L09-L10 Depression Flashcards
Pharmacological & psychological treatments should be 1st-line Tx in cases of mild depression. True or false?
False!
Psychosocial Tx ALONE should be the 1st-line Tx for MILD depression.
Pharmacological Tx is added on as mainstay Tx for moderate & severe depression.
Among persons with a mental illness, it is unlikely that they too have a chronic physical illness. True or false?
False.
Among persons with a mental illness, 50.6% also have a chronic physical illness.
Which psychiatric conditions significantly increase the risk of early mortality?
Schizophrenia, major depression & alcohol-use disorders.
- For each completed suicide, there were 7 unsuccessful attempts.
Which independent predictors are used to detemine the suicidality risk in psychiatric patients?
1) Hx of attempted suicide using highly lethal means
2) Coexisting significant physical illness
3) Delusions
What is the clinical presentation of a psychiatric patient diagnosed with major depressive disorder (MDD)?
ALL three criteria MUST be fulfilled:
1) At least 5 symptoms of In SAD CAGES present during the same 2-week period representing change from previous functioning WITH either (a) depressed mood or (b) loss of interest
In SAD CAGES:
- Interest (decreased; anhedonia)
- Sleep (insomnia/hypersomnia), Appetite (decreased; weight loss), Depressed (irritable in children)
- Concentration (impaired decision making), Activity (psychomotor retardation/agitation), Guilt (worthlessness), Energy (fatigue) & Suicidality
2) Significant distress or impairment in social, occupational or other impt areas of functioning
3) NOT caused by underlying medical condition or substance
Antidepressants are appropriately indicated as first-line Tx for patients diagnosed with bipolar affective disorder. True or false?
False!!
AVOID antidepressants due to immediate mood swings to mania, which exacerbates the condition!
Antidepressants are appropriately indicated as first-line Tx for patients diagnosed with adjustment disorder with depressed mood. True or false?
False!
Adjustment disorders are NOT indicated for pharmacological Tx.
Non-pharmacological approaches preferred since etiology is NOT biological in nature!
- Smx occur w/in 3 months of onset of a stressor, BUT once stressor is terminated, smx do NOT persist for additional 6 months.
What are two important screening questions to ask psychiatric patients in determining their suitability to antidepressant Tx?
1) Any Hx of manic/hypomanic episodes?
- Antidepressants may cause “manic switch” in pt. w/ underlying bipolar disorder.
2) Any suicidal/homicidal ideations & risks?
- Conduct mental state exam (MSE) for accurate diagnosis, including suicidality risk!
- If yes, likely need antidepressants.
What lab parameters should be investigated to exclude other differential diagnoses from MDD?
- Vitals, weight & BMI
- FBC (WBC in particular for infections e.g. meningitis/encephalitis)
- Renal panel: Urea, electrolyte, creatinine
- LFTs
- TFTs (thyroid) for hypothyroidism
- ECG for CV risk
- Folate & Vit B12 for anemia
- Fasting blood glucose for hypoglycemia & diabetes
- Lipid panel for CV risk
- Urine toxicology for substance misuse & pregnancy
Depression is a diagnosis of EXCLUSION!
What are some of the more common examples of psychiatric rating scales used in clinical settings for depression?
Clinician-rated: Hamilton Rating Scale for Depression (HAM-D)
- Remission = HAM-D score <= 7
- Therapy Goal = smx-free
- Response = 50% improvement
Self-rated: Patient Health Questionaire
- Screening: PHQ-2
- Assessment: PHQ-9
What are some non-pharmacological recommendations to manage patients diagnosed with MDD?
1) Lifestyle/Behavioural Changes
- Sleep hygiene
- Exercise
- Relaxation techniques
2) Psychotherapy
- NOT suitable as monotherapy for moderate & severe depression
- Combine w/ antidepressant for moderate & severe depression
3) Neurostimulation
- Electroconvulsive Treatment (ECT): for severe/refractory cases
- Repetitive Transcranial Magnetic Stimulation (rTMS)
What are some general risk factors that increase the suicidality risk in the general population?
