Neuropsychiatric Pharmaceuticals 3rd year 2nd semester Flashcards

Question

What is the first-line treatment for mild to moderate anxiety disorders during pregnancy? A) Selective serotonin reuptake inhibitors (SSRIs) B) Cognitive-behavioral therapy (CBT) C) Benzodiazepines D) Beta-blockers

Answer 1

Answer: B) Cognitive-behavioral therapy ✅ CBT and interpersonal therapy are first-line treatments for mild to moderate anxiety during pregnancy. Explanation: ❌ SSRIs are used if anxiety symptoms are severe but are not first-line for mild cases. ❌ Benzodiazepines should be avoided due to fetal risks. ❌ Beta-blockers are not primary treatments for anxiety disorders.

Answer 2

Answer: B) Duloxetine ✅ Duloxetine is the only antidepressant officially approved for generalized anxiety disorder (GAD) in children and adolescents (ages 7–17) in the U.S. **D for daycare, and depression if that helps, ** Explanation: ❌ Sertraline and fluoxetine are used off-label but are not officially approved. ❌ Venlafaxine has an increased risk of suicide in children and adolescents. ** GAD DRUG OPTIONS for children – SSRI/SNRI ** * Less robust data exists for SNRI – the agents with sufficient data to justify their use are duloxetine and venlafaxine * Duloxetine is the only antidepressant with an official indication in the US (not Canada) for the treatment of anxiety in children and adolescents, specifically for generalized anxiety disorder in children and adolescents 7–17 years of age

Answer 3

**Answer: (A) Correct – Fluoxetine, fluvoxamine, paroxetine, and sertraline have sufficient evidence for treating anxiety disorders in children and adolescents.** Explanation: (B) Incorrect – Escitalopram is commonly used for anxiety but lacks strong evidence specifically in children and adolescents. (C) Incorrect – Citalopram is not included in the SSRIs with sufficient evidence for treating anxiety in younger patients. (D) Incorrect – Duloxetine is an SNRI, not an SSRI, and is only approved in the US for treating generalized anxiety disorder in children and adolescents. **GAD DRUG OPTIONS for children – SSRI/SNRI** * The SSRIs for which there is sufficient evidence are fluoxetine, fluvoxamine, paroxetine, and sertraline * There are no SSRIs indicated for the treatment of anxiety disorders in children and adolescents in Canada or the US * All carry a warning about the risk of suicidal ideation and suicidal behavior (up to age 18 in Canada and 24 in the US)

Answer 4

**Answer: B) Risk of suicidal ideation and behavior; All SSRIs carry a warning about the risk of suicidal ideation and behavior, particularly up to age 18 in Canada and 24 in the US.** Explanation: (A) Incorrect – SSRIs do not increase the risk of psychosis. (C) Incorrect – There is no evidence linking SSRIs to permanent cognitive impairment. (D) Incorrect – Metabolic syndrome is more commonly associated with antipsychotics, not SSRIs. **GAD DRUG OPTIONS for children – SSRI/SNRI** * The SSRIs for which there is sufficient evidence are fluoxetine, fluvoxamine, paroxetine, and sertraline * There are no SSRIs indicated for the treatment of anxiety disorders in children and adolescents in Canada or the US * All carry a warning about the risk of suicidal ideation and suicidal behavior (up to age 18 in Canada and 24 in the US)

Answer 5

**Answer: (B) Correct – Venlafaxine (an SNRI) has been associated with a greater risk of suicide in children and adolescents compared to other pharmacological agents.** Explanation: (A) Incorrect – Sertraline carries a general warning for suicidal ideation but is not specifically identified as having a higher risk than other SSRIs. (C) Incorrect – Paroxetine has evidence for use in children but does not carry a significantly higher risk than venlafaxine. (D) Incorrect – Fluoxetine is generally considered safer for children and adolescents. **SUICIDALITY from psychiatric medications** * Risk of suicidal ideation and behaviour is estimated at 0.7% with a NNH of 143 * NNT is 3 * In children and adolescents, venlafaxine is potentially associated with a greater risk of suicide than other pharmacological agents ================================== **Why does Velnafaxine has a higher risk of suicide in children and adolescents compared other drugs?** Venlafaxine has been associated with a higher risk of suicide in children and adolescents compared to other pharmacological agents, likely due to its noradrenergic activity and withdrawal effects. Here’s why: Noradrenergic Effects – Unlike SSRIs, which primarily increase serotonin levels, venlafaxine (an SNRI) also increases norepinephrine levels at higher doses. Elevated norepinephrine can lead to increased anxiety, agitation, and impulsivity, which may contribute to suicidal thoughts or behaviors in younger patients. Severe Discontinuation Symptoms – Venlafaxine has a short half-life, meaning it leaves the body quickly. This can result in withdrawal symptoms (such as irritability, dizziness, and mood instability) if a dose is missed or stopped suddenly, potentially increasing emotional distress and suicidality. Higher Rates of Treatment-Emergent Suicidal Ideation – Studies have suggested that venlafaxine is linked to an increased incidence of new-onset suicidal ideation in children and adolescents compared to SSRIs like fluoxetine or sertraline. Because of these risks, venlafaxine is not typically a first-line option for treating anxiety or depression in children and adolescents.

Answer 6

**Answer: D) They do not have any sexual side effects; SSRIs frequently cause sexual dysfunction, including decreased libido and difficulty with arousal/orgasm.** Explanation: (A) Correct – SSRIs are preferred for their tolerability, ease of dosing, and affordability. (B) Correct – SSRIs can increase GI bleeding risk, especially with NSAID use. (C) Correct – All SSRIs, except fluoxetine, are commonly associated with discontinuation effects. ================================== DRUG OPTIONS - SSRI * First-choice antidepressants due to greater tolerability, ease of dosing, and relatively low cost * SSRIs can increase the risk of GI bleeding, particularly in patients with additional risk factors such as concomitant NSAID therapy or a history of GI bleeding * They should be used with caution in patients already at higher risk of GI bleeding * Unlike GI or CNS side effects, sexual dysfunction is more likely to persist during SSRI therapy and can involve impairment of desire, arousal and/or orgasm/ejaculation * Consider the importance of sexual function to the patient when prescribing an antidepressant and preferably choose sexually neutral options (bupropion, vortioxetine, mirtazapine, moclobemide) as appropriate DRUG OPTIONS - SSRI * Six SSRIs are currently available in Canada (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) * With the exception of fluoxetine, all SSRIs are commonly associated with discontinuation effects when stopping therapy

Answer 7

**Answer: (B) Correct – Bupropion is a dual-action antidepressant that inhibits norepinephrine and dopamine reuptake and is approved for smoking cessation.** Explanation: (A) Incorrect – Vortioxetine is effective for depression but not used for smoking cessation. (C) Incorrect – Amitriptyline is a tricyclic antidepressant (TCA) with sedative properties but is not used for smoking cessation. (D) Incorrect – Sertraline is an SSRI, not a dual-action antidepressant. ================================= **Antidepressant Drug OPTIONS with DUAL ACTION ANTIDEPRESSANTS** * Bupropion is thought to exert antidepressant effects through norepinephrine and dopamine reuptake inhibition * First-line agent for MDD and is also indicated for smoking cessation * Lowers the seizure threshold in a dose-dependent manner and is contraindicated in patients with a seizure disorder or recent history of anorexia or bulimia nervosa, and should be used with extreme caution where there is a history of head trauma or seizure * Causes less GI disturbance and sexual dysfunction than SSRIs

