Antidepressant Agents Flashcards
1
Q
Lifetime prevalence of depression in men and women:
A
-10-25% of women
-5-10% of men
2
Q
___-___% of diagnosed individuals receive treatment for depression, and 25% of those who recieve treatment get adequate treatment
A
25-50
3
Q
Average age of onset of depression is late ____
A
20s
4
Q
Depression usually lasts ___-___ if untreated and also has a release risk
A
6 months-2 years
5
Q
____ is prevalent in those who are depressed; an estimated 8-25 attempts occur per every suicide death
A
Suicide
6
Q
In 2004, suicide was the ____ leading cause of death in those aged 10-14, 15-19, and 20-24
A
3rd
7
Q
In May of 2007, the FDA extended a warning of SSRI to young adults aged ___-___
A
19-24
8
Q
It is now estimated that ____% of adults with depression do not receive antidepressant therapy (no compensatory increases in other pharmacotherapies) (prior to the warning, 20% did get treatment)
A
30
9
Q
What are types of unipolar depression?
A
-Major depressive disorder
-Dysthymia
-Double depression
-Psychotic depression (not the same as depression secondary to schizophrenia)
-Seasonal affective disorder
-Postpartum depression
10
Q
What are examples of depression symptoms?
A
-Sleep patterns altered
-Interests gone
-Guilt
-Energy or fatigue
-Concentration/memory problems
-Appetite increased or decreased
-Psychomotor changes: agitation or retardation
-Suicidal thoughts; thoughts of death
11
Q
“Too much” neurotransmission means that hyperexcitable neurons fire in the absence of appropriate stimuli, like with ____ disorders
A
Seizure
12
Q
When too many neurotransmitters bind to postsynaptic receptors, it causes ____
A
Psychosis
13
Q
When too few neurotransmitters bind to postsynaptic receptors, it can lead to things like…
A
-Depression
-Parkinson’s disease
-ADHD
14
Q
The monoamine hypothesis of depression says that depression is caused by a functional insufficiency of the monoamine neurotransmitters ____, ____, or both
A
Norepinephrine, serotonin
15
Q
There may also be a deficiency in ____ with depression
A
Dopamine
16
Q
What are the goals of antidepressant drugs?
A
-Increase neurotransmitter synthesis or release
-Prolong time of the neurotransmitter in the synapse
-Inhibiting the enzymes that degrade neurotransmitters
-Administering agonists that act at post-synaptic receptors
17
Q
What impacts the “nurture” pathophysiology of depression?
A
-Stress and hypothalamic-pituitary axis
-Childhood neglect
18
Q
What impacts the “nature” pathophysiology of depression?
A
-Genetics
-Environmental exposure
19
Q
Observations made in the 1950s of the effects of ____ and ____ in altering monoamine neurotransmitter levels and affecting depressive symptoms gave indications of the pathophysiology of depression
A
Reserpine and isoniazid
20
Q
What is the process of neuronal transmission?
A
-Action potential reaches of synapse
-Neurotransmitter is released and interacts with post-synaptic receptors
-Neurotransmitter action is terminated by “reuptake” pumps that rapidly remove neurotransmitter from the synapse
-Monoamine oxidase (MAO) metabolized excess neurotransmitter in terminal preventing accumulation
21
Q
Selecting manipulation of the ____ transmitters (dopamine, serotonin, norepinephrine) has been the common denominator for all the currently marketed antidepressants (the same systems are implicated in anxiety)
A
Aminergic
22
Q
Most currently availble drugs increase monoamine mediated neurotransmission in key areas of the limbic system that regulate…
A
-Mood
-Arousal
-Appetite
-Sleep
23
Q
General mechanism of increasing monoamine neurotransmission include increasing the ___ ___ ___
A
Synaptic residence time
24
Q
What are two mechanisms to increase synaptic residence time?
A
-Blocking the reuptake of norepinephrine, serotonin, and dopamine into nerve terminals
-Blocking the metabolism of norepinephrine and serotonin in nerve terminals (MAOIs)
25
Antidepressants selectively alleviate symptoms of depression rather than acting as general ___ ___
CNS stimulants
26
Neurotransmitter levels in the synapse ____ soon after administration of most antidepressants, yet alleviation of depression is slow (weeks)
Increases
27
Stopping the antidepressant agent suddenly will result in rapid ____ of neurotransmitters
Release
28
One course of pharmacotherapy for depression is approximately ___ ___ long
1 year
29
Antidepressant medications do not work for everyone; about ____% of people are considered non-responders
30
30
The treatment goal in the acute phase of depression is to...
-Reduce and eliminate symptoms
31
The treatment goal in the continuation phase is to...
-Prevent relapse and return of symptoms
32
The treatment goal of the maintenance phase is to...
-Protect susceptible patients against recurrence of future depressive episodes
33
What are some examples of nonpharmacological treatment options for depression?
-Psychotherapy
-Phototherapy and chronotherapy
-Electroconvulsive therapy
-Vagal nerve stimulation
-Transcranial magnetic stimulation
34
What are examples of pharmacological treatment options for depression?
-MAOIs
-TCA
-SSRI, SNRI, NRI
-Other (trazadone, nefazodone, bupropion, mirtazapine, venlafaxine, duloxetine)
35
The choice of antidepressant depends on...
