Psychopharmacology Flashcards
Korn et al. (2005) found mirtazapine significantly more effective than placebo in preventing symptoms in OCD with what maximum dose range?
60 mg
What action does mirtazapine have at 5-HT2, 5-HT3 and alpha-2 receptors?
potent antagonist
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?
sertraline increased 38.5%; escitalopram increased 81.8% (almost twofold)
Among the SSRIs, sertraline is second only to ______ in potency for serotonin reuptake blockade.
paroxetine
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.
30%; 5%
Tricyclics can (uncommonly) cause acute hepatitis, particularly imipramine or desipramine. What is the characteristic pattern of LFT changes if this occurs?
very high enzyme levels (e.g. AST > 800) within days of initiation; not dose-related
What effect will fluoxetine or bupropion have on exposure to vortioxetine due to CYP2D6 inhibition?
double the exposure (area under the curve)
What are the direct causes of death in NMS?
dysrhythmias, renal failure secondary to rhabdo, aspiration pneumonia, or respiratory failure
Which MAOI should not be given to patients with celiac disease, because the tablets contain gluten?
phenelzine
In the SADHART study (2002), sertraline was found to be most beneficial for patients with what characteristics?
- depressive episodes predated ACS, 2. past history of MDD, 3. episodes of greater severity
What effect do all tricyclics have on heart rate?
they cause tachycardia
Which tricyclic demonstrates the least orthostatic hypotension?
nortriptyline
Based on data from the 8-week EMBOLDEN I and II trials, was there a dose-response relationship between quetiapine and weight gain?
yes
What is the classic treatment of the hypertensive reaction with an MAOI and a tyramine-rich food?
phentolamine 5 mg IV
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?
cholestatic jaundice
Sertraline is more potent at blocking ______ reuptake than any of the other SSRIs or TCAs.
dopamine
What dose range is approved for quetiapine XR for adjunctive treatment in major depressive disorder?
150-300 mg
Agranulocytosis is defined as a drop in ANC to less than _____/mm3.
500/mm3
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?
none
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.
fivefold; threefold
What is the main side effect reported in patients on initiation of vortioxetine, leading to discontinuation in 1%-4% of patients?
nausea
___% higher dosages of paroxetine CR are necessary to achieve the same bioavailability as the immediate-release form.
20%
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.
79%-82%
In children and adolescents, do tricyclics demonstrate superiority over placebo for treatment of depression?
No.
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%
Nierenberg et al. 2007 found what effect of duloxetine on weight?
mean weight loss of 1 kg
What is the elimination half-life of clozapine?
12 hours
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%
In the US, milnacipran is FDA approved for _____ and levomilnacipran is FDA approved for _____.
fibromyalgia; MDD
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
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
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
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
What is the half-life of quetiapine in adults? What about extended-release?
6 hours; 7 hours
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
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
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
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%
For trazodone, the manufacturer estimates that the incidence of any abnormal erectile function is approximately 1 in _____ male patients.
6000
At therapeutic dosages, how do venlafaxine and desvenlafaxine affect cardiac conduction and seizure threshold?
no significant effect
In the Consta formulation, risperidone microspheres begin to release appreciable amounts of the drug _____ after injection.
3 weeks
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
How are clozapine levels affected by smoking?
decreased
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
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
Trazodone is a mild 5-HT ______, but its active metabolite m-chlorophenylpiperazine (mCPP) is a potent, direct 5-HT ______.
antagonist; agonist
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
Fluoxetine is extensively metabolized to an active metabolite, norfluoxetine. While fluoxetine is a potent CYP ______ inhibitor, norfluoxetine is a moderate CYP _____ inhibitor.
CYP2D6; CYP3A4
What is buspirone’s action at presynaptic 5-HT1A receptors in the dorsal raphe?
full agonist, inhibiting neuronal 5-HT synthesis and firing
What electrolyte abnormality is associated with SSRIs in patients aged 70+ years?
hyponatremia
How is elimination half-life of mirtazapine affected by severe hepatic or renal impairment?
increased 30%-40% with hepatic; 30%-50% with renal
Half-life of vortioxetine?
66 hours; requires 2 weeks for steady-state
In extensive metabolizers of risperidone (90% of Caucasian patients and 99% of Asian patients), the half life is _____ hours.
