Psychopharmacology Flashcards
(282 cards)
1
Q
Korn et al. (2005) found mirtazapine significantly more effective than placebo in preventing symptoms in OCD with what maximum dose range?
A
60 mg
2
Q
What action does mirtazapine have at 5-HT2, 5-HT3 and alpha-2 receptors?
A
potent antagonist
3
Q
In a 2015 study of coadministration of proton pump inhibitors and SSRIs, what were the effects of esomeprazole on serum levels of sertraline and escitalopram, both of which are metabolized by CYP2C19?
A
sertraline increased 38.5%; escitalopram increased 81.8% (almost twofold)
4
Q
Among the SSRIs, sertraline is second only to ______ in potency for serotonin reuptake blockade.
A
paroxetine
5
Q
Jeste et al. (1999) randomly treated 122 elderly patients with low-dosage haloperidol (median daily dose 1 mg) versus risperidone (median daily dose 1 mg). After 9 months, treatment-emergent TD rates were ____% with haloperidol versus less than ____% with risperidone.
A
30%; 5%
6
Q
Tricyclics can (uncommonly) cause acute hepatitis, particularly imipramine or desipramine. What is the characteristic pattern of LFT changes if this occurs?
A
very high enzyme levels (e.g. AST > 800) within days of initiation; not dose-related
7
Q
What effect will fluoxetine or bupropion have on exposure to vortioxetine due to CYP2D6 inhibition?
A
double the exposure (area under the curve)
8
Q
What are the direct causes of death in NMS?
A
dysrhythmias, renal failure secondary to rhabdo, aspiration pneumonia, or respiratory failure
9
Q
Which MAOI should not be given to patients with celiac disease, because the tablets contain gluten?
A
phenelzine
10
Q
In the SADHART study (2002), sertraline was found to be most beneficial for patients with what characteristics?
A
- depressive episodes predated ACS, 2. past history of MDD, 3. episodes of greater severity
11
Q
What effect do all tricyclics have on heart rate?
A
they cause tachycardia
12
Q
Which tricyclic demonstrates the least orthostatic hypotension?
A
nortriptyline
13
Q
Based on data from the 8-week EMBOLDEN I and II trials, was there a dose-response relationship between quetiapine and weight gain?
A
yes
14
Q
What is the classic treatment of the hypertensive reaction with an MAOI and a tyramine-rich food?
A
phentolamine 5 mg IV
15
Q
What hypersensitivity reaction to chlorpromazine typically manifests during the first 1-2 months of treatment and presents with nausea, malaise, fever, pruritus, abdominal pain, and hyperbilirubinemia?
A
cholestatic jaundice
16
Q
Sertraline is more potent at blocking ______ reuptake than any of the other SSRIs or TCAs.
A
dopamine
17
Q
What dose range is approved for quetiapine XR for adjunctive treatment in major depressive disorder?
A
150-300 mg
18
Q
Agranulocytosis is defined as a drop in ANC to less than _____/mm3.
A
500/mm3
19
Q
In Whitehorn et al. 2004, after exposure to quetiapine 500–600 mg/day for a mean of 22.4 months, how many of the patients developed any ocular changes?
A
none
20
Q
In Koro et al. 2002, a large database of British patients, use of olanzapine conferred a _____-fold increase in the risk of dyslipidemia over an untreated control condition and a _____-fold increase over conventional antipsychotics, whereas risperidone did not increase the risk.
A
fivefold; threefold
21
Q
What is the main side effect reported in patients on initiation of vortioxetine, leading to discontinuation in 1%-4% of patients?
A
nausea
22
Q
___% higher dosages of paroxetine CR are necessary to achieve the same bioavailability as the immediate-release form.
A
20%
23
Q
Risperidone at 6 mg total for the day occupies ___% of D2 receptors on average and can be expected to exceed the EPS threshold in some patients.
A
79%-82%
24
Q
In children and adolescents, do tricyclics demonstrate superiority over placebo for treatment of depression?
A
No.
25
Tiihonen et al. 2017, in a large systematic review (n=29,823), found that in patients with schizophrenia, all LAIs except fluphenazine were associated with \_\_% reduction in hospitalization risk compared to no AP and \_\_\_% reduction compared to oral olanzapine.
14%-49%; 20%-35%
26
Nierenberg et al. 2007 found what effect of duloxetine on weight?
mean weight loss of 1 kg
27
What is the elimination half-life of clozapine?
12 hours
28
Tiihonen et al. 2017, in a large systematic review (n=29,823), found that in patients with schizophrenia, clozapine monotherapy was associated with a \_\_\_% lower risk of hospitalization vs periods with no antipsychotic and \_\_\_% lower risk vs olanzapine monotherapy.
47%, 42%
29
In the US, milnacipran is FDA approved for _____ and levomilnacipran is FDA approved for \_\_\_\_\_.
fibromyalgia; MDD
30
What feature differentiates risperidone and paliperidone from other SGAs, and likely accounts for the greater risk of EPS and hyperprolactinemia?
they do not differ from FGAs in dissociation constant from the D2 receptor
31
Tohen et al. 1999 studied olanzapine in Bipolar Disorder. How did it compare to placebo in improving mania? Depression?
beats placebo on mania; not on depression
32
In an inpatient loading-dose strategy for olanzapine (40 mg/day x 2 days, then decrease to 20-30 mg/day), how did the rates of sedation and hypotension compare to treatment as usual? Reduction in agitation was more rapid. (Baker et al. 2003)
didn't see increased rates of sedation and hypotension
33
The irreversible MAO-B inhibitor selegiline is most often used to treat Parkinson's disease. When used to treat depression, is a higher or lower dose required?
higher; 10-20 mg daily compared with 5-10 mg
34
What is the half-life of quetiapine in adults? What about extended-release?
