areas of the brain
  • Brain areas stimulated include the … cortex, which is involved in executive functions, and the … system which include anatomical structures involved in behaviour, motivation, and emotion, such as the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala
A
  • Both serotonin (5-HT) and noadrenaline (NA) are neurotransmitters that have ascending tracts to the cerebral cortex and limbic area, as well as descending tracts to the spinal cord
  • The cell bodies for these tracts originate in major nuclei of the midbrain. For the central nervous system, the 5-HT cell bodies are located in the raphe nuclei and the largest cluster of NA cells are located in the locus coeruleus
  • Each of these midbrain nuclei has ascending tracts, which project to brain regions thought to be involved in depressive symptoms, as well as ascending and descending tracts involved in pain suppression
  • The monoamine theory of depression suggests that a relative deficiency in synaptic levels of serotonin and noradrenaline in key central nervous system pathways underlies depressive illness (CNS = brain + spinal cord)
  • 5-HT- and NA -secreting neurons project upward from their respective nuclei in the brainstem, directly stimulating many areas of the brain
  • Brain areas stimulated include the prefrontal cortex, which is involved in executive functions, and the limbic system which include anatomical structures involved in behaviour, motivation, and emotion, such as the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala
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13
Q

Gene-environment interactions

  • Effect on depression
A
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14
Q

HPA dysfunction in Mood Disorders

  • Lack of … suppression (Cortisol still high)
  • Glucocorticoid Receptor alterations
  • Depression in … Disease
A
  • Lack of dexamethasone suppression (Cortisol still high)
  • Glucocorticoid Receptor alterations
  • Depression in Cushing’s Disease
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15
Q

Neuroplasticity alterations and neuronal atrophy

  • … and chronic … alters:
    • Neuroplasticity (reduction of dendrites, dendritic spine density decrease, decreased NMDA or AMPA receptors, decreased synaptic proteins)
    • Neuronal atrophy also reported in the …
A
  • Depression and chronic stress alters:
    • Neuroplasticity (reduction of dendrites, dendritic spine density decrease, decreased NMDA or AMPA receptors, decreased synaptic proteins)
    • Neuronal atrophy also reported in the hippocampus
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16
Q

Human neuroimaging evidence Enigma MDD working group

  • Hippocampus and other sub… reasons
    • Depression vs controls - mega-analysis shows that there is a clear … of volume in depression patients (also effect of chronic stress in animal models)
A
  • Hippocampus and other subcortical reasons
    • Depression vs controls - mega-analysis shows that there is a clear reduction of volume in depression patients (also effect of chronic stress in animal models)
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17
Q

GABA and glutamate

  • Chronic stress/depression: decreased or increased GABA & Glutamate?
  • Balanced control: Reverses stress/depression deficit/surplus?
  • Ketamine :
    • NMDAR blocker
    • single dose has rapid … effects
    • stimulates synaptogenesis
    • reverses stress/depression Gaba&Glutamate deficit/surplus?
A
  • Chronic stress/depression: Decreased GABA & Glutamate
  • Balanced control: Reverses stress/depression deficits
  • Ketamine :
    • NMDAR blocker
    • single dose has rapid antidepressant effects
    • stimulates synaptogenesis
    • reverses stress/depression Gaba&Glutamate deficits
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18
Q

GABA and glutamate

  • Chronic stress/depression: Decreased GABA & Glutamate
  • Balanced control: Reverses stress/depression deficits
  • K… :
    • NMDAR blocker
    • … dose has rapid antidepressant effects
    • stimulates …genesis
    • reverses stress/depression Gaba&Glutamate deficits
A
  • Chronic stress/depression: Decreased GABA & Glutamate
  • Balanced control: Reverses stress/depression deficits
  • Ketamine :
    • NMDAR blocker
    • single dose has rapid antidepressant effects
    • stimulates synaptogenesis
    • reverses stress/depression Gaba&Glutamate deficits
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19
Q

What effect does ketamine have on depression?

