What is clomipramine and what is its primary classification as a medication?

Clomipramine, sold under brand names like Anafranil, is classified as a tricyclic antidepressant (TCA). Tricyclic antidepressants are a class of medications primarily used to treat depression, but they also have effects on other neurotransmitter systems.

For which specific condition is clomipramine primarily FDA-labeled in the United States?

In the United States, clomipramine is primarily FDA-labeled for the treatment of obsessive-compulsive disorder (OCD). While it is effective for other conditions, OCD is its sole indication approved by the U.S. Food and Drug Administration.

Beyond OCD, what other medical conditions can clomipramine be used to treat?

Clomipramine is used to treat a variety of other conditions, including hyperacusis, panic disorder, major depressive disorder (MDD), trichotillomania, body dysmorphic disorder, chronic pain, premature ejaculation, and the cataplexy associated with narcolepsy. It may also help with other narcolepsy symptoms like hallucinations.

What potential risk is associated with clomipramine use in individuals under 25 years old?

Similar to other antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), clomipramine may paradoxically increase the risk of suicidal behavior in individuals under the age of 25, especially during the initial weeks of treatment. This is a known warning for many antidepressant medications.

How is clomipramine typically administered, and are there alternative methods?

Clomipramine is typically taken orally, but intravenous preparations are also available and sometimes used. The route of administration can depend on the specific medical situation and physician's recommendation.

What are some of the common side effects reported with clomipramine use?

Common side effects of clomipramine include dry mouth, constipation, loss of appetite, sleepiness, weight gain, sexual dysfunction, and difficulty urinating. These effects are often related to its anticholinergic properties.

What serious side effects should be monitored when a patient is taking clomipramine?

Serious side effects that require monitoring include an increased risk of suicidal behavior in young adults, seizures, mania, and liver problems. Patients should be aware of these potential serious adverse effects.

What might occur if clomipramine is stopped abruptly, and how is this managed?

If clomipramine is stopped suddenly, a withdrawal syndrome may occur, characterized by symptoms such as headaches, sweating, and dizziness. Gradual tapering of the medication is the recommended approach to mitigate withdrawal symptoms.

Is clomipramine considered safe for use during pregnancy?

It is unclear whether clomipramine is safe for use during pregnancy. Its use in pregnant individuals requires careful consideration of potential risks and benefits.

What is the proposed mechanism of action for clomipramine's antidepressant effects?

The mechanism of action for clomipramine is not fully understood, but it is believed to involve increasing the levels of serotonin and norepinephrine in the brain. These neurotransmitters play crucial roles in mood regulation.

When and by whom was clomipramine discovered?

Clomipramine was discovered in 1964 by the Swiss drug manufacturer Ciba-Geigy. Its development marked a significant step in the pharmacological treatment of mental health conditions.

Is clomipramine included in any major global health lists?

Yes, clomipramine is included on the World Health Organization's List of Essential Medicines. This designation highlights its importance and effectiveness in public health.

What is the status of clomipramine regarding generic availability?

Clomipramine is available as a generic medication. This means that multiple manufacturers produce and market the drug, often leading to lower costs compared to brand-name versions.

How does clomipramine's effectiveness in treating OCD compare to SSRIs?

Clomipramine has been found to be significantly more effective than SSRIs in some meta-analyses for treating OCD, although SSRIs are generally better tolerated and have a more favorable safety profile. Clomipramine is often considered a second-line agent due to its side effect profile.

What are the contraindications for using clomipramine?

Contraindications for clomipramine include known hypersensitivity to it or other tricyclic antidepressants of the dibenzazepine group, recent myocardial infarction, heart block or other cardiac arrhythmias, mania, severe liver disease, narrow-angle glaucoma, and untreated urinary retention. It must also not be used concurrently with or within three weeks of using monoamine oxidase inhibitors (MAOIs).

What specific risks are associated with clomipramine use during pregnancy and lactation?

Clomipramine use during pregnancy has been linked to congenital heart defects in newborns and reversible withdrawal effects. It is also distributed in breast milk, making nursing while taking the medication inadvisable.

