Mood Disorders
Mark is a 31-year-old patient with major depressive disorder who is considering repetetive transcranial magnetic stimulation. Which pulse range was shown to have the maximal mean effect size in a recent meta-analysis?
1200-1500 pulses
Danell has treatment-resistant depression and is beginning treatment with intravenous ketamine. According to meta-analytic analysis of randomized controlled trials, how long after the first infusion of ketamine should Danell expect the largest antidepressant effect?
24 hours
What percent of patients with bipolar II disorder have onset at age 60 years or older?
5%
The prevalence of depression among community dwelling adults aged 65 and older is estimated to be:
5-10%
Which receptor subtypes act as presynaptic autoreceptors to inhibit serotonin release?
5HT1A and 5HT1B/D receptors
Which of the following secondary properties of quetiapine may contribute to its efficacy in depression?
5HT1A partial agonism, 5HT2C antagonism, Norepinephrine reuptake inhibition
Psilocybin is a hallucinogen that is being studied in depression, anxiety, and PTSD. Psilocybin is predominantly a...
5HT2A agonist
A 48-year-old patient with depression was recently started on 20 mg/day fluoxetine to combat his presenting symptoms of apathy, fatigue, problems concentrating, and hypersomnia. The patient reports that he is feeling much more energized and can see improvements in his cognition and attention within a day or two of starting fluoxetine. Which of the following properties of fluoxetine is theoretically most likely responsible for this patient's positive response?
5HT2C antagonism
A 27-year-old patient who has been taking an atypical antipsychotic for bipolar disorder for the last 2 years has just found out that she is 12 weeks pregnant. Cumulative data for atypical antipsychotic use in pregnancy show an increased risk of:
Abnormal muscle movements in infants and Withdrawal symptoms in infants
A 36-year-old patient has only partially responded to his second monotherapy with a first-line antidepressant. Which of the following has the best evidence of efficacy for augmenting antidepressants in patients with inadequate response?
Adding an atypical antipsychotic. Atypical antipsychotics have been studied as adjuncts to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitor (SNRIs), with approvals for aripiprazole, brexpiprazole, quetiapine XR, and olanzapine (in combination with fluoxetine). Overall, most studies of atypical antipsychotics show a benefit of combination treatment over monotherapy, although effect sizes have been modest. Although atypical antipsychotics have the best evidence of efficacy for augmenting antidepressants in patients with inadequate response, their adverse event profiles may still put them later in the treatment algorithm. · Although adding buspirone, a serotonin 1A partial agonist, to a first-line antidepressant makes sense mechanistically, the limited data that exist are mixed/weak. · The limited controlled data for stimulant augmentation in depression show a trend of benefit; however, this strategy is not as well documented as is augmentation with atypical antipsychotics.
Maria is a 27-year-old woman with a family history of major depressive disorder who is pregnant with her first child. According to the American College of Obstetricians and Gynecologists (ACOG), women should be screened for symptoms of depression and anxiety how often during the perinatal period?
At least once
A 24-year-old man with moderate depression achieves remission after 16 weeks on a therapeutic dose of an antidepressant. According to the neurotrophic hypothesis of depression, which of the following is most likely true of his BDNF expression before and after his successful treatment?
BDNF expression was abnormally low while he was depressed, and increased during antidepressant treatment.
A 28-year-old man with moderate depression achieves remission after 16 weeks on a therapeutic dose of an antidepressant. According to the neurotrophic hypothesis of depression, which of the following is most likely true of his brain-derived neurotrophic (BDNF) expression before and after his successful treatment?
BDNF expression was abnormally low while he was depressed, and increased during antidepressant treatment. The neurotrophic hypothesis of depression posits that depression results from decreased neurotrophic support, leading to neuronal atrophy, decreased hippocampal neurogenesis, and that antidepressant treatment blocks or reverses this deficit, thereby reversing atrophy and cell loss. Several meta-analyses have reported deficient BDNF levels in patients with major depressive disorder and an elevation in BDNF following antidepressant treatment.
A 28-year-old man with moderate depression achieves remission after 16 weeks on a therapeutic dose of a monoaminergic antidepressant. According to the neurotrophic hypothesis of depression, which of the following is most likely true of his BDNF expression before and after his successful treatment?
BDNF expression was abnormally low while he was depressed, and increased during monoaminergic antidepressant treatment
A 58-year-old patient with a history of depression is currently taking agomelatine, which has what mechanism of action?