Answer 8

**✅ B) 2 weeks is correct – A minimum therapeutic dose should be maintained for at least 2 weeks before increasing it if there is no response.** Explanation: ❌ A) 1 week is incorrect – One week is too short to assess full therapeutic effects. Most antidepressants take several weeks to show benefits. ❌ C) 4 weeks and D) 8 weeks are incorrect – If there’s no response after 2 weeks, increasing the dose within the next 4–6 weeks is recommended rather than waiting too long. **Timeframe for increasing Depression Drugs** * A minimum therapeutic dose should be achieved in the first 2 weeks of treatment and increased if necessary, over the next 4–6 weeks * Patients need to be informed of common side effects and that some of these unwanted effects usually subside within 2 weeks * Consider switching within the same class during weeks 3–8 if a favourable response is overshadowed by persistent and troublesome side effects that do not respond to measures such as adjusting the dose or time of administration

Answer 9

**✅ B) Switching within the same class (SSRI) during weeks 3–8 is correct – If side effects persist despite adjustments, switching to a different SSRI may help while maintaining efficacy.** Explanation: ❌ A) Discontinuing immediately is incorrect – Abrupt discontinuation may cause withdrawal symptoms and worsen depression. ❌ C) Reducing the dose below therapeutic levels is incorrect – This may lead to treatment failure without effectively managing side effects. ❌ D) Hoping for tolerance is incorrect – While some side effects resolve within 2 weeks, persistent ones should not be ignored. **Timeframe for increasing Depression Drugs** * A minimum therapeutic dose should be achieved in the first 2 weeks of treatment and increased if necessary, over the next 4–6 weeks * Patients need to be informed of common side effects and that some of these unwanted effects usually subside within 2 weeks * Consider switching within the same class during weeks 3–8 if a favourable response is overshadowed by persistent and troublesome side effects that do not respond to measures such as adjusting the dose or time of administration

Answer 10

✅ B) Amitriptyline, venlafaxine, escitalopram are correct – A meta-analysis identified amitriptyline, venlafaxine, escitalopram, mirtazapine, paroxetine, agomelatine, and vortioxetine as more effective than other antidepressants. Explanation: ❌ A, C, and D are incorrect – While some of these drugs are effective, not all were ranked as the most effective based on network meta-analysis data. **Most researched Drug Options for Antidepressant** * Based on a network meta-analysis of 21 antidepressants involving over 100 000 patients, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were identified as more effective than other antidepressants * When acceptability (based on drop-out rates) was considered, the leading agents were agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine

Answer 11

✅ A) Agomelatine, citalopram, escitalopram, sertraline are correct – These drugs showed the best balance between effectiveness and tolerability, leading to fewer dropouts in clinical studies. Explanation: ❌ B) Amitriptyline and venlafaxine are incorrect – These may be more effective but are associated with more side effects and dropouts. ❌ C) Mirtazapine and duloxetine are incorrect – While mirtazapine is effective, weight gain and sedation can lead to discontinuation. ❌ D) Paroxetine and desvenlafaxine are incorrect – Paroxetine has more withdrawal symptoms, and desvenlafaxine has noradrenergic side effects. **Most researched Drug Options for Antidepressant** * Based on a network meta-analysis of 21 antidepressants involving over 100 000 patients, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were identified as more effective than other antidepressants * When acceptability (based on drop-out rates) was considered, the leading agents were agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine

Answer 12

Explanation: ✅ D) Any SSRI, especially with NSAIDs, is correct – All SSRIs can increase the risk of GI bleeding, especially in patients taking NSAIDs or with a history of ulcers. ❌ A, B, C are incorrect – While individual SSRIs (fluoxetine, paroxetine, citalopram) can contribute to GI bleeding, the risk applies to the entire SSRI class. **First line DRUG OPTIONS for Depression SSRI** * First-choice antidepressants due to greater tolerability, ease of dosing, and relatively low cost * SSRIs can increase the risk of GI bleeding, particularly in patients with additional risk factors such as concomitant NSAID therapy or a history of GI bleeding * They should be used with caution in patients already at higher risk of GI bleeding * Unlike GI or CNS side effects, sexual dysfunction is more likely to persist during SSRI therapy and can involve impairment of desire, arousal and/or orgasm/ejaculation * Consider the importance of sexual function to the patient when prescribing an antidepressant and preferably choose sexually neutral options (bupropion, vortioxetine, mirtazapine, moclobemide) as appropriate

Answer 13

Explanation: ✅ B) It lowers the seizure threshold and increases seizure risk is correct – Bupropion is contraindicated in patients with anorexia or bulimia due to an increased seizure risk, particularly in malnourished individuals. ❌ A is incorrect – Bupropion does not increase appetite; it’s often associated with weight loss. ❌ C is incorrect – Food intake does not reduce its antidepressant effects. ❌ D is incorrect – Bupropion has fewer withdrawal effects than SSRIs. ============================== **Further your understanding** i understand that malnutition lowers the seizure threshold but how, as in I understand the sodium and potassium exchange there is suppose to be more potassium in the cell and more sodium out but how does this effect the action threshold? 1. Resting Membrane Potential & Ion Gradients Neurons communicate via electrical signals, which depend on the movement of sodium (Na⁺) and potassium (K⁺) ions across the cell membrane. At rest, the inside of the neuron is negative (~ -70 mV) relative to the outside. This is maintained by the sodium-potassium pump (Na⁺/K⁺ ATPase), which: Pumps 3 Na⁺ out Pumps 2 K⁺ in This keeps more K⁺ inside and Na⁺ outside the cell. 2. How Malnutrition Affects the Seizure Threshold Malnutrition disrupts ion balance, neurotransmitters, and energy production, leading to hyperexcitability of neurons. A. Electrolyte Imbalances (Na⁺ & K⁺ Disruptions) 🔹 Low potassium (hypokalemia) Less K⁺ inside the neuron → the resting potential becomes less negative (closer to threshold). This makes it easier for a neuron to fire an action potential. 🔹 Low sodium (hyponatremia) or fluctuating Na⁺ levels Disrupts depolarization and repolarization, leading to erratic firing. B. Energy Deficiency & ATP Depletion The Na⁺/K⁺ pump requires ATP to function. Malnutrition = Low ATP, meaning the pump works less efficiently. This causes Na⁺ buildup inside and K⁺ loss outside, making the neuron unstable and prone to excessive firing. C. Neurotransmitter Imbalance (GABA & Glutamate) Malnutrition decreases GABA (inhibitory neurotransmitter) and increases glutamate (excitatory neurotransmitter). Less inhibition + more excitation = lower seizure threshold. D. Hypoglycemia & Brain Excitability Glucose is the brain's main fuel. In malnutrition, glucose levels drop → neurons don’t function properly. This can cause neuronal hyperactivity and seizures. 3. Why Eating Disorders (e.g., Anorexia) Increase Seizure Risk Severe calorie restriction → ATP depletion → Na⁺/K⁺ pump dysfunction → easier neuronal firing. Electrolyte imbalances (low Na⁺, K⁺, Mg²⁺, and Ca²⁺) make neurons unstable. Dehydration worsens electrolyte shifts, further increasing seizure risk. Summary Malnutrition lowers the seizure threshold by: Disrupting ion gradients (less K⁺ inside, more Na⁺ inside). Reducing ATP availability, impairing the Na⁺/K⁺ pump. Decreasing inhibitory GABA while increasing excitatory glutamate. Causing hypoglycemia, making neurons more excitable. This is why bupropion is contraindicated in patients with anorexia or bulimia—it already lowers the seizure threshold, and malnutrition makes it worse.

