Pharmacological Treatment of Affective and Anxiety Disorders Flashcards

1
Q

Antidepressants - mechanism

A
  • Not fully known
  • To do with the neurotransmitters serotonin and noradrenaline
    • Increase levels of these in brain
    • This changes receptors in the brain
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2
Q

Antidepressants - indications

A
  • Unipolar and bipolar depression
  • Organic mood disorders
  • Schizoaffective disorder
  • Anxiety disorders
    • Including OCD, panic, social phobia, PTSD
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3
Q

Antidepressants - general guidelines

A
  • Antidepressant efficacy is similar, so selection based on past history of response, side effect profile and coexisting medical conditions
  • Delay of 2-4 weeks after therapeutic dose is achieved before symptoms improve
    • If no symptoms seen after at least 2 months and adequate dose, switch to another antidepressant or augment with another agent
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4
Q

What is selection of antidepressant based on?

A
  • Antidepressant efficacy is similar, so selection based on past history of response, side effect profile and coexisting medical conditions
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5
Q

How long do antidepressants take to work?

A
  • Delay of 2-4 weeks after therapeutic dose is achieved before symptoms improve
    • If no symptoms seen after at least 2 months and adequate dose, switch to another antidepressant or augment with another agent
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6
Q

What are the different classess of antidepressants?

A

Classification:

  • Tricyclics (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin/noradrenaline reuptake inhibitors (SNRIs)
  • Novel antidepressants
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7
Q

What does the following stand for:

  • TCAs
  • MAOIs
  • SSRIs
  • SNRIs
A
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8
Q

What are the 2 types of TCAs?

A
  • Tertiary TCAs
    • Have tertiary amine side chains
    • These are prone to cross react with other types of receptors leading to side effects
    • Drugs – Imipramine, Amitriptyline, Doxepin, Clomipramine
  • Secondary TCAs
    • Often metabolites of tertiary amines
    • Primarily blocks noradrenaline
    • Drugs – Desipramine, Notritriptyline
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9
Q

Mechanism of:

  • tertiary TCAs
  • secondary TCAs
A
  • Tertiary TCAs
    • Have tertiary amine side chains
    • These are prone to cross react with other types of receptors leading to side effects
    • Drugs – Imipramine, Amitriptyline, Doxepin, Clomipramine
  • Secondary TCAs
    • Often metabolites of tertiary amines
    • Primarily blocks noradrenaline
    • Drugs – Desipramine, Notritriptyline
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10
Q

Drugs of:

  • tertiary TCAs
  • secondary TCAs
A
  • Tertiary TCAs
    • Have tertiary amine side chains
    • These are prone to cross react with other types of receptors leading to side effects
    • Drugs – Imipramine, Amitriptyline, Doxepin, Clomipramine
  • Secondary TCAs
    • Often metabolites of tertiary amines
    • Primarily blocks noradrenaline
    • Drugs – Desipramine, Notritriptyline
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11
Q

Effect - TCAs

A
  • Increases both serotonin, dopamine and noradrenaline
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12
Q

Side effects - TCAs

A
  • Potentially unacceptable side effect profile
    • Antihistaminic
    • Anticholinergic
  • Lethal in overdose
  • Can cause QT lengthening
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13
Q

Mechanism - MAOIs

A
  • Bind irreversible to monoamine oxidase, preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
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14
Q

Indications - MAOIs

A
  • Resistant depression
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15
Q

Side effects - MAOIs

A
  • Orthostatic hypertension
  • Weight gain
  • Dry mouth
  • Sedation
  • Sexual dysfunction
  • Sleep disturbance
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16
Q

Drug interactions - MAOIs

A
  • Tryamine-rich foods or sympathomimetics
    • Causes “cheese reaction”, which is a hypertensive crises
    • Foods include cheese and red wine
  • If taken with meds that increase serotonin or have sympathomimetic actions
    • Serotonin syndrome
    • Side effects – abdominal pain, diarrhoea, sweats, tachycardia, HTN, myoclonus, irritability, delirum. Maybe even hyperpyrexia, cardiovascular shock and death
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17
Q

What is the most commonly used class of antidepressants?

A

SSRIs

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18
Q

Drugs - SSRIs

A
  • Sertraline
  • Fluoxetine (Prozac)
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19
Q

Mechanism - SSRIs

A
  • Block the presynaptic serotonin reuptake
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20
Q

Indications - SSRIs

A
  • Anxiety
  • Depression
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21
Q

Side effects - SSRIs

A
  • GI upset
  • Sexual dysfunction (30+%)
  • Anxiety
  • Restlessness
  • Nervousness
  • Insomnia
  • Fatigue or sedation
  • Dizziness
  • Very little risk of cardiotoxicity in OD
  • Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria if stopped quickly
  • Activation syndrome
    • Caused by increase in serotonin
    • Symptoms – nausea, increased anxiety, panic and agitation
    • Typically lasts 2-10 days
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22
Q

What is activation syndrome caused by?

