Neuropsychiatric Pharmaceuticals 3rd year 2nd semester Flashcards
What is the approximate lifetime prevalence of anxiety disorders in the general population?
A) 10%
B) 24%
C) 31%
D) 40%
Correct Answer: C) 31%
Explanation: Anxiety disorders are among the most common psychiatric illnesses, with a lifetime prevalence of 31%. While 24% of Canadians report experiencing an anxiety disorder, the global prevalence is slightly higher.
Which of the following is NOT a primary goal of therapy for anxiety disorders?
A) Complete remission of symptoms
B) Prevention of recurrence
C) Elimination of all sources of stress
D) Improvement of functional recovery
Correct Answer: C) Elimination of all sources of stress
Explanation: The goals of therapy include symptom reduction, functional recovery, and relapse prevention. However, eliminating all sources of stress is unrealistic and not a goal of therapy. Stress management techniques can help but do not eliminate stress entirely.
**GOALS OF THERAPY** * Eliminate or reduce symptomatic anxiety * Eliminate or reduce anxiety-based disability * Facilitate complete remission of symptoms and functional recovery * Prevent recurrences Treat comorbid conditions
Which of the following best describes Generalized Anxiety Disorder (GAD)?
A) Recurrent, unexpected panic attacks with persistent worry about recurrence
B) Excessive worry and anxiety about various events for at least 6 months
C) Severe anxiety triggered by a specific object or situation
D) Anxiety caused by a medical condition or substance use
Correct Answer: B) Excessive worry and anxiety about various events for at least 6 months
Explanation: GAD is characterized by excessive worry and anxiety about multiple aspects of life for 6 months or more. Panic disorder involves recurrent panic attacks, specific phobias involve triggers like heights or spiders, and substance-induced anxiety results from drugs or medical conditions.
Which statement about panic disorder is TRUE?
A) Panic disorder has a lifetime prevalence of approximately 10%
B) All SSRIs have demonstrated efficacy in treating panic disorder
C) SSRIs are ineffective for panic disorder with agoraphobia
D) Venlafaxine is ineffective in panic disorder
Correct Answer: B) All SSRIs have demonstrated efficacy in treating panic disorder
Explanation: SSRIs are effective in treating panic disorder with or without agoraphobia. The lifetime prevalence of panic disorder is 4.7–5.1%, not 10%. Venlafaxine (an SNRI) is also effective.
Why should antidepressants be tapered gradually when discontinuing treatment for anxiety?
A) To reduce the risk of withdrawal symptoms and symptom relapse
B) To allow the body to adjust to a lack of medication before switching to benzodiazepines
C) To prevent worsening of psychotic symptoms
D) To increase the effectiveness of the next antidepressant
Correct Answer: A) To reduce the risk of withdrawal symptoms and symptom relapse
Correct Answer: A) To reduce the risk of withdrawal symptoms and symptom relapse
Why is gradual tapering necessary?
Prevents Withdrawal Symptoms – Stopping antidepressants suddenly can cause discontinuation syndrome, leading to:
Dizziness, nausea, headaches
Irritability, mood swings
“Brain zaps” (electric shock-like sensations)
Sleep disturbances
Flu-like symptoms
Reduces Risk of Relapse – Abrupt discontinuation can lead to a return of anxiety or depression symptoms, sometimes worse than before.
Allows the Brain to Adjust – SSRIs and SNRIs alter serotonin levels over time, so stopping too quickly can cause neurochemical imbalances. Tapering helps the brain gradually return to normal neurotransmitter function.
Certain Medications Have Higher Risks – Paroxetine (SSRI) and Venlafaxine (SNRI) have short half-lives, meaning they leave the body quickly and have a higher risk of withdrawal symptoms. Longer half-life drugs, like fluoxetine, naturally taper themselves more slowly.
General tapering strategy:
Reduce dose gradually over several months
Monitor for withdrawal symptoms
If withdrawal occurs, slow down the taper or temporarily increase the dose before resuming a slower taper
Explanation: Sudden discontinuation of antidepressants can cause withdrawal symptoms (e.g., dizziness, nausea, irritability) and anxiety relapse. Tapering over several months minimizes these effects.
GENERAL APPROACH to tapering off of psychiatric medications
* Most patients suffering from anxiety disorders must continue pharmacotherapy for at least 12–24 months to achieve functional remission and prevent relapses
* When discontinuation of treatment is considered, tapering of the antidepressant should be done gradually over several months
* Sudden dose reduction or discontinuation of the medication may result in withdrawal syndrome and an increase in anxiety symptoms
Why are TCAs not first-line for Panic Disorder?
Why are Tricyclic Antidepressants (TCAs) considered second-line for panic disorder despite their efficacy?
