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depression Flashcards

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1
Q

what is mood

A

conscious state of mind or predominant emotion

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2
Q

definition of mood disorder

A

psychological - abnormal elevation or lowering of mood

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3
Q

what are the two types of unipolar depression?

A

Reactive depression
endogenous depression

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4
Q

What is reactive depression?

A

75%
non-familial
associated with stressful event
anxiety and agitation
temporary

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5
Q

What is Endogenous depression?

A

25%
familial
not related to external stressors
more likely episodic, recurrent & chronic

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6
Q

What are the emotional symptoms of depression?

A

misery
apathy
pessimism
negative thoughts
loss of self-esteem
feelings of guilt
feelings of inadequacy
indecisiveness
lack of motivation
anhedonia
loss of reward
suicidal thoughts

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7
Q

What are the biological symptoms of depression?

A

retardation of thought
slowness of action
loss of libido
sleep disturbance
loss of appetite
weight loss
GI disturbances

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8
Q

Monoamine hypothesis is a theory of depression. What are the amino acid precursors?

A

Catecholamines:
catechol ring (benzene 2 hydroxyl side groups)
Dopamine - DA
Noradrenaline - NA
Adrenaline - A

Indolamine:
indole ring (six-membered benzene ring fused to a five-membered nitrogen-containing)
Serotonin - 5HT

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9
Q

What are the steps of synthesis and inactivation for Catecholamines?

A

Synthesis:
tyrosine
- Hydroxylation
L-DOPA
- Decarboxylation
dopamine
In noradrenergic neurones (only)
- Hydroxylation
Noradrenaline

Inactivation:
Reuptake
- NET (norepinephrine transporter)
- DAT (dopamine transporter)
Degradation
- monoamine oxidase (MAO)
- catechol-o-methyltransferase (COMT)

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10
Q

What are the steps of synthesis and inactivation for 5HT (seratonin)

A

Synthesis:
tryptophan
- Hydroxylation & Decarboxylation
5HT

Inactivation:
Reuptake
- SERT (seratonin transporter)
Degradation
- monoamine oxidase (MAO)

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11
Q

What is the monoamine theory of depression?

A
  • Depression - a functional deficit of 5HT and/or noradrenaline in the brain
  • Mania - functional excess
  • Originally from observations that:
    1. reserpine depletes NA/5HT vesicular stores – depression like behaviour
    2. isoniazid used for TB - elevated mood - blocked MAO
    3. ECT for psychosis elevated mood – increased amine metabolites
  • Subsequently found
    4. tryptophan increased 5HT elevated mood
    5. tryptophan hydroxylase blockade depresses mood
    6. inhibiting NA synthesis – depresses mood/calms mania
    7. tricyclic antidepressants - developed for psychosis – elevated mood - blocked amine re-uptake
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12
Q

Monoamine oxidase inhibitors (MAO) - to treat depression

A

Preferred substrates
- MAOA: NA and 5HT
- MAOB: DA
Elevates monoamines in cytoplasm not vesicles
Spontaneous leakage increases receptor activation
Cheese reaction
- Tyramine (cheese etc) normally metabolized fully in gut by MAO
- In high quantities…….
- Tyramine: sympathomimetic effects
- Severe hypertension

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13
Q

What are the conventional antidepressants?

A

MAO inhibitors
TCAs
SSRIs
SNRIs
Atypical

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14
Q

How to treatdepression with ‘classical’ tricyclic antidepressants?

A

First generation, still widely used, serious side effects
Block re-uptake of amines by nerve terminals
- 5HT=NA&raquo_space;DA (5-HT and NA
transporter blockade )
Elevate released amines in synaptic cleft
Competitive block with natural substrate
- Non-selective - imipramine,
amitriptyline, clomipramine
- NA selective - nortriptyline,
desipramine
Also block postsynaptic receptors
- Side effects : Muscarinic ACh,
histamine, 5HT

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15
Q

What are the issues with tricyclic antidepressants (TCAs)?

A

Major side effects
- Sedation
- Atropine-like (muscarinic
blockade)
- Postural hypotension
- Mania and convulsions
- Dysrhythmia and heart block
Acute overdose
- Prominent antimuscarinic
- Confusion, mania
- Cardiac arrhythmias
- Coma
- Respiratory depression
- Hypoxia
Drug interactions
- Alcohol
- Hypotensives
- NSAIDs
- MAOIs

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16
Q

What are Selective Seritonin Reuptake Inhibitors?

