dosulepin

Action and Spectrum

Actions and spectrum: 

dosulepin is a tricyclic antidepressant that acts by inhibiting reuptake of serotonin & norepinephrine in the brain, results in increased levels of neurotransmitters in the synapses. This action helps alleviate symptoms of depression and other mood disorders. dosulepin also has sedative properties, which can be beneficial for managing anxiety and sleep disturbances.

The onset of action for dosulepin might require between 4 and 6 weeks to begin showing its effects.

It may also be used off-label for other conditions, such as neuropathic pain and migraine prophylaxis. However, it is essential to note that dosulepin should be used with caution and under medical supervision due to its potential for side effects and interactions with other medications.

Drug Interaction

Adverse Reaction

Frequency not defined 

• Drowsiness 
• Change in heart rate 
• Constipation 
• blurred vision 
• Excessive sweating 
• Difficulty in urination 
• Mental Confusion 
• Increase/decrease in libido 
• Nausea or Vomiting 
• Dry mouth 
• Slurred speech 
• Intestinal obstruction 

Black Box Warning

Black Box Warning: 

dosulepin carries a black box warning due to its potential to increase the risk of suicidal thoughts and behaviours, especially in children, adolescents, and young adults. Antidepressant medications, including dosulepin, have been associated with an increased risk of suicidal ideation during the early stages of treatment. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Patients with a known hypersensitivity or allergy to dosulepin or any of its components should not take this medication. 
• Recent Myocardial Infarction: dosulepin should not be used in patients who have recently experienced a heart attack. 
• Cardiac Arrhythmias: Patients with severe heart rhythm disturbances, such as atrioventricular block or other significant cardiac conduction abnormalities, should not take dosulepin. 
• Acute Intoxication: It is not recommended to use dosulepin in patients with acute intoxication from alcohol, sedatives, or other central nervous system depressants. 
• Urinary Retention: Patients with urinary retention, a condition where they have difficulty emptying their bladder, should not use dosulepin. 
• Use with Monoamine Oxidase Inhibitors (MAOIs): Co-administration of dosulepin with MAOIs or within 14 days of discontinuing MAOIs is contraindicated, as it may lead to severe adverse effects.

Caution: 

• Cardiovascular Conditions: Patients with cardiovascular diseases, including heart failure, angina, or conduction abnormalities, should be closely monitored while using dosulepin, as it may worsen these conditions. 
• History of Seizures: dosulepin may lower the seizure threshold, so caution is advised in patients with a history of seizures or epilepsy. 
• Elderly Patients: Elderly individuals may be more sensitive to the effects of dosulepin, so lower doses or careful monitoring may be necessary. 
• Hepatic Impairment: dosulepin is primarily metabolized in the liver, so caution is needed in patients with mild to moderate hepatic impairment to avoid excessive drug accumulation. 
• Renal Impairment: dosulepin is eliminated through the kidneys, and caution should be exercised in patients with impaired renal function to adjust the dosage as needed. 
• Hypothyroidism: dosulepin may cause alterations in thyroid function tests, so caution is advised in patients with hypothyroidism. 
• Mania/Hypomania: dosulepin may induce or exacerbate symptoms of mania or hypomania in bipolar disorder. 
• Pregnancy and Lactation: dosulepin should only be used during pregnancy or lactation if the potential benefits outweigh the risks, and under the supervision of a healthcare professional.

Comorbidities: 

• Anxiety disorders: anxiety disorders co-occur with depression, and dosulepin may be used to treat both conditions when necessary. 
• Chronic pain conditions: Depression can be associated with chronic pain, and dosulepin’s sedative and analgesic effects may be beneficial in managing this comorbidity. 
• Sleep disorders: dosulepin’s sedative effects may also be useful in treating sleep disturbances commonly seen in individuals with depression. 
• Diabetes: dosulepin may affect blood sugar levels, and adjustments in diabetes medication may be necessary in patients with diabetes. 
• Epilepsy: dosulepin may lower the seizure threshold, and patients with epilepsy require careful monitoring during treatment. 
• Thyroid disorders: dosulepin can cause alterations in thyroid function tests, so it should be used with caution in individuals with thyroid disorders. 
• Glaucoma: dosulepin can increase intraocular pressure and should be used cautiously in patients with open-angle glaucoma. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category C 

