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Clomipramine is primarily classified as a Selective Serotonin Reuptake Inhibitor (SSRI).
Answer: False
Clomipramine is pharmacologically classified as a tricyclic antidepressant (TCA), specifically a dibenzazepine, rather than a Selective Serotonin Reuptake Inhibitor (SSRI). While it does inhibit serotonin reuptake, its broader pharmacological profile and historical classification place it within the TCA class.
The mechanism of action for clomipramine involves blocking the reuptake of serotonin and norepinephrine.
Answer: True
Clomipramine functions primarily by inhibiting the reuptake of both serotonin and norepinephrine in the synaptic cleft, thereby increasing the availability of these neurotransmitters.
Clomipramine's metabolite, desmethylclomipramine, has a stronger affinity for the serotonin transporter (SERT) than clomipramine itself.
Answer: False
The active metabolite, desmethylclomipramine, exhibits a higher affinity for the norepinephrine transporter (NET) and a lower affinity for the serotonin transporter (SERT) compared to the parent compound, clomipramine.
Clomipramine is chemically classified as a dibenzazepine.
Answer: True
Chemically, clomipramine is classified as a tricyclic compound belonging to the dibenzazepine class, characterized by a three-ring structure with an attached side chain.
Clomipramine is considered a weaker Serotonin Reuptake Inhibitor (SRI) compared to most SSRIs.
Answer: False
Clomipramine is recognized as a highly potent Serotonin Reuptake Inhibitor (SRI), often demonstrating greater potency in blocking the serotonin transporter (SERT) than most Selective Serotonin Reuptake Inhibitors (SSRIs).
What is the primary classification of clomipramine as a medication?
Answer: Tricyclic Antidepressant (TCA)
Clomipramine is primarily classified as a Tricyclic Antidepressant (TCA), specifically belonging to the dibenzazepine chemical group.
Clomipramine's mechanism of action primarily involves:
Answer: Increasing the levels of serotonin and norepinephrine.
The primary mechanism of action for clomipramine involves inhibiting the reuptake of both serotonin and norepinephrine, thereby increasing their synaptic concentrations.
Besides its effects on serotonin and norepinephrine transporters, clomipramine also acts as an antagonist at which other receptor types?
Answer: Histamine H1 and Alpha1-adrenergic receptors
In addition to its primary action on serotonin and norepinephrine transporters, clomipramine exhibits significant antagonism at histamine H1 and alpha1-adrenergic receptors, contributing to its side effect profile.
The active metabolite of clomipramine, desmethylclomipramine, is noted for having:
Answer: Higher affinity for NET and lower for SERT.
Desmethylclomipramine, the primary active metabolite, demonstrates a higher affinity for the norepinephrine transporter (NET) and a lower affinity for the serotonin transporter (SERT) compared to clomipramine.
Clomipramine's high potency as a Serotonin Reuptake Inhibitor (SRI) means:
Answer: It is the strongest SRI among commonly used antidepressants.
The high potency of clomipramine as an SRI indicates that it is among the most effective agents for blocking serotonin reuptake, often requiring lower doses to achieve significant transporter occupancy compared to many SSRIs.
In the United States, clomipramine's sole FDA-approved indication is for the treatment of major depressive disorder (MDD).
Answer: False
While clomipramine is effective for major depressive disorder (MDD) and approved for it in many regions, its sole FDA-approved indication in the United States is for the treatment of obsessive-compulsive disorder (OCD).
Clomipramine is exclusively used to treat obsessive-compulsive disorder (OCD) and has no other therapeutic applications.
Answer: False
Clomipramine has demonstrated therapeutic efficacy in a range of conditions beyond obsessive-compulsive disorder (OCD), including major depressive disorder (MDD), panic disorder, trichotillomania, and others, although its primary FDA approval in the US is for OCD.
Clomipramine is only available in oral tablet form.
Answer: False
Clomipramine is commonly administered orally via tablets, but intravenous preparations are also available and may be utilized in specific clinical scenarios.
