Psychiatric Disorders Flashcards
Drugs to relieve anxiety
Sedatives
Drugs to encourage sleep
Hypnotics
An effective anxiolytic should…
…reduce anxiety and exert a calming effect.
An effective hypnotic drug should…
…produce drowsiness and encourage the onset and maintenance of a state of sleep.
What happens when taking higher levels of barbiturates and alcohol than needed for hypnosis?
- May lead to a state of anesthesia
- may depress respiratory and vasomotor centers in the medulla, leading to coma and death
Benzodiazepines
Widely used sedative-hypnotics
Buspirone
A slow-onset anxiolytic agent whose actions are different than conventional sedative-hypnotics.
What effect a sedative-hypnotic has on the neonate if given predelivery?
May contribute to the depression of neonatal vital functions.
Can sedative-hypnotics cross the placenta barrier during pregnancy?
Yes
Are sedative-hypnotic detectable in breast milk?
Yes and can exert depressant effects in the nursing child.
What plays a major role in determining the rate at which a particular sedative-hypnotic enters the CNS?
Lipid solubility
Necessary for clearance of sedative-hypnotics from the body.
Metabolic transformation to more water-soluble metabolites.
Zoplicone is similar to Benzodiazepines (BDZs) in all of the following ways EXCEPT:
a) works at BZD receptor
b) not to be taken with other CNS depressants such as alcohol
c) Zoplicone has lower risk of rebound insomnia than BZDs
d) All of the above
e) A+C
C. Compared to BZDs, Zoplicone has lower risk of rebound insomnia and dependence
Which BDZ is most indicated for significant generalized daytime anxiety that has insomnia as a secondary symptom?
a) Lorazepam
b) Clonazepam
c) Temazepam
d) Triazolam
e) All of the above
B. Clonazepam is a long-acting BZD that’s indicated for anxiety disorder with insomnia. Note that it is inappropriate to use another shorter-acting BDZ at night to help with sleep onset if already taking Clonazepam.
For optimal monitoring of moderate to severe insomnia, how long should a patient be taking a BDZ before doing a first follow-up?
a) Within one week
b) 3-4 weeks
c) 6-8 weeks
d) 1-2 weeks
e) None of the above
D. The impact of BDZs should be monitored by 1-2 weeks and tapered after that. Using BDZ regularly over several weeks is associated with rebound insomnia, anxiety, agitation on discontinuation
Which of the following adverse effects are associated with BDZ use in the elderly population?
a) Confusion
b) Ataxia, leading to falls
c) Amnesia at higher doses
d) Withdrawal symptoms with long-term use
e) All of the above
E. Although all of these adverse effects may impact any patient taking BDZs, the risk of confusion/hangover effects and risk of falls dues to ataxia are particular concerns and limit use of BDZ in elderly population.
Which adverse effects are more associated with Zoplicone than BDZs?
a) bitter, metallic taste in mouth
b) morning drowsiness
c) rebound insomnia with discontinuation
d) additive effect of CNS depressants
e) A+C
A. The most common adverse effect of Zoplicone is metallic/bitter taste. All of the other advese effects listed are possible with both BDZs and Zoplicone.
Which of the following treatments are considered appropriate for mild insomnia?
a) Cognitive Behavioural Therapy
b) Sleep hygiene guidelines
c) 1-2 week trial of low-dose BDZ
d) Assessment of possible comorbid conditions
e) A+B+D
E. For mild insomnia, recommending non-pharmacologic treatments alone is the standard approach. Using medications is not recommended unless the insomnia is moderate to severe (ie. Significant daytime impairment). When patient initially presents with sleep disruption, it is always prudent to R/O or R/I comorbid conditions like depression, substance abuse, etc
Zoplidem use in pregnancy is associated with increased risk of:
a) post-partum anxiety
b) pre-term delivery
c) small-for-gestational-age infants
d) cesarian delivery
e) B+C+D
E. Zoplidem is not recommende for use in pregnancy. BDZs are also not used in pregnancy but Zoplicone can be used (based on limited safety data). Non-pharm approaches are always first-line tx.
Melatonin has been shown to:
a) Shorten time to sleep onset
b) Lengthen overall sleep time
c) Improve overall sleep quality
d) All of the above
D. In a meta-analysis of 19 studies, melatonin use had been shown to reduce sleep onset time (by 7 min or so), lengthen total sleep time (by 8.25 min of so), and improve overall sleep quality. Overall effect size, though, is smaller than pharm tx.
Which of the following BDZs are specifically used for onset-type insomnia more than maintenance-type insomnia?
a) Lorazepam
b) Triazolam
c) Temazepam
d) Flurazepam
e) Clonazepam
B. Triazolam has the fastest onset and short duration of action, so it is more suited for onset-type insomnia than maintenance-type insomnia. Its shorter duration of action means that it should be used for an even shorter duration (5-7 days) than other BDZs. Also CI in elderly due to unique dose-related AEs of agitation, confusion and amnesia in this population.
The following medications with sedative effects may be used as first-line treatments for moderate to severe insomnia to avoid using a BDZ or BDZ agonist:
a) Quetiapine
b) Mirtazapine
c) Diphenhydramine
d) Trazadone
e) None of the above
E. According to CTC 7, it is not appropriate to use other sedating medications in place of using BDZs and BDZ agonists in cases where the latter are the drug of choice. With quetiapine, can be used off-label as a second line agent (and at a lower dose than tx of psychotic disorder).
All of the following are appropriate prescribing principles when using BDZs for insomnia:
a) use a high dose initially to resolve insomnia and then reduce to minimal effective dose
b) try using intermittent dosing (ie less than 4 times per week)
c) limit use to 2-4 weeks
d) actively monitor daytime impairment symptoms as well as adverse effects of BDZ
e) B+C+D
E. With BDZ, recommended to use minimal effective dose from the outset due to risk of adverse effects with higher doses. All of the other recommendations were mentioned by Adil in his lecture.
The following medications are considered first-line tx for generalized anxiety EXCEPT:
a) SSRIs
b) Venlafaxine
c) Pregabalin
d) MAOIs
e) Benzodiazepines
D) All other medications listed except MOAIs would be considered first-line therapy. Given their higher risk of AEs, MAOIs may be used if first-line therapies are ineffective.
What is the most typical monitoring schedule for treating uncomplicated GAD?
a) Follow-up in 1-2 weeks after starting medication(s), then follow-up at 4-weeks and monthly for 12 months.
b) Follow-up at 4 weeks and then every other month indefinitely
c) Refer patient immediately to a psychiatrist
d) If patient is also doing CBT in addition to medications, can delay follow-up until 6-8 weeks.
A) This is the most typical monitoring schedule, whether patient is doing CBT or not. Refer patient to a psychiatrist if patient doesn’t improve (sx reduced 50% or more) after two separate trials of different long-term medications (ie. Meds other than BDZs).
What are the advantages of using benzodiazepines in treating anxiety?
a) Works on GABA receptors
b) can be used PRN
c) can be effective for both GAD and panic disorder
d) can be helpful for treating maintenance-type insomnia
e) A+B+C
E) BZDs have all these advantage and can be helpful in treating onset-type insomnia (on short-term basis)
Busprione is the treatment of choice for acute episodes of panic disorder T/F
False. Busprione takes longer to have anxiolytic effect (up to 3-6 weeks), so not effective to acutely treat panic. Benzodiazepines.
At low doses (5-30mg), Buspirone most strongly works at:
a) postsynaptic partial agonist 5-HT 1A receptors
b) GABA receptors
c) Presynaptic partial agonist 5-HT 1A receptors
d) Dopamine receptors
e) All of the above
C) Presynaptic partial agonist 5-HT 1A receptors
(At high-doses (30-60mg), busprione works most strongly at post-synaptic partial agonist 5-HT 1A receptors)
Which medications are typically prescribed for acute treatment of performance phobia, especially public speaking fear:
a) Buspirone
b) Propranolol
c) Lorazepam
d) Alprazolam
e) B+C+D
E) Low-dose propranolol, low-dose (.5mg) lorazepam, and alprazolam (.25mg) can be used PRN for performance phobia. Buspirone is not used acutely because it takes weeks to take effect.
When switching from long-term BDZ treatment to Buspirone, the patient should stop the BZD immediately to avoid potentially dangerous drug interactions with Buspirone. T/F
False. There is no cross-tolerance or drug interactions between BDZ and Busprione, and so it is actually important to gradually taper BDZ to avoid withdrawal symptoms.
All of the following medications can be used to treat post-partum anxiety disorders in breastfeeding moms EXCEPT:
a) Lorazepam
b) Sertaline
c) Paroxetine
d) Clonazepam
e) A+D
E) Benzodiazepines are not recommended for use in breastfeeding due to concerns of potential accumulation, sedation and impaired temperature regulation in babies. Sertaline and paroxetine, since they have low concentrations in breast milk, can be used during breastfeeding.
Benzodiazepines can be used in short-term (6-8 weeks) to:
a) rapidly reduce acute anxiety symptoms
b) be used on as-needed/PRN basis
c) to mitigate possible agitation related to initial dosing of SSRI/SNRI
d) All of the above
D) Although Adil would probably say that you never prescribe one drug to treat the adverse effects of another drug, using BDZs can be helpful not only to rapidly reduce anxiety symptoms while long-term treatment (eg. SSRI/SNRI) sets in, but also helps to mitigate the usually temporary agitation associated with initiating SSRI/SNRI meds.