-Previous response to pharmacotherapy
-Concomitant medications and disease states
-Tolerance of specific adverse effect profile
-Potential for suicide
-Need for multiple treatment effects
-Lifestyle considerations and cost
36
Patients who discontinue a prescription prior to 1 year of appropriate pharmacotherapy are ___ more likely to relapse within 1 year
2
37
Who might receive a lifelong prescription for an antidepressant?
-2+ episodes + family history + additional diagnosis
-3+ episodes
38
A pharmacologic ____ is seen when there is adequate dosage for adequate time period
Response
39
Early response can be seen in 2-3 weeks, but can often take ___-___ weeks
4-6
40
If there is no evidence of response in 2-3 weeks at the top dose, switch to a new ___
Drug
41
Often, patients are considered to be "____ ____" even though they have never had even one antidepressant titrated to the top dosage for long enough to work
Treatment resistant
42
____ are first line antidepressants for most patients
SSRIs
43
SSRIs block the presynaptic reuptake of ____
Serotonin
44
The observed therapeutic effect of SSRIs is delayed by several ____
Weeks
45
Adverse effects of SSRIs are apparent within the first ____
Week
46
With SSRIs, there is a ____ over-dose potential
Lower
47
What are some examples of available SSRIs?
-Fluoxetine (Prozac)-> first SSRI approved
-Sertraline (Zoloft)
-Fluvoxamine (Luvox)
-Paroxetine (Paxil)
-Citalopram (Celexa)
-Escitalopram (Lexapro)
-Vilazodone (Viibryd)
48
SSRIs are no more effective than TCAs, but they have a more favorable ___-___ profile
Side effect
49
SSRIs have little or no affinity for muscarinic acetylcholine, a1-adrenergic and histamine H1 receptors, therefore have more favorable side effect profile; decreased anticholinergic activity = less ____
Cardiotoxicity
50
Most SSRIs are administered in the ____ (since they may cause insomnia)
Morning
51
____ is the only SSRI that would be given at bedtime since it is sedating
Paroxetine
52
SSRIs have a delayed ____, but it may be somewhat less than with TCAs
Efficacy
53
SSRIs have an ____ effect of blocking 5-HT (serotonin) reuptake into nerve terminals
Immediate
54
A delayed effect of SSRIs is ____ changes in the CNS
Adaptive
55
What adaptive changes in the CNS can SSRIs cause?
-Desensitization of 5-HT1A (serotonin) autoreceptors on serotonin terminals (inhibition of serotonin release when activated)
-Desensitization of 5-HT1A (serotonin) autoreceptors on serotonin neurons (negative feedback on firing activity when activated)
56
The end result of the mechanism of SSRIs is long-term ____ of serotonin neurotransmission
Increase
57
SSRI adverse side effects:
-GI disturbances (nausea, diarrhea, cramping, heartburn)
-CNS excitation or stimulation (restlessness, insomnia, anxiety; sedation from paroxetine)
-Significant anorexia and weight loss during early treatment; possible weight gain with long-term use
-Decreased libido and significant sexual dysfunction (anorgasmia, ejaculatory delay, impotence)
-Withdrawal syndrome has been described that includes nausea, dizziness, anxiety, tremor, and palpitations
58
SSRIs undergo metabolism in the ____
Liver
59
Choosing among SSRIs is primarily related to differences in...
-Half-life
-Inhibition of cytochrome p450
-Other drugs being used
60
In general, SSRIs inhibit what enzyme of CYP450?
-2D6
61
SSRIs can cause elevated concentrations of drugs metabolized by 2D6; this is important for drugs with a narrow ____ ____ like TCAs or type IC antiarrhythmics
Therapeutic index
62
____ is an SSRI that inhibits its own metabolism and exhibits nonlinear kinetics
Paroxetine
63
_____ is an SSRI that has the most drug-drug interactions due to its effect on so many CYP450 enzymes
Fluoxetine (Prozac)
64
____ and ____ have the least amount of drug-drug interactions
Citalopram (Celexa); Escitalopram (Lexapro)
65
There are numerous potential drug interactions with SSRIs due to inhibition of other drugs by ____ enzymes
CYP450
66
SSRIs taken with monoamine oxidase inhibitors can cause ___ ___
Serotonin syndrome
67
What are symptoms of Serotonin Syndrome?
-Rapid mental status changes
-Seizures
-Coma
-Death
68
Lexapro (Escitalopram) contains only the ____-enantiomer of Celexa (citalopram)
S
69
The S-enantiomer is therapeutically ____, while the R-enantiomer is not
Active
70
Lexapro (escitalopram) is more ____ with less side effects than Celexa
Potent
71
Lexapro ____ mg produces the same efficacy as ____ mg of Celexa
10; 40
72
What are other clinical uses for SSRIs?
-Generalized anxiety disorder
-Social phobia
-Panic disorder
-OCD
-Bulimia Nervosa
-Migraine headache
-PMDD
-PTSD
-Seasonal affective disorder
-Post-partum depression
73
What are symptoms of SSRI withdrawal?
-Flu-like symptoms, malaise
-Dizziness
-GI effects
-Parasthesia
-Mood, appetite, and sleep changes
74
____ withdrawal is a problem with drugs like amitriptyline, protriptyline, imipramine, etc
Anticholinergic
75
We can ____ taper doses to minimize withdrawal effects of antidepressants
Gradually
76
Serotonin syndrome is a pharmacodynamic interaction caused by over-potentiation of serotonin effects that can cause side effects like...