Meta-analyses suggest clomipramine is less effective than SSRIs for treating OCD.
Answer: False
While SSRIs are generally better tolerated, meta-analyses often indicate that clomipramine can be significantly more effective than SSRIs in treating obsessive-compulsive disorder (OCD), though its use may be limited by its side effect profile.
Clomipramine was the first medication proven effective for Obsessive-Compulsive Disorder (OCD).
Answer: True
Clomipramine holds historical significance as the first medication demonstrated to be effective for the treatment of Obsessive-Compulsive Disorder (OCD).
Which condition is clomipramine primarily FDA-labeled for in the United States?
Answer: Obsessive-Compulsive Disorder (OCD)
In the United States, clomipramine's sole FDA-approved indication is for the treatment of Obsessive-Compulsive Disorder (OCD).
Besides OCD, which of the following is listed as a condition treatable with clomipramine?
Answer: Hyperacusis
Clomipramine is indicated for several conditions beyond OCD, including hyperacusis, major depressive disorder, panic disorder, and trichotillomania, among others.
How does clomipramine generally compare to SSRIs in terms of effectiveness for OCD?
Answer: Clomipramine is significantly more effective in some studies, though less tolerated.
While SSRIs are generally better tolerated, clomipramine has demonstrated superior efficacy in some studies for OCD, though its side effect profile is more challenging.
What historical status did clomipramine hold in the treatment of OCD?
Answer: It was the first drug proven effective and considered the 'gold standard'.
Historically, clomipramine was regarded as the 'gold standard' for OCD treatment, being the first pharmacotherapy proven effective. While largely supplanted by SSRIs due to tolerability, it may retain superior efficacy in certain patient populations.
What is the typical maximum recommended daily dose of clomipramine?
Answer: 250 mg
The generally accepted maximum recommended daily dosage for clomipramine is 250 mg, although higher doses may be considered in specific refractory cases under strict medical supervision.
Common side effects of clomipramine include dry mouth, constipation, sleepiness, and weight gain.
Answer: True
The profile of common side effects associated with clomipramine frequently includes anticholinergic effects such as dry mouth and constipation, as well as somnolence (sleepiness) and potential weight gain.
Seizures and liver problems are considered minor side effects of clomipramine.
Answer: False
Seizures and significant liver issues are considered serious adverse effects of clomipramine, not minor ones. They necessitate careful patient monitoring and prompt medical intervention.
Stopping clomipramine abruptly is recommended to minimize withdrawal symptoms.
Answer: False
Abrupt discontinuation of clomipramine is not recommended, as it can precipitate withdrawal symptoms. Gradual tapering of the dosage is the standard clinical practice to mitigate these effects.
Clomipramine can be used in patients with a history of mania or severe liver disease.
Answer: False
A history of mania and severe liver disease are considered contraindications for the use of clomipramine due to the potential for exacerbation of manic symptoms and impaired drug metabolism, respectively.
Very common side effects of clomipramine (>10%) include convulsions and elevated blood pressure.
Answer: False
While clomipramine can cause elevated blood pressure and lower the seizure threshold, convulsions are not typically listed among the *very common* (>10%) side effects. Common side effects are more often anticholinergic or related to sedation.
Neuroleptic Malignant Syndrome (NMS) is a common and mild reaction to clomipramine.
Answer: False
Neuroleptic Malignant Syndrome (NMS) is a rare but potentially life-threatening reaction associated with certain psychotropic medications, including clomipramine. It is characterized by severe symptoms and is not considered common or mild.
Withdrawal symptoms from clomipramine are primarily caused by a rebound effect from excessive cholinergic activity.
Answer: True
The withdrawal syndrome associated with clomipramine discontinuation is thought to be largely due to a rebound effect from excessive cholinergic activity, resulting from neuroadaptations during chronic treatment.
There is a specific antidote available to reverse the effects of clomipramine overdose.
Answer: False
No specific antidote exists for clomipramine overdose. Treatment is primarily supportive and symptomatic, focusing on managing the patient's clinical presentation.