6 hours; 7 hours
35
Veale et al. (2014) conducted a meta-analysis of SGAs in OCD. Of the following four medications, which two demonstrated efficacy as augmentation agents in OCD? (1) Quetiapine, (2) Aripiprazole, (3) Olanzapine, (4) Risperidone.
aripirazole and risperidone
36
What medication can be taken by mouth, with an onset of action around 5 minutes and lasting 3-5 hours, to reduce symptoms of a hypertensive reaction with an MAOI and a tyramine-rich food?
nifedipine; some clinicians suggest pts carry nifedipine with them for immediate use in event of a hypertensive crisis
37
An 11-year review by Lewis et al. (2014) of data from the California Poison Control Center found that 3.6% of all calls to the center regarding bupropion were due to intentional insufflation in order to achieve a psychostimulant effect, with an average dose of ____ mg.
1500 mg
38
Investigators from the Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) Study randomly assigned 148 clinically stable overweight outpatients with schizophrenia or schizoaffective disorder to up to 2,000 mg of metformin or placebo daily (Jarskog et al. 2013). Patients were taking either one or two of any of the FDA-approved antipsychotic medications. All patients received weekly diet and exercise counseling. After 16 weeks, how did metformin compare to placebo on weight, trigylcerides, and A1C?
significantly better; weight loss 6.6 lbs. vs. 2.2 lbs.; triglycerides -7.0 mg/dL vs. + 13.2 mg/dL; A1C -0.06% vs. + 0.011%
39
For trazodone, the manufacturer estimates that the incidence of any abnormal erectile function is approximately 1 in _____ male patients.
6000
40
At therapeutic dosages, how do venlafaxine and desvenlafaxine affect cardiac conduction and seizure threshold?
no significant effect
41
In the Consta formulation, risperidone microspheres begin to release appreciable amounts of the drug _____ after injection.
3 weeks
42
In early use of antipsychotics, what was referred to as the "neuroleptic threshold"?
assumption that minimal effective dose of AP was with onset of EPS
43
How are clozapine levels affected by smoking?
decreased
44
In a 2002 study, which of the following was found to have the highest rates of sexual dysfunction? mirtazapine, venlafaxine, sertraline, citalopram, fluoxetine, paroxetine, nefazodone, or bupropion
paroxetine
45
Based on studies (Bell et al. 1998; Kronig et al. 1995; Miller 1996; Miller et al. 1994; Potkin et al. 1994), patients are more likely to do well when their plasma levels of clozapine are greater than ____ ng/mL.
350 ng/mL
46
Trazodone is a mild 5-HT \_\_\_\_\_\_, but its active metabolite m-chlorophenylpiperazine (mCPP) is a potent, direct 5-HT \_\_\_\_\_\_.
antagonist; agonist
47
Serotonergic inhibition of the nigrostriatal dopamine pathway is likely the mechanism of what side effects which have been observed with sertraline use?
EPS, including dyskinesias, dystonias, and akathisia
48
Fluoxetine is extensively metabolized to an active metabolite, norfluoxetine. While fluoxetine is a potent CYP ______ inhibitor, norfluoxetine is a moderate CYP _____ inhibitor.
CYP2D6; CYP3A4
49
What is buspirone's action at presynaptic 5-HT1A receptors in the dorsal raphe?
full agonist, inhibiting neuronal 5-HT synthesis and firing
50
What electrolyte abnormality is associated with SSRIs in patients aged 70+ years?
hyponatremia
51
How is elimination half-life of mirtazapine affected by severe hepatic or renal impairment?
increased 30%-40% with hepatic; 30%-50% with renal
52
Half-life of vortioxetine?
66 hours; requires 2 weeks for steady-state
53
In extensive metabolizers of risperidone (90% of Caucasian patients and 99% of Asian patients), the half life is _____ hours.
3 hours
54
When olanzapine is taken orally, peak concentration is _____ hours after ingestion.
4-6 hours
55
What is the only antipsychotic to have demonstrated reduction of suicidal behavior in schizophrenia?
clozapine
56
With an MAOI, a mild tyramine reaction occurs with about ___ mg of tyramine; ___ mg can produce a moderate episode; ___ mg can produce hypertension, occipital headache, palpitations, nausea, vomiting, apprehension, chills, sweating, and restlessness.
6 mg; 10 mg; 25 mg
57
Which receptor accounts for clozapine's side effects of sedation, constipation, and ileus?
muscarinic M1 receptors
58
When was Clozapine reintroduced in the US, after convincing studies demonstrating efficacy in treatment-refractory schizophrenia?
1989
59
At what dose dose duloxetine attenuate tyramine pressor response? (Vincent et al. 2004)
120 mg/day
60
What washout period is recommended after discontinuation of fluoxetine before starting an MAOI?
5 weeks
61
Based on studies in both the general population and the elderly (Feighner et al. 1991; Weihs et al. 2000), how does bupropion compare with SSRIs on reduction of anxiety symptoms in patients with MDD?
equally effective
62
If a patient has problematic side effects with vortioxetine, but has had benefit in terms of mood, what is the recommended clinical approach?
hold the medication for 3 days and restart at half the previous dosage
63
Approximately \_\_\_\_% of a given dose of olanzapine undergoes first-pass metabolism and therefore does not reach the systemic circulation.