3 hours
When olanzapine is taken orally, peak concentration is _____ hours after ingestion.
4-6 hours
What is the only antipsychotic to have demonstrated reduction of suicidal behavior in schizophrenia?
clozapine
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
Which receptor accounts for clozapine’s side effects of sedation, constipation, and ileus?
muscarinic M1 receptors
When was Clozapine reintroduced in the US, after convincing studies demonstrating efficacy in treatment-refractory schizophrenia?
1989
At what dose dose duloxetine attenuate tyramine pressor response? (Vincent et al. 2004)
120 mg/day
What washout period is recommended after discontinuation of fluoxetine before starting an MAOI?
5 weeks
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
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
Approximately ____% of a given dose of olanzapine undergoes first-pass metabolism and therefore does not reach the systemic circulation.
40%
GABA has three target receptors: GABA-A, -B, and -C. Which one controls a chloride ion channel?
GABA-A
Of venlafaxine and desvenlafaxine, which is approved for treatment of individuals younger than 18 years?
neither
What dose of sertraline has a significant risk of toxicity in hemodialysis patients with severe end-stage renal disease?
25 mg
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
What is the estimated yearly incidence of TD in adults?
5% among adults
Which tricyclic antidepressant has nonlinear kinetics at the usual dosage range?
desipramine
Are mean plasma prolactin levels correlated to clinical side effects and libido for male and female patients on risperidone?
no
Which receptor accounts for clozapine’s high sedation as well as contributing to weight gain?
histamine (H1)
What adjustments in olanzapine are needed for renal or hepatic disease?
none (Callaghan et al. 1999)
The risk of priapism with trazodone is greatest during what period of treatment, and at what dosages?
first month; low dosages (< 150 mg/day)
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
What property of trazodone likely explains the side effect of orthostatic hypotension?
potent antagonism of post-synaptic alpha-1 receptors
Stryjer et al. 2010 found trazodone to be effective in treating antipsychotic-induced ______.
akathisia
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
Tohen et al. 2002 compared olanzapine with divalproex for mania. How did they compare?
Equivalent efficacy.
What is the relationship of dose to serum concentration for most tricyclic antidepressants?
linear
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
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
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
What is the only AP medication FDA-approved for Tourette’s? (also this medication’s only approved indication)
Pimozide
What AP medication is approved for oral or IM therapy of intractable hiccups?
chlorpromazine
Incidence of amenorrhea and galactorrhea in women, which varies between ___% and ___%, is similar for all dosages of risperidone and haloperidol.
8%-12%
In interpreting clozapine levels, which is the active form, clozapine or the metabolite norclozapine?
clozapine; trials of norclozapine have not demonstrated efficacy
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
What is the approximate half-life of duloxetine?
12 hours
MAOIs can be reversible or irreversible and can be selective or non-selective. Which one is irreversible and selective for MAO-B?
selegiline
What is sertraline’s half-life?
26-32 hours
An irreversible increase in retinal pigmentation has been described with _____ when high dosages (> 800 mg/day) are used.
thioridazine
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)
What is the rate of occurrence of sialorrhea in clozapine therapy?
over 50% of patients
Mirtazapine has ___ affinity for muscarinic receptors and ___ affinity for histamine-1 receptors.
low; high
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
Based on studies in the 1980s, rank the following in terms of effectiveness for depression with atypical features: imipramine, phenelzine, placebo.
- phenelzine 2. imipramine 3. placebo
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
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
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
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
What was the first benzodiazepine to be approved by the FDA for panic disorder, introduced in 1981?
alprazolam
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
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)
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
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
Is there a dose-response relationship when treating MDD with duloxetine?
yes
How does clozapine’s binding to 5-HT2 receptors (including A, B, and C) compare to its D2 binding?
15-30 times stronger
What is the main CYP enzyme responsible for metabolism of bupropion?
CYP2B6
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
Clozapine’s antagonism of 5-HT2A has what result in the striatum?
increased local dopamine, resulting in relief from EPS
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
At high levels (> 78%) of dopamine blockade, patients will exhibit akathisia, rigidity, and hypokinesia, AKA . . .
extrapyramidal symptoms