Lactation: excreted in 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: 

dosulepin is a tricyclic antidepressant (TCA) with a complex pharmacology. It primarily inhibits the reuptake of serotonin and norepinephrine in the brain, leading to increased synaptic concentrations of these neurotransmitters. By doing so, dosulepin restores the balance of these chemicals, which are implicated in mood regulation and emotional well-being.

Additionally, dosulepin has anticholinergic properties, which can cause blurred vision, dry mouth, and constipation. It also blocks histamine H1 receptors, contributing to its sedative effects. dosulepin is metabolized in the liver, and its active metabolite further contributes to its pharmacological effects. Proper dosing and careful monitoring are necessary to ensure the medication’s efficacy and minimize potential side effects.  

Pharmacodynamics: 

The pharmacodynamics of dosulepin, a tricyclic antidepressant (TCA), involves its action on various neurotransmitter systems in the brain. It primarily acts as a serotonin and norepinephrine reuptake inhibitor, preventing their reabsorption into nerve cells. This leads to increased levels of neurotransmitters in the synapses, enhancing their transmission and improving mood regulation. By blocking the serotonin and norepinephrine reuptake, dosulepin helps alleviate symptoms of depression and anxiety. 

The pharmacodynamics of dosulepin is complex and involves interactions with multiple neurotransmitter systems, leading to its therapeutic effects as an antidepressant. Proper dosing and monitoring are essential to achieve the desired therapeutic outcomes while minimizing adverse effects.  

Pharmacokinetics: 

Absorption 

dosulepin is well-absorbed from the gastrointestinal tract after oral administration. It reaches peak plasma concentrations within 2-4 hours. 

Distribution 

dosulepin is extensively distributed throughout the body, including the central nervous system (CNS), due to its lipophilic nature. 

Metabolism 

dosulepin is extensively metabolized in the liver via the cytochrome P450 enzyme system, primarily CYP2D6. It undergoes N-demethylation and hydroxylation, resulting in the formation of active metabolites, which contribute to its pharmacological effects. 

Elimination and excretion 

After metabolism, dosulepin and its metabolites are eliminated through the urine. Only a small fraction is excreted in the feces. 

Adminstartion

Administration: 

• Dosage: The dosulepin dosage will be based on the severity of the depression or mood disorder, the patient’s age, weight, and response to treatment. The initial dosage is usually lower and may be gradually increased as necessary to achieve the desired therapeutic effect. 
• Timing: dosulepin is typically taken once daily, preferably at bedtime. Some individuals may be advised to split the daily dose into two smaller doses, with one in the morning and one at bedtime, to reduce potential side effects. 
• Swallowing: dosulepin tablets or capsules should be swallowed whole with a full glass of water. Do not chew or crush the tablets unless instructed otherwise by the healthcare provider. 
• Compliance: It is essential to take dosulepin exactly as prescribed by the healthcare professional. Do not stop or change the dosage without consulting the doctor, even if you feel better, as abruptly discontinuing the medication can lead to withdrawal effects. 
• Duration of Treatment: The duration of dosulepin treatment will depend on the patient’s response to the medication and the nature of the condition being treated. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dosulepin 

Pronounced: (doh-soo-le-pin)  

Why do we use dosulepin? 

• Major Depressive Disorder: dosulepin is primarily prescribed for the treatment of major depressive disorder. 
• Anxiety Disorders: It may be used to alleviate symptoms of anxiety disorders and panic disorder. 
• Neuropathic Pain: dosulepin can be effective in managing certain types of chronic neuropathic pain, such as diabetic neuropathy or postherpetic neuralgia. 
• Bedwetting (Enuresis): In children, dosulepin can be used to treat bedwetting (nocturnal enuresis) that does not respond to other treatments.