“A poor, elderly, lonely man with physical/mental comorbidities & previous attempts.”
1) Poor socioeconomic status
2) Elderly >= 65 y/o
3) Male gender
4) Presence of physical/mental comorbidities
- esp. major depression, schizophrenia & alcohol-use disorders
5) Hx of suicide attempts/ideations
List some medical disorders which contribute as secondary causes to the diagnosis of depression.
1) Endocrine disorders: Hypothyroidism, Cushing Syndrome, T2DM
2) Cardiovascular: CAD, CHF, MI
3) Deficiency states: Anemia, Wernicke’s encephalopathy
4) Infections: CNS infections, STD/HIV (e.g. neurosyphilis), TB
5) Metabolic disorders: Electrolyte imbalance (hyponatremia & hypokalemia), hepatic encephalopathy
6) Malignancy
7) Neurological: Alzheimer’s disease, epilepsy, pain, Parkinson’s disease, post-stroke
Under what conditions should PHQ-9 be considered to screen for possible depression?
Positive response to either question of PHQ-2:
Over the past two weeks, how often have you been bothered by any of the following problems?
1) Little interest or pleasure in doing things
2) Feeling down, depressed or hopeless
A negative response to both questions is considered a “negative” result for depression screening.
Which classes of drugs are clinically used as first-line antidepressant monotherapy today?
EQUIVOCAL efficacy between these four classes:
SSRIs, SNRIs, Mirtazapine (NaSSA) & Bupropion (NDRI)
- Select based on target smx, comorbidities, DDI, prior response & preference (i.e. sexual dysfunction of SSRIs & SNRIs)
However, if cost is a factor:
SSRIs, SNRIs, Mirtazapine (NaSSA) & Bupropion (NDRI)
- First three drug classes are heavily subsidised by MOH
- Bupropion, while first-line under CPG, isn’t subsidised by MOH.
Explain the different phases of antidepressant Tx.
1) Acute Phase Tx:
- Adequate trial = adequate dose (i.e. lowest effective dose) + adequate duration
- Duration = 4-8 weeks, max. 12 weeks
- Pt. may get anxious & jittery upon 1st exposure
- Certain elderly pt. may take more time to respond
- Delayed onset due to downregulation of presynaptic autoreceptors (i.e. reuptake receptors)
- Physical smx (e.g. sleep & appetite) may improve in 1-2 weeks
- Mood smx take longer to improve i.e. 4-6 weeks
2) Continuation Phase:
- 1st episode of MDD: Continue for at least 4-9 months after acute-phase Tx
- i.e. TOTAL duration = at least 6-12 months = initiation + acute phase + continuation phase
3) Longer-Term Maintenance Therapy:
- Consider if high risk, at least 2 MDD episodes & geriatric MDD
- Maintain trial dose if no serious side effects reported thus far
Explain why the onset of first-line antidepressants in improving the mood symptoms associated with depression is delayed.
- Inhibition of serotonin uptake results in increased levels of 5-HT w/in synaptic cleft
- Presynaptic autoreceptors regulating synthesis & release of 5-HT keep receiving signals due to increased levels of 5-HT w/in synaptic cleft
- Led to downregulation of presynaptic autoreceptors & thus less negative feedback in regulating 5-HT neurotransmission
- Time is required to built tolerance & revert to original levels of expression of presynaptic autoreceptors
- Thus, longer onset of antidepressants
Explain the steps of chemical neurotransmission.
- Precursors are transported from blood into the brain.
- Subsequently converted into neurotransmitters via enzymatic processes & stored in synaptic vesicles.
- Neurotransmitters are released into synaptic cleft, where they either interact with:
(a) presynaptic autoreceptors to regulate synthesis & release, or
(b) postsynaptic receptors to induce events of downstream signal transduction cascade.
List all clinically available antidepressant classes in SG.