A

single dose has rapid antidepressant effects

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20
Q

Role of Immune Dysfunction in the ethiopathophysiology of MDD

  1. Evidence of associations between inflammation and depression
    • Increased incidence of psychiatric disorders in immune-mediated inflammatory disease
    • Increased … markers in depression
    • … Neuroinflammation and relationship to depressive symptoms in MS
  2. Is there a causality link?
    • Effects of pro-… challenges on mood
    • Pro-inflammatory cytokines induce “… behaviour” that overlaps with MDD symptoms
  3. Putative mechanisms
    • Effects of Inflammation on Cortico-… reward system
    • Childhood … predicts adult inflammation in a life-course study
A
  1. Evidence of associations between inflammation and depression
    • Increased incidence of psychiatric disorders in immune-mediated inflammatory disease
    • Increased inflammatory markers in depression
    • Hippocampal Neuroinflammation and relationship to depressive symptoms in MS
  2. Is there a causality link?
    • Effects of pro-inflammatory challenges on mood
    • Pro-inflammatory cytokines induce “sickness behaviour” that overlaps with MDD symptoms
  3. Putative mechanisms
    • Effects of Inflammation on Cortico-Striatal reward system
    • Childhood maltreatment predicts adult inflammation in a life-course study
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21
Q

Role of Immune Dysfunction in the ethiopathophysiology of MDD

  1. Evidence of associations between inflammation and depression
    • Increased incidence of psychiatric disorders in immune-mediated inflammatory disease
    • Increased inflammatory … in depression
    • Hippocampal Neuroinflammation and relationship to depressive symptoms in MS
  2. Is there a causality link?
    • Effects of pro-inflammatory challenges on …
    • Pro-inflammatory cytokines induce “sickness behaviour” that overlaps with MDD symptoms
  3. Putative mechanisms
    • Effects of Inflammation on Cortico-Striatal … system
    • Childhood maltreatment predicts adult … in a life-course study
A
  1. Evidence of associations between inflammation and depression
    • Increased incidence of psychiatric disorders in immune-mediated inflammatory disease
    • Increased inflammatory markers in depression
    • Hippocampal Neuroinflammation and relationship to depressive symptoms in MS
  2. Is there a causality link?
    • Effects of pro-inflammatory challenges on mood
    • Pro-inflammatory cytokines induce “sickness behaviour” that overlaps with MDD symptoms
  3. Putative mechanisms
    • Effects of Inflammation on Cortico-Striatal reward system
    • Childhood maltreatment predicts adult inflammation in a life-course study
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22
Q

Depression treatment

  • Psychotherapy
    • Alone or as … therapy
  • Pharmacotherapy
    • Effective for … Depression and Persistent …
    • Questionable effectiveness in … depression
  • Primary care supportive counselling
    • Important
A
  • Psychotherapy
    • Alone or as adjunctive therapy
  • Pharmacotherapy
    • Effective for Major Depression and Persistent MDD
    • Questionable effectiveness in minor depression
  • Primary care supportive counselling
    • Important
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23
Q

Depression treatment

  • …therapy
    • Alone or as adjunctive therapy
  • …therapy
    • Effective for Major Depression and Persistent MDD
    • Questionable effectiveness in minor depression
  • Primary care supportive …
    • Important
A
  • Psychotherapy
    • Alone or as adjunctive therapy
  • Pharmacotherapy
    • Effective for Major Depression and Persistent MDD
    • Questionable effectiveness in minor depression
  • Primary care supportive counselling
    • Important
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24
Q

3 depression treatments (broad categories)

A
  • psychotherapy
  • pharmacotherapy
  • counselling
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25
Q

1st Generation Antidepressants

  • … … inhibitors
    • Phenelzine, Tranylcypromine
    • Nonselectively inhibit enzymes involved in the breakdown of monoamines, including serotonin, dopamine, and norepinephrine
  • … antidepressants
    • Amytryptiline, Clomipramine…
    • Nonselectively inhibit the reuptake of monoamines, including serotonin, dopamine, and norepinephrine
A
  • Monoamine oxidase inhibitors
    • Phenelzine, Tranylcypromine
    • Nonselectively inhibit enzymes involved in the breakdown of monoamines, including serotonin, dopamine, and norepinephrine
  • Tryciclic antidepressants
    • Amytryptiline, Clomipramine…
    • Nonselectively inhibit the reuptake of monoamines, including serotonin, dopamine, and norepinephrine
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26
Q