A) They have a higher risk of serious side effects compared to SSRIs
B) They are not as effective as SSRIs in treating panic disorder
C) They require longer treatment duration than SSRIs
D) They have fewer drug interactions than SSRIs
Correct Answer: (A) Correct → TCAs have efficacy but are second-line due to side effects (e.g., cardiac toxicity, anticholinergic effects, overdose risk).
💡 Explanation:
(B) Incorrect → TCAs are equally effective as SSRIs but less tolerable.
(C) Incorrect → Duration of treatment is similar for SSRIs and TCAs.
(D) Incorrect → TCAs actually have more drug interactions than SSRIs.
Panic Disorder DRUG OPTIONS - TCA
* There is clinical evidence supporting the use of TCAs, including imipramine and clomipramine, in the treatment of panic disorder
* Despite having efficacy similar to SSRIs, TCAs remain second-line agents because of their significant adverse effects profile and the risk of toxicity in overdose
Why are benzodiazepines not recommended for long-term treatment of panic disorder?
A) They are ineffective for panic disorder symptoms
B) They have a high risk of dependence, withdrawal, and cognitive impairment
C) They cause hypertensive crisis if combined with certain foods
D) They take longer to work compared to SSRIs and SNRIs
Correct Answer: (B) Correct → They are associated with dependence, withdrawal symptoms, and CNS side effects.
💡 Explanation:
(A) Incorrect → Benzodiazepines are effective but are not first-line due to safety concerns.
(C) Incorrect → Hypertensive crisis is a concern with MAOIs, not benzodiazepines.
(D) Incorrect → Benzodiazepines work faster than SSRIs but should still be avoided long-term.
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DRUG OPTIONS -
BENZODIAZEPINES
* Benzodiazepines are also a second-line option in the treatment of panic disorder, and alprazolam, clonazepam, lorazepam, and diazepam have been studied for this indication
- These drugs are associated with a risk of abuse, dependence, withdrawal syndrome, falls, and CNS adverse effects, and are generally not used for long-term treatment of panic disorder
- Their use is mainly limited to the first few weeks of treatment when rapid relief of anxiety or panic attacks is necessary or to reduce the exacerbation of anxiety and agitation that may be present at the beginning of antidepressant treatment
- Clonazepam and lorazepam are generally the preferred agents, and while alprazolam and diazepam have a faster onset of action, they present a greater risk of abuse.
- In addition, with its short elimination half-life, alprazolam is associated with increased anxiety between doses and a greater withdrawal syndrome
Which of the following is a reason why MAOIs, such as phenelzine, are rarely used in the treatment of panic disorder?
A) They have a high potential for abuse and dependence
B) They require dietary restrictions to avoid hypertensive crises
C) They have no proven efficacy in panic disorder
D) They are considered first-line treatment for panic disorder
B) Correct – MAOIs require dietary restrictions (avoidance of tyramine-rich foods) to prevent hypertensive crises.
Explanation:
A) Incorrect – MAOIs are not known for high abuse potential like benzodiazepines.
C) Incorrect – Phenelzine has shown efficacy in studies but is rarely used due to adverse effects.
D) Incorrect – Phenelzine is a third-line option, not a first-line treatment for panic disorder.
High Tyramine Food
* Artisan cheeses, which are made by hand, or aged cheeses
* Cured meats
* Smoked or processed meats
* Pickled or fermented foods
* Fermented sauces
* Soybean products
- Snow peas and broad beans
(aka fava beans) - Dried or overripe fruits
- Meat tenderizers
- Yeast-extract spreads
- Alcoholic beverages
- Caffeinated beverages
- Foods that have not been
properly stored or are spoiled
Which of the following foods should be avoided when taking MAOIs due to the risk of hypertensive crisis?
A) Aged cheeses and cured meats
B) Fresh vegetables and white rice
C) Grilled chicken and plain yogurt
D) Herbal teas and lean fish
High Tyramine Food
* Artisan cheeses, which are made by hand, or aged cheeses
* Cured meats
* Smoked or processed meats
* Pickled or fermented foods
* Fermented sauces
* Soybean products
- Snow peas and broad beans
(aka fava beans) - Dried or overripe fruits
- Meat tenderizers
- Yeast-extract spreads
- Alcoholic beverages
- Caffeinated beverages
- Foods that have not been
properly stored or are spoiled
A) Correct – Aged cheeses and cured meats are high in tyramine and can cause hypertensive crises.
Explanation:
B) Incorrect – Fresh vegetables and white rice are not high in tyramine.
C) Incorrect – Grilled chicken and plain yogurt do not contain significant tyramine levels.
D) Incorrect – Herbal teas and lean fish do not pose a risk for hypertensive crises.
Which of the following drugs is NOT recommended for panic disorder due to a lack of evidence?