What are the very common side effects of clomipramine, occurring with a frequency greater than 10%?

Very common side effects of clomipramine include accommodation defects in the eye, blurred vision, nausea, dry mouth (xerostomia), constipation, fatigue, dizziness, tremor, headache, myoclonus, drowsiness, somnolence, restlessness, micturition disorder, sexual dysfunction (erectile dysfunction and loss of libido), and hyperhidrosis (excessive sweating).

What are some uncommon side effects of clomipramine, occurring with a frequency of 0.1% to 1%?

Uncommon side effects include convulsions, ataxia, arrhythmias, elevated blood pressure, and activation of psychotic symptoms. These are less frequent but still notable adverse effects.

What are some very rare side effects of clomipramine, occurring with a frequency less than 0.01%?

Very rare side effects include blood dyscrasias like pancytopenia, leukopenia, agranulocytosis, and thrombocytopenia, as well as eosinophilia. Other rare effects include SIADH (syndrome of inappropriate secretion of antidiuretic hormone), glaucoma, alopecia, hyperpyrexia, hepatitis, and neuroleptic malignant syndrome (NMS).

What is Neuroleptic Malignant Syndrome (NMS), and how can it relate to clomipramine?

Neuroleptic Malignant Syndrome (NMS) is a rare but potentially fatal reaction to certain medications, including some antidepressants like clomipramine. It is characterized by symptoms such as severe muscle rigidity, high fever, altered mental status, and autonomic instability (like rapid heart rate and sweating). It requires immediate medical attention.

What is the primary mechanism of withdrawal symptoms from clomipramine?

A major mechanism believed to cause withdrawal symptoms from clomipramine and other TCAs is a rebound effect from excessive cholinergic activity. This occurs due to neuroadaptations resulting from the chronic inhibition of cholinergic receptors by the medication.

What are the typical symptoms of clomipramine overdose?

Clomipramine overdose typically presents with symptoms of central nervous system depression (like stupor, coma, drowsiness), mydriasis (dilated pupils), convulsions, enhanced reflexes, muscle rigidity, and cardiovascular effects such as arrhythmias, tachycardia, hypotension, and cardiac arrest. Serotonin syndrome can also occur.

Is there a specific antidote for clomipramine overdose?

No, there is no specific antidote for clomipramine overdose. Treatment is purely supportive and symptomatic, focusing on managing the patient's vital signs and addressing the specific symptoms that arise.

What is the recommended initial management for a clomipramine overdose?

In cases of oral overdose, treatment with activated charcoal may be used to limit absorption. Patients suspected of overdosing should be hospitalized and closely monitored for at least 72 hours.

How does clomipramine interact with Monoamine Oxidase Inhibitors (MAOIs)?

Clomipramine must not be used in combination with or within three weeks before or after treatment with MAOIs. This combination can lead to potentially fatal serotonin syndrome due to the increased levels of serotonin and norepinephrine.

What is the relationship between clomipramine and Selective Serotonin Reuptake Inhibitors (SSRIs) regarding interactions?

Clomipramine can interact with SSRIs due to potential additive serotonergic effects, which could lead to serotonin syndrome. Additionally, SSRIs that inhibit the CYP2D6 enzyme (like fluoxetine and paroxetine) can affect clomipramine levels, potentially increasing the risk of CNS and cardiotoxicity.

How does clomipramine affect serotonin and norepinephrine levels in the brain?

Clomipramine acts as a reuptake inhibitor for both serotonin and norepinephrine. By blocking the reuptake of these neurotransmitters into neurons, it increases their extracellular concentrations in the synaptic cleft, enhancing serotonergic and noradrenergic neurotransmission.

What other receptor activities does clomipramine possess besides its effects on serotonin and norepinephrine transporters?

Clomipramine also exhibits antiadrenergic (α1-adrenergic receptor antagonism), antihistamine (H1 receptor antagonism), antiserotonergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7 receptor antagonism), antidopaminergic (D1, D2, D3 receptor antagonism), and anticholinergic activities. These activities contribute to both its therapeutic effects and side effects.

How does the metabolite desmethylclomipramine differ from clomipramine in terms of its pharmacological activity?

