Management of major depressive disorder 1.1.2

Question 1

What are the treatment options for depression?

Answer 1

• psychotherapy
• pharmacotherapy
• electroconvulsive threrapy (ECT)
• antidepressant

Question 2

What is the approptiate treatment for severity of depression?

Answer 2

• Mild depression
  
  • Psycotherapy> effectiveness than antidepressants
• Moderate depression
  
  • Psychotehrapy= effectiveness with antidepressants
• Moderate/ severe depression
  
  • antidepressants> effectiveness than psychotherapy

Question 3

What does psychological treatment of depression involve?

Answer 3

• structured problem-solving strategies
• stress management strategies
• CBT
• interpersonal psychotherapy (IPT)
• short term dynamic therapy

Question 4

What is the efficacy of pharmacotherapy in depression?

Answer 4

• indicated in moderate/ severe depression
• benefit of AD therapy increasses with severity of illness
• present evidence suggests that all AD medications have similar efficacy
• individual response varies
• drugs differ in ADV EFF profile & safety in OD

Question 5

The choice of antidepressant is based on…?

Answer 5

• prior response
• adverse effects profile
• family history of response to treatments
• potential for drug interactions
• safety in OD
• patient co morbidities
• simple dosing
• cost
• patient preference

Question 6

What are the 1st line AD?

Answer 6

• SSRIs
• SNRIs
• Mirtazapine

Question 7

What are the 2nd line AD?

Answer 7

• agomelatine
• moclobemide
• reboxetine
• TCAs
• mianserin
• irreversible non selective MAOIs

Question 8

What are examples of augmentation therapy for depression?

Answer 8

• liothyronine (T3)
• lithium
• anti-psychotics
• psychostimulants
• tryptophan

Question 9

What are some other options for pharmacotherapy?

Answer 9

• ECT
• omega-3-fatty acids
• hypericum- St Johns Wort
• exercise

Question 10

How long does it take for an AD to reach therapeutic effect?

Answer 10

• generally around 1-3 weeks

Question 11

How long does it take AD to reach the max therapeutic effect?

Answer 11

• 2-4 weeks

Question 12

How do we commence AD therapy?

Answer 12

• generally start at a low dose & gradually increase over 2-4 weeks

Question 13

What are the methods of switching AD?

Answer 13

Question 14

What are the methods of switching antidepressants?

Answer 14

• Conservative switch
  
  • Gradual tapering and cease
  • Washout period of 5 half lives
  • New drug commenced at dose as per guidelines

Why: reduce risk of adverse effects like serotonin toxicity, but patient’s risk of relapse is high as there is no antidepressant in the system. Withdrawl effects are worse but safer.

• Moderate switch
  
  • Gradual tapering and cease
  • Washout period of 2 to 4 days
  • New drug commenced at low dose

Why: reduce risk of adverse effects like serotonin toxicity, but patient’s risk of relapse is high as there is no antidepressant in the system. Withdrawl effects are worse but safer.

• Direct switch
  
  • First drug stopped
  • New drug commenced the next day at a therapeutic dose

Why: very severe side effect eg. full body rash, stopped medication suddenly. Some antidepressants cause mania so has to be stopped suddenly. Patient preference is the third reason (e.g. venlafaxine, when tapering doses, withdrawal effects start and last for weeks/months, some patients prefer to ‘suffer for a few days’ and get over it.

• Cross taper switch
  
  • Gradual tapering and cease
  • New drug commenced at low dose at some stage in the reduction
  • Dose increased to therapeutic dose when first drug has been ceased

Why: less withdrawal effect, less risk of relapse as there is medication in the body. Risk is that there is a larger risk of adverse effects as combining 2 antidepressants at the same time –> potential for serotonin syndrome and other side effects.

Hospital –> cross taper

Community –> cross taper if patient is at high risk of relapse or high risk of withdrawal symptoms

Question 15

What are some withdrawal effects of antidepressants?

What in particular for phenelzine and tranylcypromine?

Answer 15

• phenelzine: psychosis and seizures
• tranylcypromine: may cause delirium

Question 16

What can rapid withdrawal of the more potently anticholinergic tricyclic antidepressants (TCAs) (eg amitriptyline) result in?

Answer 16

• Cholinergic rebound (agitation, headache, sweating, gastrointestinal symptoms), parkinsonism and problems with balance.
• sailvation, lacrimation, urination, diarrhoea, GI distress, emesis
• SLUDGE = cholinergic effects

Question 17

What is discontinuation syndrome? When is this likely to occur? What to do to avoid this?

Answer 17

• when a drug is stopped abruptly
• with a higher dose of drug
• longer treatment duration
• shorter half life drugs
• sometimes happens when the patient misses 1 or 2 doses
• GENERAL RULE: halve the dose every week until the daily dose is half of the lowest unit available, then stop after 1 week

Question 18

What is the combinations that are used for antidepressants? How is it different to augmentation?

Answer 18

• Mirtazapine + SSRIs
• Mirtazapine + Venlafaxine
• SSRI + TCA

Different to augmentation = Involves using 2 or more antidepressant medications typically from 2 different mechanism classes

• Avoid using > 1 antidepressant drug –> Insufficient evidence to support combination therapy –> Serious adverse effects can occur

Question 19

What is ECT?

Answer 19

• electro convulsive therapy
• Delivery of an electric current to induce a seizure for a therapeutic response (uni or bilateral)
• Indicated for severe and unresponsive forms of depression
• Response rate of 50 to 80%
• Treatments given 3 times weekly or ↓ if cognitive impairment emerges
• 6 to 14 treatments (up to 24 treatments)
• Side effects
  
  • Memory loss, muscle aches and pains, headaches, transient confusion

Question 20

Things you may consider with ECT & pharmacotherapy?

Answer 20

• Benzodiazepines should ceased because they raise seizure threshold and ↓ efficacy
• Little to be gained from continuing failed antidepressants during ECT – may ↑ adverse effects
• Lithium doesn’t ↓ efficacy but may ↑ postictal confusion
• Continuation of antiepileptic drugs during ECT may ↓ efficacy, prolong course and ↑ cognitive adverse effects
• Unless antipsychotics are ineffective or result in problems with ECT (e.g. clozapine and prolonged seizures) they can be continued and may improve results

Question 21

Explain St Johns Wort

Answer 21

• efficacy in acute mild-moderate disease
• MOA- may involve increasing syaptic availability of serotonin & other neurontransmitters
• long term safety & efficacy not established
• risk of serotnin toxicity
• has a range on interactions-warfarin, COC

Question 22

When does serotonin toxicity occur?

Answer 22

• Overdose of a single agent
• Simultaneous use of two serotonergic agents
• Failing to use appropriate washout period when switching agents

Question 23

What are some symptoms associated with serotonin toxicity?

Answer 23

• can be a medical emergency & deaths have occurred
• shivering, sweating, mild tachycardia
• agitation, disorientation, muscle rigidity, tremor, hyperreflexia
• delirium, hypertension, hyperthermia,
• may have diarrhoea

Question 24

What are some treatment options for serotonin toxicity?

Answer 24

• Cyproheptadine: 12mg single dose or 4-8mg TDS
• Chlorpromazine: 12.5-50mg slow IV infusion over 30-50min