40%
64
GABA has three target receptors: GABA-A, -B, and -C. Which one controls a chloride ion channel?
GABA-A
65
Of venlafaxine and desvenlafaxine, which is approved for treatment of individuals younger than 18 years?
neither
66
What dose of sertraline has a significant risk of toxicity in hemodialysis patients with severe end-stage renal disease?
25 mg
67
Smales et al. 2015 found that which commonly prescribed sleep medication improved the Apnea-Hypopnea Index in patients with obstructive sleep apnea (OSA) without any deleterious effects on oxygen saturation or non–rapid eye movement (REM) arousal threshold?
trazodone
68
What is the estimated yearly incidence of TD in adults?
5% among adults
69
Which tricyclic antidepressant has nonlinear kinetics at the usual dosage range?
desipramine
70
Are mean plasma prolactin levels correlated to clinical side effects and libido for male and female patients on risperidone?
no
71
Which receptor accounts for clozapine's high sedation as well as contributing to weight gain?
histamine (H1)
72
What adjustments in olanzapine are needed for renal or hepatic disease?
none (Callaghan et al. 1999)
73
The risk of priapism with trazodone is greatest during what period of treatment, and at what dosages?
first month; low dosages (\< 150 mg/day)
74
In Pollack et al. 1993 and Tesar et al. 1991, what total daily dosage of clonazepam was as effective and well-tolerated as 5.3 mg of alprazolam/day?
2.5 mg/day
75
What property of trazodone likely explains the side effect of orthostatic hypotension?
potent antagonism of post-synaptic alpha-1 receptors
76
Stryjer et al. 2010 found trazodone to be effective in treating antipsychotic-induced \_\_\_\_\_\_.
akathisia
77
Tohen et al. 2005 compared lithium and olanzapine in maintenance treatment of Bipolar (preventing onset of new depressive, mixed, or manic episode). How did olanzapine compare over 52 weeks?
as effective in preventing depression relapse; lower rates of mixed or manic symptom relapse
78
Tohen et al. 2002 compared olanzapine with divalproex for mania. How did they compare?
Equivalent efficacy.
79
What is the relationship of dose to serum concentration for most tricyclic antidepressants?
linear
80
In addition to being the most potent SSRI in terms of blocking serotonin reuptake, paroxetine is also a relatively potent _______ reuptake inhibitor, particularly at higher doses.
norepinephrine
81
What is unique about selegiline that can reduce some of the severe dietary restrictions required?
available as transdermal patch in 6 mg, 9 mg and 12 mg; at 6 mg, no dietary modification required
82
Two isoenzymes, MAO-A and MAO-B are present in the CNS. Which of the two is more common in serotonergic neurons?
MAO-B; MAO-A is more common in DA and NE neurons
83
What is the only AP medication FDA-approved for Tourette's? (also this medication's only approved indication)
Pimozide
84
What AP medication is approved for oral or IM therapy of intractable hiccups?
chlorpromazine
85
Incidence of amenorrhea and galactorrhea in women, which varies between \_\_\_% and \_\_\_%, is similar for all dosages of risperidone and haloperidol.
8%-12%
86
In interpreting clozapine levels, which is the active form, clozapine or the metabolite norclozapine?
clozapine; trials of norclozapine have not demonstrated efficacy
87
On the basis of a series of placebo-controlled RCTs (Thase and Sloan 2006; Allgulander et al. 2004; Liebowitz et al. 2005), is there evidence of a dose-response relationship for venlafaxine XR in treating GAD and Social Anxiety Disorder?
no; effective dose range was 75 mg to 225 mg
88
What is the approximate half-life of duloxetine?
12 hours
89
MAOIs can be reversible or irreversible and can be selective or non-selective. Which one is irreversible and selective for MAO-B?
selegiline
90
What is sertraline's half-life?
26-32 hours
91
An irreversible increase in retinal pigmentation has been described with _____ when high dosages (\> 800 mg/day) are used.
thioridazine
92
A 2018 systematic review and meta-analysis (Lucchetta et al) found what type of association between development of dementia and use of benzodiazepines?
benzodiazepines are a risk factor for developing dementia (odds ratio 1.38, with 95% CI 1.07-1.77)
93
What is the rate of occurrence of sialorrhea in clozapine therapy?
over 50% of patients
94
Mirtazapine has ___ affinity for muscarinic receptors and ___ affinity for histamine-1 receptors.
low; high
95
Patients who have developed agranulocytosis on clozapine almost always do again if rechallenged. How are these episodes characterized in terms of severity and timeline?
faster and more aggressive
96
Based on studies in the 1980s, rank the following in terms of effectiveness for depression with atypical features: imipramine, phenelzine, placebo.
1. phenelzine 2. imipramine 3. placebo
97
Bayer et al. (1989) reported a ______ increase in maximum plasma concentration in elderly subjects compared with younger subjects following a single dose of paroxetine.
threefold
98
Emsley et al. 2000 looked at rapid titration of quetiapine (200, 400, 600, 800 over 4 days) to a slower titration (starting at 50 mg, 400 mg by day 5). How did the strategies compare in efficacy and tolerability?
similar
99
In a meta-analysis by Peterson et al. (2008), how did long-acting bupropion compare with long-acting stimulants for treatment of adult ADHD?
similar clinical effectiveness
100
A study comparing 19 male smokers with 30 male nonsmokers found that olanzapine clearance in smokers was \_\_\_\_% \_\_\_\_-er than that in nonsmokers (Callaghan et al. 1999).