Answer 14

**SNRI drugs options for depression** **(C) Venlafaxine is correct because it is known to cause dose-related hypertension at high doses.** Explanation: (A) Duloxetine is incorrect because while it is an SNRI, it is primarily indicated for neuropathic pain and fibromyalgia and does not have a strong association with hypertension. - Cigarette smokers are likely to have lower plasma levels and may require higher dosing due to CYP1A2 induction (B) Desvenlafaxine is incorrect because it has a lower risk of serious drug interactions and is used in peri- and postmenopausal patients, but it does not cause significant hypertension. (D) Levomilnacipran is incorrect because while it has a higher potency for norepinephrine reuptake inhibition, which can lead to increased blood pressure and heart rate, venlafaxine is more strongly associated with dose-related hypertension.

Answer 15

**(B) Mirtazapine is correct because is a dual action antidepressant that acts on both the noradrenergic and serotonergic systems, leading to lower rates of GI and sexual side effects but causing sedation and weight gain.** is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) Explanation: (A) Vortioxetine is incorrect because while it has a lower risk of sexual dysfunction compared to SSRIs, it is not known for sedation or weight gain. (C) Trazodone is incorrect because it causes severe daytime sedation but is not particularly associated with weight gain. (D) Sertraline is incorrect because it is an SSRI that commonly causes GI side effects and sexual dysfunction rather than sedation and weight gain. =============================== **Serotonin modulators Antidepressant DRUG OPTIONS** * Vortioxetine is a novel serotonergic antidepressant thought to involve a combination of direct 5-HT receptor modulation and serotonin transporter inhibition * Mild to moderate nausea, typically in the first week of treatment, is usually self-resolving * Treatment-emergent sexual dysfunction and disrupted sleep may be lower with vortioxetine compared with SSRIs DRUG OPTIONS – SEROTONIN MODULATORS * Trazodone is a potent postsynaptic serotonin (5- HT2) receptor antagonist with weak serotonin reuptake inhibitory effects * Rarely prescribed due to severe daytime sedation at therapeutic doses * Can be used in low doses alongside other antidepressants as a hypnotic ============================== Is the reason why mirtazapine have lower effect on GI and sexual side effect because it works at a lower efficacy on both or does the norepinephrine upregulate and counters sexual side effects.?

Answer 16

**(B) Vilazodone is correct because it is a multimodal antidepressant that requires slow titration to prevent GI side effects.** Explanation: (A) Vortioxetine is incorrect because while it can cause nausea, it does not require titration in the same way as vilazodone. (C) Trazodone is incorrect because it is primarily used as a hypnotic at low doses and does not require a titration schedule. (D) Moclobemide is incorrect because it is an MAOI that does not require titration for GI side effects. **SEROTONIN MODULATORS drug options for antidepression** * Vilazodone is a multimodal antidepressant that acts as a serotonin reuptake inhibitor and a partial agonist at 5- HT1A * Should be taken with food to ensure adequate absorption * A titration schedule is recommended to avoid GI effects * Sexual side effects occur less frequently with vilazodone compared to SSRIs

Answer 17

**(C) Vilazodone is correct because it should be taken with food to enhance its absorption and effectiveness.** Explanation: (A) Fluoxetine is incorrect because it does not have specific food requirements for absorption. (B) Mirtazapine is incorrect because while it causes weight gain and sedation, it does not require food for absorption. (D) Venlafaxine is incorrect because it does not require food for proper absorption.

Answer 18

** (A) Amitriptyline is correct because it is a TCA that is unlikely to cause serotonin syndrome.** Explanation: (B) Fluoxetine is incorrect because it is an SSRI and all SSRIs can contribute to serotonin syndrome if combined with other serotonergic agents. (C) MAOIs are incorrect because they have the highest risk of serotonin syndrome and require a minimum 2-week washout period before switching to another serotonergic agent. (D) Sertraline is incorrect because, as an SSRI, it can contribute to serotonin syndrome, especially when used with other serotonergic drugs. ADVERSE EFFECT MANAGEMENT * Serotonin syndrome * Stop the drug(s) and refer patient to the hospital * Rare, and may occur when multiple serotonergic agents are used * MAOIs have the highest risk and require a minimum 2-week washout period before another serotonergic agent is initiated * Amitriptyline, mirtazapine and trazodone are unlikely to cause serotonin syndrome

Answer 19

**(A) Bupropion is correct because it is a dual-action antidepressant that works via norepinephrine and dopamine reuptake inhibition and is also approved for smoking cessation.** Explanation: (B) Mirtazapine is incorrect because it does not have a role in smoking cessation. (C) Trazodone is incorrect because it is mainly used as a hypnotic in low doses rather than as a primary antidepressant or smoking cessation aid. (D) Clomipramine is incorrect because it is a TCA primarily used for OCD, not smoking cessation.

Answer 20

**(D) Somnolence is correct because more than half of mirtazapine users report drowsiness and sedation.** Explanation: (A) Insomnia is incorrect because mirtazapine actually helps with sleep and causes sedation rather than insomnia. (B) Weight loss is incorrect because mirtazapine is associated with weight gain, not weight loss. (C) Sexual dysfunction is incorrect because mirtazapine has a lower risk of sexual side effects compared to SSRIs.

Answer 21

**(A) Switching to bupropion is correct because it is one of the few antidepressants with minimal sexual side effects.** Explanation: (B) Increasing the dose is incorrect because higher doses increase the risk of sexual dysfunction. (C) Adding another SSRI is incorrect because SSRIs worsen sexual dysfunction, not improve it. (D) Reducing the dose might help but is not the best solution since it could also make depression worse.

Answer 22

Correct Answer: B) If the condition is in remission for an appropriate maintenance period ✅ Explanation: Antidepressants should generally be continued for 9 months to 2 years once remission is achieved to prevent relapse. Other reasons for discontinuation include intolerable adverse effects, lack of efficacy, drug interactions, or changes in coverage. ❌ Why the other choices are incorrect: A) Three months is too short; stopping too early increases relapse risk. C) Mild nausea is a common and often temporary side effect, not necessarily an indication to stop. D) Medication trials vary per individual; switching multiple times does not automatically indicate discontinuation. **DISCONTINUATION INDICATIONS for antidepressants* * The condition for which the antidepressant was started is in remission for an appropriate maintenance period * The antidepressant does not achieve a satisfactory effect * Intolerable adverse effects * New drug-drug interactions arise due to additional medications * Changes to drug coverage

Answer 23

**Correct Answer: B) Starting augmentation or combination therapy ✅ Explanation: When multiple antidepressants have been tried with only partial effect, augmentation (adding another drug to boost efficacy) or combination therapy (using two antidepressants together) may be required.** ❌ Why the other choices are incorrect: A) Stopping treatment without an alternative plan may worsen symptoms. C) Reducing dosage is unlikely to improve effectiveness. D) Increasing dose frequency could increase side effects without necessarily improving efficacy.