-Cramping
-Diarrhea
-Tremor
-Restlessness
-Tachycardia
-Hypertension
-Mania symptoms
-Confusion
-Sweating
77
Serotonin syndrome can be caused by the interaction of SSRIs with...
-Triptains
-Buspirone
-Amphetamines
-Muscle relaxants
-MAOIs
78
What are some examples of atypical antidepressants?
-Buproprion (Wellbutrin)
-Trazodone (Desyrel)
-Venlafaxine (Effexor)
-Mirtazapine (Remeron)
-Nefazodone (Serzone)
-Duloxetine (Cymbalta)
79
Bupropion (Wellbutrin) has a unique mechanism of action; it works by weakly blocking the reuptake of ____, and possibly causing some blockage of the norepinephrine and serotonin reuptake
Dopamine
80
There are three formulations of Bupropion (Wellbutrin) available for depression as well as a form called _____ that is approved for smoking cessation
Zyban
81
Bupropion (Wellbutrin) is well tolerated due to little or no ____, ____, or ____ receptor effects
Muscarinic, alpha-adrenergic, or histaminic
82
There is ____ incidence of sedation, hypotension, and weight gain with Bupropion (Wellbutrin)
Low
83
Unlike other antidepressants, Bupropion (Wellbutrin) causes few ____ side effects
Sexual
84
Bupropion (Wellbutrin) may cause ___, ___, and ___ since it is structurally similar to amphetamine, or precipitate psychotic episodes in susceptible individuals
Restlessness, insomnia, anxiety
85
There is a high risk of ____ activity with Bupropion at doses of 450 mg/day (should be given in divided doses)
Seizure
86
What are some drug interactions with Bupropion (Wellbutrin)?
-Contraindicated with MAOIs
-Caution with drugs that affect CYP3A4 or CYP2D6 (Ritonavir-> Norvir, Kaletra)
-Caution with drugs that low seizure threshold (Clozapine, illicit drugs)
87
Bupropion (Wellbutrin) is contraindicated in patients with...
-Seizure disorders
-Bulimia or anorexia nervosa
88
What is the mechanism of action of Trazodone (Desyrel)?
-Blocks 5-HT (serotonin) reuptake; antagonist at 5-HT2 receptors
-Partial agonist at 5-HT1A receptors
-Litter effect on norepinephrine uptake, but may stimulate norepinephrine release
89
Side effects of Trazodone (Desyrel):
-Sedation: low dose used for insomnia
-GI upset (nausea and vomiting)
-Dry mouth, blurred vision
-Orthostatic hypotension
-Priapism (sustained erection)-> rare but serious
90
What is the mechanism of action of Venlafaxine (Effexor)?
-Blocks reuptake of norepinephrine and serotonin
-Weakly inhibits dopamine reuptake
-Little to no effect on muscarinic, adrenergic, or histaminic receptors
91
Venlafaxine (Effexor) works like an _____ at lower doses (<200 mg/day)
SSRI
92
There is a ____ dosing conversion from Effexor to Effexor XR
Direct
93
The XR formulation of Venlafaxine (Effexor) has increased ____ and may decrease GI side effects
Complicance
94
Side effects of Venlafaxine (Effexor):
-Restlessness and insomnia
-Nausea and vomiting
-Sexual dysfunction
-Increase in blood pressure in approximately 5% of patients (dose-dependent, >300 mg/day)
95
There are minimal drug interactions with Venlafaxine (Effexor); some potential for interaction with agents that are metabolized by ____ like Clozapine and Paroxetine
CYP2D6
96
What should be included in patient counseling for Venlafaxine (Effexor)?
-Avoid use with alcohol
-May cause drowsiness and coordination impairment
-Take with food
-Do not crush or chew XR capsules
97
What is the mechanism of action of Mirtazapine (Remeron)?
-Antagonist of central presynaptic alpha2-adrenergic receptors (increases norepinephrine and serotonin release)
-Blockade of 5-HT2 and 5-HT3 receptors
98
Mirtazapine (Remeron) is ___-___, so it only requires 1 daily administration (preferably at bedtime)
Long-acting
99
Clearance of Mirtazapine (Remeron) is decreased in both ____/____ impaired patients and the elderly
Renally/hepatically
100
Side effects of Mirtazapine (Remeron):
-Sedation: blockade of histamine receptors, dose at bedtime
-Significant weight gain, increased appetite and serum lipids
101
Drug interactions with Mirtazapine (Remeron):
-Allow 14 days between stopping an MAOI and starting Mirtazapine (Remeron) and vice versa
-Alcohol/benzodiazepines increase sedation
102
Nefazodone (Serzone) is structurally analogous to ____
Trazodone
103
Mechanism of action of Nefazodone (Serzone):
-Blocks 5-HT reuptake
-Acts as an antagonist at 5-HT2 receptors
-Partial agonist at 5-HT1A
104
Side effects of Nefazodone (Serzone):
-Nausea, constipation
-Blurred vision
-Less sedation and orthostatic hypotension than trazodone
-Not associated with weight gain, priapism, or sexual side effects
105
What is the black box warning on Nefazodone (Serzone)?