While clomipramine shows a stronger affinity for the serotonin transporter (SERT), its active metabolite, desmethylclomipramine, has a much higher affinity for the norepinephrine transporter (NET) and significantly lower affinity for SERT. Desmethylclomipramine also circulates at approximately twice the concentration of clomipramine, making it a key contributor to the drug's SNRI profile.

What is the chemical structure classification of clomipramine?

Clomipramine is classified as a tricyclic compound, specifically a dibenzazepine. Its structure features three fused rings with a side chain attached.

How is clomipramine chemically related to imipramine?

Clomipramine is a chemical derivative of imipramine, distinguished by the addition of a chlorine atom to one of its rings. It is also known by the chemical name 3-chloroimipramine.

What is the chemical formula and molecular weight of clomipramine's free base form?

The free base form of clomipramine has the chemical formula C19H23ClN2 and a molecular weight of 314.857 g/mol. It is almost exclusively used commercially as its hydrochloride salt.

When was clomipramine patented and first approved for medical use in Europe?

Clomipramine was patented in 1963 and first approved for medical use in Europe for the treatment of depression in 1970. It was initially considered a 'me-too' drug by the FDA.

Why was clomipramine initially declined for depression treatment in the United States?

Clomipramine was initially declined for depression treatment in the United States by the FDA, partly because it was considered a 'me-too' drug, meaning it was similar to existing medications. Consequently, it remains the only TCA available in the US that is not approved for depression, despite its efficacy.

When did clomipramine become available in the US, and for what indication?

Clomipramine was eventually approved in the United States for the treatment of obsessive-compulsive disorder (OCD) in 1989 and became available in 1990. It was the first drug to be investigated and found effective for OCD.

What is the 'gold standard' status of clomipramine in OCD treatment history?

Clomipramine was considered the 'gold standard' for OCD treatment for many years. It was the first medication proven effective for OCD and remained so until the introduction of SSRIs, which have largely replaced it due to better tolerability, though clomipramine may still be more effective in some cases.

What are the primary brand names under which clomipramine is marketed?

Clomipramine is marketed worldwide primarily under the brand names Anafranil for human use and Clomicalm for veterinary use. These names are recognized in various countries for the medication.

What is the specific veterinary indication for clomipramine in the US?

In the United States, clomipramine is licensed specifically for treating separation anxiety in dogs, marketed under the brand name Clomicalm. It has also shown effectiveness for obsessive-compulsive disorders in both dogs and cats.

How does clomipramine's potency as a Serotonin Reuptake Inhibitor (SRI) compare to SSRIs?

Clomipramine is considered a significantly more potent SRI than selective serotonin reuptake inhibitors (SSRIs). Studies indicate that even low doses of clomipramine achieve high SERT occupancy, often exceeding that of SSRIs at comparable or higher doses, making it the strongest SRI used medically.

What is the significance of the ratio of clomipramine's dosage range to its 80% SERT occupancy dosage?

The ratio calculated from clomipramine's dosage range and the dosage required for 80% SERT occupancy suggests it is the most potent SRI among commonly used antidepressants. This indicates that a lower dose of clomipramine is needed to achieve significant serotonin transporter blockade compared to SSRIs and SNRIs.

What role does the antagonism of certain receptors play in clomipramine's side effect profile?

Clomipramine's antagonism of histamine H1, alpha1-adrenergic, and muscarinic acetylcholine receptors contributes significantly to its side effect profile. For instance, H1 antagonism causes sedation and somnolence, alpha1 antagonism can lead to orthostatic hypotension and dizziness, and muscarinic antagonism results in anticholinergic effects like dry mouth, constipation, and blurred vision.

How does clomipramine's interaction with CYP2D6 affect its safety?

Clomipramine is metabolized by the liver enzyme CYP2D6. Individuals who are poor metabolizers of CYP2D6, or those taking other medications that inhibit CYP2D6, may experience increased plasma levels of clomipramine. This can heighten the risk of central nervous system and cardiotoxicity.

What is the typical maximum recommended daily dose of clomipramine, and are higher doses ever used?