Answer 24

Correct Answer: B) Abruptly stopping or rapidly reducing the dose ✅ Explanation: Antidepressant discontinuation syndrome typically occurs when an antidepressant is stopped suddenly or tapered too quickly, leading to withdrawal-like symptoms. ❌ Why the other choices are incorrect: A) Gradual dose reduction helps prevent discontinuation syndrome. C) Switching directly can sometimes prevent withdrawal, but it depends on the drug's half-life and mechanism. D) Discontinuation syndrome occurs after at least 6 weeks of use, not just 2 weeks. **ANTIDEPRESSANT DISCONTINUATION SYNDROME** The acronym to help you notice antidepressant discontinuation syndrome * A wide array of symptoms have been described F.I.N.I.S.H. * F – Flu-like symptoms * I – Insomnia * N – Nausea * I – Imbalance (dizziness) * S – Sensory disturbances (parasthesias) * H – Hyperarousal (anxiety, irritability) * Common symptoms: insomnia, flu-like symptoms, mood disturbances, paresthesias * Other symptoms common to all antidepressant classes: fatigue, GI effects, headache, vision changes, sexual dysfunction, tachycardia **Common causes of antidepressant discontinuation syndrome** * Rapid discontinuation or dose reduction of most antidepressants may be associated with discontinuation syndrome * Any antidepressant taken for 6 weeks or more may be associated with discontinuation-related symptoms

Answer 25

Correct Answer: C) Increased appetite ✅ Explanation: Increased appetite is not a common symptom of antidepressant discontinuation syndrome. Symptoms like insomnia, flu-like symptoms, and sensory disturbances are frequently reported. ❌ Why the other choices are incorrect: A, B, and D are well-documented withdrawal symptoms.

Answer 26

Correct Answer: C) SNRIs (especially venlafaxine) ✅ Explanation: SNRIs, particularly venlafaxine, have been strongly associated with “brain zaps” due to their short half-life and strong serotonin activity. ❌ Why the other choices are incorrect: A (MAOIs): More likely to cause depression-like withdrawal. B (TCAs): Cause withdrawal symptoms but not typically brain zaps. D (NaSSAs): Mirtazapine (a NaSSA) has a lower risk of severe withdrawal. **ANTIDEPRESSANT DISCONTINUATION SYNDROME** * SNRI may be more likely to cause hyper/hypotension, syncope, diaphoresis, and stroke-like symptoms * MAOIs tend to cause depression rather than anxiety * SNRIs (especially venlafaxine) may be more likely to cause “brain zaps” than other antidepressants

Answer 27

Correct Answer: B) Discontinuation syndrome ✅ Explanation: Paroxetine has a short half-life, making it one of the highest-risk antidepressants for discontinuation symptoms if stopped abruptly. ❌ Why the other choices are incorrect: A) Weight gain is more common with long-term SSRI use, not withdrawal. C and D) Withdrawal leads to symptoms like fatigue, mood disturbances, and brain fog, not increased energy or focus.

Answer 28

Correct Answer: C) Symptoms that emerge within 1–7 days of stopping the medication ✅ Explanation: Discontinuation syndrome typically starts within 1–7 days after stopping the drug, while relapse or recurrence of depression occurs later and follows a different timeline. ❌ Why the other choices are incorrect: A) A relapse would show symptoms at their original severity, while withdrawal often includes new symptoms. B) Withdrawal symptoms usually resolve within 3 weeks, while a depressive recurrence lasts longer. D) Discontinuation syndrome often involves new symptoms (e.g., brain zaps, dizziness), not just a worsening of prior ones. **Antidepressant Discontinuation Syndrome (ADS)** 1. Risk Factors for Discontinuation Syndrome Shorter half-life drugs (e.g., paroxetine, venlafaxine) increase the risk. Patients who miss doses frequently are more likely to experience withdrawal. Long-term use of higher doses raises the likelihood of discontinuation effects. 2. Symptoms of Discontinuation Syndrome Patients experience somatic, neurologic, and psychological symptoms due to a rapid decrease in 5-HT (serotonin) within 1–7 days of stopping the drug. If untreated, symptoms typically last 3 days to 3 weeks but may persist for months.

Answer 29

Answer: C) 2 years ✅ Correct – Patients with frequent, recurrent, chronic, severe, or difficult-to-treat depression should be treated for at least 2 years to reduce the risk of relapse. ❌ A) 6 months – Too short; this is the typical duration for acute treatment, not maintenance. ❌ B) 9 months – This is the minimum duration for general maintenance therapy, but high-risk patients require longer treatment. ❌ D) Indefinitely – While some patients may require lifelong treatment, this is not the general recommendation for all cases. **RISK OF RELAPSE from antidepressants* * Maintenance antidepressant therapies should be used for a minimum of 9 months, particularly when the intervals between depressive episodes become shorter and the disability associated with each depressive episode worsens * Patients may be at risk of recurrence if they have psychiatric or other comorbidities; residual symptoms; or if episodes are frequent, recurrent, chronic, severe, or difficult to treat - In these cases, treat for at least 2 years

Answer 30

Answer: C) 50% ✅ Correct – Almost half (50%) of patients who discontinue antidepressants experience relapse or recurrence within one year. ❌ A) 10% – Underestimates the true risk. ❌ B) 20% – This is the relapse rate for patients who continue therapy, not those who discontinue. ❌ D) 80% – Overestimates the risk; while high, it is not this extreme. **RISK OF RELAPSE from antidepressants statistics** * Almost one-half of patients who stopped antidepressants experience a relapse or recurrence within one year - Risk of relapse or recurrence with ongoing therapy is around 20% * Median time to recurrence is 14 months for those who stop antidepressants compared to 48 months for those who continue

Answer 31

Answer: C) 14 months vs. 48 months ✅ Correct – Patients who stop antidepressants have a median recurrence time of 14 months, while those who continue therapy have a longer median time to recurrence of 48 months. ❌ A, B, D – These options do not reflect the correct recurrence times. **RISK OF RELAPSE from antidepressants statistics** * Almost one-half of patients who stopped antidepressants experience a relapse or recurrence within one year - Risk of relapse or recurrence with ongoing therapy is around 20% * Median time to recurrence is 14 months for those who stop antidepressants compared to 48 months for those who continue

Answer 32

Answer: C) Mild, first-time depressive episode ✅ Correct – A mild, first-time depressive episode is less likely to result in recurrence compared to other risk factors. ❌ A) Psychiatric or other comorbidities – Increase the likelihood of recurrence. ❌ B) Frequent or chronic depressive episodes – Require longer treatment to prevent relapse. ❌ D) Residual symptoms after treatment – Can indicate incomplete recovery and increase relapse risk.

Answer 33

**Answer: A) It prevents discontinuation syndrome ✅ Correct – A gradual taper helps minimize discontinuation effects such as flu-like symptoms, insomnia, mood disturbances, and sensory disturbances.** ❌ B) It prevents serotonin syndrome – Serotonin syndrome is typically caused by excessive serotonin, not withdrawal. ❌ C) It speeds up the recovery process – Tapering does not accelerate recovery; rather, it helps ease withdrawal symptoms. ❌ D) It eliminates the need for antidepressants in the future – Tapering helps with discontinuation but does not determine future need for antidepressants. **TAPERING Antidepressants** * When the goal is discontinuation of the antidepressant (scenario #1) * No formal tapering schedules have been validated * “Slower is better” is generally considered the guiding rule and tapering over longer periods (14 days or more) can reduce the risk of discontinuation effects TAPERING * Current recommendations advise antidepressant dose adjustments every 1 to 4 weeks * Go as slowly as needed to avoid discontinuation effects * This may be helped by switching to a liquid formulation, if one exists TAPERING * If the patient experiences significant discontinuation effects despite a very slow taper, it may be beneficial to switch the patient to fluoxetine, then taper the fluoxetine * Fluoxetine has a long half life and discontinuation effects are far less likely

Answer 34

Answer: B) Fluoxetine ✅ Correct – Fluoxetine has a long half-life, making it less likely to cause withdrawal symptoms, which is why it can be used to help taper off other antidepressants. ❌ A) Sertraline – Has a shorter half-life than fluoxetine and is more likely to cause withdrawal symptoms. ❌ C) Venlafaxine – Known for high risk of discontinuation syndrome. ❌ D) Moclobemide – Requires a washout period when switching to another antidepressant. **TAPERING off of antidepressants** * If the patient experiences significant discontinuation effects despite a very slow taper, it may be beneficial to switch the patient to fluoxetine, then taper the fluoxetine * Fluoxetine has a long half life and discontinuation effects are far less likely