A) Mirtazapine
B) Imipramine
C) Clonazepam
D) Venlafaxine
A) Correct – Mirtazapine has not shown sufficient evidence to be recommended for panic disorder.
Explanation:
B) Incorrect – Imipramine (a TCA) is a second-line treatment for panic disorder.
C) Incorrect – Clonazepam (a benzodiazepine) is a second-line treatment for panic disorder.
D) Incorrect – Venlafaxine (an SNRI) is a first-line treatment for panic disorder.
NOT DRUG OPTIONS for Panic Disorder
* Given the lack of evidence, mirtazapine and moclobemide cannot be recommended in the treatment of panic disorder
* Buspirone, trazodone, and propranolol are deemed ineffective for this indication
Which of the following medications is a third-line treatment for panic disorder?
A) Phenelzine
B) Sertraline
C) Clonazepam
D) Escitalopram
Explanation:
A) Correct – Phenelzine (an MAOI) is a third-line option due to its side effect profile and dietary restrictions.
B) Incorrect – Sertraline is a first-line SSRI.
C) Incorrect – Clonazepam is a second-line benzodiazepine.
D) Incorrect – Escitalopram is a first-line SSRI.
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FIRST LINE OPTIONS
* Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
* Venlafaxine
SECOND LINE OPTIONS
* Imipramine, clomipramine
* Alprazolam, clonazepam, lorazepam, diazepam
THIRD LINE OPTIONS
* Phenelzine
* Desipramine
Which of the following statements about social anxiety disorder (SAD) is FALSE?
A) It is the most common anxiety disorder
B) It often becomes noticeable during adolescence
C) SSRIs and SNRIs are first-line treatments
D) Benzodiazepines are considered first-line treatment
D) Incorrect – Benzodiazepines are not first-line; they are sometimes used but carry a risk of dependence.
Explanation:
A) Correct – SAD is the most common anxiety disorder.
B) Correct – SAD often emerges during adolescence.
C) Correct – SSRIs and SNRIs are first-line treatments for SAD.
Social Anxiety Disorder
* The most common anxiety disorder with a lifetime prevalence of 8-12%.
* May be present from childhood but often becomes noticeable in adolescence
* Characterized by avoidance of social contact or difficulty dealing with authority figures
Which of the following medications is considered a second-line treatment for social anxiety disorder?
A) Sertraline
B) Pregabalin
C) Venlafaxine
D) Fluoxetine
B) Correct – Pregabalin is a second-line option, effective at high doses but with increased risk of side effects.
Explanation:
A) Incorrect – Sertraline is a first-line SSRI.
C) Incorrect – Venlafaxine is a first-line SNRI.
D) Incorrect – Fluoxetine is not commonly used for social anxiety disorder.
Social Anxiety 1st line DRUG OPTIONS – SSRI/SNRI
* SSRIs and SNRIs are the treatment of choice for social anxiety disorder
* These agents are also effective for social anxiety related to performance
* Escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine have all demonstrated efficacy and are considered first-line agents
**Social Anxiety 2nd line DRUG OPTIONS **GABAPENTINOIDS
* Pregabalin has been shown to be effective in some studies, but only at a high dose (≥600 mg/day) and not at a lower dose (150–300 mg/day)
* When used at high doses, pregabalin leads to an increased risk of adverse effects, including cognitive impairment
* No head-to-head studies with SSRI/SNRI
DRUG OPTIONS -
BENZODIAZEPINES
* Benzodiazepines, especially clonazepam and bromazepam, have demonstrated efficacy in the treatment of social anxiety disorder
* Bromazepam is no longer available in Canada
- Shorter half-life similar to alprazolam
DRUG OPTIONS - OTHERS
* Phenelzine has been shown to be effective in several studies
* Citalopram, moclobemide, mirtazapine, and gabapentin are possible options, but limited data exist
Which of the following medications has demonstrated efficacy for social anxiety disorder but requires high doses to be effective?
A) Buspirone
B) Pregabalin
C) Propranolol
D) Moclobemide
B) Correct – Pregabalin is effective but requires high doses (≥600 mg/day).
Explanation:
A) Incorrect – Buspirone has been found ineffective for social anxiety disorder.
C) Incorrect – Propranolol is used for performance-related anxiety but is not effective for generalized social anxiety disorder.
D) Incorrect – Moclobemide is a possible option but has limited data.
- Pregabalin has been shown to be effective in some studies, but only at a high dose (≥600 mg/day) and not at a lower dose (150–300 mg/day)
- When used at high doses, pregabalin leads to an increased risk of adverse effects, including cognitive impairment
- No head-to-head studies with SSRI/SNRI
Which of the following medications is NOT recommended for social anxiety disorder?
A) Phenelzine
B) Citalopram
C) Buspirone
D) Clonazepam
C) Correct – Buspirone has been shown to be ineffective for social anxiety disorder.