Potential life-threatening liver failure
106
Drug interaction with Nefazodone (Serzone):
-Inhibits CYP3A4 = many potential drug interactions (antihistamines, benzodiazepines, digoxin, etc)
107
Duloxetine (Cymbalta) was the first drug approved for the treatment of ___ ___ ___
Diabetic peripheral neuropathy
108
Mechanism of action of Duloxetine (Cymbalta):
-Inhibits the reuptake of both norepinephrine and serotonin
109
Side effects of Duloxetine (Cymbalta):
-Nausea
-Dry mouth
-Fatigue
-Insomnia
110
What are some examples of traditional tricyclic antidepressants (TCAs)?
-Imipramine (Tofranil)
-Desipramine (Norpramin, Pertofrane)
-Amitriptyline (Elavil)
-Protriptyline (Vivactil)
-Nortriptyline (Aventyl, Pamelor)
-Doxepin (Adapin, Sinequan)
111
The precise mechanism of TCAs is ____
Unknown
112
TCAs immediately block the reuptake of ___ ____ (both norepinephrine and serotonin) to varying degrees
Monoamine neurotransmitters
113
Neurotransmitter levels in the synaptic cleft increase, but the clinical effects are delayed around ___-___ weeks
2-3
114
It takes about 2-3 weeks for the increased neurotransmitter levels in the synapse to alter post-synaptic receptor ____ or ____
Density or sensitivity
115
TCAs are generally well absorbed orally, undergo high ___-___ metabolism, and are highly protein bound
First-pass
116
TCAs have long half-lives, which allow for once-daily dosing, generally at ____
Bedtime
117
TCAs are inactivated by ____ metabolism
Hepatic
118
TCAs undergo ____ formation of active metabolites
Oxidative
119
TCAs can also be conjugated with ____ ____ and excreted
Glucuronic acid
120
Blood levels measurements of TCAs must include the ___ ___ and ___ ___
Parent drug and active metabolites
121
TCAs lost their place as first-line therapy due to ___ ___, which vary in degree with any particular TCA
Side effects
122
Side effects of TCAs are mostly related to the blockade of...
-Acetylcholine receptors
-Histamine receptors
123
The blockade of acetylcholine receptors causes what side effects?
-Sedation
-Dry mouth
-Blurred vision
-Constipation
-Urinary retention
-Cognitive impairment
124
The blockade of histamine receptors causes...
-Fatigue
-Sedation
(especially with initial therapy)
125
Despite the lag in ____ effects with TCAs, side effects may occur immediately
Therapeutic
126
At therapeutic doses, what side effects may be seen with TCAs?
-Weight gain
-Some sexual dysfunction
-Lowers seizure threshold
127
At toxic doses, what effects may be seen with TCAs?
-Cardiovascular toxicity (Conduction delays, arrhythmias)
-Severe anticholinergic effects
-Convulsions
128
TCAs have multiple possible drug _____ due to high protein binding
Interactions
129
TCAs can be displaced by other highly protein-bound drugs like...
-Phenytoin
-Aspirin
-Phenothiazines
130
TCA metabolism can be inhibited by...
-Antipsychotics
-Oral contraceptives
-SSRIs
131
TCAs have a ____ therapeutic range with dose-related toxicities
Narrow
132
___-___% of patients have insufficient enzymes to metabolize TCA drugs; this may lead to life-threatening toxicities
3-5
133
It is important to monitor ____-____ serum drug levels of TCAs by drawing levels 10-12 hours after last dose
Steady-state
134
_____ is the most sedating TCA, best used for patients with insomnia or excitation
Amitriptyline (Elavil)
135
____ and ____ are TCAs that are the most effective in counteracting motor retardation
Nortriptyline (Pamerlor) and Desipramine (Pertofrane)
136
_____ is a TCA that has antidepressant and anti-anxiety effects, therefore, it is useful when depression and anxiety are co-morbid
Doxepin (Adapin, Sinequan)
137
_____ is a TCA that has dopamine (DA2) antagonist activity in addition to reuptake blockade; it is marketed for treatment of obsessive-compulsive disorders
Clomipramine (Anafranil)
138
_____ is a TCA that is a metabolite of an antipsychotic drug; it may produce extrapyramidal symptoms similar to other antipsychotic drugs due to the blockade of dopamine receptors
Amoxapine (Ascendin)
139
The function of MAO in nerve terminals is to convert ____ ____ into inactive products
Monoamine neurotransmitters
140
MAO inhibitors potentiate monoaminergic neurotransmission by augmenting ___, ___, and ___ levels in nerve terminals
Norepinephrine, serotonin, and dopamine
141
Inhibition of MAO is _____; termination of pharmacological activity requires discontinuance of the drug and synthesis of new enzyme that takes about 2-3 weeks
Irreversible
142
Traditional MAOIs were _____ (meaning that they inhibited MAO-A and MAO-B) and irreversible
Nonselective
143
What are three examples of MAOIs?
-Phenelzine (Nardil)
-Tranylcypromine (Parnate)
-Isocarboxazid (Marplan)
144
____-____ MAO inhibitors are currently being developed and tested in clinical trials
Shorter-acting
145
Moclobemide (Manerix) is a shorter-acting MAOI that is being tested; it is a reversible, selective inhibitor of ____ with fewer side effects with less danger of food interactions
MAO-A
146
____-____ interactions severely limit the use of MAOI (usually agents of last choice)
Food-drug
147
Hepatic and intestinal MAO serve to inactive biogenic amines in food (______), as well as biogenic amines administered as drugs (in decongestants)
Tyramine
148
MAO inhibitors block the metabolism of tyramine, which could lead to a ____ ____ if a someone has a high intake of tyramine
Hypertensive crisis
149
MAOIs tend to produce ____, along with many typical
"tricyclic" side effects
Insomnia
150
What are other side effects of MAOIs?