Clomipramine's antagonism of histamine H1 receptors contributes to its sedative side effects.
Answer: True
The antagonism of histamine H1 receptors by clomipramine mediates its antihistaminic effects, which are commonly associated with sedation and somnolence, characteristic side effects of many tricyclic antidepressants.
Which of the following is NOT listed as a common side effect of clomipramine?
Answer: Increased appetite
While clomipramine can cause a range of side effects including drowsiness, blurred vision, and tremor, increased appetite is not typically listed as a common adverse effect; weight gain is more frequently cited.
What should be done if clomipramine needs to be discontinued?
Answer: Gradually taper the dosage to prevent withdrawal symptoms.
To mitigate potential withdrawal symptoms, clomipramine should be discontinued gradually through a process of dose tapering, rather than abrupt cessation.
What serious side effect requires careful monitoring when a patient is taking clomipramine?
Answer: Mania
Patients taking clomipramine require careful monitoring for the potential emergence of manic episodes, particularly those with a history of bipolar disorder.
Which of the following is a very rare side effect of clomipramine (<0.01%)?
Answer: Pancytopenia
Pancytopenia, a severe reduction in all blood cell types, is listed as a very rare side effect of clomipramine, occurring with a frequency of less than 0.01%.
What is the primary mechanism proposed for clomipramine withdrawal symptoms?
Answer: Rebound cholinergic activity
Withdrawal symptoms from clomipramine are primarily attributed to a rebound effect from excessive cholinergic activity following chronic receptor blockade.
How is clomipramine overdose typically treated?
Answer: With supportive and symptomatic care.
Treatment for clomipramine overdose is primarily supportive and symptomatic, focusing on managing vital functions and addressing specific clinical manifestations, as no specific antidote is available.
Clomipramine is known to significantly lower the seizure threshold compared to other TCAs. What is the approximate incidence of seizures at doses up to 250 mg/day?
Answer: Approximately 0.48%
The incidence of seizures associated with clomipramine at daily doses not exceeding 250 mg is approximately 0.48%. This highlights clomipramine's known effect of lowering the seizure threshold, a property shared with other TCAs like maprotiline and amoxapine.
Clomipramine's antagonism of the alpha1-adrenergic receptor can contribute to which side effect?
Answer: Orthostatic hypotension
Antagonism of alpha1-adrenergic receptors by clomipramine is a significant contributor to the side effect of orthostatic hypotension, characterized by a drop in blood pressure upon standing.
What is Neuroleptic Malignant Syndrome (NMS)?
Answer: A rare, potentially fatal reaction involving muscle rigidity and fever.
Neuroleptic Malignant Syndrome (NMS) is a severe, idiosyncratic reaction characterized by hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental status, which can be life-threatening.
Combining clomipramine with Monoamine Oxidase Inhibitors (MAOIs) is safe if done under close medical supervision.
Answer: False
The concurrent use of clomipramine and Monoamine Oxidase Inhibitors (MAOIs) is contraindicated due to the significant risk of potentially fatal serotonin syndrome. A washout period is required between these medications.
Which of the following is a contraindication for using clomipramine?
Answer: Concurrent use of Monoamine Oxidase Inhibitors (MAOIs)
Concurrent use with Monoamine Oxidase Inhibitors (MAOIs) is a significant contraindication for clomipramine due to the risk of serotonin syndrome.
What is the main danger of combining clomipramine with MAOIs?
Answer: Potentially fatal serotonin syndrome.
The primary danger of combining clomipramine with Monoamine Oxidase Inhibitors (MAOIs) is the potentially fatal risk of serotonin syndrome, a condition of excessive serotonergic activity.
Which enzyme system is involved in clomipramine metabolism, and can lead to interactions with certain SSRIs?
Answer: CYP2D6
Clomipramine is metabolized by the cytochrome P450 enzyme CYP2D6. Inhibition of this enzyme, for instance by certain SSRIs, can significantly alter clomipramine levels and increase toxicity risk.