A
  • Caused by increase in serotonin
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23
Q

What are symptoms of activation syndrome?

A
  • Symptoms – nausea, increased anxiety, panic and agitation
  • Typically lasts 2-10 days
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24
Q

Drugs - SNRIs

A
  • Venlafaxine
  • Duloxetine
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25
Q

Mechanism - SNRIs

A
  • Inhibit serotonin and noradrenergic reuptake like the TCAs
    • But without the antihistamine, antiadrenergic or anticholinergic side effects
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26
Q

Indications - SNRIs

A
  • Depression
  • Anxiety
  • Possibly neuropathic pain
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27
Q

Drugs - novel antidepressants

A
  • Mirtazapine
28
Q

Mechanism - novel antidepressants

A
  • 5HT2 and 5HT3 receptor antagonist
29
Q

Side effects - noval antidepressants

A
  • Increase of serum cholesterol
  • Sedating
  • Weight gain
30
Q

What can be done to overcome treatment resistance?

A
  • Combination of antidepressants
    • Such as SNRI with Mirtazepine
  • Or adjunctive treatment with lithium
  • Or adjunctive treatment with atypical antipsychotic
    • Such as Quetipaine, Olanzapine or Aripiprazole
  • ECT
31
Q

What is a typical combination of antidepressants to overcome treatment resistance?

A
  • Such as SNRI with Mirtazepine
32
Q

What are examples of atypical antipsychotis combined with antidepressants to overcome treatment resistance?

A
  • Such as Quetipaine, Olanzapine or Aripiprazole
33
Q

How is medication used for prophylaxis?

A

When you treat someone for an episode, continue medication for prophylaxis for future relapse:

  • First episode
    • Continue for 6 months to year
  • Second episode
    • Continue for 2 years
  • Third episode
    • Discuss lifelong
34
Q

How long should someone be given prophylaxis antidepressants after:

  • first episode
  • second episode
  • third episode
A
  • First episode
    • Continue for 6 months to year
  • Second episode
    • Continue for 2 years
  • Third episode
    • Discuss lifelong
35
Q

Describe the pharmacological management of anxiety?

A
  • Serotonergic anti-depressant agents so SSRIs and SNRIs
  • Tricyclic Chlomipramine
  • Adjunctive treatments mainly anti-psychotics Risperidone or Quetiapine
  • Avoid symptomatic relief such as diazepam
36
Q

What are indications for mood stabilisers?

A
  • Bipolar
  • Cyclothymia
  • Schizoaffective
37
Q

What are the different classes of mood stabilisers?

A
  • Lithium
  • Anticonvulsants
  • Antipsychotics
38
Q

How do you decide what mood stabiliser to use?

A

Which one you select depends on what you are treating and side effect profile

39
Q

Lithium - mechanism

A
  • Not sure completely how it works
40
Q

Lithium - indications

A
  • Long term prophylaxis for
    • Mania
    • Depressive episodes
41
Q

What are some factors predicting a positive response to lithium?

A
  • Prior long-term response or family member with good response
  • Classic pure mania
  • Mania is followed by depression
42
Q

What should be done before starting lithium?

A
  • Before starting
    • Baseline U&E and TSH
    • In woman, pregnancy test as during first trimester associated with Ebsteins anomaly
  • Monitoring
    • Steady state achieved after 5 days, check 12 hours after last dose
    • Once stable check level 3 months and TSH and creatinine 6 months
  • Goal
    • Blood level between 0.6-1.2
43
Q

How is lithium use monitored?

A
  • Before starting
    • Baseline U&E and TSH
    • In woman, pregnancy test as during first trimester associated with Ebsteins anomaly
  • Monitoring
    • Steady state achieved after 5 days, check 12 hours after last dose
    • Once stable check level 3 months and TSH and creatinine 6 months
  • Goal
    • Blood level between 0.6-1.2
44
Q

What are the goal levels for lithium use?

A
  • Blood level between 0.6-1.2
45
Q

Lithium - side effects

A
  • GI distress
    • Including reduced appetite, nausea/vomiting, diarrhoea
    • Most common
  • Thyroid abnormalities
  • Nonsignificant leukocytosis
  • Polyurua/polydipsia secondary to ADH antagonist
    • Small number can interstitial renal fibrosis leading to renal failure
  • Hair loss, acne
  • Reduces seizure threshold, cognitive slowing, intention tremor
  • Lithium toxicity
46
Q

What are the different severities of lithium toxicity?