The typical maximum recommended daily dose of clomipramine is 250 mg. However, in treatment-resistant cases of depression and OCD, doses ranging from 255 to 300 mg per day, or even higher, may be necessary and have been found to be relatively well-tolerated in some patients. Caution is advised with higher doses due to an increased risk of seizures.

What is the estimated incidence of seizures with clomipramine at doses up to 250 mg/day?

The incidence of seizures with clomipramine at daily doses of 250 mg or less is estimated to be around 0.48%. It is known that clomipramine, along with maprotiline and amoxapine, significantly lowers the seizure threshold compared to other TCAs.

How does clomipramine's effectiveness in OCD compare to its effectiveness in major depressive disorder (MDD)?

Clomipramine is considered particularly effective for OCD, being the first drug approved for this condition and showing superior efficacy in some studies compared to other TCAs and even SSRIs. While also effective for MDD, its unique potency in OCD is often highlighted, and it is approved for MDD in Japan and other regions, though not as its primary FDA-labeled indication in the US.

What is the half-life of clomipramine and its active metabolite, desmethylclomipramine?

Clomipramine has a terminal elimination half-life of approximately 32 hours. Its major active metabolite, desmethylclomipramine, has a longer terminal half-life, estimated at around 69 hours. These relatively long half-lives contribute to the drug's sustained effects.

What is the oral bioavailability of clomipramine?

The oral bioavailability of clomipramine is approximately 50%. This means that about half of the orally administered dose reaches systemic circulation unchanged.

How does clomipramine's interaction with the dopamine receptors compare to its effects on serotonin and norepinephrine transporters?

While clomipramine is primarily known for its potent inhibition of serotonin and norepinephrine reuptake, it also acts as a mild but clinically significant antagonist of dopamine D1, D2, and D3 receptors at higher concentrations. This additional activity might contribute to its therapeutic effects, particularly in conditions like OCD where dopamine modulation may play a role.

What is the role of clomipramine's antagonism of the H1 receptor?

Clomipramine's antagonism of the histamine H1 receptor is responsible for its antihistamine effects, including common side effects like sedation and somnolence (sleepiness). This is a characteristic shared by many tricyclic antidepressants.

What is the significance of clomipramine being on the WHO Model List of Essential Medicines?

Clomipramine's inclusion on the World Health Organization's Model List of Essential Medicines signifies its recognized importance, effectiveness, and affordability in meeting global public health needs. It indicates that the drug is considered fundamental for basic healthcare.

How does clomipramine's efficacy in treating OCD compare to other TCAs?

Clomipramine demonstrates significantly greater effectiveness in treating OCD compared to other tricyclic antidepressants (TCAs). This is attributed to its potent serotonin reuptake inhibition, which is stronger than that of other TCAs, making it uniquely effective for this disorder among the TCA class.

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Medical Uses

Obsessive-Compulsive Disorder (OCD)

Clomipramine is primarily recognized for its efficacy in treating Obsessive-Compulsive Disorder (OCD). It is the only tricyclic antidepressant (TCA) approved by the U.S. Food and Drug Administration (FDA) specifically for this indication. Its potent serotonergic activity makes it highly effective, often considered a benchmark against which other treatments are measured.

Major Depressive Disorder (MDD)

While not its primary FDA-approved use in the US, Clomipramine is widely utilized off-label for Major Depressive Disorder (MDD). Clinical evidence suggests it may offer superior efficacy compared to some other antidepressants, particularly in severe or treatment-resistant cases. Its effectiveness is attributed to its balanced inhibition of serotonin and norepinephrine reuptake.

Other Applications

Clomipramine demonstrates utility across a spectrum of other conditions, including:

Panic Disorder
Body Dysmorphic Disorder
Trichotillomania (compulsive hair pulling)
Chronic Pain management
Premature Ejaculation
Cataplexy associated with Narcolepsy
Sleep Paralysis
Enuresis (bedwetting) in children

Its broad applicability stems from its complex pharmacological profile affecting multiple neurotransmitter systems.