-Dizziness
-Blurred vision
-Weight gain
-Urinary hesitancy
-Serotonin Syndrome when combined with SSRI or overdose
151
_____ is an MAOI that was approved for treatment of Major Depressive Disorder in 2003
EmSam (Selegiline transdermal)
152
EmSam (Selegiline transdermal) is _____ and inhibits both MAO-A and MAO-B enzymes in the central nervous system, while avoiding inhibition of intestinal or liver MAO-A enzymes
Nonselective
153
EmSam is different from other MAOIs because it does not require someone to have any ___ restrictions
Dietary
154
The onset of effect of EmSam is just a few ____
Days
155
EmSam has excellent ____ rates and side effect profile
Compliance
156
____ ____ major depressive disorder means that there has been no improvement after 2+ full courses of monotherapy regimens
Treatment-refractory
157
With "treatment-refractory" major depressive disorders, it is important to see if drugs were dosed for ____ enough with adequate dosage
Long
158
What are options for those with treatment-refractory major depressive disorder?
-Switching monotherapy
-Augmentation therapy
-Non-pharmacologic strategies
159
What are some examples of non-Rx treatment options for refractory MDD?
-Psychotherapy modalities
-Phototherapy
-Transcranial magnetic stimulation therapy (TMS)
-Electroconvulsive therapy (ECT)
-Vagal nerve stimulation therapy (VNS)
160
Bipolar disorder affects 2.5 million people in the United States, and symptoms can begin as early as ___-___ years old
5-6
161
The mean age of onset of bipolar disorder is in the late ___-___, but symptoms may be more evident between ages 40-50 years old
20-30
162
Prevalence of bipolar disorder is equal in ___ and ___
Men and women
163
Someone is at a higher risk of developing bipolar disorder if they have family members with...
-Depression (90%)
-OCD
-Substance abuse
164
What are examples of mood disorders?
-Major depressive disorder
-Dysthymic disorder
-Bipolar I disorder
-Bipolar II disorder
-Cyclothymic disorder
-Bipolar disorder NOS
165
____ ____ ____ is the most common presentation of bipolar disorder
Bipolar II Depression
166
Patients with _____ episodes are typically elated and adaptive, while ____ patients often lack specific recall of these episodes (this may result in misdiagnosis of unipolar depression)
Hypomanic; depressed
167
With bipolar depression, someone has ____ episodes that alternate with episodes of ____; these episodes may last several weeks to months
Manic; depression
168
____ cycling of bipolar disorder means that someone has more than 4 cycles of either depression or mania per year
Rapid
169
Patients with bipolar disorder will often need to be managed with more than one medication; only ____% of patients respond to more than one mood stabilizer
30
170
Symptoms of hypomania and mania:
-Exaggerated optimism
-Decreased need for sleep
-Grandiose delusions
-Inflated sense of self-importance
-Excessive irritability
-Increased mental or physical activity
-Racing speech; flight of ideas
-Impulsiveness, poor judgment, reckless behavior
-Easy distracted
-Psychosis
171
Mania usually begins with changes in ____ ____; symptoms gradually develop over three days in three stages
Sleep patterns
172
Stage 1 of episode development is hypomania; this includes symptoms like...
-Racing thoughts
-Liable affect
-Grandiosity
-Increased activity/speech
173
Stage 2 of episode development is mania; this includes symptoms like...
-Cognitive effects
-Anger
-Delusions
-Increased irritability
-Dysphoria
-Hostility
174
Stage 3 of episode development is the progression of mania to a psychotic state; this includes symptoms like...
-Terror
-Hallucinations
-Frenzied activity
-Panic
-Bizzare behavior
175
Symptoms of bipolar depression are not secondary to...
-Substance use
-General medical condition
176
What are three examples of "step" based pharmacology for bipolar depression?
-Texas Medication Algorithm Project (TMAP)
-Systematic Treatment Enhance Program for Bipolar Disorder (STEP-BD)
-American Psychiatric Association (APA) Guidelines
177
Acute stabilization for someone in a manic state will relieve the most ____ symptoms and resolve the episode
Severe
178
The continuation phase of treatment lasts for ___-___ months after the end of the episode; this prevents relapse/cycling
2-6
179
During the continuation phase of treatment, ___ ___ are adjusted and antipsychotics/benzodiazepines are tapered off
Mood stabilizers
180
In the maintenance phase of bipolar disorder treatment, what two types of drugs are used?
-Mood stabilizers
-Antidepressants and antipsychotics
181
What are some examples of mood stabilizers that might be used during the maintenance phase of bipolar treatment?