A
  • Mild
    • Levels 1.5-2
    • See vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
  • Moderate
    • Levels 2-2.5
    • See nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
  • Severe
    • >2.5
    • Generalised convulsions, oligura and renal failure
47
Q

What are clinical features of lithium toxicity:

  • mild
  • moderate
  • severe
A
  • Mild
    • Levels 1.5-2
    • See vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
  • Moderate
    • Levels 2-2.5
    • See nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
  • Severe
    • >2.5
    • Generalised convulsions, oligura and renal failure
48
Q

What are lithium blood levels for the following severities of lithium toxicity:

  • mild
  • moderate
  • severe
A
  • Mild
    • Levels 1.5-2
    • See vomiting, diarrhoea, ataxia, dizziness, slurred speech, nystagmus
  • Moderate
    • Levels 2-2.5
    • See nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
  • Severe
    • >2.5
    • Generalised convulsions, oligura and renal failure
49
Q

Anticonvulants - drugs

A
  • Valproic acid (Depakote)
  • Carbamazepine (Tegretol)
  • Lamotrigine (Lamictal)
50
Q

Valproic acid - indications

A
  • Mania prophylaxis
    • As effective as lithium, not as effective in depression prophylaxis
51
Q

What are factors predicting a positive response to Valproic acid?

A
  • Rapid cycling patients (F>M)
  • Comorbid substance issues
  • Mixed patients
  • Patients with comorbid anxiety disorders
52
Q

What should be done before giving Valproic acid?

A
  • Before
    • Baseline LFT, pregnancy test and FBC
  • Monitoring
    • Steady state achieved after 4 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level between 50-125
53
Q

How is Valproic acid monitored?

A
  • Before
    • Baseline LFT, pregnancy test and FBC
  • Monitoring
    • Steady state achieved after 4 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level between 50-125
54
Q

What is the target blood level of Valproic acid?

A
  • Before
    • Baseline LFT, pregnancy test and FBC
  • Monitoring
    • Steady state achieved after 4 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level between 50-125
55
Q

Valproic acid - contraindications

A
  • Woman of child bearing age
56
Q

Valproic acid - side effects

A
  • Thrombocytopenia and platelet dysfunction
  • Nausea, vomiting and weight gain
  • Sedation, tremor
  • Hair loss
57
Q

Carbamazepine - indications

A
  • First line treatment for acute mania and mania prophylaxis
  • Rapid cyclers and mixed patients
58
Q

What should be done before giving Carbamazepine?

A
  • Before
    • Baseline LFT, FBC, ECG
  • Monitoring
    • Steady state achieved after 5 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level 4-12mcg/ml
59
Q

How is Carbamazepine monitored?

A
  • Before
    • Baseline LFT, FBC, ECG
  • Monitoring
    • Steady state achieved after 5 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level 4-12mcg/ml
60
Q

What is the goal blood level of Carbamazepine?

A
  • Before
    • Baseline LFT, FBC, ECG
  • Monitoring
    • Steady state achieved after 5 days, check 12 hours after last dose and repeat CBC and LFTs
  • Goal
    • Target level 4-12mcg/ml
61
Q

Carbemazepine - side effects

A
  • Rash
    • Most common
  • Nausea, vomiting, diarrhoea
  • Sedation, dizziness, ataxia, confusion
  • AV conduction delays
  • Aplastic anaemia and agrunocytosis
  • Water retention
  • Drug-drug interactions
    • Check BNF
62
Q

Lamotrigine - indications

A
  • Similar to other anticonvulsants
  • Also used for neuropathic/chronic pain
63
Q

What should be done before giving lamotrigine and what dose should be used?

A
  • Before
    • Baseline LFT
  • Initiation
    • Start with 25mg daily for 2 weeks then increase to 50mg after 2 weeks then increase to 100mg after 2 weeks
64
Q

Lamotrigine - side effects

A
  • If titrate up doses to quickly
    • Serious rash – toxic epidermal necrolysis and Stevens Johnson’s syndrome
    • If any rash develops, discontinue medication immediately
  • Nausea/vomiting
  • Sedation, dizziness, ataxia, confusion
65
Q

Lamotrigine - drug interactions

A
  • Drugs that increase Lamotrigine levels
    • VPA (doubles concentration so use slower dose titration)
    • Sertraline
66
Q

What antipsychotics can be used as mood stabilisers?

A