Cognitive Behavioural Therapy (CBT) is considered as effective as SSRIs for treatment of uncomplicated GAD. T/F
True. Depending on patient preference and availability of CBT in their area, CBT is considered to be a reasonable first-line monotherapy for mild to moderate GAD.
Although Quetiapine is considered an effective monotherapy for GAD, it is regarded as a second-line choice because it:
a) takes much longer, up to 12-14 weeks, to have a significant impact on anxiety
b) worsen insomnia which is a common symptom of GAD
c) may cause weight gain
d) may be related to metabolic dysregulation
e) C+D
f) All of the above
e. Quetiapine, an atypical antipsychotic. Can be used as monotherapy or augmentation to antidepressant medication. At a moderate dose of 150mg daily po, it can rapidly improve primary symptoms of anxiety. Its use is reserved to second-line due to its adverse effect profile, including weight gain, sedation, and possible metabolic dysregulation.
For simple phobias other than performance phobia, medication treatment is superior to CBT. T/F
False. Exposure therapy, a form of CBT, significantly improves symptoms in 90% of cases. Medications are not typically used to treat simple phobias.
When prescribing donepezil to treat Alzheimer’s disease, all of the following statements are correct
EXCEPT:
a) Starting dose is 5mg daily
b) Initial dose should be maintained for 4 weeks before any dose increase is considered
c) Rivastigmine and galantamine are believed to be more effective than donepezil
d) Weight loss is a concern
e) Donepezil is associated with GI adverse effects and headaches
C. All of the cholinesterase inhibitors are believed to be equally effective for treating mild to moderate Alzheimer’s disease (page 59, CTC 7th edn). Nausea, vomiting and anorexia are common adverse effects, frequently leading to weight loss. Initial dosing is 5mg daily and clinicians can increase the dose to 10mg daily after 4 weeks.
Which of the following drugs is NOT likely to have a drug interaction with a cholinesterase inhibitor such as donepezil or galantamine?
a) Oxybutynin (for urinary incontinence)
b) Carbamazepine
c) Ramipril
d) Timolol
e) Benztropine
C. ACE Inhibitors such as ramipril do not interact with cholinesterase inhibitors.
Drugs with anticholinergic activity such as oxybutynin or benztropine, can antagonize the effect of cholinesterase inhibitors (Table 2, page 65 of Therapeutics Choices).
Drugs commonly known to induce P450, CYP 3A4 or CYP 2D6 enzymes, such as carbamazepine or phenytoin, will decrease the effectiveness of cholinesterase inhibitors.
Beta blockers such as timolol or metoprolol can have additive bradycardic effects.
Choose the CORRECT statement about the treatment of opioid withdrawal:
a) Methadone discontinuation should be slowly tapered over many weeks
b) Clonidine is an effective treatment against the muscle aches and cravings
c) Methadone has a half-life of about 2 to 4 hours
d) Naltrexone has no effect on the euphoric effects of opioids
e) Clonidine is used as a long-term therapy
A. Any discontinuation of methadone should be slowly tapered since drug craving can persist for several months. Methadone can be given once a day because it has a half-life of about 30 hours (page 166, CTC 7th edn).
Clonidine is only used for 7-12 days to blunt the withdrawal symptoms in acute detoxification but it has no effect on the muscle aches and cravings.
Naltrexone is a long-acting opioid antagonist used to block agonist effects such as euphoria.
Red Flags by condition and drug induced conditions: ADHD
INT SSRI Atomoxetine
(for ADHD)
- Inhibitors of CYP2D6 can increase plasma levels (Fluoxetine, paroxetine, quinidine)
- Slow-metabolizer (some Asian populations) may have extended elimination half-lives
- Concurrent use of salbutamol may increase HR
Red Flags by condition and drug induced conditions: ADHD
INT STIMULANTS
- Avoid concurrent use with MAOI
- Concurrent theophylline may INC. tachycardia, palpitations, dizziness, weakness
- Methylphenidate- may INC. plasma levels of phenytoin, phenobarbital, TCAs, warfarin. Carbamazepine DEC. plasma levels.
- Dextroamphetamine- Acidifying agents can DEC. absorption and elimination (fruit juice and ascorbic acid), alkalinizing agents can INC. absorption and elimination (sodium bicarbonate)
- ADVERSE EFFECTS- Common (anorexia, insomnia, irritability, dizziness, weepiness, HA, abdominal pain), Transient (Zombie-like effect, psychotic reactions, agitation, tachycardia, growth failure, rebound hyperactivity, leukopenia).
- OD - Glassy-eyes, insomnia, hyperactivity
- Significant- Sudden cardiac death, neurologic sxs, worsening of tics
Red Flags by condition and drug induced conditions: ADHD
Atomoxetine
- When switching from stimulant therapy, a lower dose can be continued and tapered over 3 wks while the new dose takes effect
- ADVERSE EFFECT- HA, rhinorrhea, upper abdominal pain, N/V, sedation, fatigue, emotional lability, ↑ HR/BP. ↑ In suicidal ideation and cardiac death. Possible liver toxicity and exacerbation of tics
How to taper drugs when patient is on stimulant therapy for ADHD?
Taper at 50%, 25% etc. every couple of days, if the child has been on for 6mo+
Red Flags by condition and drug induced conditions: Anxiety
BENZODIAZEPINES
Avoid in pregnancy
CI in patients w/known hx of substance abuse
CI’d with alcohol
Caution in elderly
Bad withdrawal Sx
Red Flags by condition and drug induced conditions: Anxiety
INT Benzodiazepines
- Additive CNS depression w/use of alcohol, other depressants
- Temazepam (Hypnotic – insomnia) → Substrate of CYP3A4, metabolism ↑’d by inducers (carbamazepine, smoking, phenytoin) and ↓’d by inhibitors (cimetidine, clarithromycin, erythromycin, grapefruit, itraconazole, ketoconazole, ritonavir)
- +Azoles: fluconazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Significant - Monitor Closely
Red Flags by condition and drug induced conditions: Anxiety
INT BUSPIRONE
CI`d with MAOI
Red Flags by condition and drug induced conditions: Anxiety
INT SSRI Atomoxetine
(for ADHD)
- Inhibitors of CYP2D6 can ↑ plasma levels (Fluoxetine, paroxetine, quinidine)
- Slow-metabolizer (some Asian populations) may have extended elimination half-lives
- Concurrent use of salbutamol may ↑ HR
Red Flags by condition and drug induced conditions: Anxiety
INT SSRI
● + SNRI
Red Flags by condition and drug induced conditions: Anxiety
INT SSRI
Serotonin sydrome: SSRI + TCAs, Mirtaepine, SNRI, Buspirone, MAOI, amphetamines
(tremor, agitation, hypomania, hyperthermia, HTN) combining 2+ serotonergic agents. Can cause death
● Caution w/other serotonergic drugs (Amphetamine derivatives, dextromethorphan, dihydroergotamine, linezolid, Lithium, meperidine, pentazocine, selegiline, St.Johns Wort, Trazodone, Triptans, Tryptophan)
Red Flags by condition and drug induced conditions: Anxiety
INT SSRIs
- NSAIDs INC Bleeding
- P450 inhibitors may ↑ levels → Cimetidine, clarithromycin, erythromycin, fluconazole, idinavir, isoniazid, ketoconazole, quinidine, ritonavir
- ↓ Clearance of → Clozapine, methadone, mexiletine, phenytoin, pimozid, propafenone.
- ↓ Enzymatic conversion of prodrug to active form → Clopidogrel, codeine, tamoxifen
- P450 inducers may ↑ clearance → Carbamazepine, phenobarbital, phenytoin, rifampin
Red Flags by condition and drug induced conditions: Anxiety
SSRIs FLOUXETINE & SERTRALINE
More stimulating
Red Flags by condition and drug induced conditions: Anxiety
SNRIs
Cautions w/SS as above.
* Venlafaxine → Inhibitors of CYP2D6 OR 3A4 may ↑ levels (HTN at high dose)
* Desvenlafaxine → Potent inhibitors of 3A4 may ↑ levels
* Duloxetine → DO NOT use with potent inhibitors of CYP1A2 (Ciprofloxacin, Fluvoxamine or Ketoconazole
* Current data does not support the use of SNRIs as primary treatment in youth depression.
Red Flags by condition and drug induced conditions: Anxiety
SSRIs
- Taper over at least 2 weeks, but can suddenly switch w/in class (applies to SSRI & SNRI
Generally, there is no need for wash-out, cross-over techniques can be applied when changing from drug to drug. EXCEPT - ● TO irreversible MAOI, FROM another AD → 5-t½ wash-out period
- ● FROM irreversible MAOI, TO another AD → 2-wk wash-out period
- ● FROM Moclobemide, TO another AD → 5-day wash-out period
- ● FROM Fluoxetine, TO irreversible MAOI → 5- wk wash-out period
- o Exercise caution when starting other AD when Fluoxetine has been d/c, due to its excessive t½.
- ● Paroxetine & Venlfaxine are the most likely to cause discontinuation symptoms (insomnia, dizziness, nausea, diarrhea)
Red Flags by condition and drug induced conditions: Anxiety
Buspirone
If switching from a benzo to buspirone (usually in GAD), make sure not to discontinue the benzo abruptly, as this could precipitate withdrawal Sxs. There is no cross-tolerance between benzos and buspirone, so a titrated dose approach is most effective.