1st Generation Antidepressants

  • Monoamine oxidase inhibitors
    • Phenelzine, Tranylcypromine
    • Nonselectively … enzymes involved in the breakdown of monoamines, including serotonin, dopamine, and norepinephrine
  • Tryciclic antidepressants
    • Amytryptiline, Clomipramine…
    • Nonselectively inhibit the … of monoamines, including serotonin, dopamine, and norepinephrine
A
  • Monoamine oxidase inhibitors
    • Phenelzine, Tranylcypromine
    • Nonselectively inhibit enzymes involved in the breakdown of monoamines, including serotonin, dopamine, and norepinephrine
  • Tryciclic antidepressants
    • Amytryptiline, Clomipramine…
    • Nonselectively inhibit the reuptake of monoamines, including serotonin, dopamine, and norepinephrine
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27
Q

What are two classes of first generation antidepressants?

A
  • Monoamine oxidase inhibitors (Phenelzine, Tranylcypromine)
    • Nonselectively inhibit enzymes involved in the breakdown of monoamines, including serotonin, dopamine, and norepinephrine
  • Tryciclic antidepressants (Amytryptiline, Clomipramine…)
    • Nonselectively inhibit the reuptake of monoamines, including serotonin, dopamine, and norepinephrine
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28
Q

2nd generation antidepressants

  • SSRI: .. .. … …
    • Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine
  • SNRI: Serotonin-… reuptake inhibitors
    • Venlafaxine, Duloxetine
  • ​alpha2 and 5-HT2Cantagonist [modulate serotonin and NA release]
    • Mirtazapine
  • …-noradrenaline reuptake inhibitor
    • Bupropion (not approved as antidepressant in UK)
A
  • SSRI: Selective serotonin reuptake inhibitors
    • Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine
  • SNRI: Serotonin-noradrenaline reuptake inhibitors
    • Venlafaxine, Duloxetine
  • ​alpha2 and 5-HT2Cantagonist [modulate serotonin and NA release]
    • Mirtazapine
  • Dopamine-noradrenaline reuptake inhibitor
    • Bupropion (not approved as antidepressant in UK)
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29
Q

2nd generation antidepressants

  • SSRI: Selective serotonin reuptake inhibitors
    • Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine
  • SNRI: Serotonin-noradrenaline reuptake inhibitors
    • Venlafaxine, Duloxetine
  • ​alpha2 and 5-HT2Cantagonist [modulate serotonin and NA release]
    • Mirta…
  • Dopamine-noradrenaline reuptake inhibitor
    • … (not approved as antidepressant in UK)
A
  • SSRI: Selective serotonin reuptake inhibitors
    • Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine
  • SNRI: Serotonin-noradrenaline reuptake inhibitors
    • Venlafaxine, Duloxetine
  • ​alpha2 and 5-HT2Cantagonist [modulate serotonin and NA release]
    • Mirtazapine
  • Dopamine-noradrenaline reuptake inhibitor
    • Bupropion (not approved as antidepressant in UK)
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30
Q

Give examples of SSRIs

A
  • Sertraline, Citalopram, Escitalopram, Fluoxetine, Vortioxetine
31
Q

Give examples of SNRIs

A

Venlafaxine, Duloxetine

32
Q

alpha2 and 5-HT2Cantagonist [modulate serotonin and NA release] example (antidepressant 2nd gen)

A

Mirtazapine

33
Q

What antidepressant that is a dopamine-noradrenaline reuptake inhibitor is not approved as an antidepressant in the UK?