23% higher
101
What was the first benzodiazepine to be approved by the FDA for panic disorder, introduced in 1981?
alprazolam
102
Clozapine was the first AP drug without EPS, introduced to the market in Europe in 1972. Why was it withdrawn in 1975?
fatalities from agranulocytosis
103
Tricyclics inhibit sodium/potassium ATPase, stabilizing electrically excitable membranes in the heart, causing what type of changes in cardiac rhythm?
delayed conduction (particularly His ventricular conduction)
104
In addition to functioning as an SSRI, vortioxetine has what other prominent effects on serotonin receptors?
5-HT3 antagonist 5-HT1A full agonist 5-HT7 antagonist
105
Per Settle et al. (1999), a series of large randomized, placebo-controlled multicenter trials, what were the most common adverse effects leading to discontinuation of bupropion?
rash, nausea, agitation, migraine
106
Is there a dose-response relationship when treating MDD with duloxetine?
yes
107
How does clozapine's binding to 5-HT2 receptors (including A, B, and C) compare to its D2 binding?
15-30 times stronger
108
What is the main CYP enzyme responsible for metabolism of bupropion?
CYP2B6
109
In comparison studies (Böhm et al. 1990a; Goldberg and Finnerty 1982; Rickels et al. 1982), how did buspirone do compared to diazepam when each was dosed tid at average of 20-25 mg/day over 4 weeks?
comparable efficacy
110
Clozapine's antagonism of 5-HT2A has what result in the striatum?
increased local dopamine, resulting in relief from EPS
111
In the bipolar depression study by Calabrese et al. (2005), the mean changes in glucose levels were ___ mg/dL and ___ mg/dL with quetiapine dosages of 600 mg/day and 300 mg/day, respectively.
6 & 3
112
At high levels (\> 78%) of dopamine blockade, patients will exhibit akathisia, rigidity, and hypokinesia, AKA . . .
extrapyramidal symptoms
113
6 months after stopping a benzodiazepine after long-term use, what effects have been found on cognitive impairments? (Tata et al. 1994)
only partial recovery
114
What is buspirone's mean elimination half-life via CYP 3A4?
3-4 hours (prolonged with food)
115
Which side effect of typical APs (more common in youth, recent cocaine users, and with IM doses of high-potency APs) is an acute, sustained, painful muscular contraction?
acute dystonia
116
Duloxetine was patented in 1991 but was not approved by the FDA for treatment of MDD and diabetic neuropathy until 2004. Why the long delay?
initial testing was with doses of 5-20 mg/day
117
Risperidone has a very high affinity for 5-HT\_\_\_ receptors and a moderate affinity for D2, H1, and alpha-1 and alpha-2 receptors. It has much lower affinity for any other serotonin receptors.
5-HT2A
118
Does venlafaxine show a dose-response relationship for efficacy in MDD? (Kelsey 1996; Khan et al. 1998; Rudolph et al. 1998; Thase et al. 2006)
yes
119
Per Wilson et al. 1994, what is the rate of seizures in patients treated with clozapine without prior history of seizures or head trauma?
6.3%
120
Patients who reported poor or very poor sexual functioning have been shown to have what response when switched to (but not augmented on) mirtazapine?
return of normal sexual functioning
121
What is the acute treatment for dystonia?
antihistaminergic or anticholinergic medication
122
Per Skegg et al. 1979, how does the rate of serious MVA compare between patients on benzodiazepines and controls?
nearly 5x more likely on benzos
123
At therapeutic doses of clozapine, what percentage of D2 receptors are occupied?
40-60%
124
Between doses of 0.5 and 25 mg/day, risperidone exhibits _____ pharmacokinetics.
linear
125
What was the first medication to receive an FDA approval for seasonal depressive symptoms?
bupropion XL
126
The Quetiapine Experience with Safety and Tolerability (QUEST) study (Mullen et al. 2001) looked at quetiapine vs risperdal. At week 16, how did the quetiapine group (mean dosage of 317 mg/day) compare to the risperidone group (mean dose 4.5 mg/day) on HAM-D?
much more improved in quetiapine group
127
Antipsychotic-induced parkinsonism occurs in \_\_\_% of patients after several weeks of tx with typical APs.
15%
128
What type of depression has been repeatedly found to be highly responsive to treatment with MAOIs?
atypical (depression with anxiety or chronic pain, reverse vegetative symptoms, and rejection sensitivity)
129
How are clozapine levels affected by fluvoxamine and ciprofloxacin?
dramatic increase
130
In one report (Holzbach et al. 1998), the cases of 2 patients who had overdosed with 30–50 times the average daily dose of mirtazapine were presented. What were the outcomes?
full recovery without complications
131
In a naturalistic study following 543 patients, \_\_\_\_% of patients taking clozapine reported de novo obsessive-compulsive symptoms, compared with 20.1% taking olanzapine and 23.2% taking risperidone (Scheltema Beduin et al. 2012).
38.9%
132
SSRI discontinuation symptoms are reported most frequently with ______ and least frequently with \_\_\_\_\_.
paroxetine; fluoxetine
133
For risperidone, no significant prolongation of the QTc interval was detected at dosages of up to ___ mg/day in early safety trials, and no relationship between QTc interval and risperidone dose was apparent.
25 mg/day
134
Structurally, the antipsychotic _______ differs from clozapine only by an additional methyl group, a sulfur, and the lack of a chloride moiety.
olanzapine
135
With IM injection of a typical AP, what is the average time to peak plasma levels?