First-line antidepressant monotherapy:
1) SSRIs (serotonin selective reuptake inhibitors)
2) SNRIs (serotonin-norepinephrine reuptake inhibitors)
3) NaSSA (noradrenaline & specific serotonin antidepressants)
4) NDRIs (norepinephrine-dopamine receptor inhibitors)
Alternative:
1) TCAs (tricyclic antidepressants)
2) RIMAs (reversible inhibitors of monoamine oxidase i.e. MAO-A selective inhibitors)
3) SMSs (serotonin modulators & stimulators)
4) Melatonin receptor antagonists
5) SARI (serotonin antagonist & reuptake inhibitor)
Name a few examples of SSRIs used clinically.
Drug -> Active metabolite:
1) Fluoxetine -> Norfluoxetine
2) Fluvoxamine
3) Escitalopram / Citalopram
4) Sertraline
5) Paroxetine
Name a few examples of SNRIs used clinically.
Drug -> Active metabolite:
1) Venlafaxine -> Desvenlafaxine
2) Duloxetine
Name an example of NaSSA used clinically.
Mirtazapine
Name an example of NDRI used clinically.
Bupropion
Name a few examples of TCAs used clinically as an alternative to first-line antidepressant monotherapy.
Drug -> Active metabolite:
1) Amitriptyline -> Nortriptyline
2) Imipramine -> Desipramine
3) Dothiepin (Dosulepin)
4) Clomipramine (more for OCD)
Name an example of each alternative drug class (except TCAs) used clinically as an alternative to first-line antidepressant monotherapy.
1) RIMAs: Moclobemide
2) SMSs: Vortioxetine
3) Melatonin receptor antagonists: Agomelatine
4) SARI: Trazodone
Which particular first-line antidepressant is clinically indicated in patients with diabetic neuropathy?
Duloxetine
Aside from being used as a first-line antidepressant monotherapy, what other clinical indications is duloxetine used for?
1) Diabetic neuropathy
2) Stress urinary incontinence
3) Fibromyalgia
4) Chronic musculoskeletal pain
Which antidepressant drug is used for off-label indication of insomnia?
Trazodone
Which SSRI is used for the treatment of bulimia nervosa?
Fluoxetine
Which particular first-line antidepressant is used in the pharmacological treatment of smoking cessation?
Buproprion
Describe the dose-dependent pharmacological effects of venlafaxine.
Low dose: Primarily 5-HT reuptake inhibition
Higher dose: Primarily NA reuptake inhibition
Very high dose: Primarily DA (dopamine) reuptake inhibition
Which SNRI displays a balanced 5-HT & NA reuptake inhibition?
Duloxetine
Which antidepressants have extremely long half-lives as compared to the others (i.e. in days)?
Fluoxetine = 4-6 days w/ chronic dosing Norfluoxetine = 4-16 days Vortioxetine = 66 days
Which SSRI should be taken with food to enhance its bioavailability/absorption?
Sertraline
Which antidepressant is indicated as second-line for obsessive-compulsive disorder (OCD)?
Clomipramine
Which particular first-line antidepressant is clinically indicated in patients with fibromyalgia?
Duloxetine
Which TCAs have lower anticholinergic, sedative & cardiotoxic side effects?
Secondary amines: Nortriptyline & desipramine
Why are TCAs NOT used as first-line antidepressants despite their clinical efficacy?
While highly effective, TCAs are highly toxic due to multiple adverse side effects present, as compared to safer alternatives (i.e. SSRIs, SNRIs, mirtazapine & bupropion).
Moreover, TCAs tend to concentrate more in cardiac muscles, resulting in possible QT prolongation.
What are some side effects of TCAs?
FATAL ON OVERDOSE!!
1) GI side effects
2) Sexual dysfunction
3) Anticholinergic SE: blurry vision, dry mouth & constipation
4) Antihistaminic SE: sedation & weight gain
5) Antiadrenergic SE: orthostatic hypotension
6) Cardiotoxicity: arrhythmias, seizures & QT prolongation
Which special patient population is TCAs preferred over standard first-line antidepressant monotherapy options for the Tx of MDD?
Pregnant patients (i.e. nortriptyline), esp. in last trimester
VL is a 29-year-old female newly diagnosed with major depressive disorder and is currently 8 months into her pregnancy. Recommend an appropriate antidepressant for her.