Answer 35

Answer: B) 2 weeks ✅ Correct – A 2-week washout period is needed when switching from an irreversible MAOI (e.g., phenelzine, tranylcypromine) to an SSRI/SNRI to prevent serotonin syndrome. ❌ A) 1 week – Too short; does not allow enough time to clear the MAOI. ❌ C) 5 days – This is the washout period for moclobemide, not irreversible MAOIs. ❌ D) 6 weeks – This is required when switching from fluoxetine to an MAOI, not the other way around. **WASHOUT PERIODS of antidepressants** Washout period - is the time required for a drug to be fully eliminated from the body before starting a new medication. This is crucial when switching between certain antidepressants to prevent dangerous drug interactions—especially serotonin syndrome (a potentially fatal condition caused by excessive serotonin levels). * When switching from fluoxetine to an irreversible MAOI or moclobemide – 5 – 6 weeks * When switching from moclobemide to any SSRI/SNRI/TCA – 5 days * When switching from an irreversible MAOI to any SSRI/SNRI – 2 weeks (3 weeks if switching to clomipramine or imipramine)

Answer 36

Correct Answer: B ✅ Augmentation is used when a patient has only a partial response to the first antidepressant. 🔴 A is incorrect – If there is no response, switching the antidepressant is usually preferred rather than augmentation. 🔴 C is incorrect – If a patient cannot tolerate the first antidepressant, a different medication is chosen instead. 🔴 D is incorrect – Augmentation is generally used for moderate to severe or treatment-resistant depression, not mild cases. **Augmentation of medicine** * Recommended when a patient tolerates the first antidepressant but has only a partial response * For moderate-severe depression, or refractory depression, combination therapy should be strongly considered, particularly in individuals with a history of more than 3 previous depressive episodes

Answer 37

Correct Answer: C ✅ Antipsychotic augmentation requires close monitoring for movement disorders (e.g., tardive dyskinesia), weight gain, and metabolic issues. 🔴 A is incorrect – Antipsychotic augmentation is not recommended for long-term use due to side effects. 🔴 B is incorrect – There is some evidence of increased mortality risk in non-elderly patients using atypical antipsychotics for augmentation. 🔴 D is incorrect – Antipsychotics are used only after partial response to an antidepressant, not as first-line treatment. **AUGMENTATION** * Antipsychotic augmentation is not recommended for long- term use, and close monitoring for movement disorders, weight gain, and cardiometabolic effects is indicated * There is some evidence for increased mortality risk in non-elderly patients who receive augmentation with atypical antipsychotics * The combination of bupropion with SSRIs is also an option

Answer 38

Correct Answer: C ✅ Citalopram is an SSRI, not an augmentation agent. It is a primary antidepressant, not typically added to another antidepressant as augmentation. 🔴 A is incorrect – Aripiprazole is an atypical antipsychotic used for augmentation. 🔴 B is incorrect – Lithium is commonly used for augmentation in treatment-resistant depression. 🔴 D is incorrect – Modafinil can be used as augmentation, particularly for fatigue and cognitive symptoms.

Answer 39

Correct Answer: B ✅ Mild depression is best managed with psychotherapy (e.g., CBT, interpersonal therapy) before considering medication. 🔴 A is incorrect – Antidepressants can be used in pregnancy when benefits outweigh risks, especially for moderate to severe depression. 🔴 C is incorrect – SSRIs are NOT major teratogens but may have some risks, such as persistent pulmonary hypertension of the newborn (PPHN). 🔴 D is incorrect – Not all pregnant patients need antidepressants; treatment depends on severity and risk-benefit analysis.

Answer 40

Correct Answer: B ✅ Untreated depression during pregnancy is linked to postpartum depression, suicide risk, and negative effects on the baby. 🔴 A is incorrect – Depression can persist or worsen postpartum without treatment. 🔴 C is incorrect – Antidepressants are not always stopped; the decision is based on risk vs. benefit. 🔴 D is incorrect – Suicide risk can increase if antidepressants are stopped abruptly in patients with severe depression.

Answer 41

Correct Answer: B ✅ Fluoxetine and paroxetine have been associated with higher risks, such as persistent pulmonary hypertension of the newborn (PPHN) and poor neonatal adaptation syndrome. 🔴 A is incorrect – Sertraline and escitalopram are generally preferred due to lower risks. 🔴 C is incorrect – Bupropion and mirtazapine have less evidence of harm but are not first-line choices. 🔴 D is incorrect – Venlafaxine and duloxetine are SNRIs with some risk, but not as high as fluoxetine and paroxetine.

Answer 42

Correct Answer: C ✅ Poor neonatal adaptation syndrome (PNAS) includes tremors, irritability, increased muscle tone, sleep disturbances, and respiratory distress but is typically transient. 🔴 A is incorrect – While some studies suggest an association between antidepressant exposure and autism, the evidence is not strong enough to confirm causation. 🔴 B is incorrect – Congenital heart defects are not a universal risk, although paroxetine may slightly increase risk. 🔴 D is incorrect – There is no established link between in utero antidepressant exposure and schizophrenia. ========================== **RISKS OF ANTIDEPRESSANTS DURING PREGNANCY** * Poor neonatal adaptation syndrome is typically transient neonatal withdrawal and/or toxicity after exposure to antidepressants in utero * Signs and symptoms include tremors, shaking, irritability, increased muscle tone, sleeping disturbances and respiratory distress * Incidence is highly variable in studies, but likely to be around 30%

Answer 43

**Correct Answer: B ✅ The Canadian Paediatric Society (2021) concluded that the risk of serious adverse effects from SSRIs/SNRIs in pregnancy is low.** 🔴 A is incorrect – SSRIs and SNRIs can be used when needed. 🔴 C is incorrect – SSRIs are NOT major teratogens. 🔴 D is incorrect – Untreated depression also poses risks, so medication is sometimes necessary.

Answer 44

**B) Close monitoring for movement disorders, weight gain, and cardiometabolic effects is necessary. ✅ → Correct. Atypical antipsychotics can cause tardive dyskinesia (a movement disorder), metabolic syndrome (weight gain, increased blood sugar, and cholesterol changes), and cardiovascular effects. These risks require close monitoring. ** A) Atypical antipsychotics should only be used long-term without close monitoring. ❌ → Incorrect. Long-term use of atypical antipsychotics without monitoring can lead to serious side effects like tardive dyskinesia, weight gain, and cardiometabolic issues. C) Augmentation with atypical antipsychotics is recommended for all patients. ❌ → Incorrect. Not all patients benefit from atypical antipsychotic augmentation. It is typically considered only when other treatments have not worked. D) Atypical antipsychotics should never be used for augmentation. ❌ → Incorrect. While long-term use is not always recommended, augmentation with atypical antipsychotics can be helpful in certain cases when used carefully.

Answer 45

**C) To enhance the effect of fluoxetine in treating depression. ✅ → Correct. Augmentation with risperidone can help boost the effects of fluoxetine in cases where the antidepressant alone is not providing enough symptom relief.** A) To reduce fluoxetine dose to avoid side effects. ❌ → Incorrect. The goal is not to reduce fluoxetine but to enhance its effect in treatment-resistant depression. B) To help manage symptoms of anxiety. ❌ → Incorrect. While risperidone may have some effects on anxiety, its primary role here is to enhance antidepressant efficacy rather than directly treat anxiety. D) To address potential sleep disturbances caused by fluoxetine. ❌ → Incorrect. Risperidone is not primarily used to address fluoxetine-induced sleep disturbances. Other medications (e.g., trazodone) are more commonly used for that purpose.