Explanation:
A) Incorrect – Phenelzine (an MAOI) has shown efficacy in social anxiety disorder.
B) Incorrect – Citalopram is a possible option but has limited data.
D) Incorrect – Clonazepam is effective, although not first-line.
Which of the following benzodiazepines is NO LONGER available in Canada but was previously used for social anxiety disorder?
A) Alprazolam
B) Bromazepam
C) Clonazepam
D) Diazepam
B) Correct – Bromazepam is no longer available in Canada.
Explanation:
A) Incorrect – Alprazolam is still available in Canada.
C) Incorrect – Clonazepam is still available and used for anxiety disorders.
D) Incorrect – Diazepam is still available in Canada.
Social Anxiety DRUG OPTIONS -
BENZODIAZEPINES
* Benzodiazepines, especially clonazepam and bromazepam, have demonstrated efficacy in the treatment of social anxiety disorder
* Bromazepam is no longer available in Canada
- Shorter half-life similar to alprazolam
Which of the following medications has been shown to be effective in several studies for treating social anxiety disorder?
A. Buspirone
B. Desvenlafaxine
C. Phenelzine
D. Gabapentin
Answer: C. Phenelzine: This MAOI has demonstrated efficacy in several studies for treating social anxiety disorder.
Explanation:
A. Buspirone: This medication has been shown to be ineffective in the treatment of social anxiety disorder.
B. Desvenlafaxine: Similarly, desvenlafaxine has been shown to be ineffective for this condition.
D. Gabapentin: While gabapentin is a possible option, limited data exist regarding its effectiveness in treating social anxiety disorder.
Social Anxiety DRUG OPTIONS - MAOI
* According to one study, the MAOI phenelzine is effective in the treatment of panic disorder, but remains rarely used in practice because of its adverse effect profile, the necessary dietary restrictions to avoid hypertensive crises and the numerous potential drug interactions
What is the treatment of choice for specific phobias?
A) Exposure therapy
B) Fluoxetine
C) Alprazolam
D) Paroxetine
Answer: A) Exposure therapy
Explanation:
✅ Exposure therapy is the first-line treatment for specific phobias.
❌ Fluoxetine has been shown to be effective but is not the preferred treatment.
❌ Alprazolam may be used occasionally before exposure but is not a primary treatment.
❌ Paroxetine is used for generalized anxiety disorder (GAD), not specific phobias.
SPECIFIC PHOBIA THERAPEUTIC OPTIONS
* Exposure therapy is the treatment of choice
* Drug options are not usually needed and there is little data to support options
* Pregabalin or alprazolam taken occasionally before exposure may be helpful
* Fluoxetine has been shown to be effective
Which of the following is considered a first-line pharmacological treatment for generalized anxiety disorder (GAD)?
A) Pregabalin
B) Imipramine
C) Escitalopram
D) Alprazolam
Answer: ✅C) Escitalopram (along with paroxetine, sertraline, venlafaxine, and duloxetine) is first-line for GAD.
Explanation:
❌ Pregabalin is a second-line treatment due to its abuse potential.
❌ Imipramine (TCA) is effective but limited by side effects and overdose risk.
❌ Alprazolam (benzodiazepine) is second-line due to dependency concerns.
General Anxiety Disorder First line DRUG OPTIONS – SSRI/SNRI
* SSRIs and SNRIs are established as first-line treatment for generalized anxiety disorder with comparable efficacy
* Escitalopram, paroxetine, sertraline, venlafaxine
and duloxetine have demonstrated efficacy
Why is pregabalin considered a second-line treatment for generalized anxiety disorder?
A) It is not effective for anxiety disorders
B) It has a high risk of abuse
C) It is associated with congenital abnormalities in pregnancy
D) It is more expensive than SSRIs
Answer: B) It has a high risk of abuse
✅ Pregabalin is effective, but its abuse potential makes it a second-line option.
Explanation:
❌ It is effective in studies, so option A is incorrect.
❌ Congenital abnormalities are not a major concern for pregabalin (option C).
❌ Cost is not the primary reason it is second-line (option D).
General Anxiety Disorder 2nd line DRUG OPTIONS - GABAPENTINOIDS
* Although several studies support the use of pregabalin for generalized anxiety disorder, the risk of abuse is a growing concern, making it a second- line treatment
Which of the following drugs is potentially fatal in overdose due to cardiac dysrhythmias and hypotension?
A) Venlafaxine
B) Imipramine
C) Sertraline
D) Duloxetine
Answer: B) Imipramine
Explanation:
✅ Imipramine (TCA) can be fatal in overdose, causing cardiac dysrhythmias, critical hypotension, convulsions, and coma.
❌ Venlafaxine, sertraline, and duloxetine are not as toxic in overdose.