A

5HT>NA Generally
Based on concept that
- ‘biological’ components of
depression sensitive to effects
on NA
- ‘emotional’ components
sensitive to effects on 5-HT
fluoxetine (Prozac) first in class
- fluvoxamine, paroxetine,
citalopram, sertraline followed
- most commonly prescribed antidepressants

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17
Q

Issues with SSRIs?

A

Unwanted effects
General increased stimulation of 5HT receptors
With MAOIs – risk of Serotonin Syndrome (CAN BE FATAL)
- Tremor, agitation, increased
reflexes, hyperthermia,
cardiovascular collapse
Withdrawal effects
- Adaptation changes linked
with chronic treatment?
- Anxiety / agitation
- Dose reduction

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18
Q

Facts about Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

A

Non selective for 5-HT and NA
Duloxetine
Venlafaxine

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19
Q

Issues with SNRIs?

A

Unwanted effects
- Largely due to enhanced
activation of adrenoreceptors
- Headache
- Insomnia

Overdose – CNS depression

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20
Q

Rapid-Actin antidepressants (RAADs)

A
  • Ketamine (NMDA receptor
    antagonist)
  • Rapid and sustained
    antidepressant effects
  • Rarely in UK – looked at for
    patients who have not
    responded to treatments
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21
Q

What are the bipolar disorders?

Study These Flashcards
A

Bipolar 1
Bipolar 2
Cyclothymia
Mania

22
Q

Bipolar 1 disorder

Study These Flashcards
A

severe mood swings from mania to depression.

23
Q

Bipolar 2 disorder

Study These Flashcards
A

milder mood swings milder mania (hypomania) alternating with severe depression.

24
Q

Cyclothymia disorder

Study These Flashcards
A

brief hypomania alternating with brief milder depressive symptoms
- not as long-lasting as seen in
full mania or depressive
episodes.