-Lithium (Lithobid, Eskalith)
-Carbamezapine (Tegretol, Tegretol-XR)
-Oxcarbazepine (Trileptal)
-Valproic Acid (Depakote, Depakote-ER)
-Lamotrigine
182
More research is needed to make any definitive recommendations regarding the use of ____ and ____ in the maintenance phase of bipolar treatment
Antidepressants and antipsychotics
183
____ is effective for manic phase and for long-term maintenance of bipolar
Lithium
184
Lithium stabilized mood without causing ____
Sedation
185
The effect of Lithium starts within days, but the full effect is seen within ___-___ weeks (the exact mechanism of Lithium is unknown)
2-4
186
Lithium is not effective for rapid-cycling, but can decrease ____ of manic or depressive episodes
Frequency
187
Lithium may be given with an ____ or ____ during a depressive episode
SSRI or bupropion
188
Lithium is available in what dosage forms?
-Regular release
-Controlled release
-Syrup
189
If someone is on Lithium, they should maintain proper ____ and ____ intake
Fluid, sodium
190
Side effects of lithium include...
-Nausea
-Diarrhea
-Weight gain
-Polyuria
-Tremor
-Hypothyroidism
191
What can cause an increase lithium level in the body if someone is taking lithium?
-Dehydration
-ACE inhibitors (Captopril, enalapril)
-Metronidazole
-NSAIDS
-Thiazide diuretics, phenothiazines, haloperidol, fluoxetine
192
What can cause decreased lithium levels in the body if someone is taking lithium?
-Calcium channel blockers
-Theophylline (increases lithium excretion)
193
What can cause increased neurotoxicity in someone taking lithium?
-Antipsychotics
-SSRI's
-Haloperidol (Haldol)
-Neuroleptic Malignant Syndrome
194
Mild/early symptoms of lithium toxicity develop gradually over several _____
Days
195
Symptoms of mild lithium toxicity include...
-Ataxia
-Coarse tremor
-Confusion
-Diarrhea
-Drowsiness
-Muscle twitches
-Slurred speech
196
Treatment for lithium toxicity:
-Hold doses
-Assessment of signs and symptoms
-Obtain lithium level
-Check vital signs
-Patient education
197
Moderate/severe lithium toxicity (>2mEq/L) has either a ___ or ___ onset
Gradual or sudden
198
Signs and symptoms of moderate/severe lithium toxicity include...
-Muscle tremor
-Hyperreflexia
-Pulse irregularities
-Hyper/hypotension
-EKG changes
-Visual/tactile hallucinations
-Oliguria/anuria
-Seizures
-Coma
-Death
199
Treatment for moderative/severe lithium toxicity:
-Hold ALL doses
-Assessment of signs and symptoms of toxicity
-Obtain lithium level
-Check vital signs and consciousness
-Protect airway, O2
-BUN, SCr, urinalysis, CBC with diff
-ECG
-Hydration
-Gastric lavage, emetic
-Hemodialysis is the most reliable method
200
Lithium is the ____ for drug therapy of bipolar due to 40 years of experience
Standard
201
Lithium is the standard treatment for ___ ___ and ____
Euphoric mania and hypomania
202
Lithium is effective for ____ and ____ therapy
Maintenance and prophylactic
203
Lithium may provide more protection for patients with ____ during their episodes versus valproic acid
Suicidality
204
Lithium can be used alone or in combination, has a variety of dosage forms, and is _____
Inexpensive
205
If someone is on lithium, what types of laboratory evaluation should they receive?
-Renal
-Thyroid
-Cardiac
-CBC/diff
-Electrolytes
206
One downside of lithium is that it has a ____ onset of effect
Slow
207
Lithium has a ____ therapeutic index (acute: 0.8-1.2 mEq/L); maintenance: 0.6-1.0 mEq/L)
Narrow
208
Lithium has many side-effects, which leads to ____
Noncompliance
209
Carbamazepine (Tegretol, Tegretol-XR) is an _____ drug that may be used to treat acute mania or for prophylactic therapy
Anticonvulsant
210
Carbamazepine (Tegretol) works well for stabilizing ____-____ patients
Rapid-cycling
211
The max daily dose of Carbamazepine (Tegretol) is ____ mg/day
1200
212
Therapeutic range of Carbamazepine (Tegretol) is between ___-___ micrograms/mL
4-12
213
At concentrations of Carbamazepine over 8 micrograms/mL, patients may experience...
-Nausea
-Vomiting
-Lethargy
-Dizziness
-Drowsiness
-Headache
-Blurred vision
-Diplopia
-Ataxia
214
Toxic effects of Carbamazepine (Tegretol) are typically seen when dosing changes are made ____
Abruptly
215
Side effects of Carbamazepine:
-Blood dyscrasias (thrombocytopenia, leukopenia, rare aplastic anemia)
-Skin reactions: Steven-Johnson Syndrome
-Hyponatremia
-Cognitive effects (sedation, ataxia, dizziness)
-Neuromuscular effects
216
What drugs increase Carbamazepine levels?
-Calcium channel blockers
-Cimetidine
-Erythromycin
-Valproate
217
What drug decreases carbamazepine levels?
-Phenobarbital
218
Carbamazepine causes decreased drug effects/levels of...
-Hormonal contraception
-Theophylline
-Warfarin
219
Carbamazepine was approved for the management of ____ and paroxysmal ____ ____
Epilepsy; pain disorders
220
A benefit of Carbamazepine is that is has a more ____ onset than Lithium
Rapid
221
Generally, Carbamazepine is well-tolerated and may be more effective than Lithium for "___ ___" and "___ ___"
Mixed mania; rapid cyclers
222
Carbamazepine is ____ and generally available
Inexpensive
223
What are some disadvantages of Carbamazepine (Tegretol):
-Stimulates own oxidative metabolism
-Drug interactions
-Lab evaluation: CBC-differential; liver and kidney function
224
Oxcarbazepine (Trileptal) has a similar mechanism of action to ____
Carbamazepine
225
What are the indication for Oxcarbazepine (Trileptal)?