Binding to 5HT2C receptors AND Binding to melatonin receptors in the suprachiasmatic nucleus
A 21-year-old female has been suffering from severe depression for the last 3 years. She is experiencing relief of numerous symptoms on her current treatment; however, she has residual complaints of physical fatigue/lack of energy and difficulty concentrating. What pharmacological strategies may be most likely to target these residual symptoms?
Boost norepinephrine and/or dopamine
A 25-year-old patient with first-episode major depressive disorder is being prescribed an antidepressant. The time course for therapeutic effects of antidepressants correlates with:
Changes in receptor sensitivity
The age class with the worst risk/benefit ratio for suicidality with use of antidepressants is:
Children under age 12
The loss of growth factors, which may lead to neuroprogression, may be caused by which of the following environmental factors?
Chronic stress, Chronic Inflammation, and Early life adversity
Higher blood levels of which of the following medications have been associated with a greater likelihood of improving in adolescents with treatment-resistant depression?
Citalopram
A clinician is considering options for a 45-year-old man with severe treatment-resistant depression who has exhibited only partial response to first-line and older generation antidepressants and who is unwilling to attempt electroconvulsive therapy or other stimulation therapy. One option, with extreme caution and under expert guidance, is to combine a monoamine oxidase inhibitor (MAOI) with a tricyclic antidepressant; however, which of the following should absolutely NOT be used in combination with an MAOI, even by an expert?
Clomipramine
A 56-year-old male patient with major depression is brought to the ER with cardiac arrhythmia and possible cardiac arrest. While at the hospital, he suffers a seizure. His wife states that he may have ingested an increased dose of his medication. Which of the following is most likely responsible for this apparent overdose reaction?
Clomipramine. Clomipramine, a tricyclic antidepressant (TCA), may be most likely to cause these effects in overdose. TCAs block voltage-sensitive sodium channels (VSSCs) in both the brain and the heart. This action is weak at therapeutic doses, but in overdose may lead to coma, seizures, and cardiac arrhythmia, and may even prove fatal. · Atomoxetine, a norepinephrine reuptake inhibitor, does not block VSSCs and is not noted to have severe cardiac impairments upon overdose; rather sedation, agitation, hyperactivity, abnormal behavior, and GI symptoms are most commonly reported. · Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), also does not block VSSCs and does not generally cause severe cardiac impairment in overdose. · Venlafaxine is a serotonin norepinephrine reuptake inhibitor (SNRI). Although some data have suggested that SNRIs can affect heart function in overdose and also may carry increased risk of death in overdose compared to selective serotonin reuptake inhibitors, their toxicity in overdose is less than that for tricyclic antidepressants.
Devan is a 22-year-old male presenting with distress. After evaluation, subthreshold mood and anxiety symptoms and a family history of bipolar disorder are revealed. According to clinical staging models of bipolar disorder, which intervention would be most appropriate?
Cognitive Behavioral Therapy
A 26-year-old woman began treatment for a major depressive episode 8 months ago. Two months into her treatment she began to experience noticeable symptom improvement, and for the last 5 months she has been mostly symptom free, except for persistent cognitive dysfunction. Which of the following statements regarding cognitive dysfunction in depression is most accurate?
Cognitive dysfunction is one of the most common residual symptoms following recovery and Cognitive dysfunction can be treated with serotonergic modulation of glutamate transmission. Cognitive dysfunction is one of the most common residual symptoms of major depressive disorder and can endure longer than mood symptoms following recovery. Moreover, cognitive dysfunction is strongly correlated with physical, mental, and functional disability. Pharmacotherapies used to treat depression that have action on glutamate signaling via serotonergic modulation also show pro-cognitive effects. The prime example is vortioxetine, which has agonist action at 5HT1A, weak partial agonist action at 5HT1B/D, and antagonist action at 5HT3, 5HT1D, 5HT7, and the serotonin transporter. Antagonism of 5HT3 disinhibits glutamate release, while antagonism of 5HT7 enhances release of glutamate release in the prefrontal cortex. In addition, agonism of 5HT1A (full) and 5HT1B (partial) may enhance or suppress glutamate transmission based on neuronal localization
In addition to treating depressed mood, preclinical data indicate that serotonin 5HT3 receptor antagonists may have clinical utility as adjunct treatment for which symptoms?