30-60 minutes
136
A 2-year retrospective study of 21,473 patients, of whom 326 were taking clozapine, found a [decreased or increased?] number of inpatient days and total psychotropic medication burden for those treated with clozapine (Nielsen et al. 2012)
decreased
137
In the Sustenna formulation, IM injection in the deltoid produces blood levels approx. _____ higher than those produced with gluteal injection.
28%
138
With drugs that inhibit the NET (e.g. SNRIs), what is the overall short-term effect on the firing rate of noradrenergic neurons?
reduced rate
139
In a recent meta-analysis of 15 antipsychotics that included 43,049 patients and considered often-used antipsychotics including clozapine, olanzapine, risperidone, haloperidol, quetiapine, and aripiprazole, _______ was found to be the most effective antipsychotic based on change in symptoms (Leucht et al. 2013).
clozapine
140
The affinity of paroxetine for the muscarinic cholinergic receptor is similar to that of which TCA?
desipramine (the least anti-cholinergic TCA)
141
In the SADHART study (2002), patients with recent MI or unstable angina who also met criteria for depression were randomized to sertraline 50-200 mg daily vs placebo. What significant treatment-emergent effects of sertraline occurred on cardiac measures?
none
142
Tiihonen et al. 2017, in a large systematic review (n=29,823), found that in patients with schizophrenia, periods of antipsychotic polypharmacy were associated with a \_\_\_% reduction in risk of hospitalization compared with olanzapine monotherapy.
39%
143
What was the first benzodiazepine, patented in 1959?
chlordiazepoxide
144
Based on studies in the 1990s, in outpatient populations, does the designation of melancholic features predict an advantage for tricyclics over SSRIs?
No.
145
If patients develop agranulocytosis on clozapine, are they at risk for the same effect of olanzapine?
no
146
Because it potently inhibits its own metabolism via the CYP2D6 enzyme, paroxetine ______ pharmacokinetics, with disproportionately _____ plasma drug concentrations at higher doses.
nonlinear; greater
147
Per Nogami et al. 2013, what dosages of milnacipran produce SERT occupancy of 40% and 60%?
100 mg and 200 mg (typical dose range is 50 mg to 100 mg daily for fibromyalgia)
148
In both placebo-controlled trials and comparison-trials with duloxetine, vortioxetine showed what specific benefit for patients with depression (2012-2015)?
cognitive improvement
149
In patients older than 60 years, what are the maximum recommended doses of citalopram and escitalopram?
20 mg and 10 mg
150
What is the recommended dose for duloxetine in treating stress urinary incontinence?
40 mg bid
151
What property of trazodone likely explains its effectiveness at promoting sleep?
moderate antihistaminergic activity
152
Which tricyclic is the least anticholinergic?
desipramine
153
Which tricyclic carries risk of NMS and TD?
amoxapine
154
What is the main CYP enzyme for quetiapine metabolism?
CYP 3A4
155
Maximal inhibition of norepinephrine reuptake at higher doses of venlafaxine is 61%. By comparison, with paroxetine it is \_\_\_\_%.
33%
156
What combination medication received approval in 2013 for treatment of obesity or overweight in patients who have at least one cardiovascular risk factor?
Contrave = bupropion + naltrexone
157
The potency of olanzapine IM is ___ times more than the PO drug.
5 times
158
Chang et al. 2017 examined association between medication use for ADHD and risk of motor vehicle accidents (n=2,319,450). In within-individual analyses, medication was associated with a \_\_\_% lower risk of MVA in men and \_\_\_% lower risk in women.
38% and 42%
159
What is the estimated mortality rate of NMS?
20%-30%
160
What is the only SSRI that was placed in category D for pregnancy?
paroxetine
161
How does clearance of olanzapine vary by age?
in elderly patients, clearance 30% lower and half-life 50% longer
162
Among SSRIs, fluoxetine has uniquely been observed to induce beta-adrenergic receptor downregulation. This may relate to an observed increase in extracellular _________ in the prefrontal cortex.
norepinephrine
163
The elimination half-life of fluoxetine is ____ days and that of norfluoxetine (the longest of any SSRI or active metabolite) is ____ days.
4-6 days; 4-16 days
164
What are the half-lives of milnacipran and levomilnacipran?
8 hours
165
How does buporopion compare to SSRIs on weight gain, sedation, withdrawal symptoms, and sexual side effects?
much better toleration
166
Clozapine is predominantly metabolized by CYP \_\_\_\_.
CYP1A2
167
In the Sustenna formulation, systemic availability begins on ______ and can last as long as ______ after injection.
day 1; 126 days
168
Because of paliperidone’s longer half-life, its serum concentrations at steady state are approximately ___ to \_\_\_-fold higher than risperidone concentrations in CYP2D6 extensive metabolizers treated with risperidone.
5- to 10-fold
169
In general, patients taking irreversible MAOIs (e.g. tranylcypromine, phenelzine, isocarboxazid) should be on what vitamin supplement?
B6
170
Mean half-life of olanzapine is _____ hours.
30-36 hours
171
Does desvenlafaxine show a dose-response relationship for efficacy in MDD? (Thase et al. 2009)
no; drug vs placebo differences are the same at 50 mg/day as at higher doses
172
Honigfeld et al. 1998 reviewed clozapine registry data for 99,502 patients over 5 years. \_\_\_\_% of patients developed WBC \< 3500/mm3 and \_\_\_\_% of patients developed ANC \< 500/mm3. \_\_\_\_% of the agranulocytosis cases were fatal.