-Monotherapy or adjunctive for partial seizures in adults
-Adjunctive therapy of partial seizures for children
226
Unlabeled uses of Oxcarbazepine (Trileptal) include...
-Acute mania
-Atypical panic disorder
227
Side effects of Oxcarbazepine (Trileptal):
-Dose-dependent: headache, drowsiness, dizziness, ataxia, tiredness, nausea
-Idiopathic: hyponatremia, rash, weight gain
228
Laboratory monitoring is ___ ___ for someone on Oxcarbazepine (Trileptal)
Not required
229
There is an interaction between Oxcarbazepine and hormonal ____
Contraception
230
Valproic acid (Divalproex-Depakote) is another anticonvulsant approved by the FDA in 1995 for use in ___ and ___ ____ states
Mania and mixed bipolar
231
Valproic acid is useful in ___-___ bipolar patients
Rapid-cycling
232
The max dose of valproic acid is ____ mg/kg/day
60
233
The therapeutic range of Valproic acid is between ____ and ____ micrograms/mL
50-150
234
Valproic acid toxicity is better tolerated than lithium, but more ____
Sedating
235
At levels over 75 micrograms/mL of Valproic acid, someone might experience...
-Ataxia
-Sedation
-Lethargy
-Fatigue (decreased with continued usage)
236
At levels over 100 micrograms/mL of Valproic acid, someone might experience...
-Tremor
-Trouble concentrating
237
At levels over 175 micrograms/mL of Valproic acid, someone might experience...
-Stupor
-Coma
238
Valproic acid may also cause more ___ ___ and ___ ___ than other anticonvulsants
Weight gain; hair loss
239
Valproic acid cause cause ___ ___ Syndrome
Polycystic Ovary
240
Valproic acid can rarely cause ____, more commonly in children
Hepatotoxicity
241
The therapeutic range of Valproic acid is between ___-___ mg/day
750-3000
242
Valproic acid may be administered as an oral ___ dose for inpatient treatment
Loading
243
____ increases Valproic acid levels
Fluoxetine
244
____ and ____ taken with Valproic acid increase bleeding time
Aspirin and Warfarin
245
Valproic acid increases levels of ____ in the blood
Phenytoin
246
____ is a monotherapy for generalized seizures in adults and children
Lamotrigine (Lamictal)
247
Lamotrigine (Lamictal) can be used as adjunct therapy to ____ seizures (refractory)
Partial
248
Lamotrigine (Lamictal) inhibits the release of ____, which is an excitatory amino acid
Glutamate
249
Labeled use of Lamotrigine (Lamictal) is for...
-Maintenance mood stabilizer in bipolar I depression
250
Unlabeled use of Lamotrigine (Lamictal) is for...
-Mood stabilizer in rapid cycling bipolar II
251
Dosage of Lamotrigine (Lamictal) is reduced by 50% when taken with ___ ____ because it will cause a rash
Valproic acid
252
Lamotrigine (Lamictal) has no interaction with hormonal ____
Contraception
253
Lamotrigine (Lamictal) is a pregnancy category ____ drug, but may be updated to category C
B
254
Adverse effects of Lamotrigine (Lamictal):
-Dizziness
-Headache
-Diplopia
-Ataxia
-Nausea
-Blurred vision
-Somnolence
-Skin rash
255
Topiramate (Topamax) is approved for partial and complex ____, but not for bipolar disorder
Seizures
256
There have been no systematic studies to establish ___ or ____ of Topiramate (Topamax) for mood disorders
Safety, efficacy
257
Topiramate (Topamax) may be useful for "hard-to-treat" or "resistant" patients with comorbid ____ ___ and ___ ___ disorders
Substance abuse; impulse control
258
Topiramate (Topamax) is usually dosed in addition to other ____ ____
Mood stabilizers
259
The dosage titration rate of Topiramate (Topamax) is limited by ____ ____
Cognitive dulling
260
Topiramate (Topamax) may be helpful in minimizing ____ ____ from other medications
Weight gain
261
Topiramate (Topamax) has a possible interaction with hormonal _____
Contraception
262
What are some adverse effects of Topiramate (Topomax)?
-Somnolence
-Dizziness/vision problems
-Unsteadiness
-Nervousness
-Nausea
-Hot flashes (increases body temp; caution against use in children)
263
Gabapentin (Neurontin) is effective for the treatment of...
-Complex partial seizures
-Generalized seizures
-Neuropathic pain
264
Gabapentin (Neurontin) is not effective for the treatment of ____ disorders (only agent to date to test worse than placebo)
Bipolar
265
2/3 patients are unresponsive to ____ monotherapy
Lithium
266
What are four possible drug regimens for refractory patients?
-Lithium + anticonvulsant
-2 anticonvulsants
-Lithium + 2 anticonvulsants
-Levothyroxine for rapid cyclers
267
_____ can be used for acute management of bipolar disorder
Benzodiazepines
268
Antidepressants are less likely to produce robust, sustained responses in ____ disorders
Bipolar
269
"_____ _____" are treatment-emergent events that are not uncommon; they include mania/hypomania, rapid cycling states, and treatment resistance
Antidepressant misadventures
270
When would antidepressants be indicated for bipolar depression?