A

Bupropion (not approved as antidepressant in UK)

34
Q

SSRIs

  • Efficacy equal to … in outpatients
  • Large spectrum of action (OCD, PTSD, Panic, GAD, social anxiety)
  • Low … and safe in …
  • The … treatment phase is the most delicate, due to prevalence of side effects over benefits – slow ..
  • Side effects
    • gastro-intestinal symptoms (nausea, diarrhea)
    • headache, Irritability, Anxiety
    • reduction of libido and sexual dysfunction
  • Gradual suspension to avoid … symptoms (worse with venlafaxine and paroxetine due to short half-ife)
A
  • Efficacy equal to tryciclics in outpatients
  • Large spectrum of action (OCD, PTSD, Panic, GAD, social anxiety)
  • Low toxicity and safe in overdose
  • The initial treatment phase is the most delicate, due to prevalence of side effects over benefits – slow titration
  • Side effects
    • gastro-intestinal symptoms (nausea, diarrhea)
    • headache, Irritability, Anxiety
    • reduction of libido and sexual dysfunction
  • Gradual suspension to avoid withdrawal symptoms (worse with venlafaxine and paroxetine due to short half-ife)
35
Q

SSRIs

  • Efficacy equal to tryciclics in outpatients
  • Large spectrum of action (list some conditions)
  • Low toxicity and safe in overdose
  • The initial treatment phase is the most delicate, due to prevalence of side effects over benefits – slow titration
  • Side effects
    • …-… symptoms
    • headache, i…, a…
    • reduction of … and sexual …
  • Gradual suspension to avoid withdrawal symptoms (worse with venlafaxine and paroxetine due to … half-ife)
A
  • Efficacy equal to tryciclics in outpatients
  • Large spectrum of action (OCD, PTSD, Panic, GAD, social anxiety)
  • Low toxicity and safe in overdose
  • The initial treatment phase is the most delicate, due to prevalence of side effects over benefits – slow titration
  • Side effects
    • gastro-intestinal symptoms (nausea, diarrhea)
    • headache, Irritability, Anxiety
    • reduction of libido and sexual dysfunction
  • Gradual suspension to avoid withdrawal symptoms (worse with venlafaxine and paroxetine due to short half-ife)
36
Q

Side effects of Tricyclics (5)

A

Constipation, orthostatic hypotension, dry mouth, drowsiness, cardiac toxicity in overdose

37
Q

Side effects of MAOi (antidepressants) (7)

A
  • Dry mouth, GI side effects, headache, drowsiness, insomnia, dizziness, food interactions (hypertension crises)
38
Q

Side effects of Venlafaxine (4)

A
  • nausea, vertigo, headache, insomnia.
39
Q

Side effects of Mirtazapine antidepressant (5)

A

drowsiness, sedation, hypotension, increased appetite and weight gain

40
Q

Role of Immune dysfunction in the etiopathophysiology of MDD

  • What are the implications for treatment?
    • Lack of response to traditional antidepressants is associated to higher levels of …
    • Could be used as a common … to predict non-response to treatment
    • meta-analyses of using anti-inflammatory = … effect on depressive symptoms
A
  • Lack of response to traditional antidepressants is associated to higher levels of CRP
  • Could be used as a common marker to predict non-response to treatment
  • meta-analyses of using anti-inflammatory = beneficial effect on depressive symptoms
41
Q

Bipolar Disorder: Causal Factors

  • Genes
    • ..-..% of 1st degree relatives can be expected to have Bipolar
    • MZ=72-80% DZ=14%
  • Biochemical
    • … levels
  • Psychosocial
    • … live events can trigger episodes
    • Early life … increase risk to develop BPAD
A
  • Genes
    • 8-10% of 1st degree relatives can be expected to have Bipolar
    • MZ=72-80% DZ=14%
  • Biochemical
    • Monoamines levels
  • Psychosocial
    • Stressful live events can trigger episodes
    • Early life trauma increase risk to develop BPAD
42
Q

Bipolar Disorder: Causal Factors

  • Genes
    • 8-10% of 1st degree relatives can be expected to have Bipolar
    • MZ=…-…% DZ=…%
  • Biochemical
    • Monoamines levels
  • Psychosocial
    • Stressful live events can trigger episodes
    • … life trauma increase risk to develop BPAD
A
  • Genes
    • 8-10% of 1st degree relatives can be expected to have Bipolar
    • MZ=72-80% DZ=14%
  • Biochemical
    • Monoamines levels
  • Psychosocial
    • Stressful live events can trigger episodes
    • Early life trauma increase risk to develop BPAD
43
Q