Cognitive symptoms. Serotonergic neurons synapse with noradrenergic neurons, cholinergic neurons, and GABAergic interneurons, all of which contain serotonin 5HT3 receptors. When serotonin is released, it binds to 5HT3 receptors on GABAergic neurons, which release GABA onto noradrenergic, glutamatergic, and cholinergic neurons, thus reducing release of norepinephrine, glutamate, and acetylcholine, respectively. In addition, serotonin may bind to 5HT3 receptors on noradrenergic and cholinergic neurons, further reducing release of those neurotransmitters. This may theoretically contribute to symptoms of depressed mood and impaired cognition. Therefore, treatment with 5HT3 receptor antagonists improve depressed mood and cognitive problems.
Dopamine (DA) receptors can be categorized as D1-like (D1 and D5 receptors) and D2-like (D2, D3, and D4 receptors). What differentiates the two groups of receptors?
D1-like receptors are excitatory and D2-like receptors are inhibitory
When norepinephrine binds alpha 2 receptors, what effect does it have on norepinephrine neurotransmission?
Decrease norepinephrine
Which of the following is a pharmacodynamic alteration that occurs as a result of aging:
Decreased cholinergic activity
Lithium has a steady state half-life of 20-24 hours. The advantages of single daily lithium dosing include:
Decreased long term renal dysfunction (polyuria) and decreased inpatient staff time or outpatient inconvenience
Which of the following is true about depression and reproductive hormones?
Depression is linked to estrogen levels in women across their life cycles
A 36-year-old man with depression has had 3 therapeutic trials of serotonin reuptake inhibitors (SRIs) without notable improvement. His clinician is now considering switching the patient's SRI to a monoamine oxidase inhibitor (MAOI). Which of the following is an appropriate switching strategy in this situation?
Discontinue SRI, then wait 5 half-lives before initiating MAOI
A 13-year-old boy meets DSM-5 criteria for major depressive disorder and has been treated with paroxetine 40 mg daily for 8 weeks. He has had minimal improvement in depressive symptoms. Which of the following represents an evidence-based treatment option?
Discontinue paroxetine and begin citalopram 10 mg qAM
A patient with depression is prescribed mirtazapine as adjunctive treatment to venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Mirtazapine acts on alpha 2 receptors to produce what effect?
Disinhibition of norepinephrine and serotonin release via alpha 2 antagonism. Norepinephrine turns off its own release via alpha 2 presynaptic receptors; therefore, alpha 2 antagonism with mirtazapine facilitates disinhibition of norepinephrine. Furthermore, norepinephrine migrating from a norepinephrine terminal can also turn off serotonin release via alpha 2 presynaptic heteroreceptors on serotonin neurons. Therefore, alpha 2 antagonists like mirtazapine can have a dual effect on facilitating the release of both norepinephrine and serotonin.
According to recent meta-analyses, which of the following medications has the largest effect size for treating bipolar depression?
Divalproex
Miryam is a 24-year-old woman with a major depressive episode that is only partially responding to treatment with a selective serotonin reuptake inhibitor. In particular, she continues to display reduced positive affect. She is prescribed adjunctive bupropion to manage this symptom. Through which mechanism(s) does bupropion theoretically ameliorate reduced positive affect?
Dopamine and Norepinephrine inhibition. Bupropion has weak reuptake blocking properties for dopamine (dopamine transporter [DAT] inhibition), and for norepinephrine (norepinephrine transporter [NET] inhibition). Human positron emission tomography scans suggest that as little as 10-15% and perhaps no more than 20-30% of striatal DATs may be occupied at therapeutic doses of bupropion. NET occupancy would be expected to be in this same range.
A 48-year-old woman with a history of treatment-resistant depression is currently taking duloxetine 60 mg/day with partial response as well as trazodone 50 mg/day for insomnia. Despite reporting strict adherence to her medication dosages, she states that she feels empty and useless, and she admits to having thoughts of death. She states that she does not have plans to kill herself because it would harm her family and pets. Her clinician decides to try tranylcypromine, a monoamine oxidase inhibitor (MAOI) and one of the few agents that she has not yet tried. Which of the patient's current medications MUST you discontinue BEFORE initiating tranylcypromine?
Duloxetine. Duloxetine is a serotonin norepinephrine reuptake inhibitor. Inhibition of the serotonin transporter leads to increased synaptic availability of serotonin. Similarly, inhibition of MAO leads to increased serotonin levels. In combination, these two mechanisms can cause excessive stimulation of postsynaptic serotonin receptors, which has the potential to cause a fatal "serotonin syndrome" or "serotonin toxicity. Because of the risk of serotonin toxicity, complete washout of duloxetine is necessary before starting an MAOI. Duloxetine must be down-titrated as tolerated, after which one must wait five half-lives of duloxetine (at least 3-4 days) before initiating the MAOI. · Although trazodone does have serotonin reuptake inhibition at antidepressant doses (150 mg or higher), this property is not clinically relevant at the low doses used for insomnia. In fact, because there is a required gap in antidepressant treatment when switching to or from an MAO inhibitor, low-dose trazodone can be useful as a bridging agent when switching.