-Patients who cannot wait 4-6 week delay before a response to mood stabilizer
-Patients who have a history of response to previous treatment with antidepressants
-Patients who have not responded to mood stabilizers or psychotherapy in the past
271
We should try to limit antidepressant use to the management of ____ episodes of bipolar
Acute
272
Antidepressants may accelerate the course of bipolar disorder and induce ____ ____
Rapid cycling
273
Antidepressants mainly induce a switch to ____, especially with TCAs
Mania
274
If antidepressants are used for bipolar, there should be simultaneous use of a ___ ___
Mood stabilizer
275
Patients experiencing a depressive episode should stay on antidepressants for ___-___ months, and then slowly taper on a patient-by-patient basis
6-12
276
Some patients may require a maintenance antidepressant adjunctively with their maintenance ____ ____
Mood stabilizer
277
If someone needs to be on an antidepressant for bipolar, ____ might be a good choice since it may be less likely than TCAs to induce a switch (SSRIs, venlafaxine, nefazodone, and mirtazapine would also be options)
Bupropion
278
What are three mood stabilizer options for those with BPD?
-Lamotrigine
-Lithium
-Carbamazepine (?)
279
What drugs are given to patients during a state of mania or hypomania?
-Benzodiazepines
-Antipsychotics (Haldol)
-Atypical antipsychotics
280
What are the indications of benzodiazepines for BPD?
-May have faster onset for non-psychotic agitation
281
What are two examples of Benzodiazepines that may be used for the treatment of BPD?
-Lorazepine (Ativan)
-Clonazepam (Klonapin)
282
Lorazepam (Ativan) can be given by mouth or IM, and should be tapered when _____ stabilizes, about 1-2 weeks
Agitation
283
Clonazepam (Klonopin) is the agent of choice (long-acting) in patients with prior history or susceptible to ____ abuse
Substance
284
What are the indications of atypical antipsychotics for patients with BPD?
-Acute treatment of mixed or psychotic mania
-Maintenance treatment and prophylaxis
285
What is the proposed mechanism of antipsychotics for the treatment of BPD?
-Enhancing serotonin and norepinephrine activities reduce symptoms of mood and anxiety
-Antagonize serotonin and alpha-2-adrenergic receptors to varying degrees
-May have an earlier onset of therapeutic effect versus "traditional mood stabilizers"
286
Indication of Aripiprazole (Abilify) for BPD:
-Acute mania and maintenance
287
Indication of Olanzapine (Zyprexa) for BPD:
-Acute mania and maintenance
288
Indication of Olanzapine/Fluoxetine (Symbyax) for BPD:
-Acute mania and maintenance
289
Indication of Quetiapine (Seroquel) for BPD:
-Acute mania
290
Risperidone (Risperdal) is FDA approved in ___ and ___
Children and adolescents
291
All patients receiving an "atypical antipsychotic" must receive monitoring for the potential development of...
-Weight gain
-Obesity
-T2D
-Metabolic syndrome
292
There is a high rate of relapse within ___ months following remission of an acute episode; we should use an antipsychotic to control persistent psychosis or as prophylaxis against recurrence
6
293
What are some alternative pharmacotherapies for bipolar disorders?
-Thyroid hormone (T3 and/or T4)
-Electroconvulsive therapy
-Pramipexole (Mirapex)
-Omega-3 fatty acids
294
____ hormone would be adjuvant therapy and may be more useful in "rapid cyclers"
Thyroid
295
Electroconvulsive therapy may be preferred when a patient's behavior is extremely ___ ____ and a rapid response is needed
Life threatening
296
Pramipexole (Mirapex) should be used in cation with people who have history of impulse control disorders and ____
Addictions
297
Mood stabilizers are not recommended to mothers while ____ because they can transfer to the child
Lactating
298
What agents should be avoided while a mother is lactating?
-Valproic acid
-Lithium
299
Lithium during pregnancy can cause ____ ____
Epstein's anomaly
300
Carbamazepine during pregnancy can cause...
-Neural tube defects
-Craniofacial defects
301
Valproic acid during pregnancy can cause...
-Neural tube defects
302
Treatment of bipolar during the postpartum period includes...
-Prophylactic mood stabilizer in women with BPD during the postpartum period
-Resume mood stabilizer treatment a few days after delivery
303
Patients should discontinue mood stabilizers during the ____ trimester if possible
1st
304
If mood stabilizers much be given during pregnancy, ____ _____ counseling should be given and fetal monitoring at 16-18 weeks gestation should be done using high resolution ultrasound
Reproductive risk
305
If a pregnant mother is on mood stabilizers, serum and fluid ____ levels should be checked and a fetal echocardiography should be done
a-fetoprotein
306
Patients should discontinue mood stabilizers a few days before ____ to minimize toxic effects on the infant
Delivery
307
What are steps for implementing a plan to achieve remission in those with BPD?
-Assure the patient can pay for medication
-Make information available to patient
-Encourage patient to self-monitor
-Individualization of medication, incorporating patient preferences
-Assume patient can recognize emergence of recurrent symptoms and follow up with treating clinician
-Consider concomitant disorders
-Alert patients to side effects
-Verify current and previous medical history