Nortriptyline (esp. in late pregnancy)
Which first-line antidepressants are highly susceptible to acute toxicity upon co-administration of a CYP450 competitive inhibitor?
1) Fluoxetine (CYP2D6)
2) Fluvoxamine (CYP1A2 & CYP2C19)
3) Paroxetine (CYP2D6)
4) Bupropion (CYP2D6)
Which SSRI is the least preferred to be dispensed to a geriatric patient diagnosed with MDD?
Paroxetine
- Most anticholinergic & sedating
- Greatly increased risk of weight gain
- Short half-life makes it susceptible to withdrawal symptoms upon abrupt discontinuation
What are some side effects of SSRIs?
1) GI SE: Nausea (5-HT3 agonism)
2) Sexual dysfunction (5-HT2 agonism)
3) Headaches & transient nervousness/jitteriness during initiation (classical SE)
- Insomnia esp. for fluoxetine
4) Hyponatremia (SIADH: syndrome of inappropriate antidiuretic hormone secretion)
5) Bleeding risk (esp. elderly)
6) Extrapyramidal SE (occasional): akathisia, dystonia & tardive dyskinesia
When should fluoxetine be taken when indicated as Tx for MDD? Why so?
OM, due to potential insomnia as side effect & less sedating in nature
Which particular SSRI may result in QT prolongation if administered at a high dose in elderly patients diagnosed with MDD?
Escitalopram & citalopram
Which class of antidepressants has a similar chemical structure to tramadol?
SNRIs: Venlafaxine, desvenlafaxine & duloxetine
Which first-line antidepressant should not be used in a patient diagnosed with MDD with vital signs: Temp 36.9 degC, BP 170/110 & HR 20 & is currently not on any medications?
SNRIs: Venlafaxine, desvenlafaxine & duloxetine
- Contraindicated in pt. w/ uncontrolled hypertension due to increased BP as side effect of drug class
What are some side effects of SNRIs?
Similar to SSRIs:
1) GI SE: Nausea (5-HT3 agonism)
2) Sexual dysfunction (5-HT2 agonism)
3) Headaches & transient nervousness/jitteriness during initiation (classical SE)
4) Hyponatremia (SIADH: syndrome of inappropriate antidiuretic hormone secretion)
5) Bleeding risk (esp. elderly)
6) Extrapyramidal SE (occasional): akathisia, dystonia & tardive dyskinesia
Additional SE for SNRIs:
7) Hypertension (C/I in uncontrolled hypertension pt.)
8) Urinary hesitation (for duloxetine ONLY)
Which particular first-line antidepressant is clinically indicated in patients with chronic musculoskeletal pain?
Duloxetine
What are some side effects of mirtazapine?
Antihistaminic SE: Somnolence, increased appetite & weight gain
Describe the mechanism of action of mirtazapine.
5-HT2, 5-HT3, alpha-2 adrenoceptor & H1 antagonist
What advantage does mirtazapine have over SSRIs & SNRIs for the Tx of MDD?
Reversal of GI (nausea) & sexual SE of SSRIs & SNRIs.
- Due to lack of serotonergic antagonism activity at presynaptic autoreceptors
What are some side effects of bupropion?
Seizure, insomnia & psychosis
- NOT suitable for eating disorders as a result due to increased risk of seizures
What advantage does bupropion have over SSRIs & SNRIs for the Tx of MDD?
Decreased risk of GI (nausea) & sexual SE of SSRIs & SNRIs.
- Due to lack of serotonergic antagonism activity at presynaptic autoreceptors
Under what conditions are bupropion contraindicated in the Tx of MDD?
Epilepsy patients
Hx of seizures
Which antidepressants are used primarily for Tx of insomnia, instead of treating mood symptoms for depression?
Trazodone & agomelatine
What is the mechanism of action of trazodone?
Blocks reuptake of 5-HT & antagonise 5-HT2A, H1 & alpha-1 adrenergic receptors
What is the mechanism of action of agomelatine?