A 36-year-old man with major depressive disorder is having lab work done to assess his levels of inflammatory markers. Based on the current evidence regarding inflammation in depression, which of the following results would you most likely suspect for this patient?
Elevated levels of tumor necrosis factor-alpha (TNF-alpha). There is growing evidence that inflammation may play an important role in the pathophysiology of major depression. Clinical studies have shown that depressed patients have significantly higher concentrations of several inflammatory central and peripheral markers, including the pro-inflammatory cytokines TNF-alpha and interleukin-6. Patients with depression also have higher concentrations of C-reactive protein, which is synthesized by the liver in response to pro-inflammatory cytokines, and reduced interferon gamma, which is a proinflammatory cytokine. Furthermore, both cytokines and cytokine inducers can cause symptoms of depression. For example, as many as 50% of patients receiving chronic therapy with the cytokine interferon develop symptoms consistent with idiopathic depression.
A 31-year-old woman is diagnosed with severe postpartum depression 3 weeks after giving birth. Treatment with brexanolone, a positive allosteric modulator of gamma amino butyric acid (GABA) at the GABA-A receptor, ameliorated her symptoms. GABA has more recently been implicated in the neurobiology of depression. Theoretically, individuals with depression may display a lack of normal GABAergic tonic inhibition via:
Extrasynaptic benzodiazepine-insensitive GABA-A receptor. Extrasynaptic benzodiazepine-insensitive GABA-A receptor subtypes are thought to mediate tonic inhibition. Tonic inhibition may be regulated by the ambient levels of extracellular GABA molecules that have escaped presynaptic reuptake and enzymatic destruction and persist between neurotransmissions and is boosted by allosteric modulation at these sites. Thus, tonic inhibition is thought to set the overall tone and excitability of the postsynaptic neuron, and to be important for certain regulatory events such as the frequency of neuronal discharge in response to excitatory inputs. Since neuroactive steroids have antidepressant properties, this has led to the proposal that some depressed patients may have a lack of normal tonic inhibition, and thus too much excitability in some brain circuits. Indeed, in the case of postpartum depression, it may be potentially explainable on the basis that pregnant women have high circulating and presumably brain levels of neuroactive steroids. When they deliver, there is a precipitous decline in circulating neuroactive steroid levels, hypothetically triggering the sudden onset of a major depressive episode when tonic inhibition is lost. Restoring neuroactive steroid levels—and tonic inhibition—via brexanolone may be enough for the patient to respond by reversing their depression and then having some additional time to accommodate to the lower levels of neuroactive steroids postpartum. · Postsynaptic benzodiazepine-sensitive GABA-A receptors are thought to mediate phasic inhibition
A mother whose daughter has just been diagnosed with major depressive disorder wants to know more about the underlying cause. Recent research largely supports the hypothesis that depression is due to a measurable deficiency of monoamines in the brain.
False
Boys with ADHD are more likely than girls to have a comorbid internalizing condition like anxiety or depression.
False
Stimulants should never be used in patients with ADHD and history of SUD:
False
A patient presents to a new clinician with a major depressive episode. In addition to taking a patient's history, the two factors most useful for helping to determine if a presenting depressive episode is part of a unipolar or bipolar illness include:
Family history and input from someone close to the patient
Which psychotherapeutic intervention has substantial evidence for youth with, or at risk for, bipolar disorder?
Family-focused therapy
A 52-year-old man presents to the emergency room with symptoms of hypertensive crisis after an evening dining out with friends. He is currently taking a monoamine oxidase inhibitor (MAOI). Which of the following foods must be avoided by patients taking MAOIs?
