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Pharmacotherapeutics Theory 2 > Major Depressive Disorder > Flashcards

Major Depressive Disorder Flashcards

1
Q

What criteria is used for the diagnosis of MDD?

A

DSM V is used for the diagnosis of Major Depressive Disorder

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2
Q

What is MDD?

A

MDD is a mood state characterised by significantly lowered mood and a loss of interest or pleasure in activities that are normally enjoyable

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3
Q

A major depressive episode can be distinguished from ‘normal’ depression by what?

A

A major depressive episode can be distinguished from ‘normal’ depression by its severity, persistence, duration and the presence of characteristic symptoms e.g. sleep disturbances

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4
Q

What are the Signs of Depression

  • Emotional/Mental Signs
  • Physical Signs
A
  • Emotional/Mental Signs
    • Depressed mood
    • Anhedonia
    • Low self-esteem
    • Anxiety
    • Pre-occupation with negative thoughts
    • Poor concentration
    • Confused and indecisive
  • Physical Signs
    • Headache
    • Chronic fatigue
    • Disturbed sleep
    • GI complaints
    • Sexual dysfunction
    • Menstrual problems
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5
Q

Assessing Severity

What is a Mild Episode?

A

Few symptoms beyond the minimum required to make the diagnosis

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6
Q

Assessing Severity

What is a Severe Episode?

A
  • Most criteria present
  • Marked interference with social and/or occupational functioning, producing clear-cut observable disability
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7
Q

When Assessing Severity, what else should be considered?

A

Nature of symptoms (e.g. suicidal thoughts and behaviour) should also be considered in assessing severity

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8
Q

What is the Self-Test for Depression?

A

PHQ-9

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9
Q

What are the 5 Subtypes of Depression?

A
  • Severe with psychotic features
    • Hallucination, delusions
  • Chronic depression
    • MDD for at least 2 years and several episodes
    • The more recurrent episodes left untreated → becomes chronic
  • With atypical features
    • Eat a lot, weight gain, sleep a lot
  • With seasonal pattern
    • Don’t see much sunlight
  • Postpartum onset
    • Happens within 4 wks after birth
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10
Q

What factors should be assessed when assessing a patient with depression?

A
  • Risk – suicide, self-harm
  • Psychosocial aspects
  • Premorbid personality – how they manage stress
  • Medication – change in meds, new drugs
  • Bipolar disorder
  • Comorbid anxiety
  • Comorbid substance abuse
  • Other physical conditions
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11
Q

What is the Aim of Treating MDD?

A
  • Relieve psychological and physical symptoms
  • Improve functional capacity
  • Reduce the likelihood of self-harm or suicide
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12
Q

What are the 2 Treatment Options for MDD?

A
  • Non-pharmacological: psychological, ECT, others
  • Pharmacological: Antidepressants, complementary therapies
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13
Q

List the Types of Non-Pharmacological Therapies

A
  • Psychotherapy
    • Cognitive Behavioural Therapy
    • Interpersonal Therapy
  • Electroconvulsive Therapy (ECT)
  • Others
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14
Q

Non-Pharmacological Therapies: Psychotherapy

  • When is it used?
  • Is it used in Combination?
A
  • First line in mild to moderate disease if patient is able and willing to participate
  • Combination of psychotherapy and medication may be advantageous for those who have partial response to either treatment alone or those with chronic course of illness
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15
Q

Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT)

  • What is it?
  • Does it work quickly?
  • How is it administered?
  • Is treatment the same for everyone?
A
  • Passing an electric current through the brain to produce a seizure for a therapeutic purpose
  • Quick results
  • Administered under GA and muscle relaxant
  • Personalised treatment to reduce risk of adverse effects and also look at brain
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16
Q

Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT) should be considered in who?

A
  • Should be considered in severely depressed patients who have any of the following (first line):
    • Psychotic depression
    • Poor response to several adequate courses of antidepressant drug
    • Severe reduction in food and fluid intake
    • Strong suicidal ideation
    • Catatonia
    • Previous good response to ECT
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17
Q

Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT)

  • What drugs need to be stoped in ECT?
A
  • ECT and psychotropic drugs
  • BZDs – tapered and ceased
  • Anti-epileptics – different approaches
  • Antidepressants – taper and discontinue before ECT
  • Lithium – doesn’t impair effectiveness but can cause severe postictal confusion even at low serum concentration
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18
Q

Non-Pharmacological Therapies: What are the Other Therapies?

A
  • To reserve unhealthy or destructive lifestyle habits and consider other activities that may relieve stress and facilitate well-being
    • Exercise
    • Light therapy (SAD)
    • Relaxation therapy
    • Message
    • Yoga
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19
Q

The choice of drug in MDD is determined by what?

