Antidepressants CA2 Flashcards
Physical illness and mental illness are not related. T/F?
False. More than half of those with mental illness also have a chronic physical illness.
Etiology and pathophysiology of depression.
Primary cause:
Monoamine hypothesis: reduced number of neurotransmitters in brain (e.g. norepinephrine (NE), serotonin (5-HT), dopamine (DA)).
Secondary causes:
Endocrine disorders: hypothyroidism, T2DM in women
Cardioavascular: CAD, CHF, MI
Clinical presentation for MDD (In. SAD. CAGES)
o At least 5 symptoms have been present during the same 2-week period
o One of the symptoms must be depressed mood or lost of interest
Interest: decreased interest
Sleep: insomnia
Appetite: decreased appetite
Depressed: depressed mood
Concentration: impaired concentration and decision making
Activity: psychomotor retardation or agitation
Guilt: feelings of guilt or worthlessness
Energy: decreased energy or fatigue
Suicidal thoughts or attempts
o Symptoms cause significant distress or impairment in social, occupational or other important areas of functioning.
o Symptoms are not caused by an underlying medical condition or substance.
Assessments for depression
Clinician-rated
- Hamilton Rating Scale for Depression (HAM-D): “gold standard”
- Remission = HAM-D score ≤ 7 (Therapy goal: symptom-free)
Self-rated:
- Screening tool: Patient Health Questionnaire (PHQ-2)
- Assessment tool: PHQ-9
Score above 5 to be considered depressed
Treatment principle
Combination of non-pharmacological and pharmacological treatment method
Non-pharmacological therapy for depression
- Sleep hygiene
- Psychotherapy
Pharmacological therapies (in general)
- Antidepressants ± adjunctive medicines
- First-line (antidepressant monotherapy): SSRI, SNRI, Mirtazapine or Bupropion
Types of TCAs
Amitriptyline, clomipramine, dothiepin, imipramine, nortriptyline
Types of SSRIs
Escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram
Types of SNRIs
Venlafaxine, duloxetine
Type of SMS
Vortioxetine
Type of NaSSA
Mirtazapine
RIMA
Moclobemide
Others
Bupropion, trazodone, agomelatine
Other psychiatric indication in addition to depression
- OCD
- Clomipramine, fluoxetine, fluvoxamine, sertraline - Anxiety disorders
- Escitalopram, paroxetine - Panic disorder
- Citalopram, sertraline - Generalized Anxiety Disorder
- Venlafaxine, duloxetine - Social Anxiety Disorder
- Moclobemide - Off-label for insomnia
- Trazodone - Smoking cessation
- Bupropion
TCAs:
- Type of antidepressants
- MOA
- Side effects
- Notes
Types: Amitriptyline -> Nortriptyline Imipramine -> Desipramine Dothiepin Clomipramine
MOA:
Blocks reuptake of 5HT and NA
Side effects:
- GI and sexual dysfunction
- Anticholinergic, sedation, orthostatic hypotension, seizures, weight gain, arrhythmia.
- Fatal on overdoses
Notes:
- 2° amines (nortriptyline, desipramine) have lower anticholinergic, sedation and cardiotoxic side effects
Phases of treatment
- Acute Phase Treatment
- Adequate trial = adequate dose + duration
- Delayed onset due to down-regulation of pre-synaptic autoreceptors.
- Time course of treatment response
» Physical symptoms may improve in 1-2 weeks (e.g. sleep, appetite)
» Mood symptoms take longer time to improve (e.g. 4-6 weeks) - Continuation Phase
- Initiation + Acute Phase + Continuation = total at least 6-12 months
SSRIs:
- Type of antidepressants
- MOA
- Side effects
- Notes
Types: Fluoxetine -> norfluoxetine Fluvoxamine Escitalopram Citalopram Paroxetine Sertraline
MOA:
Selective 5-HT antagonism
Side effects:
- GI and sexual dysfunction
- Headache, transient nervousness during initiation.
- Insomnia (fluoxetine)
- Hyponatremia
- Bleeding risk, EPSE
Notes:
- Long half-life for fluoxetine (4-6 days)
- Norfluoxetine has the longest t1/2.
- Paroxetine: most anticholinergic, sedating, weight gain, short half-life. Can go into withdrawal syndrome.
- Escitalopram/citalopram: QTc prolongation of high dose in elderly.
SNRIs:
- Type of antidepressants
- MOA
- Side effects
- Notes
Types:
Venlafaxine -> desvenlafaxine
Duloxetine
MOA:
5 HT, NA antagonism
Side effects:
- Same as SSRI. Increased BP. Urinary incontinence (duloxetine)
- Venlafaxine: low chance of causing seizures. Very low: anticholinergic side effects, sedation. None: orthostatic hypotension
- Duloxetine (safer option): very low chance of anticholinergic side effects and orthostatic hypotension. None for the rest.