Foods to Avoid: - Dried, aged, smoked, fermented, spoiled, or improperly stored meat, poultry, and fish - Broad bean pods - Aged cheeses - Tap and unpasteurized beer - Marmite - Soy products/tofu - Banana peel - Sauerkraut, kimchee - Tyramine-containing nutritional supplements *Not necessary for 6-mg transdermal or low-dose oral selegiline. Foods Allowed: - Fresh or processed meat, poultry, and fish - All other vegetables - Processed cheese slices, cottage cheese, ricotta cheese, cream cheese, yogurt - Bottled or canned beer and alcohol - Brewer's and baker's yeast - Peanuts - Bananas, avocados, raspberries
A 35-year old woman with postpartum depression is being treated with brexanolone, a cyclodextrin-based intravenous formulation of the naturally occurring neuroactive steroid allopregnanolone. Brexanolone's mechanism of action is to bind to a specific allosteric site on:
GABA-A receptors
Allopregnanolone, a metabolite of progesterone, is thought to modulate HPA axis activity through its actions on:
GABA-A receptors
What kind of H coil was designed to target addiction circuits, and has recently demonstrated success in smoking cessation in a large trial?
H4
Randomized, double-blind clinical data in older patients (mean age 68.0 years) with bipolar I disorder indicate that lithium:
Has comparable response rates to divalproex
The syndrome of bipolar disorder
Has many varied presentations
Agents that block reuptake of norepinephrine have what effect on dopamine in the prefrontal cortex?
Increase its synaptic availability
A clinician has decided to administer an alpha 2 antagonist to his patient. Alpha 2 antagonists have what effect on neurotransmission?
Increase norepinephrine and increase serotonin
Which of the following attributes makes you consider that the patient has bipolar depression rather than unipolar depression?
Increased appetite
A mechanism of neuroprotection includes the promotion of neural plasticity and survival. Which of the following is a biomarker of this mechanism in bipolar disorder?
Increased brain-derived neurotrophic factor and Increased hippocampal volume
Ketamine/esketamine is hypothesized to exert its rapid antidepressant actions by:
Increased density of dendritic spines
Amir is a 19-year-old patient with depression. He requests treatment with a serotonin norepinephrine reuptake inhibitor (SNRI) because he heard they are more effective than selective serotonin reuptake inhibitors (SSRI). Theoretically, what is the therapeutic advantage of a SNRI over a SSRI?
Increased norepinephrine and dopamine via norepinephrine transporter inhibition. In addition to boosting serotonin like SSRIs (via inhibition of serotonin reuptake by the serotonin transporter [SERT]), SNRIs can boost norepinephrine by inhibiting reuptake by the norepinephrine transporter (NET). Additionally, in the prefrontal cortex, SNRIs can boost dopamine levels. In prefrontal cortex, SERTs and NETs are present in abundance on serotonin and norepinephrine nerve terminals, respectively, but there are very few dopamine transporters (DATs) on dopamine nerve terminals. Therefore, dopamine action is terminated either by enzymatic degradation or NET. If NET is inhibited by an SNRI then it cannot terminate the action of dopamine and dopamine levels increase in this brain region.
A 65-year-old patient on theophylline for chronic obstructive pulmonary disease (COPD) and fluvoxamine for recurring depressive episodes required a decreased dose of theophylline due to increased blood levels of the drug. Which of the following pharmacokinetic properties may be responsible for this?
Inhibition of CYP450 1A2 by fluvoxamine. Fluvoxamine is a strong inhibitor of CYP450 1A2. Theophylline is metabolized in part by CYP450 1A2, and thus strong inhibition of this enzyme by fluvoxamine may require a dose reduction of theophylline if the two are given concomitantly, so as to avoid increased blood levels of the drug. · Of all SSRIs, fluvoxamine shows the least interaction with CYP450 2D6. · Fluvoxamine is also a moderate inhibitor of CYP450 3A4, but since theophylline is neither a substrate nor an inhibitor of 3A4, this should not affect theophylline blood levels.
41-year-old woman with a long history of bipolar disorder had been stable on a maintenance lithium treatment for the past year. Which of the following statements best describes a current working hypothesis about the molecular mechanism of action of lithium?
Inhibition of GSK-3ß and IMPase
A 24-year-old woman has been taking lithium to treat her bipolar disorder for 6 years. Lithium's hypothesized mechanism of action is:
Inhibition of second messenger enzymes and Interaction with downstream signal transduction cascades
A 24-year-old woman presents with a history of major depressive episodes and current symptoms of depression. She is prescribed a tricyclic antidepressant and develops treatment-emergent activation syndrome (TEAS). The offending agent is discontinued and TEAS resolves. What would be an appropriate next-step treatment?
Initiation of a mood stabilizer as monotherapy
A 34-year-old man presents with a major depressive episode characterized by depressed mood, insomnia, problems concentrating, weight loss, and suicidal ideation. Which of the following symptoms is the most likely to be residual following otherwise successful treatment?