2.95% with leukopenia; 0.38% with agranulocytosis; 3% of agranulocytosis cases were fatal
173
In addition to its action at 5-HT1A, buspirone binds to what two types of dopamine receptors? (Bergman et al. 2013; Le Foll and Boileau 2013)
D3 and D4
174
Poyurovsky (2003, 2006) found mirtazapine to be effective in reducing what side-effect of antipsychotic medications at 15 mg daily?
akathisia
175
Is transdermal selegiline associated with drug-drug interactions similar to other MAOIs?
yes; no reduction in risk of interactions
176
What syndrome associated with AP medications is characterized by muscle rigidity, hyperpyrexia, autonomic instability, and altered consciousness?
neuroleptic malignant syndrome
177
Clinical estimates are that paliperidone is roughly \_\_\_\_% as potent as risperidone, perhaps due to reduced bioavailability.
50%
178
Paroxetine has a half-life of approximately \_\_\_\_\_\_.
11 hours
179
In a study in 2006, Ninan et al. found that patients who were unresponsive after 16 weeks of treatment with sertraline 200 mg daily had greater improvement in Y-BOCS scores after increase to what dosage range?
250-400 mg daily
180
In 2D6 poor metabolizers and patients concurrently taking 2D6 inhibitors, risperidone concentrations may be _____ than paliperidone concentrations.
higher
181
In one study of 9 patients treated with risperidone, addition of fluoxetine resulted in a \_\_\_% increase in blood levels of the active moiety (risperidone + 9-hydroxyrisperidone); two patients developed parkinsonian side effects (Spina et al. 2002).
75%
182
Onset of clinical effects from olanzapine IM is within ____ of administration.
2 hours
183
Trazodone is a relatively weak SSRI, and has _____ effects on NE and DA reuptake.
minimal
184
In a study spanning 1970 to 2004, the overall rate of potentially fatal cardiomyopathy or myocarditis was around \_\_\_\_% (Merrill et al. 2005).
0.015% to 0.188%
185
Is there a relationship between the degree of sedation with a benzodiazepine and memory impairment? (Scharf et al. 1988)
largely independent effects
186
All of the inhibitory activity of citalopram on serotonin reuptake resides in which enantiomer?
the S enantiomer
187
What was the first selective SNRI, developed in the late 1980s and early 1990s?
venlafaxine
188
How does desvenlafaxine (Pristiq) compare with venlafaxine in terms of NET blockade?
greater potency
189
Which MAOI has a mild stimulant effect, and can cause physical dependence, with withdrawal symptoms such as anxiety, restlessness, depression, and headache?
tranylcypromine
190
In Tauscher et al. 2004, D1:D2 receptor occupancy ratio was compared for risperidone, olanzapine, clozapine, and quetiapine. Rank them from highest to lowest.
clozapine (0.88), olanzapine (0.54), quetiapine (0.41), risperidone (0.31)
191
Name some foods that are recommended to be restricted when patient is taking an MAOI.
restriction of cheese (except cream cheese and cottage cheese) red wine, sherry, liqueurs pickled fish overripe (aged) fruit brewer’s yeast fava beans beef and chicken liver fermented products
192
In general, high-potency typical APs cause ____ weight gain than low-potency?
less
193
Sexual side effects with SSRIs: dose-dependent? reversible? diminish with prolonged administration?
yes; yes; no
194
The CATIE trial looked at QTc prolongation risk of quetiapine compared to other SGAs and perphenazine. What was found?
no evidence of increased risk
195
What rare, inherited disorder is characterized by deletion of both MAO-A and MAO-B genes, leading to severe intellectual disability and blindness?
Norrie's disease
196
What chemical property of diazepam explains why it is faster at reducing anxiety than lorazepam or chlordiazepoxide?
more lipophilic and crosses BBB more quickly
197
In the STAR\*D program, how did augmentation of an SSRI with buspirone compare with augmentation with bupropion?
comparable efficacy
198
The first report of persistant orobuccal movements with long-term antipsychotics was reported in France in 1959. What is the term for this?
tardive dyskinesia
199
Sexual dysfunction or gynecomastia occurs in \_\_\_% of men treated with risperidone (4–6 mg/day).
15%
200
Alpha2 receptors normally act to _____ transmission at serotonergic and noradrenergic axon terminals.
inhibit
201
What is the recommended approach to switching to/from vortioxetine and an SSRI or SNRI?
gradual crossover strategy, with the exception of fluoxetine
202
Does risperidone have affinity for muscarinic acetylcholine receptors?
no
203
What is buspirone's action at postsynaptic 5-HT1A receptors in the hippocampus and cortex?
partial agonist
204
Per Rosenbaum et al. 1984, what percentage of patients receiving benzodiazepines may have treatment-emergent hostility?
up to 10%; unrelated to pretreatment hostility
205
It has been hypothesized that the addition of a CYP2D6 inhibitor (e.g., fluoxetine) could decrease risperidone-induced prolactin elevation by _____ the ratio of risperidone to 9-hydroxyrisperidone (Troost et al. 2007), but this has not been rigorously tested.
increasing
206
All tricyclics can increase risk of seizure, but which three (one is actually tetracyclic) present the highest risk, particularly in patients with prior history of seizures, presence of brain injury, or use of antipsychotics?
amoxapine, maprotiline (tetracyclic), clomipramine
207
What are the recommendations for monitoring CRP, eosinophil count, and troponins when initiating clozapine?
check weekly for first 4 weeks
208
With an MAOI, the reaction to tyramine-containing food typically occurs about _____ minutes after ingestion.