Mood disorders amonst relatives

  • Family members are about … times more likely to also have BPAD
  • Many genes are involved
  • Multiple genes of small effect
A
  • Family members are about 7 times more likely to also have BPAD
  • Many genes are involved
  • Multiple genes of small effect
44
Q

Neurobiology of Bipolar Disorder

  • Complex
    • … neurotransmitters (Dopamine – Serotonin)
    • Intracellular signaling alterations
    • … Axis
    • Neuro… – neuronal …
  • Multi-factorial
    • multiple genes each having small effects
  • Largely unknown
    • L.. and serendipity
A
  • Complex
    • Monoamine neurotransmitters (Dopamine – Serotonin)
    • Intracellular signaling alterations
    • HPA Axis
    • Neuroplasticity – neuronal atrophy
  • Multi-factorial
    • multiple genes each having small effects
  • Largely unknown
    • Lithium and serendipity
45
Q

Mitochondrial alterations in Bipolar Disorder

  • … Mitochondrial Complex I in Pre-frontal cortex
  • Altered brain mitochondria morphology and distribution
  • … mRNA for genes encoding ETC components and antioxidants
  • BPAD diagnosis associated with SNPs of mitochondrial genes and nuclear genes encoding ETC components
  • Altered … levels in blood and CSF
  • Increased markers of … stress
  • Reduced … levels
A
  • Reduce Mitochondrial Complex I in Pre-frontal cortex
  • Altered brain mitochondria morphology and distribution
  • Reduced mRNA for genes encoding ETC components and antioxidants
  • BPAD diagnosis associated with SNPs of mitochondrial genes and nuclear genes encoding ETC components
  • Altered lactate levels in blood and CSF
  • Increased markers of oxidative stress
  • Reduced antioxidants levels
46
Q

Multiple line of evidence suggesting alterations of … in Mood Disorders particularly BPAD

A

Multiple line of evidence suggesting alterations of mitochondria in Mood Disorders particularly BPAD

47
Q

Mitochondria - neuronal function

  • Mitochondria are organelles providing chemical energy by oxidative metabolism
  • The central nervous system consumes about …% all of oxygen inspired at rest
  • Neurons function and survival critically depend on … function and … supply
A
  • Mitochondria are organelles providing chemical energy by oxidative metabolism
  • The central nervous system consumes about 20% all of oxygen inspired at rest
  • Neurons function and survival critically depend on mitochondrial function and oxygen supply
48
Q

Primary mitochondrial diseases increase susceptibility to bipolar affective disorder study

  • cross-sectional cohort study
  • On prevalence of Bipolar Disorder Type I and II and other major affective syndromes [major depressive episodes, generalised anxiety disorder]
  • in adults patients with genetically confirmed Primary Mitochondrial Disorders
A
  • cross-sectional cohort study
  • On prevalence of Bipolar Disorder Type I and II and other major affective syndromes [major depressive episodes, generalised anxiety disorder]
  • in adults patients with genetically confirmed Primary Mitochondrial Disorders
49
Q

Bipolar Disorder Treatment - phases

  • Short-term treatment
    • to reduce the … and … the duration of the acute episode and achieve … of symptoms
  • Long-term treatment
    • prevention of … episodes and to achieve adequate …-episode control of residual or chronic mood symptoms
A
  • Short-term treatment
    • to reduce the severity and shorten the duration of the acute episode and achieve remission of symptoms
  • Long-term treatment
    • prevention of new episodes and to achieve adequate inter-episode control of residual or chronic mood symptoms
50
Q

Bipolar Disorder Treatment - phases

  • Short-term treatment
    • …
  • Long-term treatment
    • …
A
  • Short-term treatment
    • to reduce the severity and shorten the duration of the acute episode and achieve remission of symptoms
  • Long-term treatment
    • prevention of new episodes and to achieve adequate inter-episode control of residual or chronic mood symptoms
51
Q

Overview of drug categories for Bipolar Disorder treatment (4)

A
  • Lithium
  • Antipsyhcotics
  • Anticonvulsants
  • Antidepressants
52
Q

Treatment of Depressive episodes (bipolar)