A
  • Antidepressant safety in overdose
  • Response (or lack of) to previous antidepressant treatment
  • Adverse effect profile (or previous treatment)
  • Family history of response to treatment
  • Patient comorbidities
  • Risks of drug interaction with other concomitantly administered drugs
20
Q

The choice of drug in MDD is determined by what: Antidepressant safety in overdose

  • Most Toxic:
  • Mid-Range:
  • Least Toxic:
A
  • Most Toxic: TCAs and MAOis
  • Mid-Range: Venlafaxine
  • Least Toxic: SSRis, Mirtazapine, Reboxetine, Mianserin, Moclobemide
21
Q

The choice of drug in MDD is determined by what: Adverse effect profile (or previous treatment)

A
  • Weight gain and sedation (mirtazapine)
    • Shouldn’t be taken in morning but suitable for patients with depression + insomnia (taken at night)
    • Concurrent use with other meds that increases the risk of weight gain
      • Not significant especially depression + anorexia
  • Anti-cholinergic side effects (TCAs)
    • Dry mouth, cracked lips, constipation, mydriasis, blurred vision
22
Q

Expectations of Starting Treatment

  • Time after starting: 4-6 Weeks
  • Expectation of Treatment:
A
  • Time after starting: 4-6 Weeks
  • Expectation of Treatment: Adequate Trial Period
23
Q

What are the Recommendations for someone who has initiated treatment?

  • Responder
  • Partial Repsonder
  • Non-Responder
A
  • Either way, initiate treatment and assess response after 2-4 weeks
  • Responder = continue treatment at this dose​
  • Partial Repsonder = increase dose
  • Non-Responder = increase dose
  • Then
    • Assess response after 2-4 weeks
      • Partial responder
        • Increase dose further if possible
        • Change drug
      • Non-Responder
        • Change drug
24
Q

If Treatment Fails what do you have to consider?

A
  • If patient cycling - is patient bipolar?
  • Is patient adhering?
  • Underlying conditions?
  • Patient experiencing A/Es so not taking meds?
  • Is dose and duration adequate to identify non-responder?
  • Is there concomitant drug and substance abuse?
  • Drug interactions affecting serum levels?
25
Q

What is a washout period?

A

An appropriate interval when changing from one antidepressant to another is recommended to avoid interactions (washout period)

26
Q

What do you have to be mindful of when switching antidepressants?

A
  • Patient’s particular situation (concurrent medication, drug history, physical health, considerable inter-individual variation in elimination half-lives)
  • Dose of old and new drugs (includes PK of parent drug, presence of an active metabolite)
27
Q

List the 3 types of Switching Strategies

A
  • Conservative switch
  • Moderate switch
  • Direct switch
28
Q

Switching Strategies: What is Conservative Switch?

A
  • Gradually reduce and stop first A/D
  • Drug-free washout interval of five half-lives of the first A/D
  • The new A/D is started according to its dose recommendation
29
Q

Switching Strategies: What is Moderate Switch?

A
  • Gradually reduce and stop first A/D
  • Drug-free washout interval of 2-4 days
  • The new A/D is started at low dose
30
Q

Switching Strategies: What is Direct Switch?

A
  • The first A/D is stopped
  • The second A/D is started the next day at the usual therapeutic dose
31
Q

List the 4 options for Treatment-Resistant Depression

A
  • ECT
  • Augmentation with lithium
  • Augmentation with second generation antipsychotics
  • Augmentation with T3
32
Q

Treatment-Resistant Depression: Discuss ECT

A

Quick response, follow up with drug treatment

33
Q

Treatment-Resistant Depression: Discuss Augmentation with lithium

A

Has unfavourable ADR profile and long-term risk of thyroid and renal dysfunction

34
Q

How Long should Treatment Last in MDD?

  • To reduce the risk of relapse?
  • People at high risk?
  • Risk factors include
A
  • To reduce the risk of relapse, continue for 6-12 months after remission of symptoms
  • People at high risk of recurrence should continue for 2-3 years or more
  • Risk factors include:
    • Residual depressive symptoms
    • History of 3 or more prior episodes, or 2 or more in the last 5 years
    • History of severe depression (with psychotic symptoms or serious suicide attempt)
35
Q

How should treatment be discontinued?

A
  • Should be tapered slowly, rather than stopped abruptly, to reduce the risk of discontinuation syndrome (insomnia, nausea, postural imbalance, sensory disturbances, hyperarousal and flu-like symptoms)
  • General rule: every week, reduce by half until patient is taking half the lowest dose possible after which you can stop a week later
  • If ceasing completely, tapering may need to be undertaken more slowly to prevent relapse
36
Q

How to avoid withdrawal effects?

  • End of Rx course
  • Changing drugs
A
  • End of Rx Course: Taper slowly and monitor for withdrawal
  • Changing Drugs: Stopping or rapid tapering to minimise disruption to Rx. Patients should be educated about possible effects to watch out for
37
Q

What are 4 issues to consider with A/Ds?