Contraindications

Absolute Contraindications

Clomipramine should not be administered under the following circumstances:

Known hypersensitivity to Clomipramine or other dibenzazepine derivatives.
Recent myocardial infarction (heart attack).
Existing cardiac arrhythmias or heart block.
Concurrent use or recent cessation (within 3 weeks) of Monoamine Oxidase Inhibitors (MAOIs), with a specific washout period required.
Active mania.
Severe liver disease.
Narrow-angle glaucoma.
Untreated urinary retention.

Pregnancy and Lactation

Use during pregnancy is associated with potential risks, including congenital heart defects and reversible withdrawal effects in newborns. Clomipramine is excreted in breast milk, making its use during lactation generally inadvisable.

Side Effects Profile

Common Side Effects

The most frequently reported side effects, occurring in over 10% of patients, include:

Anticholinergic effects: Dry mouth, constipation, blurred vision, urinary hesitancy.
Central Nervous System effects: Drowsiness, dizziness, tremor, headache, restlessness.
Gastrointestinal effects: Nausea, loss of appetite, vomiting.
Other: Weight gain, sexual dysfunction, hyperhidrosis (excessive sweating).

Less Common & Rare Side Effects

Uncommon effects (1-10%) include weight loss, cognitive impairment, orthostatic hypotension, and elevated liver enzymes. Rare but serious effects (<0.01%) involve hematological changes (e.g., agranulocytosis, thrombocytopenia), SIADH, neuroleptic malignant syndrome, and cardiac conduction abnormalities, particularly in overdose scenarios.

Withdrawal Considerations

Withdrawal Syndrome

Abrupt cessation of Clomipramine can precipitate a withdrawal syndrome. Symptoms may include nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, nervousness, anxiety, dizziness, and worsening of psychiatric symptoms. Differentiating these from a relapse of the underlying condition is crucial.

Management of Withdrawal

Gradual tapering of the dosage is recommended to mitigate withdrawal symptoms. In some cases, anticholinergic medications like benztropine may help manage specific symptoms. Neonatal withdrawal symptoms can occur if used during pregnancy.

Overdose Management

Clinical Presentation

Clomipramine overdose presents a significant risk, primarily affecting the central nervous system (CNS) and cardiovascular system. Symptoms include CNS depression (stupor, coma), seizures, anticholinergic effects (mydriasis), cardiac arrhythmias (including QTc prolongation, torsades de pointes), hypotension, and potentially cardiac arrest.

Treatment Principles

There is no specific antidote. Treatment is supportive and symptomatic, focusing on airway management, seizure control (e.g., with benzodiazepines), and cardiovascular stabilization. Activated charcoal may be used for recent oral ingestions. Patients require close monitoring for at least 72 hours.

Drug Interactions

Critical Interactions

Clomipramine interacts significantly with several drug classes:

MAOIs: Concurrent use is contraindicated due to the risk of serotonin syndrome and hypertensive crisis. A substantial washout period is necessary.
SSRIs: Increased risk of serotonin syndrome due to additive serotonergic effects. Pharmacokinetic interactions via CYP2D6 inhibition can also elevate Clomipramine levels.
CYP2D6 Inhibitors: Can increase Clomipramine plasma concentrations, raising the risk of CNS and cardiotoxicity.
Diuretics: Potential for hypokalemia, which increases the risk of QTc prolongation.
Other CNS Depressants: Additive sedative effects.

Pharmacokinetic Considerations

Clomipramine is metabolized primarily by CYP2D6. Co-administration with potent inhibitors or inducers of this enzyme system can significantly alter Clomipramine's plasma concentrations and therapeutic effect or toxicity profile.

Pharmacology Deep Dive

Pharmacodynamics

Clomipramine is a potent inhibitor of serotonin reuptake (SRI) and a moderate inhibitor of norepinephrine reuptake (NRI), classifying it as a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI). Its active metabolite, desmethylclomipramine, contributes significantly to NRI activity. Additionally, it exhibits antagonism at various receptors, including histamine H1, alpha-1 adrenergic, muscarinic acetylcholine, and dopamine D1/D2/D3 receptors, contributing to both its therapeutic effects and side effect profile.