  • Antipsychotics (Quetiapine, lurasidone)
  • F…/Olanzapine combinations
  • … to be co-prescribed with an anti-… drug
  • Consider … (usually with antimanic drug)
A
  • Antipsychotics (Quetiapine, lurasidone)
  • Fluoxetine/Olanzapine combinations
  • Antidepressants to be co-prescribed with an anti-manic drug
  • Consider Lamotrigine (usually with antimanic drug)
53
Q

Treatment of Depressive episodes (Bipolar)

  • Antipsychotics (Q…, L..)
  • Fluoxetine/Olanzapine combinations
  • Antidepressants to be …-… with an anti-manic drug
  • Consider Lamotrigine (usually with … drug)
A
  • Antipsychotics (Quetiapine, lurasidone)
  • Fluoxetine/Olanzapine combinations
  • Antidepressants to be co-prescribed with an anti-manic drug
  • Consider Lamotrigine (usually with antimanic drug)
54
Q

Treatment of Acute Manic episodes

  • … antagonists (haloperidol, olanzapine, risperidone and quetiapine)
  • v…
  • Discontinue any … treatment
A
  • Dopamine antagonists (haloperidol, olanzapine, risperidone and quetiapine)
  • Valproate
  • Discontinue any antidepressant treatment
55
Q

Long-term treatment - Prevention of new episodes (Bipolar)

  • Consider long-term treatment following a … severe … episode
  • … as initial monotherapy (target serum level range: 0.6-0.8 mmol/l)
  • Alternatives (if … ineffective, poorly tolerated or unlikely adherence to treatment):
    • V…
    • D… antagonists/partial agonists
    • C…
A
  • Consider long-term treatment following a single severe manic episode
  • Lithium as initial monotherapy (target serum level range: 0.6-0.8 mmol/l)
  • Alternatives (if Lithium ineffective, poorly tolerated or unlikely adherence to treatment):
    • Valproate
    • Dopamine antagonists/partial agonists
    • Carbamazepine
56
Q

Long-term treatment - Prevention of new episodes (Bipolar)

  • Consider long-term treatment following a single severe manic episode
  • Lithium as initial monotherapy (target serum level range: …-… mmol/l)
  • Alternatives (if Lithium ineffective, poorly … or unlikely … to treatment):
    • Valproate
    • Dopamine …/partial …
    • Carba..
A
  • Consider long-term treatment following a single severe manic episode
  • Lithium as initial monotherapy (target serum level range: 0.6-0.8 mmol/l)
  • Alternatives (if Lithium ineffective, poorly tolerated or unlikely adherence to treatment):
    • Valproate
    • Dopamine antagonists/partial agonists
    • Carbamazepine
57
Q

Antipsychotics

  • D2/D3 antagonist
    • 1st generation: H…
  • D2/D3 antagonists (also targeting 5-HT)
    • (2nd generation: Olanzapine, Risperidone, Quetiapine, Lurasidone, Asenapine, Amisulpride, Clozapine)
  • DA partial … (Aripiprazole)
  • Rapid anti-… effect
  • Often used long-term to maintain same treatment effective in acute episode
  • Long-term adverse effects on …, glucose regulation and lipids [except for Aripiprazole, Amisulpride, and Lurasidone]
  • Full D2 antagonism (Haloperidol) may cause EPSEs
A
  • D2/D3 antagonist
    • 1st generation: Haloperidol
  • D2/D3 antagonists (also targeting 5-HT)
    • (2nd generation: Olanzapine, Risperidone, Quetiapine, Lurasidone, Asenapine, Amisulpride, Clozapine)
  • DA partial agonist (Aripiprazole)
  • Rapid anti-manic effect
  • Often used long-term to maintain same treatment effective in acute episode
  • Long-term adverse effects on weight, glucose regulation and lipids [except for Aripiprazole, Amisulpride, and Lurasidone]
  • Full D2 antagonism (Haloperidol) may cause EPSEs
58
Q

Lithium

  • Element, present in food and drinking water
  • Multiple … of actions
    • Multiple … (including DA)
    • … signalling
    • … factors
  • Anti-… effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
A
  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
59
Q