20-60 minutes
209
Tompkins et al. 1980 found what effect of buspirone on aggressive monkeys?
taming effect
210
Which receptor likely accounts for clozapine's side effects of orthostatic hypotension and tachycardia?
alpha-1
211
If a patient on an MAOI develops paresthesia, what should the clinician evaluate for (2 things)?
peripheral neuropathy and B6 deficiency
212
Kane et al. 2001 found that \_\_\_\_\_\_% of patients with treatment-refractory illness improved after a 29-week trial of clozapine.
60%
213
For Bupropion SR at doses up to 300 mg daily, how do seizure rates compare of those with SSRIs and with TCAs?
around 0.1%; comparable to SSRIs, lower than rates with TCAs
214
Which tricyclic antidepressant is the most anticholinergic and the most likely to produce delirium?
amitriptyline
215
What are the recommendations for monitoring A1C and lipids when treating with clozapine?
baseline and then q 6-12 months
216
When clozapine is discontinued on identification of agranulocytosis, patients usually recover within _____ days with no long-term consequences.
14-24 days
217
What is the role of the CYP system in metabolism of milnacipran and levomilnacipran?
no involvement
218
At what dose range does venlafaxine attenuate the tyramine pressor response (used as a proxy for NET reuptake inhibition)? (Blier et al. 2010; Debonnel et al. 2007)
225-375 mg/day
219
If a patient on an MAOI develops a headache, what are some features that likely indicate it is a histamine headache, rather than a hypertensive crisis?
hypotension, colic, loose stools, salivation, lacrimation
220
Which highly-sedating tricyclic is FDA-approved for treatment of insomnia?
doxepin
221
In studies in the late 1970s and early 1980s, what percentage of hospitalized patients with severe, melancholic depression had a response to imipramine or desipramine? Of note, these patients did not have hx of treatment resistance or personality d/o.
85%
222
What rare, inherited disorder is caused by a mutation in the MAO-A gene, causing impulsive aggressiveness and mild intellectual disability?
Brunner syndrome
223
A pretreatment QTc interval of ____ ms indicates that conduction is already delayed and that the patient is not a candidate for TCA treatment.
450 ms
224
What is the result of mirtazapine's antagonism at 5-HT2 and 5-HT3 receptors on 5-HT1A-mediated transmission?
increase
225
The affinity of risperidone for D2 receptors is approximately \_\_\_-fold greater than that of clozapine and approximately \_\_\_%–\_\_\_% that of haloperidol.
50-fold; 20%-50%
226
Clozapine-associated myocarditis and cardiomyopathy occur within the first _____ months 85% of the time.
within the first 2 months
227
Most benzodiazepines, at their peak concentration, cause what neurocognitive side effect?
anterograde amnesia
228
For patients taking amitriptyline, there is a moderately increased risk of delirium at _____ ng/mL and substantially increased risk at _____ ng/mL.
300 ng/mL; 450 ng/mL
229
In the studies leading to the approval of quetiapine's indication for bipolar depression, how did efficacy compare between 300 mg and 600 mg daily?
both efficacious
230
What specific interaction has been observed with coadministration of paroxetine and tamoxifen?
potent CYP2D6 inhibition reduces conversion of tamoxifen to active metabolite, increasing risk of death from breast cancer
231
In a study of 157 inpatients (Citrome et al. 2001), clozapine resulted in greater reductions in the ______ item from the Positive and Negative Syndrome Scale (PANSS) than did the FGAs and other SGAs.
hostility
232
What effect does fluoxetine have on REM and non-REM sleep?
decreased REM, increased non-REM
233
What was found by Baldwin et al. (2016) on vortioxetine and sexual side effects?
At 5 mg or 10 mg, no difference from placebo. At 20 mg, rates comparable to duloxetine 60 mg.
234
How does clearance of olanzapine vary by sex?
25%-30% lower in women
235
With quetiapine tablets, how long until peak serum levels after ingestion? Extended release?
1.5-2 hours; 6 hours
236
What CYP enzyme is inhibited by bupropion?
CYP2D6
237
Which tricyclic is FDA-approved for treatment of nocturnal enuresis in children?
imipramine (usually 25-50 mg at bedtime)
238
What is a persistent syndrome of choreoathetoid movements of the head, limbs, and trunk, usually developing after 3-6 months of exposure to antipsychotics?
tardive dyskinesia
239
Which SSRI is the most selective for serotonin reuptake inhibition?
escitalopram
240
What is the association of seizure risk and dosage of clozapine?
risk goes up with doses higher than 600 mg/day
241
What is the timeline to peak plasma levels of clozapine after PO administration?
2 hours
242
Tricyclics can increase seizure risk and can cause a fine, rapid tremor. Are these effects dose-dependent?
yes
243
Recommended effective dose range of vortioxetine?
5-20 mg daily
244
What is the current best guess for the mechanism of sialorrhea in clozapine therapy?
alpha-adrenergic receptor blockade
245
What percentage of serotonin transporter binding sites are occupied following 20- to 40-mg daily dosages of paroxetine?
85%-100%
246
Per Roache and Griffiths 1985, 1987, to what extent are benzodiazepine-treated subjects typically aware of their memory impairment?
unaware of or underestimate impairment
247
Allison et al. (1999) compared AP meds on weight gain over 10 weeks. Rank the following from highest to lowest weight gain: (1) placebo, (2) clozapine, (3) risperidone, (4) olanzapine, (5) haloperidol.
clozapine (9.8 lbs), olanzapine (9.1 lbs), risperidone (4.6 lbs), haloperidol (2.4 lbs), and placebo (lost 1.6 lbs).