Receptor Binding Profile

Clomipramine demonstrates high affinity for the serotonin transporter (SERT) and moderate affinity for the norepinephrine transporter (NET). Its receptor binding profile is extensive, influencing its clinical effects and potential adverse events:

Clomipramine (and metabolite) Receptor Binding Affinities (K_i nM)
Site	Clomipramine (CMI)	Desmethylclomipramine (DCMI)	Species	Ref
SERT	0.14–0.28	31.6	Human/rat	¹⁰³¹⁰⁴¹⁰⁵
NET	38–53.7	0.32	Human/rat	¹⁰³¹⁰⁴¹⁰⁵
DAT	≥2,190	2,100	Human/rat	¹⁰³¹⁰⁴¹⁰⁵
5-HT_1A	≥7,000	19,000	Human/und	¹⁰⁶¹⁰⁴¹⁰⁵
5-HT_2A	27–35.5	130	Human/und	¹⁰⁶¹⁰⁴¹⁰⁵
H₁	13–31	450	Human/und	¹¹²¹¹¹¹⁰⁵
α₁-adrenergic	3.2–38	190	Human/und	¹⁰⁴¹¹¹¹⁰⁵
Muscarinic Acetylcholine	37	92	Human/und	¹¹¹¹⁰⁵
Dopamine D₁	219	320	Human/und	¹⁰⁷¹⁰⁵
Dopamine D₂	77.6–190	1,200	Human/und	¹⁰⁴¹¹¹¹⁰⁵

Values are K_i (nM). Lower values indicate higher affinity. The extensive binding profile contributes to both therapeutic effects and potential side effects.

Pharmacokinetics

Clomipramine exhibits approximately 50% oral bioavailability. Peak plasma concentrations are reached within 2-6 hours. It is extensively bound to plasma proteins (~97-98%) and extensively metabolized in the liver, primarily by CYP2D6. The terminal half-life of Clomipramine is around 32 hours, while its active metabolite, desmethylclomipramine, has a longer half-life of approximately 69 hours. Excretion occurs mainly via urine (60%) and feces (32%).

Chemical Structure & Properties

Molecular Profile

Clomipramine belongs to the dibenzazepine class of tricyclic compounds. Its chemical name is 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine. The molecular formula is C₁₉H₂₃ClN₂, with a molar mass of approximately 314.86 g/mol. It is typically administered as the hydrochloride salt.

Key Identifiers:

CAS Number: 303-49-1 (free base)
PubChem CID: 2801
SMILES: CN(C)CCCN1c2ccccc2CCc2ccc(Cl)cc21

Synthesis & Analogs

Developed as a chlorinated derivative of imipramine, Clomipramine's structure facilitates potent serotonin reuptake inhibition. Its classification as a tertiary amine TCA places it alongside other well-known agents like imipramine and amitriptyline, though its specific pharmacological actions differentiate its clinical utility.

Historical Context

Development and Approval

Clomipramine was synthesized by Geigy (later Ciba-Geigy) in the early 1960s and patented in 1963. It gained initial medical approval in Europe for depression in 1970. Its journey to FDA approval in the United States was notably delayed, initially being considered a "me-too" drug. It was eventually approved for OCD in 1989, becoming the first medication specifically indicated for this disorder.

Clinical Evolution

Initially considered the gold standard for OCD treatment, Clomipramine's use has evolved with the advent of Selective Serotonin Reuptake Inhibitors (SSRIs). While SSRIs offer improved tolerability and safety profiles, Clomipramine often retains an edge in efficacy, particularly in severe or treatment-resistant cases. Its unique pharmacological properties continue to make it a valuable therapeutic option.

Society & Nomenclature

Nomenclature and Branding

Commonly known by the brand name Anafranil, Clomipramine is available globally. Its generic names include Clomipramine (English, French, Spanish, Italian) and Clomipramin (German). The hydrochloride salt is the standard pharmaceutical form.

Global Availability

Clomipramine is listed on the World Health Organization's Model List of Essential Medicines, underscoring its importance in global healthcare systems. It is available in numerous countries, reflecting its established role in psychiatric pharmacotherapy.