Answer 46

**B) Citalopram, escitalopram, and sertraline. ✅ → Correct. These SSRIs have the best safety profiles for use during pregnancy and are considered first-line options.** A) Paroxetine and fluoxetine. ❌ → Incorrect. Paroxetine has been linked to congenital malformations, and fluoxetine has a more controversial safety profile, making them second-line choices. C) Mirtazapine and duloxetine. ❌ → Incorrect. While these medications can be used during pregnancy, they are not first-line choices. D) Desvenlafaxine and venlafaxine. ❌ → Incorrect. These SNRIs are considered second-line choices due to potential risks to fetal development.

Answer 47

** B) Fluoxetine. ✅ → Correct. Fluoxetine has a more controversial safety profile and has been associated with possible major malformations, although evidence is mixed** A) Sertraline. ❌ → Incorrect. Sertraline is one of the safer options during pregnancy. tions, although evidence is mixed. C) Escitalopram. ❌ → Incorrect. Escitalopram is a first-line choice and has a lower risk profile compared to fluoxetine. D) Citalopram. ❌ → Incorrect. Citalopram is also a first-line choice with lower risk compared to fluoxetine and paroxetine. **PHARMACOLOGIC CHOICES DURING PREGNANCY** * If pharmacologic therapy is indicated, citalopram, escitalopram, and sertraline are first-line options * Fluoxetine is a second-line option since its association with major malformations is more controversial * Paroxetine has been associated with risk for major malformations, and although the clinical magnitude is questionable, it is still not recommended for perinatal depression, unless the patient was stable on it prior to conception **Second-line options in the treatment of perinatal depression** - include bupropion, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, TCAs (e.g., amitriptyline, imipramine and nortriptyline) and venlafaxine **Why Are Citalopram, Escitalopram, and Sertraline First-Line Options During Pregnancy?** These SSRIs (Selective Serotonin Reuptake Inhibitors) are considered first-line options for perinatal depression due to their favorable safety profiles for both the parent and the fetus. Here’s why: 1. Lower Risk of Major Malformations Unlike paroxetine and fluoxetine, which have been associated with higher risks of congenital malformations, citalopram, escitalopram, and sertraline have lower teratogenic risk. While no antidepressant is completely risk-free, these three have the most consistent evidence of safety. 2. Fewer Neonatal Complications Late-pregnancy SSRI use can be linked to neonatal adaptation syndrome (jitteriness, respiratory distress, feeding issues), but sertraline, escitalopram, and citalopram are less likely to cause severe symptoms compared to fluoxetine. Paroxetine and fluoxetine have longer half-lives, meaning they stay in the baby’s system longer, increasing the risk of withdrawal-like symptoms in the newborn. 3. Lower Risk of Persistent Pulmonary Hypertension of the Newborn (PPHN) Late-pregnancy exposure to SSRIs has been associated with PPHN, but the risk is relatively lower with citalopram, escitalopram, and sertraline compared to other SSRIs. 4. Efficacy in Treating Depression These medications are proven to be effective in treating moderate to severe depression, which is critical because untreated depression itself poses serious risks (preterm birth, low birth weight, and postpartum depression). They are well-tolerated by most patients, making them a good option when medication is necessary. 5. Better Suitability for Breastfeeding Sertraline has the lowest breast milk transfer rate, making it the preferred SSRI for breastfeeding mothers. Escitalopram and citalopram also have acceptable safety profiles for breastfeeding, unlike fluoxetine, which has a long half-life and accumulates in breast milk. Bottom Line Citalopram, escitalopram, and sertraline are first-line because they balance effectiveness with the lowest risk of birth defects and neonatal complications. Paroxetine and fluoxetine are second-line due to their higher risks of congenital malformations and withdrawal symptoms in newborns. If medication is needed during pregnancy, these first-line SSRIs are the safest options available.

Answer 48

**B) Monitoring and supportive care, as the condition is self-limiting. ✅ → Correct. Postpartum blues are very common (up to 80%) and do not require medication, just monitoring and support.** A) Immediate pharmacological intervention. ❌ → Incorrect. Postpartum blues are self-limiting and do not typically require medication. C) Referral to psychiatric care for urgent medication. ❌ → Incorrect. Postpartum major depression may need urgent psychiatric care, but postpartum blues do not. D) Hospitalization for observation. ❌ → Incorrect. This is unnecessary for postpartum blues unless symptoms worsen significantly. **POSTPARTUM MOOD DISTURBANCES** * Postpartum mood disturbances is a term that encompasses the following 3 presentations: - postpartum “blues,” which affect up to 80% of patients after a pregnancy - postpartum major depression, which occurs in up to 16% of patients in Canada after a pregnancy - postpartum psychosis, which occurs in ≤0.1% * The blues are not a disorder per se, given that they are so common and symptoms are self-limiting, requiring only monitoring and supportive care. However, patients with postpartum blues are at risk of developing a depressive episode.

Answer 49

**B) Untreated depression may lead to negative effects on the fetus, patient, and others. ✅ → Correct. Depression during pregnancy can increase the risk of preterm birth, low birth weight, and postpartum depression, affecting both the mother and baby.** A) It has no impact on the fetus or neonate. ❌ → Incorrect. Untreated depression does affect fetal development and increases risks for complications. C) Untreated depression is only a risk for the pregnant individual, not the fetus. ❌ → Incorrect. The fetus can also be affected, leading to developmental issues and other complications. D) There are no associated risks with untreated depression during pregnancy. ❌ → Incorrect. Studies show clear risks of untreated depression for both the parent and the baby.

Answer 50

**B) Untreated depression may lead to negative effects on the fetus, patient, and others. ✅ → Correct. Depression during pregnancy can increase the risk of preterm birth, low birth weight, and postpartum depression, affecting both the mother and baby.** A) It has no impact on the fetus or neonate→ Incorrect. Untreated depression does affect fetal development and increases risks for complications. C) Untreated depression is only a risk for the pregnant individual, not the fetus. ❌ → Incorrect. The fetus can also be affected, leading to developmental issues and other complications. D) There are no associated risks with untreated depression during pregnancy. ❌ → Incorrect. Studies show clear risks of untreated depression for both the parent and the baby.