Lithium

  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and … behaviours
  • Strongest evidence for prevention of … of any polarity
  • … therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
A
  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
60
Q

Lithium

  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every … months for the 1st year
  • Adverse long-term effects on … function with excessive levels
  • Risk of Lithium …
A
  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
61
Q

Lithium

  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including …)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-… effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow … index
  • blood tests every 3 months for the … year
  • Adverse long-term effects on … function with excessive levels
  • Risk of Lithium toxicity
A
  • Element, present in food and drinking water
  • Multiple mechanisms of actions
    • Multiple neurotransmitters (including DA)
    • Cellular signalling
    • Neurotrophic factors
  • Anti-suicidal effects
  • Possible efficacy on impulsive and violent behaviours
  • Strongest evidence for prevention of relapses of any polarity
  • Narrow therapeutic index
  • blood tests every 3 months for the 1st year
  • Adverse long-term effects on Kidney function with excessive levels
  • Risk of Lithium toxicity
62
Q

Antipsychotics

  • …/… antagonist
    • 1st generation: Haloperidol
  • …/… antagonists (also targeting 5-HT)
    • (2nd generation: O…, Risperidone, Quetiapine, Lurasidone, Asenapine, Amisulpride, Clozapine)
  • DA partial agonist (Ar…)
  • Rapid anti-manic effect
  • Often used long-term to maintain same treatment effective in acute episode
  • Long-term adverse effects on weight, … regulation and … [except for Aripiprazole, Amisulpride, and Lurasidone]
  • Full D2 antagonism (Haloperidol) may cause EPSEs
A
  • D2/D3 antagonist
    • 1st generation: Haloperidol
  • D2/D3 antagonists (also targeting 5-HT)
    • (2nd generation: Olanzapine, Risperidone, Quetiapine, Lurasidone, Asenapine, Amisulpride, Clozapine)
  • DA partial agonist (Aripiprazole)
  • Rapid anti-manic effect
  • Often used long-term to maintain same treatment effective in acute episode
  • Long-term adverse effects on weight, glucose regulation and lipids [except for Aripiprazole, Amisulpride, and Lurasidone]
  • Full D2 antagonism (Haloperidol) may cause EPSEs
63
Q

Full D2 antagonism (H…) may cause extrapyramidal side effects

A

Full D2 antagonism (Haloperidol) may cause extrapyramidal side effects

64
Q

Full D… antagonism (Haloperidol) may cause … side effects

A

Full D2 antagonism (Haloperidol) may cause extrapyramidal side effects

65
Q

Anticonvulsants

  • Valproate (valproic acid and sodium valproate)
    • Actions via …, intracellular signalling, sodium channel blockade, epigenetic modulation, etc.
    • Anti-manic and effective in prevention of …
    • Useful in combination, but potential pharmacokinetic interactions
    • not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development
  • Lamotrigine
    • actions via GABA, Glutamate and sodium channel blockade
    • Mostly effective in prevention of depressive relapses
    • … as anti-manic agent
  • Carbamazepine
    • less effective in maintenance treatment than … but may be used as monotherapy if .. ineffective
    • especially in patients who do not show the classical pattern of episodic euphoric mania
A
  • Valproate (valproic acid and sodium valproate)
    • Actions via GABA, intracellular signalling, sodium channel blockade, epigenetic modulation, etc.
    • Anti-manic and effective in prevention of mania
    • Useful in combination, but potential pharmacokinetic interactions
    • not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development
  • Lamotrigine
    • actions via GABA, Glutamate and sodium channel blockade
    • Mostly effective in prevention of depressive relapses
    • Ineffective as anti-manic agent
  • Carbamazepine
    • less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective
    • especially in patients who do not show the classical pattern of episodic euphoric mania
  • almost exclusively effective against manic relapse
  • pharmacokinetic interactions
66
Q