GAD TCA Drug options
* Imipramine has been shown to be effective
* Limited by adverse effects
* Potentially fatal with overdose
- Cardiac dysrhythmia, critical hypotension, convulsions, coma, confusion, hyperactive reflexes, hypothermia
Which of the following medications is preferred for treating anxiety disorders during pregnancy?
A) Paroxetine
B) Sertraline
C) Clonazepam
D) Fluoxetine
Answer: B) Sertraline ✅ Sertraline (along with citalopram and escitalopram) is a preferred SSRI during pregnancy.
Explanation:
❌ Paroxetine is linked to congenital cardiac abnormalities and should be avoided.
❌ Clonazepam (a benzodiazepine) has risks of miscarriage and low birth weight.
❌ Fluoxetine crosses the placenta and is more frequently associated with neonatal behavioral syndrome.
Drugs for anxiety disorders DURING PREGNANCY
* If anxiety symptoms are severe and cause significant impairment or distress, pharmacotherapy can be appropriate and effective in pregnant patients
* The two main classes of medications used for anxiety disorders during pregnancy are SSRI or SNRI antidepressants and benzodiazepines
CHOICES DURING PREGNANCY
* The use of SSRIs during the first trimester of pregnancy has been linked to spontaneous abortions, although no risk factors have been clearly identified
* SSRI exposure during the first trimester is not associated with major congenital anomalies except for paroxetine, which is associated with congenital cardiac abnormalities
Why should benzodiazepines be avoided during breastfeeding?
A) They increase the risk of serotonin syndrome
B) They can cause sedation and temperature dysregulation in the infant
C) They reduce milk production
D) They are completely ineffective for anxiety
Answer: B) They can cause sedation and temperature dysregulation in the infant
✅ Benzodiazepines accumulate in breast milk, leading to sedation, impaired temperature regulation, and breathing issues in infants.
Explanation:
❌ Serotonin syndrome (option A) is associated with SSRIs, not benzodiazepines.
❌ Benzodiazepines do not affect milk production (option C).
❌ They are effective for anxiety, but their risks outweigh benefits (option D).
Benzodiazepines During Pregnancy
* Prenatal exposure to benzodiazepines was reported to be associated with increased risks of several perinatal adverse events, including spontaneous miscarriage, preterm birth, low birth weight, low Apgar score, and admission to the neonatal intensive care unit
* First-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects
Which SSRI is associated with congenital cardiac abnormalities when used in the first trimester of pregnancy?
A) Escitalopram
B) Sertraline
C) Paroxetine
D) Fluvoxamine
Answer: C) Paroxetine
✅ Paroxetine is linked to congenital cardiac abnormalities in the first trimester.
**Maybe think P (paroxetine) is the only SSRI that is not for Pregnancy
Explanation:
❌ Escitalopram and sertraline are preferred SSRIs in pregnancy.
❌ Fluvoxamine is not first-line for anxiety and lacks strong pregnancy safety data.
Drug choices for GAD During Pregnancy
* The use of SSRIs during the first trimester of pregnancy has been linked to spontaneous abortions, although no risk factors have been clearly identified
* SSRI exposure during the first trimester is not associated with major congenital anomalies except for paroxetine, which is associated with congenital cardiac abnormalities
GAD drug choices to avoid DURING 3rd trimester of PREGNANCY
* In the third trimester, SSRIs may lead to behavioural syndrome of the newborn that is characterized by symptoms such as tremors, agitation, increased muscle tone, digestive or nutritional disorders, breathing difficulties, and sometimes convulsions
* Paroxetine and fluoxetine have been involved more frequently in the onset of this syndrome, possibly because these molecules cross the placental barrier more than other SSRIs
* Studies on the association between SSRI exposure in utero and the development of autism spectrum disorder remain contradictory
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: 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.
Which of the following medications is the only one officially indicated for anxiety disorders in children and adolescents in the U.S.?
A) Sertraline
B) Duloxetine
C) Fluoxetine
D) Venlafaxine
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
Which of the following SSRIs has sufficient evidence to support its use in children and adolescents for anxiety disorders?
A) Fluoxetine
B) Escitalopram
C) Citalopram
D) Duloxetine
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)
What warning is associated with all SSRIs used for treating anxiety disorders in children and adolescents?
A) Increased risk of psychosis
B) Risk of suicidal ideation and behavior
C) Permanent cognitive impairment
D) Risk of metabolic syndrome
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)
Which antidepressant has been found to have a higher risk of suicidal behavior in children and adolescents compared to other pharmacological agents?
A) Sertraline
B) Venlafaxine
C) Paroxetine
D) Fluoxetine
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
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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.
Which of the following statements about SSRIs in depression treatment is FALSE?
A) They are first-choice antidepressants due to tolerability and cost.
B) They can increase the risk of GI bleeding, particularly in patients using NSAIDs.