MT-1 & MT-2 agonist & antagonise 5-HT2C receptors
What are some side effects of trazodone?
Similar to SSRIs:
1) GI SE: Nausea (5-HT3 agonism)
2) Sexual dysfunction (5-HT2 agonism)
3) Headaches & transient nervousness/jitteriness during initiation (classical SE)
4) Hyponatremia (SIADH: syndrome of inappropriate antidiuretic hormone secretion)
5) Bleeding risk (esp. elderly)
6) Extrapyramidal SE (occasional): akathisia, dystonia & tardive dyskinesia
Additional SE for trazodone:
7) Orthostatic hypotension
8) Sedation
9) Rare: Priapism (i.e. prolonged erection of penis)
What are some side effects of agomelatine?
GI side effects & increased LFTs
- Check LFTs at baseline & week 3, 6, 12 & 24
Which drugs are contraindicated for a patient on agomelatine?
Fluvoxamine, ciprofloxacin & CYP1A2 inhibitors
- Agomelatine is a CYP2D6 substrate that may competitively inhibited fluvoxamine & ciprofloxacin.
Which class of antidepressants exhibits less anticholinergic side effects, less pro-convulsant activities, as well as some levels of analgesic properties?
SNRIs esp. duloxetine
What are some adjunctive medications used in the Tx of MDD?
Hypnotics:
1) Benzodiazepines (BZDs)
2) Z-Hypnotics (e.g. zolpidem & zolpiclone)
3) 1st Gen Antihistamines (e.g.: promethazine & hydroxyzine)
Others:
4) 2nd Gen Antipsychotics (e.g. aripiprazole, brexpiprazole, quetiapine & olanzapine)
5) NMDA Receptor Antagonist: Esketamine
Why are adjunctive medications administered alongside first-line antidepressants for the Tx of MDD?
To tide the slow/delayed onset of first-line antidepressants (i.e. SSRIs, SNRIs, mirtazapine & bupropion).
To alleviate the physical symptoms of MDD via fast-onset sedatives.
What are some side effects of benzodiazepines (BZDs)?
1) CNS depressive effects (Common):
- Drowsiness -> sedation
- Amnesia
- Muscle weakness & ataxia (i.e. impaired muscle coordination)
2) CNS depressive effects (Less common):
- Slurred speech
- Vertigo
- Headache
- Confusion
3) Acute toxicity / overdose:
- Severe respiratory depression (esp. w/ concomitant use of alcohol)
4) Tolerance & dependence:
- Tolerance is dependent on frequency of use (develop faster for epilepsy than insomnia)
- Dependence can result in withdrawal effects if abrupt
- Withdrawal effects: Disturbed sleep, rebound anxiety, tremors & convulsions
- Has abuse potential
Which BZD is more commonly used as an adjunctive to first-line antidepressant monotherapy?
How is it administered & why so?
Lorazepam PO 0.5-2mg HS PRN
- Due to shorter half-life of 12h vs diazepam (T1/2 = 20-54h)
- Minimise risk of dependence by LIMITING to 2-weeks PRN short course therapy at LOWEST effective dose.
What are some side effects of Z-hypnotics?
Common: Taste disturbances (specific to zolpiclone)
Less common:
- N/V
- Dizziness
- Drowsiness
- Dry mouth
- Headache
Rare:
- Amnesia
- Confusion
- Hallucinations & nightmares
- Complex sleep behaviours (sleep-walking)
List the dosing regimen administered for Z-hypnotics.
Zolpidem:
- > 18 y/o = PO 10mg HS PRN
- Controlled-released: PO 6.25-12.5mg HS PRN
- Half all dose for females for PGx
- Elderly / Debilitated: PO 5mg HS PRN
Zopiclone:
- > 18 y/o = PO 7.5mg HS PRN
- Elderly: PO 3.75mg HS PRN
Which Z-hypnotic is used due to greater ease to induce sedation & faster elimination?
Zolpidem (T1/2 = 1.5-4h) > Zopiclone (T1/2 = 6h)
Which second-generation antipsychotics (SGA) are adjuncts to antidepressants used for Tx of MDD?