Red Flags by condition and drug induced conditions: Anxiety
Benzodiazepines
Discontinue gradually; avoid rebound anxiety (e.g. Diazepam lasts for 1 wk)
ADVERSE EFFECTS- Drowsiness, dizziness, ↓ concentration, retrograde amnesia, physical dependence, rare paradoxical anger
Red Flags by condition and drug induced conditions: Anxiety
Benzodiazepines INTX WITH AZOLES
- fluconazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Significant - Monitor Closely
Red Flags by condition and drug induced conditions: Anxiety
Drug-induced anxiety
● Anticonvulsants: carbamazepine
● Antidepressants: SSRIs and tricyclic antidepressants
● Antihypertensives: felodipine
● Antibiotics: quinolones, isoniazid
● Bronchodilators: albuterol, theophylline
● Corticosteroids: prednisone
● Dopa agonists: levodopa
● Herbals: ma huang, ginseng, ephedra
● NSAIDs: ibuprofen
● Stimulants: amphetamines, methylphenidate, caffeine, cocaine
● Sympathomimetics: pseudoephedrine
● Thyroid hormones: levothyroxine
● Toxicity: anticholinergics, antihistamines, digoxin
● Withdrawal: alcohol, sedatives
Red Flags by condition and drug induced conditions: Dementia/Alzheimer’s
INT CHOLINESTERASE INHIBITORS
● Theoretical concern regarding antagonistic effects of cholinesterase inhibitors + anticholinergics
*● Additive bradycardia w/ß-blockers + CCBs – BE CAREFUL IF HYPERTENSION PT WITH DEMENTIA
o Donepezil & Galantamine→ toxicity may be ↑ by CYP2D6/3A4 inhibitors (Paroxetine, erythromycin, prednisone, grapefruit juice). Effectiveness ↓ by CYP2D6/3A4 inducers (Carbamazepine, phenytoin, rifampin)
o Rivastigmine → Not metabolized by P450, no reported interactions
* ADVERSE EFFECTS- Theoretically ↓ seizure threshold, ↑ risk of GI ulcerations, bleeding and exacerbate asthma/COPD. <10% experience vomiting, anorexia, fatigue, sleep disturbance, syncope, mm cramps, urinary frequency
Red Flags by condition and drug induced conditions: Depression
BUPROPION
CI in epilepsy, anything that incr risk of seizures: extreme caution in head trauma, hx of seizure, eating disorder,heavy alcohol use, LV dysfxn, CNS tumour
Red Flags by condition and drug induced conditions: Depression
INT Bupropion
● Inhibits CYP2D6, may ↓ clearance of → Atamoxetine, duloxetine, fluoxetine, fluvoxamine, paroxetine, risperidone, sertraline, venlafaxine.
● May ↓ effectiveness of → Codeine, tamoxifen
● DO NOT USE w/MAOI
● *Monitor for HTN when used in combo with nicotine replacement therapy
Red Flags by condition and drug induced conditions: Depression
LITHIUM
Very narrow therap window, therap drug monitoring:
Lithium (.6–1.2 (1.5) mmol/l – therapeutic range)
○ Common SE include: Thyroid, renal and hematological changes.
○ Monitor blood levels for toxicity: N/D/V, neurological deficits and coma.
○ Serum and toxicity levels do not correlate at all times, caused by high variability.
Red Flags by condition and drug induced conditions: Depression
NORTRIPTYLLINE (TCA)
Caution in CVD or arrythmias
Red Flags by condition and drug induced conditions: Depression
PAROXETINE (SSRI)
CI in youth (only give fluoxetine to teens), difficult discontinuation
Red Flags by condition and drug induced conditions: Depression
INT SSRI Atomoxetine
(for ADHD)
● Inhibitors of CYP2D6 can ↑ plasma levels (Fluoxetine, paroxetine, quinidine)
● Slow-metabolizer (some Asian populations) may have extended elimination half-lives
● Concurrent use of salbutamol may ↑ HR
Red Flags by condition and drug induced conditions: Depression
INT SSRI
Serotonin sydrome: SSRI + TCAs, Mirtrazepine, SNRI, Buspirone, MAOI, amphetamines
(tremor, agitation, hypomania, hyperthermia, HTN) combining 2+ serotonergic agents. Can cause death
● Caution w/other serotonergic drugs (Amphetamine derivatives, dextromethorphan, dihydroergotamine, linezolid, Lithium, meperidine, pentazocine, selegiline, St.Johns Wort, Trazodone, Triptans, Tryptophan)
Red Flags by condition and drug induced conditions: Depression
INT SSRI
● + SNRI
● Current data does not support the use of SNRIs as primary treatment in youth depression.
Red Flags by condition and drug induced conditions: Depression
INT SSRIs
● + NSAIDs → Bleeding
● P450 inhibitors may ↑ levels → Cimetidine, clarithromycin, erythromycin, fluconazole, idinavir, isoniazid, ketoconazole, quinidine, ritonavir
● ↓ Clearance of → Clozapine, methadone, mexiletine, phenytoin, pimozid, propafenone.
● ↓ Enzymatic conversion of prodrug to active form → Clopidogrel, codeine, tamoxifen
● P450 inducers may ↑ clearance → Carbamazepine, phenobarbital, phenytoin, rifampin
Red Flags by condition and drug induced conditions: Depression
SSRIs FLOUXETINE & SERTRALINE
● More stimulating
Red Flags by condition and drug induced conditions: Depression
SSRI and kids
● Fluoxetine and Citalopram are 1st line
Red Flags by condition and drug induced conditions: Depression
SNRIs
Cautions w/SS as above.
o Venlafaxine → Inhibitors of CYP2D6 OR 3A4 may ↑ levels (HTN at high dose)
o Desvenlafaxine → Potent inhibitors of 3A4 may ↑ levels
o Duloxetine → DO NOT use with potent inhibitors of CYP1A2 (Ciprofloxacin, Fluvoxamine or Ketoconazole)
o VENLAFAXINE possible dose-related hypertension (>225mg )
Red Flags by condition and drug induced conditions: Depression
TCAs (Clomipramine)
● May ↑ effects of anticholinergics, CNS depressants and warfarin
● Do not use with MAOIs
● Cardiotoxicity w/overdose
● ADVERSE EFFECTS- CNS Effects (initial agitation, confusion, drowsiness), Anticholinergics (dry mouth, blurred vision, constipation), weight gain, CV effects (tachycardia, arrhythmias, orthostatic hypotension), anorgasmia, ED
Red Flags by condition and drug induced conditions: Depression
SSRIs
Taper over at least 2 weeks, but can suddenly switch w/in class (applies to SSRI & SNRI
Generally, there is no need for wash-out, cross-over techniques can be applied when changing from drug to drug. EXCEPT
● TO irreversible MAOI, FROM another AD → 5-t½ wash-out period
● FROM irreversible MAOI, TO another AD → 2-wk wash-out period
● FROM Moclobemide, TO another AD → 5-day wash-out period
● FROM Fluoxetine, TO irreversible MAOI → 5- wk wash-out period
o Exercise caution when starting other AD when Fluoxetine has been d/c, due to its excessive t½.
● Paroxetine & Venlfaxine are the most likely to cause discontinuation symptoms (insomnia, dizziness, nausea, diarrhea)
Red Flags by condition and drug induced conditions: Depression
Doxepin (TCA)
Antidepressant with antihistamine properties; for chronic urticaria. Contraindicated – CHF and those taking MAOIs
Red Flags by condition and drug induced conditions: Depression
Drug-induced depression
● Antihypertensives
● Clonidine
● Diuretics
● Guanethidine sulfate
● Hydralazine hydrochloride
● Methyldopa
● Propranolol (all B blockers)
● Reserpine
● Steroids/adrenocorticotropic
● Hormonal therapy - Oral contraceptives
● Acne therapy Isotretinoin
● Interferon-beta-1a
MAOI drugs
Isocarboxazid, linezolid, moclobemide, phenelzine, rasagiline, Selegiline and tranylcypromine
MAOI major side effects
hypertension, jaundice and hyperthermia
What enzyme MAOIs block?
monoamine oxidase
monoamine oxidase
enzyme blocked by MAOIs. This enzyme breaks down excess tyramine in the body. Blocking this enzyme helps relieve depression. However, tyramine can quickly reach dangerous levels if you eat high tyramine foods, which may cause a spike in blood pressure and require emergency treatment.
