dibenzepin

Action and Spectrum

Actions and spectrum: 

Actions: 

• Serotonin-Norepinephrine Reuptake Inhibition (SNRI): Like other tricyclic antidepressants, dibenzepin inhibits the reuptake of the neurotransmitter’s serotonin and norepinephrine. By blocking the reuptake of these neurotransmitters, dibenzepin increases their levels in brain, which can lead to improved mood and emotional stability. 
• Anticholinergic Effects: dibenzepin has anticholinergic properties, meaning it can block the activity of acetylcholine. This can result in various side effects, including dry mouth, blurred vision, constipation, and urinary retention. 
• Histamine H1 Receptor Blocking: dibenzepin can also block histamine H1 receptors, which can contribute to sedation and drowsiness, common side effects of TCAs. 

Spectrum: 

dibenzepin is primarily indicated for the treatment of depression. It falls within the broader category of tricyclic antidepressants and shares similarities in its mechanism of action and effects with other TCAs. Its spectrum of activity is focused on mood disorders, specifically depression, and it is not typically used to treat other conditions. 

It is important to note that the use of dibenzepin should be guided by a healthcare provider’s prescription and monitoring due to potential side effects and interactions with other medications. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Dry mouth 

Constipation 

increased heart rate 

blurred vision 

urinary retention 

Drowsiness  

Sedation 

dizziness 

Irregular heartbeats, 

increased heart rate 

confusion. 

Nausea,  

vomiting,  

gastrointestinal discomfort. 

Reduced libido, 

erectile dysfunction 

Agranulocytosis 

suicidal thoughts 

Black Box Warning

Black Box Warning: 

dibenzepin carries a black box warning regarding the increased risk of suicidal thoughts & behaviors, particularly in children, adolescents, and young adults during initial treatment phases. Close monitoring for any signs of worsening depression, agitation, or unusual behavior is essential. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Contraindicated in individuals with a known hypersensitivity or allergy to dibenzepin or other tricyclic antidepressants (TCAs). 
• Recent Myocardial Infarction: Use is contraindicated in individuals who have experienced a recent heart attack (myocardial infarction) due to potential cardiac effects. 
• Narrow-Angle Glaucoma: Contraindicated in patients with narrow-angle glaucoma, a type of eye disorder. 
• Urinary Retention: dibenzepin is contraindicated in individuals with urinary retention, as it may exacerbate this condition. 
• Concurrent Monoamine Oxidase Inhibitors (MAOIs): Use is contraindicated in individuals taking or within 14 days of discontinuing MAOIs due to the risk of serotonin syndrome. 
• Concurrent Linezolid or Methylene Blue: Contraindicated when co-administered or within 14 days of stopping linezolid or methylene blue due to its risk of serotonin syndrome. 
• Concurrent Use of Pimozide: Contraindicated in combination with pimozide, a medication used to treat Tourette’s syndrome and certain psychiatric disorders. 
• Concurrent Use of Thioridazine: Contraindicated when used with thioridazine due to potential cardiac effects.

Caution: 

• Cardiovascular Conditions: dibenzepin may have cardiac effects, including arrhythmias, tachycardia, and changes in blood pressure. Caution is advised in patients with cardiovascular disorders. 
• Elderly Patients: Elderly individuals may be more sensitive to the sedative and anticholinergic effects of dibenzepin, increasing the risk of cognitive impairment, and other side effects. 
• Urinary Retention: dibenzepin can exacerbate urinary retention. Caution is necessary in patients with urinary issues. 
• Glaucoma: Caution is advised in individuals with open-angle glaucoma due to the anticholinergic effects of dibenzepin. 
• Liver and Kidney Impairment: Adjustments to dosing may be required in impaired liver or kidney function. 
• Pregnancy and Lactation: Use during pregnancy or breastfeeding should be carefully considered, weighing potential risks and benefits. 
• Anticholinergic Effects: Be cautious about the potential for anticholinergic effects, which can cause dry mouth, constipation, blurred vision, and urinary retention. 

Comorbidities: 

• Anxiety Disorders: Depression frequently coexists with generalized anxiety disorder, or social anxiety disorder. 
• Bipolar Disorder: dibenzepin’s use should be cautious in patients with bipolar disorder due to the risk of inducing manic episodes. 
• Diabetes: Depression is more prevalent in individuals with diabetes, and dibenzepin’s impact on blood glucose levels should be considered. 
• Thyroid Disorders: Thyroid dysfunction can impact mood, and coexisting thyroid disorders should be evaluated and managed. 
• Chronic Pain: dibenzepin may be used to manage depression in patients with chronic pain conditions, as pain and depression often coexist. 
• Eating Disorders: Mood disorders and eating disorders can be interconnected, requiring a comprehensive treatment approach. 
• Sleep Disorders: Depression and sleep disorders frequently occur together, necessitating careful consideration of treatment approaches. 
• Personality Disorders: Patients with personality disorders may have more complex treatment needs when managing depression. 
• Gastrointestinal Disorders: Depression may worsen symptoms of gastrointestinal conditions, and the potential anticholinergic effects of dibenzepin should be considered. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy category: C 