Aripiprazole, brexpiprazole & quetiapine XR
Which second-generation antipsychotics (SGA) are adjuncts to antidepressants used for Tx of treatment-resistant depression (TRD)?
Olanzapine + Fluoxetine
What are some key side effects to look out for when administering SGAs as adjunct to first-line antidepressant monotherapy?
Aripiprazole & Brexpiprazole: EPSE
- Tardive dyskinesia, acute dystonia & akathisia
Quetiapine XR & Olanzapine: Metabolic disorders
- Drug-induced weight gain
What are some key side effects to look out for when administering esketamine as an adjunct to first-line antidepressant monotherapy?
Dissociation, dizziness, nausea, sedation, anxiety & hypertension.
Which particular complementary medication should we be looking out for before prescribing first-line antidepressants to patients diagnosed with MDD?
St John’s Wort
- Significant drug interactions w/ antidepressants
- Do NOT use concomitantly w/ antidepressants
What are the available approaches in managing partial or no response to first-line antidepressants?
1) Switching
- Switch to alternative antidepressant when ineffective or intolerable to adequate dose in 1-4 weeks
- i.e. SSRI switched to SNRI, mirtazapine, bupropion, agomelatine or vortioxetine
(a) Cross-Titration: Watch for serotonin syndrome!! (e.g. decrease fluoxetine/venlafaxine and initiate & increase mirtazapine)
(b) Direct Switch: Stop one SSRI completely and initiate next serotonergic agent.
(c) If switching from serotonergic antidepressant used daily for past 2 months to non-serotonergic agent (i.e. SSRI/SNRI -> buproprion), gradual cross-tapering over several weeks REQUIRED!!
- Minimise risk of Antidepressant Discontinuation Syndrome!!
(d) Wash-out period is NECESSARY for RIMA/MAOIs (i.e. moclobemide)!!
- Moclobemide -> another antidepressant: 24h washout
- Another antidepressant -> moclobemide: wash-out for at least 1 week (for 5 weeks for fluoxetine)
2) Augmentation
- Combine 2nd antidepressant w/ different MOA to existing Tx for partial response
- e.g. Add mirtazapine (NaSSA), bupropion SR (NDRI), T3 (liothyronine), or lithium
- e.g. Adjunctive SGAs: Quetiapine XR, aripiprazole, or brexpiprazole
3) Treatment-Resistant Depression
- i.e. NO response to 2 ADEQUATE trials of antidepressants
- Add neurostimulation: ECT, rTMS
- Switch to olanzapine 6mg + fluoxetine 25mg
- Add esketamine adjunct to SSRI/SNRI Tx
JN is a 28-year-old female newly diagnosed with major depressive disorder and is currently 4 months into breastfeeding her newborn son. Recommend an appropriate antidepressant for her.
Sertraline or Mirtazapine
IP is a 59-year-old male newly diagnosed with major depressive disorder and has a PMH of CKDS3. Recommend an appropriate antidepressant for him.
Vortioxetine
JP is a 56-year-old male newly diagnosed with major depressive disorder and has a PMH of hepatic impairment. What are some considerations to take note of before dispensing an appropriate antidepressant?
AVOID agomelatine!!
If mild-moderate hepatic impairment: consider vortioxetine
Which class of antidepressants should be avoided in elderly patients?
TCAs
What are some considerations when prescribing an appropriate antidepressant to elderly patients diagnosed with MDD?
1) Avoid TCAs for anticholinergic, CNS, hypotensive & other cardiac SE
2) Monitor for hyponatremia due to SIADH, especially in elderly pt.
- e.g. drowsiness, confusion or convulsion
- Associated w/ ALL antidepressants; mostly reported for SSRIs
- Possibly lower risk w/ agomelatine, mirtazapine & bupropion
- MONITOR serum Na+ at baseline, 2nd week, 4th week then 3-monthly
AT is a 21-year-old female newly diagnosed with major depressive disorder. What non-pharmacological recommendation MUST be provided during dispensing counselling of first-line antidepressant monotherapy?