C) They commonly cause discontinuation effects, except for fluoxetine.
D) They do not have any sexual side effects.
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.
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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
Which antidepressant is identified as effective for major depressive disorder (MDD) and also used for smoking cessation?
A) Vortioxetine
B) Bupropion
C) Amitriptyline
D) Sertraline
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
When adjusting antidepressant doses, how long should a minimum therapeutic dose be maintained before increasing it?
A) 1 week
B) 2 weeks ✅
C) 4 weeks
D) 8 weeks
✅ 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
If a patient experiences persistent and troublesome side effects from an SSRI, what is the recommended next step?
A) Discontinue the SSRI immediately and start a new antidepressant
B) Switch to another drug within the same class (SSRI) during weeks 3–8 ✅
C) Reduce the dose to below the therapeutic level
D) Continue the same dose indefinitely and hope for tolerance
✅ 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
Which antidepressants have been identified as the most effective based on a large meta-analysis?
A) Fluvoxamine, citalopram, duloxetine
B) Amitriptyline, venlafaxine, escitalopram ✅
C) Mirtazapine, bupropion, trazodone
D) Sertraline, fluoxetine, vortioxetine
✅ 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
Which antidepressants have the best acceptability (based on dropout rates)?
A) Agomelatine, citalopram, escitalopram, sertraline ✅
B) Amitriptyline, venlafaxine, fluvoxamine
C) Mirtazapine, trazodone, duloxetine
D) Paroxetine, fluoxetine, desvenlafaxine
✅ 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
Which antidepressant should be avoided in patients at high risk for GI bleeding?
A) Fluoxetine
B) Paroxetine
C) Citalopram
D) Any SSRI, especially with NSAIDs
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
Why should bupropion be avoided in patients with a history of eating disorders?
A) It can increase appetite and cause weight gain
B) It lowers the seizure threshold and increases seizure risk
C) It interacts with food intake and reduces antidepressant effects
D) It has stronger withdrawal symptoms than other antidepressants
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?
- 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.
Which of the following SNRIs is associated with dose-related hypertension at high doses?
A) Duloxetine
B) Desvenlafaxine
C) Venlafaxine ✅
D) Levomilnacipran
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.
Which antidepressant is associated with lower rates of GI and sexual side effects but causes sedation and weight gain?
A) Vortioxetine
B) Mirtazapine ✅
C) Trazodone
D) Sertraline
(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.?
Which serotonin modulator requires a titration schedule to avoid gastrointestinal (GI) effects?
A) Vortioxetine
B) Vilazodone ✅
C) Trazodone
D) Moclobemide
(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
Which antidepressant should be taken with food to ensure adequate absorption?
A) Fluoxetine
B) Mirtazapine
C) Vilazodone ✅
D) Venlafaxine
(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.
Which of the following antidepressants is least likely to cause serotonin syndrome?
A) Amitriptyline ✅
B) Fluoxetine
C) MAOIs
D) Sertraline
**
(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
Which antidepressant is a first-line agent that is also used for smoking cessation?
A) Bupropion ✅
B) Mirtazapine
C) Trazodone
D) Clomipramine
(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.
Which of the following adverse effects is most commonly reported with mirtazapine?
A) Insomnia
B) Weight loss
C) Sexual dysfunction
D) Somnolence ✅
(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.
What is the best course of action for managing antidepressant-induced sexual dysfunction?
A) Switch to bupropion ✅
B) Increase the dose of the current antidepressant
C) Prescribe an additional SSRI
D) Reduce the dose of the current antidepressant and hope for improvement
(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.
When is it appropriate to discontinue an antidepressant?
A) After the patient has been on the medication for at least 3 months
B) If the condition is in remission for an appropriate maintenance period
C) If the patient reports mild nausea as a side effect
D) Only if the patient has taken at least three different antidepressants
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
SCENARIO #3
* A few different drugs have been tried with only partial effect
- For example, started on SSRI, switched to SNRI, switched to serotonin modulator, switched to dual action antidepressant with partial benefit
Which of the following is a possible outcome in Scenario #3, where multiple antidepressants have provided only partial relief?
A) Discontinuing all medications and observing symptoms
B) Starting augmentation or combination therapy
C) Reducing the dosage of the current medication
D) Increasing the frequency of doses
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.
What is the most common cause of antidepressant discontinuation syndrome?
A) Gradual dose reduction over several months
B) Abruptly stopping or rapidly reducing the dose
C) Switching to another antidepressant immediately
D) Taking an antidepressant for less than 2 weeks
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
Which symptom is NOT typically associated with antidepressant discontinuation syndrome?
A) Insomnia
B) Flu-like symptoms
C) Increased appetite
D) Sensory disturbances (e.g., “brain zaps”)
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.