Lactation: excreted into breast milk: yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

dibenzepin, also known by its trade name Noveril, is a tricyclic antidepressant (TCA) with a complex pharmacological profile. It primarily functions by inhibiting the reuptake of neurotransmitters serotonin and norepinephrine, leading to increased availability of these chemicals in the brain. This mechanism contributes to its mood-stabilizing effects in treating depression.

Additionally, dibenzepin possesses anticholinergic properties, blocking the activity of acetylcholine and resulting in side effects like dry mouth and blurred vision. Its histamine receptor-blocking action may contribute to sedation. dibenzepin’s efficacy in managing depressive symptoms underscores its role as an option in addressing mood disorders, though its use requires careful consideration of potential benefits and side effects based on individual patient characteristics.  

Pharmacodynamics: 

• Serotonin-Norepinephrine Reuptake Inhibition (SNRI): dibenzepin inhibits the reuptake of neurotransmitters serotonin and norepinephrine at the synaptic cleft, thereby enhancing their availability in the brain. This action contributes to mood stabilization and alleviation of depressive symptoms. 
• Blockade of Postsynaptic Receptors: dibenzepin antagonizes certain postsynaptic receptors, including serotonin (5-HT2) and norepinephrine (α1) receptors. This receptor blockade modulates neurotransmitter activity and can impact mood, cognition, and behavior. 
• Anticholinergic Activity: dibenzepin has anticholinergic effects, blocking the activity of the neurotransmitter acetylcholine. This action can lead to side effects like dry mouth, blurred vision, constipation, and urinary retention. 
• Histamine H1 Receptor Blocking: dibenzepin can block histamine H1 receptors, contributing to sedation and drowsiness often associated with TCAs. 
• Downregulation of Adrenergic and Serotonergic Receptors: Chronic use of dibenzepin can lead to downregulation of certain adrenergic and serotonergic receptors, influencing the overall neurotransmitter balance and contributing to its therapeutic effects. 
• Neuroplasticity and Synaptic Changes: Prolonged treatment with dibenzepin may lead to neuroplastic changes, including alterations in synaptic structure and receptor densities, contributing to its antidepressant actions.

Pharmacokinetics: 

Absorption 

dibenzepin is well-absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are typically reached within several hours. 

Distribution 

dibenzepin has a high volume of distribution, indicating extensive distribution into body tissues. It can cross the blood-brain barrier, allowing access to the central nervous system (CNS) where it exerts its antidepressant effects. The drug also binds extensively to plasma proteins. 

Metabolism 

dibenzepin undergoes extensive hepatic metabolism via cytochrome P450 enzymes, primarily CYP2D6 and CYP1A2. It is metabolized into several active and inactive metabolites, which may contribute to its overall pharmacological effects and potential variations in individual response. 

Elimination and excretion 

Metabolites of dibenzepin and a small portion of unchanged drug are excreted primarily in the urine. The elimination half-life of dibenzepin and its metabolites varies between individuals due to factors such as genetic differences in metabolizing enzymes. 

Adminstartion

Administration: 

• Dosage: The dosage of dibenzepin can vary widely based on the severity of the condition, individual patient factors, and the healthcare provider’s judgment. It is important to start with a low dose and gradually titrate to the effective therapeutic dose while monitoring for any adverse effects. 
• Frequency: dibenzepin is usually taken multiple times per day, with most dosing regimens involving two to three divided doses. The frequency of dosing is determined by the healthcare provider based on the drug’s half-life and the desired therapeutic effect. 
• Timing: dibenzepin is commonly taken with meals to help reduce stomach upset. The exact timing of administration should be discussed with a healthcare provider to optimize the drug’s absorption and minimize potential side effects. 
• Duration: dibenzepin is typically used as a long-term treatment for depression and related mood disorders. It may take several weeks to experience the full therapeutic effects, so it’s important to continue taking the medication as prescribed even if improvement is not immediately noticeable. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dibenzepin 

Pronounced: (dye-BEN-zuh-peen)  

Why do we use dibenzepin? 

dibenzepin is a tricyclic antidepressant medication that is primarily used to treat various mood disorders, particularly depression. 

Major Depressive Disorder: dibenzepin is prescribed to alleviate symptoms of major depressive disorder, including persistent sadness, changes in sleep, loss of interest, appetite, and feelings of worthlessness or guilt.