Association with suicidality in patients <= 24 y/o
- Requires counselling to patients & caregivers for close
monitoring & regular review.
- Documented in medical/medication records.
What are some clinically significant pharmacodynamic DDI we should watch out for the Tx of MDD?
1) Serotonin Syndrome:
- i.e. combination use of 2 (high-dose) serotonergic agents (e.g. 5-HT agonist, sibutramine, opioids (tramadol, fentanyl, pethidine), dextromethorphan, linezolid & ritonavir)
- Mild: Insomnia, anxiety, N/D, hypertension, tachycardia, hyperflexia
- Moderate: Agitation, myoclonus, tremor, mydriasis, flushing, diaphoresis, low fever (<38.5 degC)
- Severe: Severe hyperthermia, confusion, rigidity, respiratory failure, coma & death
- Acute onset w/in 6-8h
2) Bleeding Risk:
- Higher risks in elderly on SSRIs w/ NSAIDs, warfarin & steroids; consider adding PPI
- Consider stopping serotonergic antidepressants 2 weeks before surgery if high bleeding risk
- Agomelatine safest
3) Increased CNS depressing effects w/ alcohol, other CNS depressants (e.g. BZDs)
- Key counselling pt. MUST include “Do NOT take antidepressants at the same time as alcohol, separate them at least 4-6h apart.”
- AVOID concomitant administration of BZDs & opioids due to increased mortality risks where possible; limit doses & duration if needed
4) Anticholinergic effects exacerbated w/ concomitant anticholinergic agents
Which antidepressants have minimal CYP interactions?
Mirtazapine, escitalopram, venlafaxine, desvenlafaxine & vortioxetine
Explain how ‘antidepressant discontinuation syndrome’ occurs.
Worse w/ abrupt discontinuation of long-term regular Tx of antidepressants
- Especially w/ short T1/2 antidepressants e.g. paroxetine & venlafaxine
- Onset = 36-72h upon abrupt discontinuation
- Duration = 3-7 days but typically recover over 1-2 weeks w/o Tx
FINISH symptoms (UNLIKE withdrawal symptoms):
- Flu-like symptoms: Fatigue, muscle aches & HA
- Insomnia
- Nausea
- Imbalance: Dizziness
- Sensory: ‘electric shock’ sensations, paresthesia
- Hyperarousal: Anxiety, agitation
If there is a need to stop a long-term antidepressant Tx of daily Tx lasting at least 8 weeks, what is the recommended approach?
Taper gradually over at least 4 weeks.
- Taper by 25% every 1-2 weeks or as gradually as clinically indicated.
Which antidepressants do NOT require gradual tapering of doses for discontinuation of antidepressant Tx?
Fluoxetine, bupropion & vortioxetine
BZDs can be given as adjunctive medications to first-line antidepressants on a long-term basis. True or false?
False!!
Lowest effective dose PRN for max 2 weeks.
Should be discontinued GRADUALLY
- Reduce by 25% weekly until reaching 50% of dose, then reduce by 1/8 every 4-7 days, or gradually as clinically indicated.
- Otherwise, induction of psychosis & fits upon abrupt discontinuation
What are some patient counselling points we should mention before dispensing antidepressants?
1) Antidepressants may take a couple of weeks to help with symptoms of low mood, poor sleep & poor appetite, and at least a couple of months to help with anxiety.
2) Do NOT take at the same time as alcohol; to space at least 4-6h apart.
3) Inform your Drs, nurses & pharmacists of the medicines you are using.
4) If you feel your condition is worsening, or feeling suicidal, agitated or experience bothersome & persistent side effects, contact Dr ASAP.
5) Possible side effects include:
- Drowsiness: Take at bedtime
- Insomnia (fluoxetine): Take in the morning
- Dizziness/Light-headedness: Rise up slowly
- Stomach upset: Take after food
- Changes in sexual function: Tell your Dr as this can be reversed & treated if it occurs; less likely with mirtazapine, bupropion & agomelatine.
6) Search for medication information on PIL available in HealthHub if interested.