Veterinary Applications

Canine Use

In veterinary medicine, Clomipramine (marketed as Clomicalm) is primarily approved in the US for treating separation anxiety in dogs. It has also shown efficacy in managing obsessive-compulsive behaviors like tail chasing and noise phobias in canine patients.

Feline Use

Clomipramine is utilized in feline patients to address behavioral issues such as urine spraying and marking. Studies indicate a significant reduction in these behaviors, making it a valuable tool for managing stress-related conditions in cats.

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References

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Adebayo, Kazeem Olaide et al. "Body dysmorphic disorder in a Nigerian boy presenting as depression: a case report and literature review." International Journal of Psychiatry in Medicine Vol. 44,4 (2012): 367-72. doi:10.2190/PM.44.4.f

Phillips, K.A., Albertini, R.S., Siniscalchi, J.M., Khan, A. and Robinson, M., 2001. "Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study." Journal of Clinical Psychiatry, 62(9), pp. 721-727.

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Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. "Cataplexyâclinical aspects, pathophysiology and management strategy." Nature Reviews Neurology. 2014 Jul, 10(7):386-95..

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Bayes, A. and Parker, G., 2019. How to choose an antidepressant medication. Acta Psychiatrica Scandinavica, 139(3), pp.280-291.

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Mandagere, V. and Rayment, D., 2024. Atypical isolated cataplexy: two case reports and a mini-review. Neurocase, pp.1-3.

Boyson S. J. (1988). Bethanechol for anticholinergic side effects. Annals of neurology, 23(4), 422â423. https://doi.org/10.1002/ana.410230429

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A full list of references for this article are available at the Clomipramine Wikipedia page

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Clomipramine Unveiled

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Medical Uses ⚕️

🧠 Obsessive-Compulsive Disorder (OCD)

😔 Major Depressive Disorder (MDD)

🏃 Other Applications

Contraindications 🚫

⚠️ Absolute Contraindications

🤰 Pregnancy and Lactation

Side Effects Profile 🌡️

📈 Common Side Effects

📉 Less Common & Rare Side Effects

Withdrawal Considerations 🛑

⚠️ Withdrawal Syndrome

📉 Management of Withdrawal

Overdose Management 🚨

⚡ Clinical Presentation

🏥 Treatment Principles

Drug Interactions ↔️

⚠️ Critical Interactions

⚙️ Pharmacokinetic Considerations

Pharmacology Deep Dive 🔬

⬆️ Pharmacodynamics

📊 Receptor Binding Profile

⏳ Pharmacokinetics

Chemical Structure & Properties 🧪

🔗 Molecular Profile

💡 Synthesis & Analogs

Historical Context 📜

🕰️ Development and Approval

⭐ Clinical Evolution

Society & Nomenclature 🏷️

📚 Nomenclature and Branding

🌍 Global Availability

Veterinary Applications 🐾

🐶 Canine Use

🐈 Feline Use

Teacher's Corner 🧑‍🏫

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Gamer's Corner 🎮

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Explore More Topics

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References

📜 References

Feedback & Support 👍

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Disclaimer ⚠️

📜 Important Information

Dive in with Flashcard Learning!

Medical Uses

Obsessive-Compulsive Disorder (OCD)

Major Depressive Disorder (MDD)

Other Applications

Contraindications

Absolute Contraindications

Pregnancy and Lactation

Side Effects Profile

Common Side Effects

Less Common & Rare Side Effects

Withdrawal Considerations

Withdrawal Syndrome

Management of Withdrawal

Overdose Management

Clinical Presentation

Treatment Principles

Drug Interactions

Critical Interactions

Pharmacokinetic Considerations

Pharmacology Deep Dive

Pharmacodynamics

Receptor Binding Profile

Pharmacokinetics

Chemical Structure & Properties

Molecular Profile

Synthesis & Analogs

Historical Context

Development and Approval

Clinical Evolution

Society & Nomenclature

Nomenclature and Branding

Global Availability

Veterinary Applications

Canine Use

Feline Use

Teacher's Corner

True or False?

Test Your Knowledge!

Gamer's Corner

Discover other topics to study!

References

Feedback & Support

Disclaimer

Important Information