Which class of antidepressants is most likely to cause “brain zaps” if discontinued abruptly?
A) MAOIs
B) TCAs
C) SNRIs (especially venlafaxine)
D) NaSSAs
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
A patient who stops paroxetine suddenly is at the greatest risk for which of the following?
A) Weight loss
B) Discontinuation syndrome
C) Increased energy and motivation
D) Enhanced concentration
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.
Which of the following symptoms best distinguishes discontinuation syndrome from a new depressive episode?
A) Original symptoms at the original severity
B) Symptoms that last over 6 months
C) Symptoms that emerge within 1–7 days of stopping the medication
D) Worsening of the original symptoms but no new ones
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.
How long should maintenance antidepressant therapy be used in patients with frequent, recurrent, chronic, severe, or difficult-to-treat depressive episodes?
A) 6 months
B) 9 months
C) 2 years
D) Indefinitely
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
What is the approximate risk of relapse or recurrence within one year after stopping antidepressants?
A) 10%
B) 20%
C) 50%
D) 80%
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
What is the median time to recurrence for patients who stop antidepressants compared to those who continue therapy?
A) 6 months vs. 24 months
B) 12 months vs. 36 months
C) 14 months vs. 48 months
D) 18 months vs. 60 months
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
Which of the following is NOT a common risk factor for recurrence of depression after stopping antidepressants?
A) Psychiatric or other comorbidities
B) Frequent or chronic depressive episodes
C) Mild, first-time depressive episode
D) Residual symptoms after treatment
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.
Why is tapering antidepressants recommended rather than abrupt discontinuation?
A) It prevents discontinuation syndrome
B) It prevents serotonin syndrome
C) It speeds up the recovery process
D) It eliminates the need for antidepressants in the future
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
Which antidepressant is often used to help with tapering due to its long half-life?
A) Sertraline
B) Fluoxetine
C) Venlafaxine
D) Moclobemide
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
When switching from an irreversible MAOI to an SSRI, what is the recommended washout period?
A) 1 week
B) 2 weeks
C) 5 days
D) 6 weeks
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)
When is augmentation recommended in the treatment of depression?
A) When a patient has no response to the first antidepressant
B) When a patient has only a partial response to the first antidepressant
C) When a patient cannot tolerate the first antidepressant
D) When a patient has mild depression
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
Which of the following is TRUE regarding antipsychotic augmentation?
A) Antipsychotics should be used long-term as augmentation therapy
B) Atypical antipsychotics have no known risks when used as augmentation
C) Close monitoring for movement disorders and weight gain is necessary
D) Antipsychotic augmentation is the preferred first-line treatment for depression
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
Which of the following is NOT a common augmentation option?
A) Aripiprazole
B) Lithium
C) Citalopram
D) Modafinil
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.
Which of the following statements about antidepressant use in pregnancy is TRUE?
A) Antidepressants should never be used during pregnancy due to fetal risks
B) Mild depression in pregnancy is best treated with psychotherapy
C) SSRIs are major teratogens and should be avoided
D) All pregnant patients with depression should immediately start antidepressants
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.
What is the risk of stopping antidepressants during pregnancy?
A) There is no risk; symptoms always resolve postpartum
B) Untreated depression can lead to postpartum depression and other complications
C) Antidepressants must always be stopped in pregnancy to prevent fetal harm
D) Stopping antidepressants in pregnancy reduces the risk of suicide
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.
Which antidepressants may have higher risks during pregnancy?
A) Sertraline and escitalopram
B) Fluoxetine and paroxetine
C) Bupropion and mirtazapine
D) Venlafaxine and duloxetine
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.
Which condition is associated with newborns exposed to antidepressants in utero?
A) Autism spectrum disorder with a 100% certainty
B) Congenital heart defects in all cases
C) Poor neonatal adaptation syndrome (PNAS)
D) Schizophrenia later in life
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%
What did the Canadian Paediatric Society conclude about SSRIs and SNRIs in pregnancy?
A) SSRIs and SNRIs should always be avoided in pregnancy
B) The risk of serious adverse effects from SSRIs or SNRIs in utero is low
C) All SSRIs cause major birth defects
D) The risks of antidepressants in pregnancy are too high to justify their use
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.
What is a key consideration when augmenting with atypical antipsychotics?
A) Atypical antipsychotics should only be used long-term without close monitoring.
B) Close monitoring for movement disorders, weight gain, and cardiometabolic effects is necessary.
C) Augmentation with atypical antipsychotics is recommended for all patients.
D) Atypical antipsychotics should never be used for augmentation.
**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.
What is the goal of augmenting a patient taking high-dose fluoxetine at 80 mg with risperidone?
A) To reduce fluoxetine dose to avoid side effects.
B) To help manage symptoms of anxiety.
C) To enhance the effect of fluoxetine in treating depression.