What is the approximate terminal elimination half-life of clomipramine?
Answer: 32 hours
Clomipramine exhibits a terminal elimination half-life of approximately 32 hours, indicating its relatively long duration of action in the body.
What is the approximate oral bioavailability of clomipramine?
Answer: 50%
The oral bioavailability of clomipramine is approximately 50%, indicating that roughly half of an orally administered dose becomes systemically available.
Clomipramine was discovered in the 21st century.
Answer: False
Clomipramine was discovered in the mid-20th century, with its development and initial approval occurring in the 1960s and early 1970s.
Clomipramine is not considered an essential medicine by global health organizations.
Answer: False
Clomipramine is recognized for its importance and is included on the World Health Organization's Model List of Essential Medicines, signifying its critical role in public health.
Clomipramine is only available as a brand-name medication and is not produced generically.
Answer: False
Clomipramine is available in both brand-name (e.g., Anafranil) and generic formulations, making it accessible through multiple manufacturers.
Clomipramine was first approved for medical use in Europe in 1964.
Answer: False
Clomipramine received its first medical approval in Europe in 1970, following its discovery in 1964.
The FDA initially approved clomipramine for depression treatment in the United States.
Answer: False
Despite its efficacy for depression, the FDA initially declined approval for clomipramine for depression treatment in the US. Its first US approval was for obsessive-compulsive disorder (OCD).
Who discovered clomipramine, and in what year?
Answer: Ciba-Geigy, 1964
Clomipramine was discovered by the pharmaceutical company Ciba-Geigy in 1964.
Clomipramine is listed on which important global health document?
Answer: The World Health Organization's List of Essential Medicines
Clomipramine is included on the World Health Organization's Model List of Essential Medicines, underscoring its global health significance.
Clomipramine was initially declined for depression treatment in the US because it was considered:
Answer: A 'me-too' drug with no added benefit.
The FDA's initial reluctance to approve clomipramine for depression in the US was influenced by its perceived status as a 'me-too' drug, suggesting it offered no significant advantage over existing treatments at the time.
Clomipramine may increase the risk of suicidal behavior in individuals under the age of 25, particularly during the initial weeks of treatment.
Answer: True
As with many antidepressant medications, clomipramine carries a potential risk of increasing suicidal thoughts and behaviors in individuals under the age of 25, especially during the early phases of therapy. Close monitoring is advised.
Clomipramine is definitively proven to be safe for use during pregnancy.
Answer: False
The safety profile of clomipramine during pregnancy remains uncertain. Its administration to pregnant individuals necessitates a thorough evaluation of potential risks versus benefits.
Using clomipramine during pregnancy has been linked to reversible withdrawal effects in newborns.
Answer: True
Neonatal exposure to clomipramine during pregnancy has been associated with reversible withdrawal symptoms in newborns, necessitating careful consideration and monitoring.
What significant risk is associated with clomipramine use in individuals younger than 25 years old?
Answer: Paradoxical increase in suicidal behavior
A notable risk associated with clomipramine, particularly in younger patients (under 25), is a paradoxical increase in suicidal ideation or behavior, especially during the initial treatment phase.
What is a potential risk associated with clomipramine use during pregnancy?
Answer: Increased risk of congenital heart defects in newborns.
Use of clomipramine during pregnancy has been associated with an increased risk of congenital heart defects in newborns, alongside potential withdrawal effects.
Clomipramine is marketed for veterinary use under the brand name Anafranil.
Answer: False
While Anafranil is the brand name for human use, clomipramine is marketed for veterinary applications under different brand names, such as Clomicalm.
In the US, clomipramine is licensed for treating separation anxiety in dogs.
Answer: True
Clomipramine is specifically licensed in the United States for the treatment of separation anxiety disorder in canine patients.
What is the brand name for clomipramine used in veterinary medicine?
Answer: Clomicalm
In veterinary medicine, clomipramine is commonly marketed under the brand name Clomicalm.