imipramine/chlordiazepoxide

Action and Spectrum

Actions and Spectrum: 

Action: 

imipramine 

imipramine is classified as a tricyclic antidepressant, and its primary mode of action involves the inhibition of neurotransmitter reuptake in the brain. Specifically, it targets the reuptake of neurotransmitters like serotonin and norepinephrine.  

chlordiazepoxide 

chlordiazepoxide is a benzodiazepine medication that acts as a central nervous system depressant. It enhances the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. By doing so, it can produce calming and sedative effects, effectively reducing anxiety and muscle tension. 

Spectrum:  

imipramine 

imipramine is primarily used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and certain types of neuropathic pain. It is not typically prescribed as a first-line treatment due to its potential for side effects and interactions with other medications. It is generally considered when other treatment options have been ineffective. 

chlordiazepoxide 

chlordiazepoxide is primarily used to manage anxiety disorders, alcohol withdrawal symptoms, and to provide short-term relief from anxiety or tension before medical procedures (preoperative anxiety).

Drug Interaction

Adverse Reaction

Frequency not defined  

Hypersensitivity reaction 

weight gain 

Blurred vision 

Constipation 

Dry mouth 

Increased appetite 

Nausea 

Tremors 

Less sedation  

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Do not use imipramine and chlordiazepoxide if you have a known hypersensitivity or allergy to either of these drugs or their components. 

Monoamine Oxidase Inhibitors (MAOIs): Avoid combining imipramine and chlordiazepoxide with MAOIs or within 14 days of discontinuing MAOI therapy. The concurrent use of these medications can lead to potentially life-threatening serotonin syndrome. 

Recent Myocardial Infarction: Individuals who have recently experienced a heart attack (myocardial infarction) should not use imipramine and chlordiazepoxide, as they can increase the risk of cardiac arrhythmias and other cardiovascular complications. 

Severe Liver Dysfunction: Both medications are metabolized by the liver, and their use may be contraindicated in individuals with severe liver dysfunction. Liver function should be closely monitored if used in such cases. 

Pregnancy and Breastfeeding: During pregnancy or while breastfeeding, it is advisable to utilize these medications solely when the potential advantages outweigh the associated risks, and always under the supervision of a healthcare expert. 

Pediatric Use: imipramine and chlordiazepoxide in children and adolescents should be carefully considered, and a healthcare provider should evaluate their safety and efficacy in this age group. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

<b>Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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:  

imipramine is a tricyclic antidepressant. chlordiazepoxide is a benzodiazepine. 

Pharmacodynamics:  

Imipramine  

imipramine works on the inhibition of neurotransmitter reuptake in the brain. Specifically, it targets the reuptake of neurotransmitters like serotonin and norepinephrine.  

Doing so increases the availability of these neurotransmitters in synaptic clefts, which helps regulate mood and alleviate symptoms of depression. 

chlordiazepoxide 

chlordiazepoxide exerts its primary pharmacological effects by enhancing the activity of GABA, which is the major inhibitory neurotransmitter in the central nervous system. It binds to specific GABA-A receptors in the brain, leading to an increase in the inhibitory actions of GABA. This results in reduced neuronal excitability and a calming effect on the CNS. 

Pharmacokinetics: 

Absorption 

imipramine is well absorbed when taken orally. 

It undergoes first-pass metabolism in the liver, which can affect its bioavailability. 

chlordiazepoxide is well absorbed when taken orally, rapidly, and completely absorbed from the gastrointestinal tract. 

Distribution 

imipramine is widely distributed throughout the body, including the brain, due to its lipophilic nature. It can bind to plasma proteins, affecting its distribution and availability at target sites. 

chlordiazepoxide is distributed throughout the body, including the brain, due to its lipophilic nature. It can bind to plasma proteins. 

Metabolism 

imipramine is extensively metabolized in the liver primarily via the cytochrome P450 enzyme system, specifically CYP2D6. 

chlordiazepoxide is extensively metabolized in the liver. 

Excretion and Elimination 

The metabolites of imipramine, including desipramine, are eliminated mainly through renal excretion. A small portion of the drug and its metabolites can be excreted in feces. 

The metabolites of chlordiazepoxide, including desmethyldiazepam, are eliminated mainly through renal excretion. 

Adminstartion

Administration:  

The combination is taken orally, typically in tablets or capsules. The duration of treatment can vary. Using it as prescribed is essential, and your doctor will determine when it’s appropriate to stop or reduce the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: imipramine/ chlordiazepoxide 

Why do we use imipramine/ chlordiazepoxide?  

This combination can be used together to treat various types of disorders. imipramine helps alleviate chronic anxiety symptoms, while chlordiazepoxide provides more immediate relief during acute anxiety episodes.  

The combination of imipramine and chlordiazepoxide can be prescribed for the treatment of panic disorder. imipramine may help reduce the frequency and intensity of panic attacks over time, while chlordiazepoxide can offer rapid relief during panic attacks.  

For individuals with depression accompanied by significant anxiety symptoms, a combination of imipramine and chlordiazepoxide may be prescribed. Imipramine addresses the depressive symptoms, while chlordiazepoxide helps manage the associated anxiety.