Insomnia
There is short-term clinical trial evidence that single doses of ___________ reduce(s) suicidal ideation in patients with active suicidality at baseline.
Intravenous ketamine
The syndrome of bipolar disorder:
Is defined by occurrence of at least one maniac episode and has many varied presentations
Which of the following have been granted Breakthrough Therapy designation by the US Food and Drug Administration for psychiatric study/treatment?
Ketamine, MDMA (ecstasy), and Psilocybin
Maria is a 57-year-old patient with bipolar disorder. Neuroimaging reveals marked gray matter loss. Based on clinical staging models of bipolar disorder, Maria is likely in the _________ of bipolar disorder.
Late stages
Tricyclic antidepressants, compared to newer agents such as serotonin selective reuptake inhibitors or serotonin norepinephrine reuptake inhibitors, have:
Less favorable tolerability profiles
Tricyclic antidepressants, compared to newer antidepressants such as serotonin selective reuptake inhibitors or serotonin norepinephrine reuptake inhibitors, have:
Less favorable tolerability profiles
A 32-year-old woman with bipolar I disorder has just found out that she is 6 weeks pregnant. Her mania has been stable on a combination of lithium, valproate, and olanzapine, but she is unsure about the safety of maintaining her medications during her pregnancy. Which of the following is true regarding the use of these medications for bipolar disorder during pregnancy?
Lithium and valproate have known teratogenic effects and are not preferred treatments
The ideal treatment would have which of the following characteristics?
Low NNT, high NNH, LHH > 1
FDA-approved treatments for bipolar depression include:
Lurasidone
Considerations for initiating a systematic deprescribing process should include the patient's:
Medical status, Current Level of Functioning, Values, and Preferences
Margaret is a 42-year-old patient with untreated depression. She is reluctant to begin antidepressant treatment due to concerns about treatment-induced weight gain. Which of the following antidepressant treatments is associated with the greatest risk of weight gain?
Mirtazapine. Meta-analysis has shown that mirtazapine, an alpha 2 antagonist, may cause both short- and long-term weight gain. This is consistent with its secondary pharmacologic properties: mirtazapine is an antagonist at both serotonin 2C and histamine 1 receptors, the combination of which has been proposed to cause weight gain. However, it should be noted that average weight gain with any antidepressant is small, and rather than a widespread effect it may instead be that a small number of individuals experience significant weight gain due to their genetic predispositions and other factors. · Although weight gain may occur, it is not commonly reported with escitalopram, and a meta-analysis suggests that the risk of both short- and long-term weight gain with escitalopram is low. · Although weight gain may occur, it is not commonly reported with fluoxetine and a meta-analysis did not find significant increase in weight over the short- or long-term. Some patients actually experience short-term weight loss with fluoxetine. · Although weight gain may occur, studies with vilazodone have suggested a lower risk for weight gain compared to many other antidepressants that block serotonin reuptake; however, head-to-head studies have not been conducted.
Which antidepressant is less likely to induce mania in youth?
NONE
A 46-year-old woman has been taking lithium for 14 years. Her latest lab work revealed that she has stage 3a chronic renal disease; urine test did not reveal proteinuria. Is lithium contraindicated in this patient?
No
Bipolar II disorder is characterized by highly recurrent depressive episodes with a substantial morbidity from alcoholism. Which of the following selective serotonin reuptake inhibitors has clinical trial evidence of effectively treating bipolar II disorder in the setting of alcohol use disorder?
No SSRI
Ben is a 67-year-old patient with bipolar disorder who has been treated with lithium for several years. Which treatment should Ben switch to in order to maximize neuroprotective effects?
No switch; lithium shows the greatest neuroprotective effects
A 27-year-old patient who has been taking an SSRI for depression for the last 2 years has just found out that she is 12 weeks pregnant. Cumulative data for SSRI use in pregnancy have established a clinically significant increased risk of:
None of the above (Cardiovascular malformation, autism, PPHN
5HT3 antagonists may improve cognitive symptoms because they increase downstream release of:
Norepinephrine and acetylcholine
In 2018, the Food and Drug Administration (FDA) approved the Brainsway H7 coil for the treatment of which mental disorder?
Obsessive Compulsive Disorder (OCD)
A 23-year-old female college student has gotten in significant trouble for her risky and impulsive behavior, stealing a fire extinguisher, driving on the common area lawn, and hostilely addressing a professor. Which of the following monoamine projections may account for her recent behavior? Projections to the:
PFC
Lithium has been shown in numerous studies to reduce the incidence of completed suicide in bipolar patients compared to which of the following:
Placebo, Depakote, and antipsychotics
Teresa is a 29-year-old woman with major depressive disorder who has not responded to 3 adequate courses of antidepressants and may be a good candidate for ketamine treatment. What additional information about Teresa would be most critical to obtain before commencing treatment?