Anticonvulsants

  • …
    • Actions via GABA, intracellular signalling, sodium channel blockade, epigenetic modulation, etc.
    • Anti-manic and effective in prevention of mania
    • Useful in combination, but potential pharmacokinetic interactions
    • not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development
  • L…
    • actions via GABA, Glutamate and sodium channel blockade
    • Mostly effective in prevention of depressive relapses
    • Ineffective as anti-manic agent
  • C…
    • less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective
    • especially in patients who do not show the classical pattern of episodic euphoric mania
A
  • Valproate (valproic acid and sodium valproate)
    • Actions via GABA, intracellular signalling, sodium channel blockade, epigenetic modulation, etc.
    • Anti-manic and effective in prevention of mania
    • Useful in combination, but potential pharmacokinetic interactions
    • not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development
  • Lamotrigine
    • actions via GABA, Glutamate and sodium channel blockade
    • Mostly effective in prevention of depressive relapses
    • Ineffective as anti-manic agent
  • Carbamazepine
    • less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective
    • especially in patients who do not show the classical pattern of episodic euphoric mania
    • almost exclusively effective against manic relapse
    • pharmacokinetic interactions
67
Q

What anticonvulsant is not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development?

A

Valproate

68
Q

Carbamazepine

  • … effective in maintenance treatment than lithium but may be used as … if lithium ineffective
  • especially in patients who do not show the classical pattern of episodic euphoric mania
  • almost exclusively effective against manic …
  • … interactions
A
  • less effective in maintenance treatment than lithium but may be used as monotherapy if lithium ineffective
  • especially in patients who do not show the classical pattern of episodic euphoric mania
  • almost exclusively effective against manic relapse
  • pharmacokinetic interactions
69
Q

Lamotrigine

  • actions via GABA, … and … channel blockade
  • Mostly effective in prevention of … relapses
  • Ineffective as anti-… agent
A
  • actions via GABA, Glutamate and sodium channel blockade
  • Mostly effective in prevention of depressive relapses
  • Ineffective as anti-manic agent
70
Q

Valproate (valproic acid and sodium valproate)

  • Actions via …, … signalling, sodium channel blockade, epigenetic modulation, etc.
  • Anti-… and effective in prevention of mania
  • Useful in combination, but potential … interactions
    • not be used for women of … … potential because of its unacceptable risk to the foetus of … and impaired intellectual development
A
  • Actions via GABA, intracellular signalling, sodium channel blockade, epigenetic modulation, etc.
  • Anti-manic and effective in prevention of mania
  • Useful in combination, but potential pharmacokinetic interactions
    • not be used for women of child bearing potential because of its unacceptable risk to the foetus of teratogenesis and impaired intellectual development
71
Q

Adverse effects of long-term pharmacological treatments for BPAD

  • … gain (most medications, particularly Olanzapine and Quetiapine)
  • … syndrome (Olanzapine, Quetiapine, Risperidone)
  • Hyper… (Dopamine antagonists)
  • Tardive … (much reduced risk with newer agents)
  • … damage (e.g. Valproate)
  • … and … dysfunction (poorly regulated Lithium)
A
  • Weight gain (most medications, particularly Olanzapine and Quetiapine)
  • Metabolic syndrome (Olanzapine, Quetiapine, Risperidone)
  • Hyperprolactinemia (Dopamine antagonists)
  • Tardive dyskinesia (much reduced risk with newer agents)
  • Liver damage (e.g. Valproate)
  • Kidney and Thyroid dysfunction (poorly regulated Lithium)
72
Q

Adverse effects of long-term pharmacological treatments for BPAD

  • Weight gain (most medications, particularly … and …)
  • Metabolic syndrome (…, …, …)
  • Hyperprolactinemia (Dopamine …)
  • Tardive dyskinesia (much reduced risk with … agents)
  • Liver damage (e.g. V…)
  • Kidney and Thyroid dysfunction (poorly regulated L…)
A
  • Weight gain (most medications, particularly Olanzapine and Quetiapine)
  • Metabolic syndrome (Olanzapine, Quetiapine, Risperidone)
  • Hyperprolactinemia (Dopamine antagonists)
  • Tardive dyskinesia (much reduced risk with newer agents)
  • Liver damage (e.g. Valproate)
  • Kidney and Thyroid dysfunction (poorly regulated Lithium)
73
Q

Valproate can cause damage to what organ?

A

liver damage

Year 2 Medicine (162 decks)

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