SMS:
- Type of antidepressants
- MOA
- Side effects
- Notes
Type:
- Vortioxetine
MOA:
- Same as SSRI.
- 5HT1A antagonist
Side effects:
- Same as SSRI
- May worsen hypertension
NaSSA:
- Type of antidepressants
- MOA
- Side effects
- Notes
Type:
- Mirtazapine
MOA:
- α2-adrenoreceptor antagonist
- 5HT and NA antagonism.
- 5HT2&3, H1 antagonism
Side effects:
- Somnolence, increased appetite, weight gain
Notes:
- Reverse GI and sexual side effects of SSRI/SNRI.
NDRI:
- Type of antidepressants
- MOA
- Side effects
- Notes
Type:
Bupropion
MOA:
- blocks uptake of NE and DA
Side effect:
- Seizure, not suitable for those with psychosis or eating disorders
Notes:
- Reduce sexual side effects of SSRI/SNRI.
MAOI:
- Type of antidepressants
- MOA
- Side effects
- Notes
Type: Moclobemide
- Reversible MAOi-A
Notes:
- Safest amongst MAOIs
Trazadone
- MOA
- Side effects
- Notes
MOA:
- Blocks reuptake of 5HT
- Antagonises 5HT2A, H1 and α1-adrenoreceptor.
Side effects:
- Same as SSRI, sedation, orthostatic hypotension
Notes:
- Used for insomnia and depression
Adjunctive hypnotics:
- Type of antidepressants
- MOA
- Side effects
- Notes
A. Benzodiazepines - MOA: potentiates GABA - Side effects: sedation, drowsiness, amnesia - Dosings: >> Lorazepam: PO 0.5-2mg HS PRN >> Diazepam: PO 2-5mg HS PRN Limit to 2-week PRN course
B. Z-Hypnotics
- MOA: causes sedation
- Side effects: taste disturbance (Zopiclone), complex sleep behaviors (sleep-walking)
- Dosings:
» Zolpidem: females, half-dose (5mg HS PRN)
» Zopiclone: 7.5mg HS PO PRN for adults, 3.75mg HS PO PRN for elderly.
C. Second generation antipsychotics
- Aripiprazole, Braxiprazole, Quetiapine
Types of complementary and alternative medicines
- Therapeutic Lifestyle/Behavioural Changes
» Sleep hygiene - Herbal
» St John’s Wort
• Significant drug interactions and cannot be used concomitantly with antidepressant
If an antibiotic has partial to no reponse:
- can switch medications, but washout period is necessary for MAOIs
Depression: Special Populations and Other Considerations
- Elderly: Avoid TCAs and anticholinergic, CNS, hypotensive or other cardiac side effects.
- Hyponatremia: common in elderly, mostly reported for SSRIs.
- Association to suicidality in patients ≤ 24 years old, require counselling.
Clinically significant drug-drug interactions
- Serotonergic agent + serotonergic agent = serotonin syndrome
- SSRIs: increase risks of bleeding
» Higher risks In elderly on NSAIDs, warfarin, steroids.
» Consider adding PPI. - Increased CNS depressant effects with alcohol and other CNS depressants.
» Do not take medication at the same time as alcohol, separate them 4-6 hours apart.
» Benzodiazepines + Opioids = Increased mortality
Drug-Drug interactions for CYP1A2
Substrates:
Theophylline, amiodarone, warfarin-R, Agomelatine
Inhibitors:
Fluvoxamine
Drug-drug interactions for CYP2C19
Substrate: Warfarin-R
Inhibitor: fluvoxamine
Drug-drug interactions for CYP2D6
Substrates: Metoprolol, Codeine, Tramadol
Inhibitors: Fluoxetine, Paroxetine, Bupropion
Drug-drug interactions for CYP3A4
Substrates: Simvastatin, lovastatin, nifedipine, amlodipine, diltazem
Inhibitors: grapefruit juice
Inducers:
Rifampicin, carbamazepine, phenytoin, St. John’s Wort
Drugs with the fewest CYP interactions
Mirtazapine, escitalopram
Symptoms of antidepressant discontinuation syndrome
Flu-like symptoms Insomnia Nausea Imbalance Sensory Hyperarousal
Which drugs are likely to have discontinuation withdrawal syndrome?
Drugs with short half-life: paroxetine, venlafaxine
How should we discontinue the medications
gradual tapering over time, around 4 weeks
Goals of major depressive disorder therapy?
remission of symptoms, treatment adherence and prevention
Drug choice of antidepressants
- SSRI, SNRI, NaSSA, Bupropion > Agomelatine, Vortioxetine > TCA > MAOIs
- Selection based on target symptoms, interactions
Amitriptyline dose
300mg max per day
fluoxetine dose
20mg om, 80mg max per day
mirtazapine dose
15-45mg per day
clomipramine dose
300mg per day