Prior or current substance abuse
Through which mechanism does lithium hypothetically exert its primary neuroprotective effect in bipolar disorder?
Promotion of neural plasticity and survival
A patient with bipolar II disorder responds well to monotherapy with lamotrigine. Lamotrigine's unique therapeutic profile in bipolar depression compared to other anticonvulsants appears to be hypothetically linked to its:
Reduction of glutamate release
A 34-year-old man with depression characterized by depressed mood, sleep difficulties, and concentration problems has not responded well to a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI). His clinician elects to switch him to vortioxetine, which has prominent 5HT7 antagonism. What may be a primary function of these receptors?
Regulation of serotonin-glutamate interactions. 5HT7 receptors are postsynaptic G protein-linked receptors. They are localized in the cortex, hippocampus, hypothalamus, thalamus, and brainstem raphe nuclei, where they regulate mood, circadian rhythms, sleep, learning, and memory. A major function of these receptors may be to regulate serotonin-glutamate interactions. Serotonin can both activate and inhibit glutamate release from cortical pyramidal neurons. Serotonin released from neurons in the raphe nucleus can bind to 5HT2A receptors on pyramidal glutamate neurons in the prefrontal cortex, activating glutamate release. However, serotonin also binds to 5HT1A receptors on pyramidal glutamate neurons, an action that inhibits glutamate release. Additionally, serotonin binds to 5HT7 receptors on GABA interneurons in the prefrontal cortex. This stimulates GABA release, which in turn inhibits glutamate release. Serotonin binding at 5HT7 receptors can also inhibit its own release. That is, when serotonergic neurons in the raphe nucleus are stimulated, they release serotonin throughout the brain, including not only in the prefrontal cortex but also in the raphe itself. Serotonin can then bind to 5HT7 receptors on GABA interneurons in the raphe nucleus. This stimulates GABA release, which then turns off serotonin release. Serotonin binding at 5HT7 receptors in the raphe inhibits serotonin release; therefore, an antagonist at this receptor would be expected to enhance serotonin release. Specifically, by blocking serotonin from binding to the 5HT7 receptor on GABA interneurons, a 5HT7 antagonist would prevent the release of GABA onto serotonin neurons, thus allowing the continued release of serotonin in the prefrontal cortex.
Wei is a 33-year-old patient with major depressive disorder beginning at age 17; his current depressive episode has persisted for 10 months. His treatment history includes fluoxetine, nefazodone, venlafaxine, mirtazapine, agomelatine, lithium augmentation, and electroconvulsive therapy. Each of these treatments produced moderate but transient response; therefore, he will begin ketamine infusions to treat his treatment-resistant depression. Which of the following statements about ketamine treatment is true?
Repeated dosing extends the duration of ketamine effects. Studies suggest that repeated dosing may extend the duration of ketamine effects. Ketamine administration of 2-3 times per week over 2-3 weeks, followed by a taper period and/or continued treatments may be most effective. · To date, the strongest evidence for ketamine's clinical benefit in psychiatric disorders is in the treatment of major depressive episodes without psychotic features associated with major depressive disorder. · High frequency ketamine administration is not recommended. Chronic high-frequency use of ketamine is associated with cognitive impairment and cystitis. · A thorough history of antidepressant treatment should be collected and documented to confirm previous adequate trials of antidepressant treatments and confirm treatment resistance.
A 40-year-old woman presents with a major depressive episode. She has previously been treated with an SSRI and experienced bothersome sexual dysfunction. Her clinician is considering prescribing vilazodone, which has what pharmacologic action that may mitigate the risk of sexual dysfunction?
Serotonin 1A partial agonism
Which of the following is the most potent property of trazodone?
Serotonin 2A antagonism
A 40-year-old woman presents with a major depressive episode. Her clinician is considering prescribing the antidepressant vilazodone, which has what two major mechanisms of action?
Serotonin reuptake inhibition and serotonin 1A partial agonism
Neuroprogression in bipolar disorder is characterized by the following clinical feature:
Shorter inter-episode intervals
Mike is a 31-year-old patient with major depressive disorder (MDD) has experienced some response with the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine XR (150 mg/day). However, the patient acknowledges that he and his wife have been having relationship problems because of his poor libido. The patient experienced this problem prior to being diagnosed and treated for MDD, but he has found that the venlafaxine has worsened this troubling symptom despite the fact that his mood has improved. He asks if there is a way to both prevent worsening of his mood and avoid this side effect. Which of the following treatment strategies would you recommend for this patient?
