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 alcohols 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 actually higher 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.
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) 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) 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
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 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
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
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
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 INC. plasma levels (Fluoxetine, paroxetine, quinidine)
- Slow-metabolizer (some Asian populations) may have extended elimination half-lives
- Concurrent use of salbutamol may INC. 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
Red Flags by condition and drug induced conditions: ADHD
Stimulant Therapy
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 wth 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)