Answer 51

Drugs That Cause Tardive Dyskinesia (TD) Tardive dyskinesia (TD) is a movement disorder characterized by involuntary, repetitive movements, often affecting the face, tongue, and limbs. It is primarily caused by long-term use of dopamine-blocking drugs, especially antipsychotics and some other medications. 1. Antipsychotics (Major Cause) These drugs block dopamine D2 receptors in the brain, leading to dopamine hypersensitivity, which is believed to cause TD over time. First-Generation (Typical) Antipsychotics – Higher Risk Haloperidol (Haldol) Fluphenazine Chlorpromazine Perphenazine Thioridazine Trifluoperazine Loxapine 🔹 Why? These drugs strongly block dopamine (D2) receptors, leading to long-term changes in the basal ganglia, which control movement. TD risk is higher with long-term use and high doses. Second-Generation (Atypical) Antipsychotics – Lower Risk, but Still Possible Risperidone (Risperdal) Olanzapine (Zyprexa) Quetiapine (Seroquel) Aripiprazole (Abilify) Brexpiprazole (Rexulti) Cariprazine (Vraylar) Ziprasidone (Geodon) 🔹 Why? Atypical antipsychotics still block dopamine, but they also affect serotonin receptors, which may reduce the risk of TD. However, risperidone and olanzapine are still associated with TD, especially at higher doses or long-term use. 2. Other Dopamine-Blocking Drugs That Can Cause TD TD isn’t just caused by antipsychotics! Other medications that block dopamine can also lead to TD: Anti-Nausea & Gastrointestinal Drugs (Dopamine Antagonists) Metoclopramide (Reglan) Prochlorperazine (Compazine) Promethazine (Phenergan) Domperidone (Motilium) 🔹 Why? These drugs block dopamine in the gut to reduce nausea but also affect dopamine in the brain, leading to TD with long-term use. Other Medications Lithium (used for bipolar disorder) – Can increase susceptibility to TD. Antidepressants (Rarely) – Some SSRIs (fluoxetine, sertraline) and tricyclic antidepressants (TCAs) have been linked to TD, but the risk is much lower than with antipsychotics. Stimulants (Rarely) – Drugs like amphetamine and methylphenidate may trigger TD-like movements, though true TD from stimulants is rare. Key Takeaways First-generation (typical) antipsychotics = Highest risk (e.g., haloperidol, fluphenazine). Second-generation (atypical) antipsychotics = Lower risk but still possible (e.g., risperidone, olanzapine). GI/nausea drugs like metoclopramide = Can also cause TD, even though they aren’t antipsychotics. Long-term use is the biggest risk factor.

Answer 52

**✅ Correct Answer: B) It has additional anti-suicidal properties and may reduce dementia risk ➡️ Explanation: Lithium is a 1st line treatment for manic episodes and it #1 in its class due to its unique anti-suicidal effects and may have neuroprotective properties.** ❌ Incorrect Answers: (A) Other mood stabilizers (e.g., divalproex) and antipsychotics are also effective. (C) Lithium can cause kidney and thyroid issues, so it is not necessarily the drug with the fewest side effects. (D) Lithium requires careful dosing and blood monitoring, making titration essential.

Answer 53

✅ Correct Answer: C) Increased appetite and weight gain ➡️ Explanation: While lithium can cause weight gain over time, it is not a sign of acute toxicity. ❌ Incorrect Answers: (A) Ataxia and tremor occur in mild lithium toxicity. (B) Confusion and tachycardia occur in moderate lithium toxicity. (D) Coma and seizures occur in severe lithium toxicity. =================================== **LITHIUM blood levels** * While high blood lithium level produces more response, it involves more risk * Consider moderate blood levels (0.8–1.0 mmol/L) and add other anti-manic agents if necessary * Because of overall value, consider lithium first, particularly in younger adults LITHIUM TOXICITY * Inform patients of signs and symptoms of toxicity such as ataxia, tremor, sedation or agitation, diarrhea, vomiting * Mild symptoms: nausea, vomiting, lethargy, tremor, and fatigue (Serum lithium concentration between 1.5-2.5 mmol/L) * Moderate intoxication: confusion, agitation, delirium, tachycardia, and hypertonia (serum lithium concentration between 2.5-3.5 mmol/L) * Severe intoxication: Coma, seizures, hyperthermia, and hypotension (serum lithium concentration (more than 3.5 mmol/L)

Answer 54

✅ Correct Answer: B) Divalproex ➡️ Explanation: Divalproex (valproate) is highly teratogenic, increasing the risk of neural tube defects and cognitive impairment in the fetus. ❌ Incorrect Answers: (A) Quetiapine does not have significant teratogenic effects. (C) Aripiprazole has a more favorable pregnancy safety profile. (D) Risperidone has some risks but is not as concerning as divalproex. MANIC EPISODES * Medication selection must balance the side effect profile with key clinical characteristics, particularly prior response and patient preferences. * Additionally, some safety considerations differ by medication: - Divalproex: caution in patients of reproductive age due to effects on menstrual irregularities and teratogenicity during pregnancy - Carbamazepine: caution due to drug-drug interactions and induction of Stevens-Johnson syndrome - Antipsychotics: caution due to adverse effects on metabolic parameters (some antipsychotics can cause weight gain & obesity, Insulin resistance & Type 2 Diabetes, Dyslipidemia and Hypertension) Which Antipsychotics Have the Highest Risk? 🔴 High Risk: Olanzapine, Clozapine, Quetiapine 🟡 Moderate Risk: Risperidone, Paliperidone 🟢 Low Risk: Aripiprazole, Lurasidone, Ziprasidone

Answer 55

✅ Correct Answer: C) Carbamazepine ➡️ Explanation: Carbamazepine is NOT a first-line option because of drug interactions and the risk of Stevens-Johnson Syndrome. ❌ Incorrect Answers: **FIRST-LINE OPTIONS In order of preference for Bipolar Manic Episode** * Lithium - Quetiapine - Divalproex - Aripiprazole - Risperidone

Answer 56

**✅ Correct Answer: B) They raise lithium levels, increasing the risk of toxicity ➡️ Explanation: These medications reduce lithium clearance, leading to toxic levels.** ❌ Incorrect Answers: (A) These drugs do not increase lithium clearance—they reduce it. (C) They do have interactions with lithium. (D) They do not make lithium work faster; they make it more dangerous. LITHIUM TOXICITY * Toxic levels may result when adding NSAIDs, ACEIs, ARBs and especially thiazide diuretics. * Avoid large changes in salt or coffee intake 1️⃣ NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) 🔺 Examples: Ibuprofen, Naproxen, Diclofenac ✅ Effect: Increase lithium levels 🛑 Why? NSAIDs reduce blood flow to the kidneys, which decreases lithium clearance, causing toxic buildup. 🔹 Exception: Aspirin and sulindac have minimal effect on lithium. 2️⃣ ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors) 🔺 Examples: Lisinopril, Enalapril, Ramipril ✅ Effect: Increase lithium levels 🛑 Why? ACEIs dilate blood vessels and reduce sodium levels, leading the kidneys to reabsorb more lithium instead of excreting it. 3️⃣ ARBs (Angiotensin II Receptor Blockers) 🔺 Examples: Losartan, Valsartan, Candesartan ✅ Effect: Increase lithium levels (but usually less than ACEIs) 🛑 Why? ARBs reduce sodium reabsorption, similar to ACEIs, causing lithium retention. 4️⃣ Thiazide Diuretics (Water Pills) 🔺🔺🔺 Examples: Hydrochlorothiazide (HCTZ), Chlorthalidone ✅ Effect: Significantly increase lithium levels (high risk!) 🛑 Why? Thiazides decrease sodium levels, and since the kidneys treat sodium and lithium similarly, the body compensates by holding onto more lithium → leading to toxicity. Why Does Salt & Coffee Matter? Salt Intake: If you suddenly reduce sodium intake, the kidneys retain more lithium, increasing toxicity risk. If you suddenly increase sodium, lithium levels drop, reducing effectiveness. Coffee (Caffeine): Increases lithium excretion (caffeine is a diuretic). If you suddenly stop drinking coffee, lithium levels can spike, leading to toxicity. 🔴 Key Takeaways AVOID NSAIDs, ACEIs, ARBs, and thiazide diuretics if possible while on lithium. Monitor lithium levels closely if these drugs must be used. Maintain a stable salt and caffeine intake to prevent dangerous fluctuations. 1️⃣ Lithium & Sodium Are Handled Similarly in the Kidneys The kidneys filter out both sodium and lithium in a similar way. When sodium levels are low, the kidneys try to hold onto sodium to prevent dehydration. Because lithium is chemically similar to sodium, the kidneys reabsorb more lithium too → higher lithium levels = risk of toxicity. When sodium levels are high, the kidneys excrete excess sodium, and lithium gets excreted along with it → lower lithium levels = risk of subtherapeutic effect.