25
Mania disorder
Mood - jolly, infectious, labile, repetitive Thought - excitement, - exaggeration - misrepresentation, distortion, delusion - hallucination Activity - incessant, disinhibited Sleep - short but deep
26
How to treat bipolar disorders?
Lithium - ~80% show stabilisation of mood - Often given with antidepressants - Used acutely - only reduce mania - Used prophylactically - can reduce both mania and depression - Potentially serious side effect = lithium toxicity - Needs plasma monitoring - effective at 0.5-1 mM but toxic >1.5 mM Anticonvulsants - faster onset, safer, less side effects - e.g. carbamazepine, valproate, lamotrigine - control neuronal excitability Atypical antipsychotics - faster onset, safer - e.g. olanzapine, risperidone, quetiapine, aripiprazole - probably same as positive effects in psychosis
27
Asessment of depression
- The DSM-V system requires at least 5 out of 9 for a diagnosis of major depression. - Symptoms should be present for at least 2 weeks and each symptom should be present at sufficient severity for most of every day. - The DSM-V system require at least one key symptom (low mood, loss of interest and pleasure or loss of energy to be present.
28
What are the key symptoms of depression?
- Persistent sadness or low mood, and/or - Marked loss of interests or pleasure. At least one of these, most days, most of the time for at least 2 weeks.
29
What are the associated symptoms of the key symptoms for depression?
- Disturbed sleep - Decreased or increased appetite and/or weight - Fatigue or loss of energy - Agitation or slowing of movements - Poor concentration or indecisiveness - Feelings of worthlessness or excessive or inappropriate guilt - Suicidal thoughts or acts.
30
What lifestyle changes should be discussed with a patient for depression?
regular physical activity, eating a healthy diet, not over-using alcohol, and getting enough sleep
31
Management of mild depression?
1. NOTHING 2. Psychological and psychosocial therapy (such as guided self-help, CBT, or BA) 3. Pharmacotherapy – SSRIs: Citalopram, Escitalopram, Sertraline, Fluoxetine 4. Herbal remedies such as St John’s Wort? NO 
32
Management of moderate to severe depression?
1. Psychological therapy AND drug therapy 2. Psychological therapy OR drug therapy Pharmacotherapy – 1) SSRIs; or 2) SNRIs; or 3) TCA 3. Electroconvulsive therapy (ECT)
33
How and when a patient should be reviewed and duration of treatment?
- Patients reviewed every 1-2 weeks at the start - Response to treatment should be assessed within 2-4 weeks - Effects of treatment usually seen within 4 weeks - Treatment should be continued for at least 6 months - Following remission - treatment continued at the same dose for at least 6 months
34
Which depression drug is safest to use in patients with unstable angina or a recent MI?
Sertraline
35
Which antidepressant should be first line for treating depression?
SSRIs - Indicated for depression and panic disorder - SSRIs are better tolerated and are safer in overdose than other classes of antidepressants - SSRIs are less sedating and have fewer antimuscarinic and cardiotoxic effects than TCAs.
36
What are the contraindications of SSRIs?
- Poorly controlled epilepsy - Should NOT be used if patient enters a manic phase - QT-interval prolongation
37
Give drug names of 6 SSRIs
1. Citalopram 2. Escitalopram 3. Fluoxetine 4. Sertraline 5. Fluvoxamine Maleate 6. Paroxetine
38
What are SNRIs indicated for?
- major depression - generalised anxiety disorder - social anxiety disorder - panic disorder - menopausal symptoms, particularly hot flushes in women with breast cancer
39
Name 3 SNRIs
1. Effexor (venlafaxine HCL) Tablets 2. Desvenlafaxine Extended Release Tablets 3. Duloxetine Delayed-release Capsules
40
What are TCAs indicated for?
- major depression - neuropathic pain - migraine prophylaxis - emotional liability in patients with multiple sclerosis - abdominal pain or discomfort (in patients who have not responded to laxatives, loperamide, or antispasmodics)
41
Name 3 TCAs
1. Amitriptyline 2. Anafranil 3. Notriptyline Tablets
42
What are MAOIs indicated for?
Mainly major depressive illness
43
When taking MAOIs what foods should be avoided due to dangerous interactions?
Foods rich in tyramine: - Cured, smoked, or processed meats include dried sausages like pepperoni and salami ... - Sauerkraut, kimchi, pickled beets, pickled cucumbers ... - Also, fermented soy products like tofu, miso, and soy sauce
44
Name 4 MAOI drugs
1. Nardil (phenelzine sulfate) - acts on MAO-A 2. Marplan (isocarboxazid) - acts on MAO-A 3. Aurorix (moclobemide) - acts on MAO-A 4. Selegiline HCL - acts on MAO-B
45
Contraindications of MAOIs
Cerebrovascular disease Not indicated in manic phase Severe cardiovascular disease phaeochromocytoma
46
What are the most common side effects for discontinuing a antidepressant?
GI disturbances, headache, anxiety, dizziness, paraesthesia, electric shock sensation in the head, neck, and spine, tinnitus, sleep disturbances, fatigue, influenza-like symptoms, and sweating.
47
Failure to respond to the drug given. What to do?
- Initially, may require an increase in the dose, or switching to a different SSRI or mirtazapine. - Second-line choices include lofepramine, moclobem ide, and reboxetine. - Other TCAs and venlafaxine should be considered for more severe forms of depression. - Irreversible MAOIs should only be prescribed by specialists. - Failure to respond to a second antidepressant: Add another antidepressant of a different class. or use of an augmenting agent (e.g. lithium, aripiprazole [unlicensed], olanzapine [unlicensed], quetiapine, or risperidone [unlicensed]). - Electroconvulsive therapy may be initiated in severe refractory depression.
48
Treatment of bipolar disorder with antipsychotics
- Haloperidol, olanzapine, quetiapine and risperidone - If response is inadequate, then lithium or valproate may be added. - Asenapine - moderate to severe manic episodes - Olanzapine - long-term management
49
treatment of bipolar disorder with benzodiazepines
- e.g. lorazepam - used in initial stages of treatment for behavioural disturbance or agitation - Should not be used for long periods due to dependence
50
Treatment for bipolar disorder with Valproate
- Valproic acid and sodium valproate - can be used for manic episodes if lithium is not tolerated or contra- indicated. - MHRA - high teratogenic risk in females of child-bearing potential.
51
Treatment for bipolar disorder with Carbamazepine
Long-term management, to prevent recurrence of acute episodes in patients unresponsive to lithium therapy

CNS 201 (9 decks)

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