248
What impact does vortioxetine have on CYP enzymes?
no inhibition or induction
249
Mirtazapine has been shown to reduce nausea, likely due to which mechanism?
5-HT3 antagonism
250
Plasma levels of clozapine greater than ____ ng/mL are not generally associated with improved outcomes in studies, but are associated with higher incidence of side effects.
600 ng/mL
251
If dystonia involves the eyes, resulting in symmetrical or unilateral upward lateral movement, what is it called?
oculogyric crisis
252
In addition to inhibition of dopamine and norepinephrine reuptake, buproprion has what effect on the cholinergic system?
antagonist at nicotinic acetylcholine receptors
253
Characterize tranylcypromine, phenelzine, and isocarboxazid in terms of reversibility and selectivity.
irreversible and non-selective
254
Which tricyclic is the most serotonergic and has well-established efficacy for treating OCD?
clomipramine
255
Risperidone 6 mg/day produces elevations in prolactin roughly comparable to those seen with haloperidol ___ mg/day.
20 mg/day
256
What are the most commonly reported side effects of sertraline?
1. GI disturbance, 2. sleep disturbance, 3. headache, 4. dry mouth, 5. sexual dysfunction
257
Which tricyclic antidepressant has antipsychotic activity in addition to antidepressant activity, due to a metabolite which blocks postsynaptic dopamine receptors?
amoxapine
258
In the STAR\*D trial, after 12 weeks of citalopram treatment without complete remission, which group had better outcomes: switch to bupropion or augment with bupropion?
more benefit from augmentation strategy
259
Which first-generation AP is considered the most "atypical" because of its structural similarity to Clozapine?
Loxapine
260
What is the effect on body weight in almost 50% of patients on MAOIs?
weight gain
261
If switching from fluoxetine to vortioxetine, what should the starting dose be due to CYP2D6 inhibition?
5 mg (instead of 10 mg)
262
After the development of the first-generation of antipsychotics, what was the percentage decrease in psychiatrically hospitalized patients from 1955 to 1988?
80%
263
For the treatment of a major depressive episode with trazodone, the suggested initial dosage is ____ mg/day, with increases of 50-mg increments every 3–4 days. The maximum dosage recommended for outpatients is ____ mg/day.
150 mg; 400 mg
264
In extensive metabolizers of paliperidone (90% of Caucasian patients and 99% of Asian patients), the half life is ____ hours.
21 hours
265
In an 11-day study of 10 male smokers, coadministration of fluvoxamine (50–100 mg/day) with olanzapine (2.5–7.5 mg/day for 8 days [beginning on day 4]) resulted in an \_\_\_% increase in olanzapine peak serum concentrations (Cmax) (Maenpaa et al. 1997).
84%; no change in half-life
266
What are the main side effects associated with transdermal selegiline?
diarrhea, skin irritation, and insomnia
267
In comparison to TCAs, trazodone shows ______ effects on muscarinic cholinergic receptors.
minimal
268
What narcotic medication sometimes used in surgical settings can cause a syndrome with MAOIs characterized by coma, hyperpyrexia, and hypertension?
meperidine (Demerol)
269
What washout period is recommended between vortioxetine and an MAOI?
14 days
270
Typical APs can reverse psychosis associated with acute and chronic amphetamine intoxication, but risk of dystonia is higher in this patient population. Why?
chronic amphetamine use downregulates dopamine receptors --\> more sensitive to rapid D2 blockade
271
All SSRIs and venlafaxine produce 80% occupancy of the SERT at their minimum effective dosages for depression. What dose of duloxetine produces 80% occupancy of SERT?
60 mg
272
When olanzapine is taken IM, peak plasma concentration is between _____ minutes after administration.
15-45 minutes
273
In 2006, a black box warning was placed on all antidepressant medications warning of suicide risk in patients up to 25 years old. Subsequently, antidepressant prescriptions dropped. Lu et al. 2014 found what effect on suicide rates?
increased 22% in adolescents and 34% in young adults
274
Which tricyclic beats placebo for treatment of ADHD (67% vs 10%) in children, but is contraindicated in children under 12 due to risk of sudden death?
desipramine
275
What side effect prompted the FDA to recommend a new cap on citalopram dosing in 2013?
dose-dependent QTc prolongation
276
What is unique about clozapine's binding and dissociation from D2 receptors?
fast-off; disassociation time \< 1 minute for 50% binding of D2 receptors
277
Orsolini and Bellantuono (2015) found that what two SSRIs are preferred agents in women who are breastfeeding, in terms of infant health?
sertraline and paroxetine
278
What possible complication of the LAI form of olanzapine means that patients must be observed for 3 hours after injection?
accidental intravascular injection causing sedation / delirium / coma
279
How does clozapine compare to haloperidol in strength of binding to D2 receptors?
50-100 times weaker
280
Although fluoxetine is perceived as "activating," a meta-analysis (Montgomery 1989) indicated efficacy in depression with what features?
anxiety and psychomotor agitation
281
In placebo-controlled trials, what is buspirone's effect on panic attacks? (Pohl et al. 1989; Sheehan et al. 1990)
no effect
282
The risk of seizures with immediate-release bupropion were found in the 1980s to be \_\_\_% at 450 mg/day and \_\_\_% at 600 mg/day.
0.3%-0.4%; 2%