Answer 57

Correct Answer: B) Quetiapine ✅ Explanation: Quetiapine is the preferred first-line option for bipolar depression because it has strong evidence for efficacy and works well both for acute episodes and long-term management. ❌ A) Incorrect: Lurasidone is a first-line option, but quetiapine is preferred due to stronger evidence of effectiveness. ❌ C) Incorrect: Lithium is effective, but it is not always the first choice for depression (better for mood stabilization overall). ❌ D) Incorrect: Divalproex is mainly used for mania, not bipolar depression. FIRST LINE OPTIONS * In order of preference 1. Quetiapine 2. Lithium or divalproex PLUS lurasidone 3. Lithium 4. Lamotrigine 5. Lurasidone

Answer 58

Correct Answer: A) Lamotrigine ✅ Explanation: Lamotrigine is a first-line option for bipolar depression, particularly because it has a good safety profile and is well-tolerated. However, it takes time to reach therapeutic levels. ❌ B) Incorrect: Fluoxetine (an SSRI) is not recommended as monotherapy because antidepressants can induce mania in bipolar disorder. ❌ C) Incorrect: Olanzapine is not a first-line option for bipolar depression (it is more often used for mania). ❌ D) Incorrect: Carbamazepine is used for mania, not depressive episodes. **Medication for Bipolar DEPRESSIVE EPISODES** * In an unmedicated patient, therapy may begin with any of the first-line treatments: lithium, lamotrigine, lurasidone, or quetiapine as monotherapies * Lamotrigine is the best tolerated option, although it may take the longest to work and may be slightly less efficacious FIRST LINE OPTIONS * In order of preference 1. Quetiapine 2. Lithium or divalproex PLUS lurasidone 3. Lithium 4. Lamotrigine 5. Lurasidone n bipolar depression why would an SSRI cause mania, I understand that SSRI are first line options for depression so I am a bit confused ChatGPT said: Great question! SSRIs (selective serotonin reuptake inhibitors) are first-line options for unipolar depression (i.e., major depressive disorder), but not for bipolar depression. The reason is that SSRIs can trigger mania in people with bipolar disorder. Here's why: **How SSRIs Can Induce Mania in Bipolar Disorder Increased Serotonin Activity:** SSRIs boost serotonin levels, which can improve mood in depression. However, in bipolar disorder, this sudden increase in serotonin can destabilize mood regulation, potentially shifting the patient into mania. Disrupting Mood Stability: Bipolar disorder is characterized by mood dysregulation (oscillating between depression and mania). SSRIs can push someone too far in the opposite direction, causing excessive energy, impulsivity, and euphoria—hallmarks of a manic episode. Lack of Mood Stabilization: In unipolar depression, SSRIs are used alone to lift mood. In bipolar disorder, a mood stabilizer (like lithium or lamotrigine) is needed to balance mood. Giving an SSRI without a mood stabilizer can push the patient into mania or rapid cycling (frequent shifts between depression and mania). Dopamine Involvement: While SSRIs mainly affect serotonin, they also influence dopamine. Increased dopamine activity can contribute to elevated mood, impulsivity, and psychotic symptoms, making mania more likely. When Are SSRIs Used in Bipolar Disorder? They are NOT first-line for bipolar depression. If an antidepressant is used, it must be combined with a mood stabilizer (e.g., lithium or quetiapine) to prevent mania. Some SSRIs (e.g., fluoxetine) are cautiously used with mood stabilizers, but many psychiatrists avoid them due to the risk of switching to mania. Key Takeaway: SSRIs work well for unipolar depression, but in bipolar disorder, they can destabilize mood and cause mania unless carefully managed with a mood stabilizer. That's why mood stabilizers and certain atypical antipsychotics (e.g., quetiapine, lurasidone, lithium, lamotrigine) are first-line treatments for bipolar depression instead.

Answer 59

**Correct Answer: B) 70% chance of another episode within 1 year ✅ Explanation: Without pharmacologic treatment, about 70% of patients relapse within a year, and 95% within five years.** ❌ A) Incorrect: The actual risk is higher than 50%. ❌ C) Incorrect: The 5-year recurrence rate is much higher (95%), not 30%. ❌ D) Incorrect: Bipolar disorder is recurrent, and most untreated patients will relapse.

Answer 60

**Correct Answer: B) Treat bipolar disorder first, then manage ADHD ✅ Explanation: Bipolar disorder is prioritized first because stimulants (used for ADHD) can worsen manic symptoms if bipolar disorder is unstable. Once bipolar symptoms are controlled, ADHD can be treated.** ❌ A) Incorrect: Treating ADHD first may worsen bipolar symptoms. ❌ C) Incorrect: Stimulants should not be used until bipolar disorder is stable. ❌ D) Incorrect: Medications are often necessary for both conditions.

Answer 61

Correct Answer: B) Lurasidone ✅ Explanation: Lurasidone has modest evidence for first-line use in pediatric bipolar depression. ❌ A) Incorrect: Quetiapine is used for mania, not as a first-line for pediatric depression. ❌ C) Incorrect: Lithium is a second-line option for pediatric depression. ❌ D) Incorrect: Lamotrigine is also second-line for pediatric depression. **TREATMENT OPTIONS for Bipolar Depression episode** * For treating mania, first-line recommendations include lithium, risperidone, aripiprazole, asenapine, and quetiapine * For pediatric bipolar depression, modest evidence supports a first-line recommendation of lurasidone, and second-line treatments include lithium and lamotrigine

Answer 62

Correct Answer: B) Cognitive dysfunction ✅ Explanation: Cognitive impairment is common in elderly bipolar patients and needs regular monitoring. ❌ A) Incorrect: Bipolar disorder does not typically become rapid-cycling in old age. ❌ C) Incorrect: Treatment resistance is not specifically unique to elderly patients. ❌ D) Incorrect: Elderly bipolar patients typically experience cognitive issues, not increased energy. *BIPOLAR DISORDER IN THE ELDERLY** * When bipolar disorder begins early in life, it is a lifelong illness that, if untreated, continues to manifest with more frequent episodes and shorter periods of recovery over the decades * It does not typically progress to an extremely rapid-cycling form * Cognitive dysfunction is a significant feature for many elderly bipolar individuals and needs regular assessment and management

Answer 63

Correct Answer: A) Lithium or divalproex ✅ Explanation: Lithium and divalproex are first-line options for elderly patients with mania, as they are well-studied and effective. ❌ B) Incorrect: Quetiapine is second-line, and carbamazepine has many drug interactions. ❌ C) Incorrect: Antidepressants (fluoxetine/sertraline) can worsen mania. ❌ D) Incorrect: Lamotrigine is not for mania, and lurasidone is for depression. **BIPOLAR DISORDER IN THE ELDERLY** * For mania, first-line treatments include lithium or divalproex, with quetiapine recommended as the only second-line agent * For bipolar depression in older individuals, options include lurasidone and quetiapine initially, with lithium and lamotrigine as the second-line recommendations

Answer 64

**Correct Answer: A) Increased risk of postpartum depression and psychosis ✅ Explanation: Untreated bipolar disorder significantly increases the risk of postpartum depression and even postpartum psychosis, which can harm both the mother and baby.** ❌ B) Incorrect: Bipolar disorder does not stabilize on its own in pregnancy. ❌ C) Incorrect: The primary concern is postpartum relapse, not congenital defects. ❌ D) Incorrect: Many patients still need medication during pregnancy.

Neuropsychiatric Pharmaceuticals 3rd year 2nd semester Flashcards

(88 cards)