D) To address potential sleep disturbances caused by fluoxetine.
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.
Which antidepressant medications are considered first-line options during pregnancy?
A) Paroxetine and fluoxetine.
B) Citalopram, escitalopram, and sertraline.
C) Mirtazapine and duloxetine.
D) Desvenlafaxine and venlafaxine.
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.
Which of the following antidepressants has been associated with a higher risk of major malformations during pregnancy?
A) Sertraline.
B) Fluoxetine.
C) Escitalopram.
D) Citalopram.
**
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:
- 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. - 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. - 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. - 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. - 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.
What is the recommended treatment for postpartum blues?
A) Immediate pharmacological intervention.
B) Monitoring and supportive care, as the condition is self-limiting.
C) Referral to psychiatric care for urgent medication.
D) Hospitalization for observation.
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.
What is the risk of untreated depression during pregnancy?
A) It has no impact on the fetus or neonate.
B) Untreated depression may lead to negative effects on the fetus, patient, and others.
C) Untreated depression is only a risk for the pregnant individual, not the fetus.
D) There are no associated risks with untreated depression during pregnancy.
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.
What is the risk of untreated depression during pregnancy?
A) It has no impact on the fetus or neonate.
B) Untreated depression may lead to negative effects on the fetus, patient, and others.
C) Untreated depression is only a risk for the pregnant individual, not the fetus.
D) There are no associated risks with untreated depression during pregnancy.
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.
Why Do Movement Disorders and Weight Gain Occur with Antipsychotics?
Tardive Dyskinesia (TD)
Caused by long-term dopamine receptor blockade in the brain.
Leads to involuntary movements, often affecting the face, tongue, and limbs.
Can become irreversible if not detected early.
Weight Gain & Metabolic Effects
Many atypical antipsychotics increase appetite and fat storage by affecting histamine, serotonin, and dopamine receptors.
Can lead to metabolic syndrome, which includes weight gain, diabetes, and high cholesterol.
Olanzapine, quetiapine, and risperidone have a higher risk of weight gain compared to others.
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.
- 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.
Why is lithium often considered the “first among equals” for bipolar treatment?
A) It is the only effective mood stabilizer
B) It has additional anti-suicidal properties and may reduce dementia risk
C) It has fewer side effects compared to all other options
D) It works immediately, requiring no titration
✅ 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.
Which of the following is NOT a sign of lithium toxicity?
A) Ataxia and tremor
B) Confusion and tachycardia
C) Increased appetite and weight gain
D) Coma and seizures
✅ 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)
Which medication should be used with caution in women of reproductive age due to teratogenic risks?
A) Quetiapine
B) Divalproex
C) Aripiprazole
D) Risperidone
✅ 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
Which of the following drugs is NOT a first-line treatment for mania?
A) Lithium
B) Quetiapine
C) Carbamazepine
D) Aripiprazole
✅ 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
Why should NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics be avoided in patients taking lithium?
A) They increase lithium clearance, making it ineffective
B) They raise lithium levels, increasing the risk of toxicity
C) They have no known interactions with lithium
D) They make lithium work faster
✅ 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.
Which treatment is considered the most effective first-line option for bipolar depression?
A) Lurasidone
B) Quetiapine
C) Lithium
D) Divalproex
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
Which of the following is considered a first-line monotherapy option for treating an unmedicated depressive episode in bipolar disorder?
A) Lamotrigine
B) Fluoxetine
C) Olanzapine
D) Carbamazepine
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.
What is the risk of untreated bipolar disorder in remission?
A) 50% chance of another episode within 1 year
B) 70% chance of another episode within 1 year
C) 30% chance of another episode within 5 years
D) 95% chance of remaining stable for life
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.
How should bipolar disorder be managed when diagnosed alongside ADHD in children?
A) Treat ADHD first, then treat bipolar disorder
B) Treat bipolar disorder first, then manage ADHD
C) Treat both simultaneously with stimulants
D) Avoid medications altogether
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.
What is the first-line treatment for pediatric bipolar depression?
A) Quetiapine
B) Lurasidone
C) Lithium
D) Lamotrigine
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
What is the primary concern for elderly patients with bipolar disorder?
A) Increased risk of rapid cycling
B) Cognitive dysfunction
C) Resistance to treatment
D) Increased energy levels
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
Which medications are preferred for treating mania in elderly bipolar patients?
A) Lithium or divalproex
B) Quetiapine and carbamazepine
C) Fluoxetine and sertraline
D) Lamotrigine and lurasidone
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
What is the biggest risk of untreated bipolar disorder during pregnancy?
A) Increased risk of postpartum depression and psychosis
B) No significant risks, as bipolar disorder stabilizes in pregnancy
C) Increased risk of birth defects
D) Decreased need for medication
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.