A
  • Bleeding
  • Hyponatraemia
  • Serotonin syndrome (toxicity)
  • SSRIs and hepatic enzymes
38
Q

Issues to Consider with A/Ds: Bleeding

  • What do SSRIs inhibit?
  • Is the risk high?
  • Increased risk with what?
A
  • SSRIs inhibit uptake of serotonin into platelets
  • Risk is relatively low
  • Increased with use of NSAIDs, anti-platelet
39
Q

Issues to Consider with A/Ds: Hyponatraemia

  • What drugs have the risk?
  • Is risk high?
  • If SSRI?
A
  • SSRIs, SNRIs, TCAs and MAOIs
  • Risk may be low
  • Can be severe: could lead to coma and death
  • If SSRI, cease agent and use different SSRI, if not successful, consider moclobemide or reboxetine
40
Q

Issues to Consider with A/Ds: Serotonin Syndrome (toxicity)

  • How can it occur?
A
  • A high dose of single drug
  • More than 1 serotonergic agents are used together
  • Inadequate washout period when switching from one to another
41
Q

Issues to Consider with A/Ds: Serotonin Syndrome (toxicity)

  • What are the causes?
A
  • Neuromuscular effects: hyper-reflexia, tremor, incoordination
  • Autonomic effects: diarrhoea, abdominal cramps, hyperthermia, shivering, fever, tachycardia
  • Mental status effects: agitation, anxiety, confusion, restlessness
42
Q

Issues to Consider with A/Ds: SSRIs and Hepatic Enzymes

  • What can SSRIs inhibit?
  • Are SSRIs metabolised by the same enzymes?
  • What SSRIs have the least potential to interact with enzymes?
A
  • SSRIs are metabolised in the liver by CYP450. They can inhibit the metabolism of many other drugs, causing increased plasma drug concentrations and possible toxicity
  • Individual SSRIs are metabolised by different isoenzymes, therefore their potential for interactions varies
  • Citalopram, escitalopram and sertraline have the least potential to interact in this way
43
Q

What are the Pharmacodynamic Interactions among antidepressants

A
  • Serotonergic syndrome/toxicity (SSRIs, SNRIs, MAOa inhibitors)
    • Combination with serotonergic drugs
    • Absolute contraindication = SSRIs + MAO inhibitors
  • Prolongs QT Interval (SSRIs)
    • Combination with drugs that also prolongs QT interval
    • Risk is higher in patients with pre-existing arrhythmia
  • Reduce Seizure Threshold (TCAs, MAO inhibitors)
    • Risk of seizures, especially in patients with high risk of epileptic episodes
    • Includes interaction with OTC or supplements (ginkgo + fluoxetine)
44
Q

What are the Pharmacokinetic Interactions among antidepressants

A
  • Half life
    • Fluoxetine and sertraline have long half life and need to be converted to active metabolite also with long half life
    • Paroxetine short half life – anti depressant change over and wash out periods
  • Interaction with CYP enzymes
    • Fluvoxamine affects all CYP enzymes
    • Long half life – cleanest = Citalopram and escitalopram
    • Short half life – cleanest = paroxetine
45
Q

What are the Medical Condition Interactions among antidepressants?

A
  • CV disorders (SNRIs)
    • Venlafaxine increase risk of HTN, palpitations, tahcycardia and orthostatic hypotension
  • Reduce seizure threshold (TCAs, MAOiS)
    • Concurrent administration with drugs that reduces seizure threshold, or drugs that raise seizure threshold
    • Risk of seizures
  • Presentation with bipolar disorder
46
Q

Depression and Pregnancy

  • What happens if A/D is stopped?
  • How should mild-moderate depression be treated?
  • How should severe depression be treated?
  • Choice of A/D dependent on?
  • What’s first line?
A
  • Majority of women will relapse if their A/D is stopped on confirmation of pregnancy
  • Mild-moderate depression should be treated with psychological therapies
  • Severe depression = A/D should be considered
  • Choice of A/D dependent on clinical factors, particularly previous efficacy, tolerability and patient preference
  • SSRIs considered first line (caution with fluoxetine and paroxetine)
47
Q

Antidepressants and Breastfeeding

  • Is there transfer of A/D?
  • What do studies suggest?
  • TCAs?
  • Moclobemide?
A
  • Placental transfer and foetal exposure to A/D in utero > breastmilk exposure
  • Most studies suggest infant plasma concentrations are either low or not detected (except fluoxetine)
  • Breastmilk transfer of TCAs is low, generally considered safe
  • Moclobemide has very low transfer into breastmilk and is probably safe

Pharmacotherapeutics Theory 2 (17 decks)

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