Red Flags by condition and drug induced conditions: Insomnia
BENZODIAZEPINES
Avoid in pregnancy, CI in patients w/known hx of substance abuse,
CI`d wth alcohol, caution in elderly
Bad withdrawal Sx
Red Flags by condition and drug induced conditions: Insomnia
INT Benzodiazepines
● Additive CNS depression w/use of alcohol, other depressants
● Temazepam (Hypnotic – insomnia) → Substrate of CYP3A4, metabolism ↑’d by inducers (carbamazepine, smoking, phenytoin) and ↓’d by inhibitors (cimetidine, clarithromycin, erythromycin, grapefruit, itraconazole, ketoconazole, ritonavir)
● +Azoles: fluconazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Significant - Monitor Closely
Red Flags by condition and drug induced conditions: Insomnia
Benzodiazepines
Discontinue gradually; avoid rebound anxiety (e.g. Diazepam lasts for 1 wk)
Red Flags by condition and drug induced conditions: Insomnia
DRUG INDUCED INSOMNIA
anticonvulsants (e.g., phenytoin, valproic acid); appetite suppressants; bronchodilators (e.g., salbutamol); corticosteroids; decongestants, diuretics
Antidepressants– bupropion, SSRIs ie.fluoxetine, SNRIs, MAOIs, TCAs; (Adil notes) SSRI Combin: +MAOI + TCA or + Buproprion + SNRI
Antihypertensives
– beta blockers, levodopa\methyldopa; Nicotine;
Sympathomimetic Amines
– amphetamines, methylphenidate, caffeine, cocaine;
levodopa, quinidine, hormones (e.g., thyroid supplements, estrogen)
Drug induced Insomnia
● Central adrenergic blockers (Alpha-blockers)
● Beta Blockers
● Selective serotonin reuptake inhibitors
● Steroids Stimulants
● ACE inhibitors AND ARBs
● Cholinesterase inhibitors- like donepezil , galantamine and rivastigmine
● H1 antagonists
● Glucosamine/chondroitin
● Statins
● amphetamines,
● methylphenidate (ADHD)
Red Flags by condition and drug induced conditions: Psychosis
INT ANTIPSYCHOTICS
2nd Gen
● Additive sedation with CNS depressants
● May potentiate antihypertensive drug effects (watch hypotension)
o Olanzapine → Inhibitors of CYP1A2 may ↑ levels (Diltiazem, Fluvoxamine or Paroxetine)
o Risperidone → Inhibitors of CYP34A may ↑ levels (Grapefruit, Clarithromycin, erythromycin, ketoconazole, prednisone). Inducers may ↓ levels (Carbamazepine, phenytoin, rifampin)
Red Flags by condition and drug induced conditions: Psychosis
2nd G ANTIPSYCHOTICS
Advise patients about body temperature dysregulation and prevention of heat stroke
Red Flags by condition and drug induced conditions: Psychosis
Pimozide INTX WITH MACROLIDES
● erythromycin base and pimozide both increase QTc interval. Contraindicated
● erythromycin base increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation
erythromycin base will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Significant - Monitor Closely
Red Flags by condition and drug induced conditions: Psychosis
Pimozide INTX WITH AZOLES
● fluconazole and pimozide both increase QTc interval. Contraindicated
● fluconazole increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation
fluconazole will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor or non-significant interaction
Red Flags by condition and drug induced conditions: Smoking Cessation
BUPROPION
CI in epilepsy, anything that incr risk of seizures: extreme caution in head trauma, hx of seizure, eating disorder,heavy alcohol use, LV dysfxn, CNS tumour
Red Flags by condition and drug induced conditions: Smoking Cessation
INT Bupropion
● Inhibits CYP2D6, may ↓ clearance of → Atamoxetine, duloxetine, fluoxetine, fluvoxamine, paroxetine, risperidone, sertraline, venlafaxine.
● May ↓ effectiveness of → Codeine, tamoxifen
● DO NOT USE w/MAOI
● *Monitor for HTN when used in combo with nicotine replacement therapy
Red Flags by condition and drug induced conditions: Smoking Cessation
NICOTINE REPLACEMENT THERAPY
CI just had an MI, unstable angina (unstable cardiac condition)
many symptoms are due to withdrawal of nicotine, however can also experience overdose Sx: H/A, dizziness, nausea/vomiting/pain/diarrhea, salivation, sweating, flushing, palpitations.
Red Flags by condition and drug induced conditions: Smoking Cessation
VARENICLINE (CHAMPIX)
INT
Not in ppl w pre-existing psych disorder (suicidal thoughts – 1% ↑)
Should NOT be combined with nicotine replacement therapy NRT (would not be effective bc Varenicline blocks nicotinic Rec)
What are the main therapeutic goals for the treatment of Major Depressive Disorder?
1) Reduce severity of or have remission depressive symptoms
2) Minimize adverse effects of medication prescribed
3) Patient education on how to take medication, how long it will take to know how well the medication is working, possible side effects, duration of treatment, etc
4) Prevent relapse of MDD
5) Improve quality of daily life/resume optimal functioning
6) Prevent suicide/mortality
What are non-pharmacological treatment options? How efficacious are these therapies
1) Cognitive behavioural therapy (CBT) & Interpersonal therapy (IPT) – meta-analyses have shown that they are efficacious as medications for mild to moderate uncomplicated depression
2) Hypericum (St John’s Wort) – research indicates that it can be used as monotherapy in mild to moderate depression; but be aware that it is an inducer of CYP3A4 and intestinal gycloprotein
3) Other NHPs with research – SAMe, Vitamin D, omega 3 fatty acids, folic acid
4) Aerobic exercise
5) ECT (although not first-line choice in North America)
What are the major classes of medications used for tx of MDD?
1) SSRIs (Selective Serotonin Reuptake Inhibitors)
2) SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
3) NaSSA – Noradrenergic and serotogenic specific antidepressants
4) NDRIs – Noradrenaline dopamine reuptake inhibitors
5) TCAs – Tricyclic antidepressants
6) RIMA – Reversible Inhibitor of Monoamine Inhbitors
RESERVED USE :
1) SARIs – Serotonin antagonist/reuptake inhibitor
2) MAOIs – Irreversible Monoamine Oxidase Inhibitor
3) Heterocyclics
What is considered the most effective first-line med?
Escitalopram
What is the CANMAT Classification of Medications?
1) First-Line Agents:
* Citalopram (SSRI)
* **Escitalopram (SSRI)
* Duloxetine (SSRI)
* Fluoxetine (SSRI)
* Fluvoxamine (SSRI)
* Paroxetine (SSRI)
* Sertaline (SSRI)
* Bupropion (NDRI)
* Desvenlaxafine (SNRI)
* Venlaxafine (SNRI)
* Mirtazepine (NaSSA)
* Moclobemide (reversible MAOI and selective MAO-A inhibitor)
2) Second-Line Agents:
* Quetiapine (Atypical Antipsychotic)
* Aripiprazole (SARI)
* Trazadone (post-synaptic serotonin receptor antagonist)
* Tricyclic and tetracyclic antidepressants
3) Third-Line Agents:
* Phenelzine (irreversible MAOI)
* Tranylcypromine (irreversible MAOI)
How long does it take to see the full effect of SSRIs?
Usually within 2-3 weeks, patients will notice an improvement in symptoms. For full effect, often 4-6 weeks is needed.
How often do you monitor the patient who is initially given pharmaceutical tx?
Have follow-up 1-2 weeks after initial prescription. Then at 4 weeks, to see how much improvement patient has experienced.
What are the major side effects of each class of medication?
1) SSRIs – Nausea, sexual dysfn, sleep disturbance (either too much or insomnia), dry mouth, sweating, increased risk of GI bleeding, discontinuation syndrome
2) SNRIs – Nausea, dry mouth, drowsiness, nervousness, sleep disturbance, HTN with higher doses (>225 mg/day)
3) Buproprion – Agitation, insomnia, loss of apetite; CI in bulimia and anorexia nervosa; can lower seizure threshold, so CI in patients with seizures
4) Mirtazapine – Weight gain, sedation
5) Trazadone – Drowsiness (not used in daytime), orthostatic hypotension, H/A, dry mouth, nausea
6) Moclobemide – Nausea, insomnia, dizziness
7) Irreversible MAOIs –
What are the most important drug interactions for SSRIs?
- Potentially fatal Serotonin syndrome in combo with MAOIs
- Cytochrome P450 inhibitors, such as cimetidine, clarithromycin, erythromycin, fluconazole, indavi, isoniazid, itraconazole, ketoconazole, quinidine, ritonavir can increase levels of SSRIs
- At same time, all SSRIs can inhibit certain elements of P450 enzymes and thus reduce clearance of following drugs—methadone, clozapine, mexiltine, phenytoin, pimozide, propafenone
- Due to same mechanism, SSRIs can inhibit enzymatic conversion of prodrugs like tamoxifen, clopidrogel, codeine
- Drugs that induce cytochrome P450 , such as carbamazepine, phenobarbital, phyenytoin, rifampin, can increase clearance of SSRIs
- In combo with NSAIDS, can increase GI bleeding
- Do not mix with meds that can prolong QT interval such as amiodarone, azithromycin, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinine, sotalol, ziprasidone
What are most important drug-food interactions for MAOIs?
- Tyramine-containing foods can lead to hypertensive crisis
- Do not use with SSRIs, SNRIs or TCAs due to risk of serotonin syndrome, incl HTN and death
Which SSRI has the longest half-life? What is the clinical implication of this?
Fluoxetine. Can be tapered more quickly b/c less risk of discontinuation syndrome. Also need longer washout if switching to MAOI.
Which medications are approved for use in the tx of MDD in children and adolescents?
No antidepressant medications are formally approved for use in children and adolescents in Canada, although HCPs do prescribe off-label. Must be quite vigilant to watch for suicidal ideation especially in first weeks of treatment.
How is depression treated in pregnancy?
For mild depression, first try psychotherapy. Meds, in particular paroxetine, related to cardio malformations in fetus. SSRI use in third trimester assoc with pulmonary HTN in newborns. Newborns can also have sx of discontinuation syndrome.
How is depression treated in postnatal period?
Post-partum ‘blues’ affects up to 80% of mothers post-partum but do not require tx as it is self-limiting. PPD occurs in 1% of moms. First-line approach is psychotherapy. If meds used, then chose paroxetine, sertraline, and nortryptiline as they have low concentration in breastmilk.
What are the clinical features of serotonin syndrome?
Tremor, agitation, hypomania, hyperthermia, HTN. Can be fatal.
What is the process of tapering patients off medication?
