Major Depressive Disorder Flashcards
What criteria is used for the diagnosis of MDD?
DSM V is used for the diagnosis of Major Depressive Disorder
What is MDD?
MDD is a mood state characterised by significantly lowered mood and a loss of interest or pleasure in activities that are normally enjoyable
A major depressive episode can be distinguished from ‘normal’ depression by what?
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
What are the Signs of Depression
- Emotional/Mental Signs
- Physical Signs
- 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
Assessing Severity
What is a Mild Episode?
Few symptoms beyond the minimum required to make the diagnosis
Assessing Severity
What is a Severe Episode?
- Most criteria present
- Marked interference with social and/or occupational functioning, producing clear-cut observable disability
When Assessing Severity, what else should be considered?
Nature of symptoms (e.g. suicidal thoughts and behaviour) should also be considered in assessing severity
What is the Self-Test for Depression?
PHQ-9
What are the 5 Subtypes of Depression?
- 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
What factors should be assessed when assessing a patient with depression?
- 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
What is the Aim of Treating MDD?
- Relieve psychological and physical symptoms
- Improve functional capacity
- Reduce the likelihood of self-harm or suicide
What are the 2 Treatment Options for MDD?
- Non-pharmacological: psychological, ECT, others
- Pharmacological: Antidepressants, complementary therapies
List the Types of Non-Pharmacological Therapies
- Psychotherapy
- Cognitive Behavioural Therapy
- Interpersonal Therapy
- Electroconvulsive Therapy (ECT)
- Others
Non-Pharmacological Therapies: Psychotherapy
- When is it used?
- Is it used in Combination?
- 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
Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT)
- What is it?
- Does it work quickly?
- How is it administered?
- Is treatment the same for everyone?
- 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
Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT) should be considered in who?
- 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
Non-Pharmacological Therapies: Electroconvulsive Therapy (ECT)
- What drugs need to be stoped in ECT?
- 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
Non-Pharmacological Therapies: What are the Other Therapies?
- 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
The choice of drug in MDD is determined by what?
- 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
The choice of drug in MDD is determined by what: Antidepressant safety in overdose
- Most Toxic:
- Mid-Range:
- Least Toxic:
- Most Toxic: TCAs and MAOis
- Mid-Range: Venlafaxine
- Least Toxic: SSRis, Mirtazapine, Reboxetine, Mianserin, Moclobemide
The choice of drug in MDD is determined by what: Adverse effect profile (or previous treatment)
- 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
Expectations of Starting Treatment
- Time after starting: 4-6 Weeks
- Expectation of Treatment:
- Time after starting: 4-6 Weeks
- Expectation of Treatment: Adequate Trial Period
What are the Recommendations for someone who has initiated treatment?
- Responder
- Partial Repsonder
- Non-Responder
- 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
- Partial responder
- Assess response after 2-4 weeks
If Treatment Fails what do you have to consider?
- 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?
What is a washout period?
An appropriate interval when changing from one antidepressant to another is recommended to avoid interactions (washout period)
What do you have to be mindful of when switching antidepressants?
- 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)
List the 3 types of Switching Strategies
- Conservative switch
- Moderate switch
- Direct switch
Switching Strategies: What is Conservative Switch?
- 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
Switching Strategies: What is Moderate Switch?
- Gradually reduce and stop first A/D
- Drug-free washout interval of 2-4 days
- The new A/D is started at low dose
Switching Strategies: What is Direct Switch?
- The first A/D is stopped
- The second A/D is started the next day at the usual therapeutic dose
List the 4 options for Treatment-Resistant Depression
- ECT
- Augmentation with lithium
- Augmentation with second generation antipsychotics
- Augmentation with T3
Treatment-Resistant Depression: Discuss ECT
Quick response, follow up with drug treatment
Treatment-Resistant Depression: Discuss Augmentation with lithium
Has unfavourable ADR profile and long-term risk of thyroid and renal dysfunction
How Long should Treatment Last in MDD?
- To reduce the risk of relapse?
- People at high risk?
- Risk factors include
- 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)
How should treatment be discontinued?
- 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
How to avoid withdrawal effects?
- End of Rx course
- Changing drugs
- 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
What are 4 issues to consider with A/Ds?
- Bleeding
- Hyponatraemia
- Serotonin syndrome (toxicity)
- SSRIs and hepatic enzymes
Issues to Consider with A/Ds: Bleeding
- What do SSRIs inhibit?
- Is the risk high?
- Increased risk with what?
- SSRIs inhibit uptake of serotonin into platelets
- Risk is relatively low
- Increased with use of NSAIDs, anti-platelet
Issues to Consider with A/Ds: Hyponatraemia
- What drugs have the risk?
- Is risk high?
- If SSRI?
- 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
Issues to Consider with A/Ds: Serotonin Syndrome (toxicity)
- How can it occur?
- A high dose of single drug
- More than 1 serotonergic agents are used together
- Inadequate washout period when switching from one to another
Issues to Consider with A/Ds: Serotonin Syndrome (toxicity)
- What are the causes?
- Neuromuscular effects: hyper-reflexia, tremor, incoordination
- Autonomic effects: diarrhoea, abdominal cramps, hyperthermia, shivering, fever, tachycardia
- Mental status effects: agitation, anxiety, confusion, restlessness
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?
- 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
What are the Pharmacodynamic Interactions among antidepressants
- 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)
What are the Pharmacokinetic Interactions among antidepressants
- 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
What are the Medical Condition Interactions among antidepressants?
- 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
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?
- 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)
Antidepressants and Breastfeeding
- Is there transfer of A/D?
- What do studies suggest?
- TCAs?
- Moclobemide?
- 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