Switch to a norepinephrine and dopamine reuptake inhibitor (NDRI). Pharmacological agents that increase dopaminergic neurotransmission and/or decrease serotonergic neurotransmission (e.g., serotonin 1A agonists or serotonin 2 antagonists) are often effective in ameliorating sexual dysfunction. Switching to an NDRI such as bupropion would be expected to increase dopaminergic neurotransmission and improve sexual function. Given that the patient experienced libido problems prior to treatment with the SNRI, and that the problem has worsened on treatment with the SNRI, it makes sense to switch to bupropion. Augmentation with bupropion to address sexual dysfunction, although commonly done in clinical practice, is not actually supported by randomized controlled studies. Serotonin plays an inhibitory role in the human sexual response, both for desire and for orgasm. · With regards to the diagnostic criteria for depression, this patient has experienced some improvement with his current dose of venlafaxine. Although lowering the dose of venlafaxine may improve this patient's sexual function, a dose reduction may also increase his depressive symptoms. · Of the available antidepressant treatments, SSRIs are associated with the greatest risk of worsening sexual function, so switching from venlafaxine to an SSRI would not be expected to improve sexual functioning. · Although it is usually best to try another antidepressant monotherapy before resorting to augmentation strategies for the treatment of side effects, for a patient such as this who is otherwise responding well it might be reasonable to augment. However, phosphodiesterase-5 inhibitors do not increase desire and thus would not be a good option to treat this patient's specific problems with sexual function.
A patient has been taking an SSRI for 9 months. She is experiencing sexual dysfunction as a side effect that she states is very troublesome. Which of the following is an evidence-based option to address this patient's sexual dysfunction?
Switch to bupropion
Which of the following statements regarding mood symptoms is true?
Symptoms related to increased negative affect are hypothetically linked to serotonergic (and noradrenergic) dysfunction
GABA-A receptors subtypes that are located extrasynaptically hypothetically mediate:
Tonic neurotransmission
What percentage of children with ADHD have comorbid major depressive disorder?
Up to 40%
A nested case-control study was performed among patients age 66 and older in Ontario, Canada which compared 413 who were admitted with lithium toxicity and 4 matched lithium treated controls. Drug-related factors that were associated with increased risk for lithium toxicity included:
Use of loop diuretics (e.g., furosemide) and Use of ACE inhibitors
Which medication for bipolar disorder has been associated with cognitive problems/lower IQ in 6-year-olds, previously exposed to this medication in utero?
Valproate
Following unsuccessful treatment with paroxetine and fluoxetine, a 15-year-old girl, who meets DSM-5 criteria for major depressive disorder, is prescribed extended-release venlafaxine which is initiated at 37.5 mg daily and titrated to 150 mg daily for 8 weeks. She has had minimal improvement in depressive symptoms. Which of the following represents a significant clinical consideration?
Venlafaxine treatment may increase her likelihood of treatment-emergent suicidality
Not all anticonvulsant medications have good evidence of efficacy in bipolar disorder. For those that do, which of the following has the strongest evidence of direct involvement in the mechanism of action of these agents?
Voltage-sensitive sodium channels
A 32-year-old woman with major depressive disorder has been taking a selective serotonin reuptake inhibitor (SSRI) with good response for months. She presents now with complaints that she feels numb, and that even when she's sad she can't cry. Her clinician is considering reducing the dose of her SSRI in an effort to alleviate this problem. Is this a reasonable option?
Yes, data suggest that SSRI-induced indifference is dose-dependent and can be alleviated by reducing the dose. Apathy and emotional blunting can be symptoms of depression, but they are also side effects associated with selective serotonin reuptake inhibitors (SSRIs). These symptoms—termed "SSRI-induced indifference"—are under-recognized but can be very distressing for patients. They are theoretically due to an increase in serotonin levels and a consequent reduction of dopamine release. The first recommended strategy for addressing SSRI-induced indifference is to lower the SSRI dose, if feasible. Additional options include adding an augmenting agent or switching to an antidepressant in another class.
A 24-year-old female presents with psychotic symptoms and moderate agitation not relieved through de-escalation measures. Which of the following atypical antipsychotics is available in a short-acting intramuscular formulation?
Ziprasidone