All of the above medications especially paroxetine and venlafaxine, need to be tapered over 4-6 weeks to prevent discontinuation syndrome.
What are the features of discontinuation syndrome?
After taking any med for more than 6 weeks, esp SSRIs, and dose is suddenly reduced, patients can experience neuro, somatic and psych symptoms (nausea, dizziness, electric sensations, agitation) within 1-7 days of stopping/drastically reducing meds. Sx usually resolve within few days to few weeks.
How to avoid discontinuation syndrome?
Taper med by gradually reducing dose 25% per week.
When do you refer patients to a psychiatrist?
When patient has psychotic symptoms, has acute suicidal ideation, or does not improve after taking three different treatment trials
What duration of meds to prevent relapse?
For first episode of MDD, minimum duration of 1 year. For recurrent episodes, treat for at least 2 years.
How to approach treatment-resistant depression?
1) Can switch within or between class. Usually there is no need for washout (except below) ; just taper the first med(s) while gradually increasing second/third med
2) According to START-D study, can augment current meds through one or more of: Lithium carbonate; Atypical antispychotics s/a aripiprazole, quetiapine, rsiperidone, olanzapine; buproprion with SSRI; adding in triiodothyronine
What is the process to switch between drug classes?
1) When switching to an irreversible MAOI from any other anti-depressants, taper with washout period of 5 half-lives
2) When switching from irreversible MAOI to any anti-depressant, use 2-week washout period
3) Switching from moclobemide to any anti-depressant, use 5-day washout;
4) When switching from fluoxetine to an irreversible MAOI, use 5-week washout
What type of drugs are the mainstay of treatment for cognitive and functional symptoms?
Cholinesterase inhibitors (not be confused with ACE inhibitors = angiotensin converting enzyme)
Actions on the parasympathetic nervous system, (the parasympathetic branch of the autonomic nervous system) may cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure.
What are three cholinesterase inhibitors?
Doneprezil, rivastigmine, galantamine
T/F: Doneprezil works better than rivastigmine and galantamine?
F: all 3 agents seem to be of equal efficacy
T/F: an annual decline of less than 2 points while on the drug therapy indicates a beneficial effect (MMSE scale)
True
How often do you monitor treatment or increase a dosage?
Monitor treatment effects 2 weeks after initiating therapy or increasing dosage, then every 3 months
Which drug is approved for all disease severities? (mild, moderate and severe)
Donepezil
How would you dose Donepezil for Alzheimers?
Start with 5mg usually at night or in the AM if sleep disturbances then increase to 10mg after 4 weeks
How would you dose Rivastigmine for Alzheimers?
Start with 1.5 mg BID and increase to 3mg BID after 30 days, max 6mb BID
Which drug is good for those who have Lewy body dementia and Parkinson’s Disease?
Rivastigmine
Which drug is good for mixed Alzheimer’s disease and vascular dementia?
Glantamine
What drug blocks glutamate induced neuronal excotoxicity ?
Memantine
What drug could you add to donepezil for Alzheimers?
Memantine
Which of the following show benefit wrt dementia?
A. Ergoloid mesylates
B. Vitamin E
C. Selegiline
D. Gingko biloba
E. All of the above
F. None of the above
Technically, C. Selegiline proved more effective than placebo but no more effective than vit E alone in delaying death, institutionalization and progression to severe dementia
What would you use for vascular dementia?
Lipid lowering agents for dyslipidemia and good control of hypertension
Which of the following are good to do to prevent dementia?
A. Treat high blood pressure
B. Take a baby aspirin daily
C. Stake a statin regularly
D. Be on estrogen
E. 30 min of a brsk walk at least 3 times a week
A & E
The preferred method to treat responsive behaviours in dementia is antidepressants.
F. Better to use nonpharmacological interventions like music therapy, aromatherapy, bright light therapy, white nose, massage and touch intervention and involvement in structured recreational activities
When choosing an antidepressant, take these factors into account
SSRIs are less likely than TCAs to cause anticholinergic side effects or to worsen orthostatic hypotension, which are common and problematic in this population.
- Start at a low dose
- Monitor patients for s/e
- Increase dosage until recommended range is reached
- Maintain therapy for 4-6 weeks after first indication of symptomatic improvement before evaluating the success of treatment (mood, appetite, sleep energy) – can take 6-8 weeks for improvements
What could happen if you use thiazide with an SSRI?
Hyponatremia. Monitor electrolytes because of the effect of hyponatremia in cognitive function
Which TCAs could you use if not using an SSRI and why
Desipramine or nortriptyline because less anticholinergic effects
How long should someone be on antidepressants?
Trial 2-3 months
Which two drugs showed benefits in reducing agitation
Sertraline and citalopram
Which antipsychotics are first line in dementia?
Risperidone starting at 0.25 mg with 1mg being the optimal dose and 2mg/day the upper limit; olanzapine started at 2.5 mg and increase to 5-10 mg/day
They also reduce aggression
Which drugs are good to reduce agitation and which aggression in dementia?
A. Sertraline
B. Citalopram
C. Risperidone
D. Olanzapine
E. Quetiapine
F. Aripiprazole
Agitation: A & B & E
Agression C & D & F
Which drugs are good to reduce agitation and which aggression in dementia?
A. Sertraline
B. Citalopram
C. Risperidone
D. Olanzapine
E. Quetiapine
F. Aripiprazole
Agitation: A & B & E (Sertraline, Citalopram, Quetiapine)
Agression C & D & F (Risperidone, Olanzapine, Aripiprazole)
What is the major s/e of risperidone?
Extrapyramidal s/e ie tardive dyskinesia
What would you use for someone with a baseline movement disorder or EPS with 2nd generation antipsychosis
Quetiapine
T or F there is an increased risk of stroke and death with antipsychotics
True
What would you use for someone with AD that has sleep disturbances?
Trazodone 50mg QHS for 2 weeks
What should you consider when using antipsychotics?
- Only for severe behavioural symptoms ie psychosis and risk of harming self or others
- Use second generation first
- Low dose, go up slowly until designated endpoint
- Evaluate therapy 1,3, 6 months, then every 6 months – symptoms may subside naturally and the antipsychotic can be tapered
- Watch for drug induced akathisis (increased motor restlessness) don’t over dose
What type of medication is best avoided in those with Lewy body dementia , rigidity, autonomic dysregulation, cognitive deterioration (delirium)
Antipsychotics
The definition of bipolar disorder includes all of the following:
A. Experiencing a manic episode (with or without a major depressive episode history)
B. Experiencing a hypomanic episode (with current or past major depressive episode)
C. Mania or hypomania must include increased goal directed activity or energy
D. All of the Above
D
T/F: Symptoms of mania include changes in mood, energy, sleep requirements, ability to concentrate, and psychotic symptoms.
True
The most common symptom of bipolar disorder depression is:
A. Profound tiredness
B. Significant weight loss/gain or change in appetite
C. Decreased cognitive abilities
D. Possibly suicidal or psychotic symptoms
A: Can be associated with insomnia or hypersomnia
What is NOT true of Bipolar Disorder:
A. It is formally divided into three categories (Bipolar I, Bipolar II, and Bipolar Disorder not otherwise specified
B. Diagnosis is difficult because the symptoms can resemble other psychiatric conditions (schizophrenia, substance abuse disorders, unipolar depression, borderline personality disorder)
C. It has a low mortality
D. It associated with a high number of episodes and high degree of comorbidity.
C. It has the highest mortality of the major psychiatric conditions
Basic blood tests should include:
A. CBC, electrolytes, lipids
B. Renal, thyroid and liver function
C. B-HCG and Fasting Blood Sugars
D. All of the above
D. Note: b-HCG is important before prescribing any drugs that are CI in pregnancy
T/F: If a patient is taking an anti-depressant at the time that mania is diagnosed, it should be discontinued.
True – antidepressants can cause mania. So should caffeine, alcohol and other illicit substances.
Which is NOT true about initiating medication in a previously unmedicated patient for BPD?
A. Start with a first line agent, like lithium.
B. If symptoms are severe, initiate treatment with a two drug combo, like lithium or divalproex plus a second generation anti-psychotic.
C. Continue treatment for 2-4 weeks at therapeutic doses before assessing if a change is necessary.
D. None of the above.
D
T/F: Psychosocial strategies, combined with lithum and divalproex are a valuable treatment strategy.
True.
The following are typical of bipolar disorder in children and adolescents, except:
A. It typically presents in adolescence as depression.
B. There is no genetic link for BPD.
C. It is often associated with severe or psychotic symptoms and unmistakable depression.
D. The key distinguishing feature from ADHD is the symptoms of BPD are episodic, which ADHD symptoms are continuous.
B. The existence of a first degree relative with BPD in an adolescent presenting with depression is suggestive of eventual BPD diagnosis.
Patients taking lithium need to monitor their:
A. Salt intake
B. Caffeine intake
C. Illnesses or changes in take that can affect electrolyte balance
D. All of the above
D
The antipsychotics, Quetiapine, Olanzipine and Risperidone (first line), can be associated with all of these, except:
A. Temperature dysregulation
B. Hypertension
C. Weight Gain
D. Sedation
E. Movement disorders
B. It causes hypotension, so caution with antihypertensives.
Which of the following drug interactions with Lithium is most prevelant?:
A. NSAIDS
B. ACEIs
C. ARBs
D. Thiazide diuretics
D
Which of the following is good for prevention of both manic and depressive episodes?
A. Lithium
B. Lamotrigine
C. Olanzapine
D. Both A and C
D.
Lamotrigine is only for prevention of depressive episodes.
Which of the following is strongly affected by inducers (such as carbamazepine, phenytoin or rifampin) or inhibitors (such as ketoconazole, quinidine, fluoxetine or paroxetine) of CYP2D6 or CYP3A4?
A. Lithium
B. Aripriprazole
C. Lamotrigine
D. Quetiapine
B. Apriprazole
Which of the following interacts with Ketoconazole?
A. Aripiprazole
B. Quetiapine
C. Olanzapine
D. A and B
D.
Olanzapine can interact with fluvoxamine and ciprofloxacin.
Which of the following should not be taken with Carbamazepine?
A. Aripriprazole
B. Paliperidone
C. Risperidone
D. Divalproex Sodium
E. All of these
E
Sub-types of ADHD
- Hyperactivity impulsive subtype
- inattentive subtype (9 sx, you need 6 to meet this)
- combined subtype (12 or more of the 18 sx to be dx, present in 2 places (school and home for example), below the age of 7yoa for at least 6 months, and need to be impairing their fx)
ADHD stimulant drugs effectiveness
70-90%
Probability of 50% reduction in CORE symptoms:
Behaviour management
40-60%
Probability of 50% reduction in CORE symptoms:
Stimulants
65-85%
Probability of 50% reduction in CORE symptoms:
non-stimulants
50-60%
Probability of 50% reduction in CORE symptoms:
antidepressants
~50%
Probability of 50% reduction in CORE symptoms:
alpha-2 agonists
~40%
ADHD Stimulants SE
sleep disruption
weight loss
how often immediate release should be dose
2-3 times a day
Concerns for ADHD stimulants (AE)
sudden death due to cardiac arrest (0.47% or ~1/200)
How long for ADHD stimulant med to be effective
from day 1 and continue over the following months
ADHD stimulant drugs overall response rate
~75%
how many kids with ADHD drugs improve in adulthood?
1/3
how many kids with ADHD drugs do not improve in adulthood?
1/3
How many kids with ADHD meds improve but sx never go away in adulthood?
1/3
how should ADHD stimulant be deprescribed?
half life is 4-5hrs. Tapper down 25%-50% for 2-3 days, then 25-50% down. observing how they are reacting. People should not go on ‘drug holiday’.
Atomoxetine SE
- decreased appetite
- nausea
- dyspepsia
- vomiting
- somnolence
- fatigue
- dizziness
- hepatic
- mood swings
- transient WL
- increased HR, SBP, DBP
- sexual dysfunction
- suicidal ideation (on kids with no depression)
how many Canadians experience a depressive event in their life?
1 out of 5
What are the main therapeutic goals for the treatment of Major Depressive Disorder?
1) Reduce severity of or have remission depressive symptoms
2) Minimize adverse effects of medication prescribed
3) Patient education on how to take medication, how long it will take to know how well the medication is working, possible side effects, duration of treatment, etc
4) Prevent relapse of MDD
5) Improve quality of daily life/resume optimal functioning
6) Prevent suicide/mortality
What are non-pharmacological treatment options? How efficacious are these therapies?
1) Cognitive behavioural therapy (CBT) & Interpersonal therapy (IPT) – meta-analyses have shown that they are efficacious as medications for mild to moderate uncomplicated depression
2) Hypericum (St John’s Wort) – research indicates that it can be used as monotherapy in mild to moderate depression; but be aware that it is an inducer of CYP3A4 and intestinal gycloprotein
3) Other NHPs with research – SAMe, Vitamin D, omega 3 fatty acids, folic acid
4) Aerobic exercise
5) ECT (although not first-line choice in North America)
What are the major classes of medications used for tx of MDD?
1) SSRIs (Selective Serotonin Reuptake Inhibitors)
2) SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
3) NaSSA – Noradrenergic and serotogenic specific antidepressants
4) NDRIs – Noradrenaline dopamine reuptake inhibitors
5) TCAs – Tricyclic antidepressants
6) RIMA – Reversible Inhibitor of Monoamine Inhbitors
RESERVED USE :
1) SARIs – Serotonin antagonist/reuptake inhibitor
2) MAOIs – Irreversible Monoamine Oxidase Inhibitor
3) Heterocyclics
What is considered the most effective first-line med?
Escitalopram
What is the CANMAT Classification of Medications?
1) First-Line Agents:
* Citalopram (SSRI)
* **Escitalopram (SSRI)
* Duloxetine (SSRI)
* Fluoxetine (SSRI)
* Fluvoxamine (SSRI)
* Paroxetine (SSRI)
* Sertaline (SSRI)
* Bupropion (NDRI)
* Desvenlaxafine (SNRI)
* Venlaxafine (SNRI)
* Mirtazepine (NaSSA)
* Moclobemide (reversible MAOI and selective MAO-A inhibitor)
2) Second-Line Agents:
* Quetiapine (Atypical Antipsychotic)
* Aripiprazole (SARI)
* Trazadone (post-synaptic serotonin receptor antagonist)
* Tricyclic and tetracyclic antidepressants
3) Third-Line Agents:
* Phenelzine (irreversible MAOI)
* Tranylcypromine (irreversible MAOI)
How long does it take to see the full effect of SSRIs?
Usually within 2-3 weeks, patients will notice an improvement in symptoms. For full effect, often 4-6 weeks is needed.
How often do you monitor the patient who is initially given pharmaceutical tx?
Have follow-up 1-2 weeks after initial prescription. Then at 4 weeks, to see how much improvement patient has experienced.
What are the major side effects of each class of medication?
1) SSRIs – Nausea, sexual dysfn, sleep disturbance (either too much or insomnia), dry mouth, sweating, increased risk of GI bleeding, discontinuation syndrome
2) SNRIs – Nausea, dry mouth, drowsiness, nervousness, sleep disturbance, HTN with higher doses (>225 mg/day)
3) Buproprion – Agitation, insomnia, loss of apetite; CI in bulimia and anorexia nervosa; can lower seizure threshold, so CI in patients with seizures
4) Mirtazapine – Weight gain, sedation
5) Trazadone – Drowsiness (not used in daytime), orthostatic hypotension, H/A, dry mouth, nausea
6) Moclobemide – Nausea, insomnia, dizziness
7) Irreversible MAOIs –
What are the most important drug interactions for SSRIs?
- Potentially fatal Serotonin syndrome in combo with MAOIs
- Cytochrome P450 inhibitors, such as cimetidine, clarithromycin, erythromycin, fluconazole, indavi, isoniazid, itraconazole, ketoconazole, quinidine, ritonavir can increase levels of SSRIs
- At same time, all SSRIs can inhibit certain elements of P450 enzymes and thus reduce clearance of following drugs—methadone, clozapine, mexiltine, phenytoin, pimozide, propafenone
- Due to same mechanism, SSRIs can inhibit enzymatic conversion of prodrugs like tamoxifen, clopidrogel, codeine
- Drugs that induce cytochrome P450 , such as carbamazepine, phenobarbital, phyenytoin, rifampin, can increase clearance of SSRIs
- In combo with NSAIDS, can increase GI bleeding
- Do not mix with meds that can prolong QT interval such as amiodarone, azithromycin, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinine, sotalol, ziprasidone
What are most important drug-food interactions for MAOIs?
- Tyramine-containing foods can lead to hypertensive crisis
- Do not use with SSRIs, SNRIs or TCAs due to risk of serotonin syndrome, incl HTN and death
Which SSRI has the longest half-life? What is the clinical implication of this?
Fluoxetine. Can be tapered more quickly b/c less risk of discontinuation syndrome. Also need longer washout if switching to MAOI.
Which medications are approved for use in the tx of MDD in children and adolescents?
No antidepressant medications are formally approved for use in children and adolescents in Canada, although HCPs do prescribe off-label. Must be quite vigilant to watch for suicidal ideation especially in first weeks of treatment.
How is depression treated in pregnancy?
For mild depression, first try psychotherapy. Meds, in particular paroxetine, related to cardio malformations in fetus. SSRI use in third trimester assoc with pulmonary HTN in newborns. Newborns can also have sx of discontinuation syndrome.
How is depression treated in postnatal period?
Post-partum ‘blues’ affects up to 80% of mothers post-partum but do not require tx as it is self-limiting. PPD occurs in 1% of moms. First-line approach is psychotherapy. If meds used, then chose paroxetine, sertraline, and nortryptiline as they have low concentration in breastmilk.
What are the clinical features of serotonin syndrome?
Tremor, agitation, hypomania, hyperthermia, HTN. Can be fatal.
What is the process of tapering patients off medication?
All of the above medications especially paroxetine and venlafaxine, need to be tapered over 4-6 weeks to prevent discontinuation syndrome.
What are the features of discontinuation syndrome?
After taking any med for more than 6 weeks, esp SSRIs, and dose is suddenly reduced, patients can experience neuro, somatic and psych symptoms (nausea, dizziness, electric sensations, agitation) within 1-7 days of stopping/drastically reducing meds. Sx usually resolve within few days to few weeks.
How to avoid discontinuation syndrome?
Taper med by gradually reducing dose 25% per week.
When do you refer patients to a psychiatrist?
When patient has psychotic symptoms, has acute suicidal ideation, or does not improve after taking three different treatment trials
What duration of meds to prevent relapse?
For first episode of MDD, minimum duration of 1 year. For recurrent episodes, treat for at least 2 years.
How to approach treatment-resistant depression?
1) Can switch within or between class. Usually there is no need for washout (except below) ; just taper the first med(s) while gradually increasing second/third med
2) According to START-D study, can augment current meds through one or more of: Lithium carbonate; Atypical antispychotics s/a aripiprazole, quetiapine, rsiperidone, olanzapine; buproprion with SSRI; adding in triiodothyronine
What is the process to switch between drug classes?
1) When switching to an irreversible MAOI from any other anti-depressants, taper with washout period of 5 half-lives
2) When switching from irreversible MAOI to any anti-depressant, use 2-week washout period
3) Switching from moclobemide to any anti-depressant, use 5-day washout;
4) When switching from fluoxetine to an irreversible MAOI, use 5-week washout
Which of the following medications are considered first-line tx EXCEPT
For generalized anxiety?
a) SSRIs
b) Venlafaxine
c) Pregabalin
d) MAOIs
e) Benzodiazepines
D) All other medications listed except MOAIs would be considered first-line therapy. Given their higher risk of AEs, MAOIs may be used if first-line therapies are ineffective.
What is the most typical monitoring schedule for treating uncomplicated GAD?
a) Follow-up in 1-2 weeks after starting medication(s), then follow-up at 4-weeks and monthly for 12 months.
b) Follow-up at 4 weeks and then every other month indefinitely
c) Refer patient immediately to a psychiatrist
d) If patient is also doing CBT in addition to medications, can delay follow-up until 6-8 weeks.
A) This is the most typical monitoring schedule, whether patient is doing CBT or not. Refer patient to a psychiatrist if patient doesn’t improve (sx reduced 50% or more) after two separate trials of different long-term medications (ie. Meds other than BDZs).
What are the advantages of using benzodiazepines in treating anxiety?
a) Works on GABA receptors
b) can be used PRN
c) can be effective for both GAD and panic disorder
d) can be helpful for treating maintenance-type insomnia
e) A+B+C
E) BZDs have all these advantage and can be helpful in treating onset-type insomnia (on short-term basis)
Busprione is the treatment of choice for acute episodes of panic disorder T/F
False. Busprione takes longer to have anxiolytic effect (up to 3-6 weeks), so not effective to acutely treat panic. Benzodiazepines.
At low doses (5-30mg), Buspirone most strongly works at:
a) postsynaptic partial agonist 5-HT 1A receptors
b) GABA receptors
c) Presynaptic partial agonist 5-HT 1A receptors
d) Dopamine receptors
e) All of the above
C)
(At high-doses (30-60mg), busprione works most strongly at post-synaptic partial agonist 5-HT 1A receptors)
Which medications are typically prescribed for acute treatment of performance phobia, especially public speaking fear:
a) Buspirone
b) Propanolol
c) Lorazepam
d) Alprazolam
e) B+C+D
E) Low-dose propranolol, low-dose (.5mg) lorazepam, and alprazolam (.25mg) can be used PRN for performance phobia. Buspirone is not used acutely because it takes weeks to take effect.
When switching from long-term BDZ treatment to Buspirone, the patient should stop the BZD immediately to avoid potentially dangerous drug interactions with Buspirone. T/F
F. There is no cross-tolerance or drug interactions between BDZ and Busprione, and so it is actually important to gradually taper BDZ to avoid withdrawal symptoms.
All of the following medications can be used to treat post-partum anxiety disorders in breastfeeding moms EXCEPT:
a) Lorazepam
b) Sertaline
c) Paroxetine
d) Clonazepam
e) A+D
E) Benzodiazepines re not recommended for use in breastfeeding due to concerns of potential accumulation, sedation and impaired temperature regulation in babies. Sertaline and paroxetine, since they have low concentrations in breast milk, can be used during breastfeeding.
Benzodiazepines can be used in short-term (6-8 weeks) to:
a) rapidly reduce acute anxiety symptoms
b) be used on as-needed/PRN basis
c) to mitigate possible agitation related to initial dosing of SSRI/SNRI
d) All of the above
D) Although Adil would probably say that you never prescribe one drug to treat the adverse effects of another drug, using BDZs can be helpful not only to rapidly reduce anxiety symptoms while long-term treatment (eg. SSRI/SNRI) sets in, but also helps to mitigate the usually temporary agitation associated with initiating SSRI/SNRI meds.
Cognitive Behavioural Therapy (CBT) is considered as effective as SSRIs for treatment of uncomplicated GAD. T/F
T. Depending on patient preference and availability of CBT in their area, CBT is considered to be a reasonable first-line monotherapy for mild to moderate GAD.
Although Quetiapine is considered an effective monotherapy for GAD, it is regarded as a second-line choice because it:
a) takes much longer, up to 12-14 weeks, to have a significant impact on anxiety
b) worsen insomnia which is a common symptom of GAD
c) may cause weight gain
d) may be related to metabolic dysregulation
e) C+D
f) All of the above
E) Quetiapine, an atypical antipsychotic. Can be used as monotherapy or augmentation to antidepressant medication. At a moderate dose of 150mg daily po, it can rapidly improve primary symptoms of anxiety. It’s use is reserved to second-line due to its adverse effect profile, including weight gain, sedation, and possible metabolic dysregulation.
For simple phobias other than performance phobia, medication treatment is superior to CBT. T/F
F. Exposure therapy, a form of CBT, significantly improves symptoms in 90% of cases. Medications are not typically used to treat simple phobias.
What symptoms are NOT characteristic of ADHD?
A. Inattention
B. Present at one of: School, work or home
C. Hyperactivity
D. Impulsivity
E. Usually presents before 8 years of age
B: Present in 2 or more of those settings
E. Usually presents before 12 years of age
What are the 3 types of ADHD?
A. Primarily Inattentive
B. Combined
C. Primarily Impulsive
D. Primarily Hyperactive/Inattentive
E. Primarily Hyperactive/Impulsive
A, B, E
Which of the above is most commonly observed?
Combined
T/F To diagnose ADHD, there must be evidence of 5 or more specific behaviours/symptoms for children.
F: There must be at least 6 or more specific behaviour/symptoms for children (5 for over 17 years of age)
The following baseline measurements should be checked in all patients being treated for ADHD with stimulants:
A. BP and Heart Rate
B. Height and Weight
C. ECG
D. All of the above
E. A and B
F. ECG is not required according to the CADDRA guideline, but is reasonable to check if there is a personal or family history of heart disease.
T/F: Behaviour modification programs mixed with pharmacologic therapies constitute the best treatment strategy for ADHD.
True
The best pharmacologic therapies for the core ADHD symptoms are stimulant medications and which of the following:
A. Atamoxetine
B. Anti-depressants
C. Alpha2-Adrenergic Agonists
D. All of the above
A
The stimulant medications include:
A. Dextroamphetamine, and Mixed Salts Amphetamine
B. Methylphenidate
C. Lisdexamfetamine
D. All of the Above
D
T/F: The efficacy of stimulant medications has been shown in patients 3 years to adult.
False – 6 years to adult.
T/F: Controlled trials consistently demonstrate that at least 70% of patients receiving stimulant therapy will have a clinically significant decrease in core ADHD symptoms.
True – they haven’t been studied for long term outcomes such as quality of life, employment, school completion, and long term morbidity or mortality.
Which of the following about stimulants is not correct:
A. Patients who don’t respond to one within 3-4 weeks should be switched to an alternative stimulant.
B. RCTs have shown there is no harm from long term stimulant therapy.
C. Children given them were on average 2 cm shorter and weighed 2.7 kg less than those who were never medicated.
D. Sustained release tablets (i.e Ritalin SR) have a longer duration of action than immediate release tablets, but often require more than once daily dosing.
B. There are no RCTS assessing the benefits and harms of long term use.
Long acting stimulants have a duration of 8-14 hours, and are recommended as first line for treatment of ADHD. Which of the following is NOT a long acting stimulant?
A. Mixed Salts amphetamine (Adderal XR)
B. Methylphenidate (Biphentin and Concerta)
C. Atomexetine
D. Lisdexamfetamine (Vyvanse)
C. Atomexetine is a norepi reuptake inhibitor.
Stimulants and Atomexetine may be associated with which of the following:
A. Sudden cardiac death in those with cardiac anomalies
B. Hallucinations and agitation
C. Priapism
D. All of the above
D
T/F Modafinil is a CNS stimulant used in narcolepsy, which is as effective as other stimulants.
F. It is less effective and is not often used.
Which of the following about Atomoxetine is NOT true?
A. It is a NE reuptake inhibitor
B. RCTs shows that after 1 week, it reduces core ADHD symptoms by at least 25-30% in 60-70% of patients.
C. Evidence has shown it should be used on patients who either do not respond or cannot tolerate stimulants
D. It can be used with comorbid substance abuse or depression.
B. RCTs show it take 6-12 weeks of treatment to have that effect
T/F: Antidepressants may benefit with comorbid disorders like depression, anxiety, enuresis or tic disorders.
T
Anti-depressants that can be used as second or third line options for ADHD include all of the following, EXCEPT:
A. Buproprion(NE and dopamine reuptake inhibitor)
B. Venlafaxine (serotonin-NE reuptake inhibitor)
C. TCAs like desipramine, imipramine and nortriptyline for short term treatment
D. Paxil
D
Compared to clonidine, guanfacine (both alpha2-adrenergic agonists) has all of the following, EXCEPT:
A. More selective neuronal activity
B. Long duration of action
C. More sedation
D. Less hypotension
C. Less sedation
T/F: Alpha-adrenergic agonists help with aggression, impulsivity and hyperactivity, as well as inattention.
F. They have less pronounced benefits on inattention.
Anti-psychotics, such as respiradone, help with which of the following:
A. Help with behavioural symptoms when stimulants alone are ineffective or not tolerated
B. Have little effect on inattention
C. Used to decrease behaviours in children with comorbid conduct disorder, oppositional defiant disorder, autistic disorders, impulse control disorders and Tourette’s syndrome
D. All of the above.
D
T/F: Adderall XR, Dexedrine spansules, Vyvanse and Biphentin capsules can be opened and sprinkled on soft foods such as yogurt or apple sauce.
T
T/F. Trials evaluating substance abuse in those with ADHD have found that adequately treated children have a lower risk of substance abuse later in life when compared to those who are untreated.
T
T/F: Improvement of core ADHD symptoms with stimulants is often observed in the first week of therapy.
T. It is reasonable to try for 3-4 weeks to be sure.
T/F: A stimulant should not be continued or tapered when switching to atomoxetine or an antidepressant.
F. It can be continued or tapered over approximately 3 weeks while the new drug takes effect.
T/F: Extended “drug holidays” from stimulants (i.e. summer holidays) is recommended for all ADHD patients.
F: Weaning the stimulant for a 2-3 week period may be tried with mild ADHD, but are generally not recommended for moderate to severe ADHD.
T/F – Benzodiazepines should be used short term only or to augment SSRI/SNRI treatment.
True
T/F – SSRI & SNRI are first line therapy for Anxiety Disorders.
True
What is a good strategy for stage fright?
Low dose propanolol (10mg) taken 30 minutes before the event.
Which SSRI’s are considered 1st line therapy?
Fluoxetine, Fluvoxamine, Paroxetine, Sertraline.
T/F – High dose Risperidone is a good augmentation of SSRI’s in response to OCD.
False. Low dose
T/F – Benzodiazepines are an effective measure for treating OCD
False
Benzodiazepines should be restricted to short term use which is how long?
6 – 8 Weeks
What are the main therapeutic goals for the treatment of Major Depressive Disorder?
1) Reduce severity of or have remission depressive symptoms
2) Minimize adverse effects of medication prescribed
3) Patient education on how to take medication, how long it will take to know how well the medication is working, possible side effects, duration of treatment, etc
4) Prevent relapse of MDD
5) Improve quality of daily life/resume optimal functioning
6) Prevent suicide/mortality
What are non-pharmacological treatment options? How efficacious are these therapies
1) Cognitive behavioural therapy (CBT) & Interpersonal therapy (IPT) – meta-analyses have shown that they are efficacious as medications for mild to moderate uncomplicated depression
2) Hypericum (St John’s Wort) – research indicates that it can be used as monotherapy in mild to moderate depression; but be aware that it is an inducer of CYP3A4 and intestinal gycloprotein
3) Other NHPs with research – SAMe, Vitamin D, omega 3 fatty acids, folic acid
4) Aerobic exercise
5) ECT (although not first-line choice in North America)
What are the major classes of medications used for tx of MDD?
1) SSRIs (Selective Serotonin Reuptake Inhibitors)
2) SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
3) NaSSA – Noradrenergic and serotogenic specific antidepressants
4) NDRIs – Noradrenaline dopamine reuptake inhibitors
5) TCAs – Tricyclic antidepressants
6) RIMA – Reversible Inhibitor of Monoamine Inhbitors
RESERVED USE :
1) SARIs – Serotonin antagonist/reuptake inhibitor
2) MAOIs – Irreversible Monoamine Oxidase Inhibitor
3) Heterocyclics
What is considered the most effective first-line med?
Escitalopram
What is the CANMAT Classification of Medications?
1) First-Line Agents:
* Citalopram (SSRI)
* **Escitalopram (SSRI)
* Duloxetine (SSRI)
* Fluoxetine (SSRI)
* Fluvoxamine (SSRI)
* Paroxetine (SSRI)
* Sertaline (SSRI)
* Bupropion (NDRI)
* Desvenlaxafine (SNRI)
* Venlaxafine (SNRI)
* Mirtazepine (NaSSA)
* Moclobemide (reversible MAOI and selective MAO-A inhibitor)
2) Second-Line Agents:
* Quetiapine (Atypical Antipsychotic)
* Aripiprazole (SARI)
* Trazadone (post-synaptic serotonin receptor antagonist)
* Tricyclic and tetracyclic antidepressants
3) Third-Line Agents:
* Phenelzine (irreversible MAOI)
* Tranylcypromine (irreversible MAOI)
How long does it take to see the full effect of SSRIs?
Usually within 2-3 weeks, patients will notice an improvement in symptoms. For full effect, often 4-6 weeks is needed.
How often do you monitor the patient who is initially given pharmaceutical tx?
Have follow-up 1-2 weeks after initial prescription. Then at 4 weeks, to see how much improvement patient has experienced.
What are the major side effects of each class of medication?
1) SSRIs – Nausea, sexual dysfn, sleep disturbance (either too much or insomnia), dry mouth, sweating, increased risk of GI bleeding, discontinuation syndrome
2) SNRIs – Nausea, dry mouth, drowsiness, nervousness, sleep disturbance, HTN with higher doses (>225 mg/day)
3) Buproprion – Agitation, insomnia, loss of apetite; CI in bulimia and anorexia nervosa; can lower seizure threshold, so CI in patients with seizures
4) Mirtazapine – Weight gain, sedation
5) Trazadone – Drowsiness (not used in daytime), orthostatic hypotension, H/A, dry mouth, nausea
6) Moclobemide – Nausea, insomnia, dizziness
7) Irreversible MAOIs –
What are the most important drug interactions for SSRIs?
- Potentially fatal Serotonin syndrome in combo with MAOIs
- Cytochrome P450 inhibitors, such as cimetidine, clarithromycin, erythromycin, fluconazole, indavi, isoniazid, itraconazole, ketoconazole, quinidine, ritonavir can increase levels of SSRIs
- At same time, all SSRIs can inhibit certain elements of P450 enzymes and thus reduce clearance of following drugs—methadone, clozapine, mexiltine, phenytoin, pimozide, propafenone
- Due to same mechanism, SSRIs can inhibit enzymatic conversion of prodrugs like tamoxifen, clopidrogel, codeine
- Drugs that induce cytochrome P450 , such as carbamazepine, phenobarbital, phyenytoin, rifampin, can increase clearance of SSRIs
- In combo with NSAIDS, can increase GI bleeding
- Do not mix with meds that can prolong QT interval such as amiodarone, azithromycin, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinine, sotalol, ziprasidone
What are most important drug-food interactions for MAOIs?
- Tyramine-containing foods can lead to hypertensive crisis
- Do not use with SSRIs, SNRIs or TCAs due to risk of serotonin syndrome, incl HTN and death
Which SSRI has the longest half-life? What is the clinical implication of this?
Fluoxetine. Can be tapered more quickly b/c less risk of discontinuation syndrome. Also need longer washout if switching to MAOI.
Which medications are approved for use in the tx of MDD in children and adolescents?
No antidepressant medications are formally approved for use in children and adolescents in Canada, although HCPs do prescribe off-label. Must be quite vigilant to watch for suicidal ideation especially in first weeks of treatment.
How is depression treated in pregnancy?
For mild depression, first try psychotherapy. Meds, in particular paroxetine, related to cardio malformations in fetus. SSRI use in third trimester assoc with pulmonary HTN in newborns. Newborns can also have sx of discontinuation syndrome.
How is depression treated in postnatal period?
Post-partum ‘blues’ affects up to 80% of mothers post-partum but do not require tx as it is self-limiting. PPD occurs in 1% of moms. First-line approach is psychotherapy. If meds used, then chose paroxetine, sertraline, and nortryptiline as they have low concentration in breastmilk.
What are the clinical features of serotonin syndrome?
Tremor, agitation, hypomania, hyperthermia, HTN. Can be fatal.
What is the process of tapering patients off medication?
All of the above medications especially paroxetine and venlafaxine, need to be tapered over 4-6 weeks to prevent discontinuation syndrome.
What are the features of discontinuation syndrome?
After taking any med for more than 6 weeks, esp SSRIs, and dose is suddenly reduced, patients can experience neuro, somatic and psych symptoms (nausea, dizziness, electric sensations, agitation) within 1-7 days of stopping/drastically reducing meds. Sx usually resolve within few days to few weeks.
How to avoid discontinuation syndrome?
Taper med by gradually reducing dose 25% per week.
When do you refer patients to a psychiatrist?
When patient has psychotic symptoms, has acute suicidal ideation, or does not improve after taking three different treatment trials
What duration of meds to prevent relapse?
For first episode of MDD, minimum duration of 1 year. For recurrent episodes, treat for at least 2 years.
How to approach treatment-resistant depression?
1) Can switch within or between class. Usually there is no need for washout (except below) ; just taper the first med(s) while gradually increasing second/third med
2) According to START-D study, can augment current meds through one or more of: Lithium carbonate; Atypical antispychotics s/a aripiprazole, quetiapine, rsiperidone, olanzapine; buproprion with SSRI; adding in triiodothyronine
What is the process to switch between drug classes?
1) When switching to an irreversible MAOI from any other anti-depressants, taper with washout period of 5 half-lives
2) When switching from irreversible MAOI to any anti-depressant, use 2-week washout period
3) Switching from moclobemide to any anti-depressant, use 5-day washout;
4) When switching from fluoxetine to an irreversible MAOI, use 5-week washout
