Depression is a common withdrawal symptom associated with many addictive substances, and it is often one of the most difficult to cope with. The presence of depression during withdrawal can greatly complicate the recovery process, intensifying distress and heightening the risk of relapse. Desipramine, an antidepressant that has been used effectively for decades, has also been shown to provide significant relief for depression during withdrawal. By potentially alleviating these depressive symptoms, desipramine can enable those in recovery to get through the withdrawal phase more comfortably and progress to the subsequent stages of addiction treatment.

What is desipramine?

Desipramine is a tricyclic antidepressant (TCA) that has been in use since its approval in the 1960s. As a member of the tricyclic class, it operates by modulating the levels of certain neurotransmitters in the brain, primarily norepinephrine and, to a lesser extent, serotonin.

Desipramine’s primary indication is the treatment of depression, including major depressive disorder and dysthymia. Beyond these conventional uses for depression, desipramine has also been used off-label in the treatment of various other conditions, including:

    Attention deficit hyperactivity disorder (ADHD)
    Bulimia nervosa

    Irritable bowel syndrome
    Drug and alcohol detox and withdrawal

Desipramine is available in various forms, most commonly oral tablets, and is prescribed under brand names including:

    Norpramin

    Pertofran
    Irene
    Pertofrane
    Nebril
    Petylyl

Desipramine administration involves careful consideration of dosage tailored to the individual’s specific needs and medical history. Treatment usually begins with a lower dose that gradually increases, depending on the patient’s response and tolerance to the medication. This cautious approach helps to minimise potential desipramine side effects and optimise therapeutic outcomes.

How is desipramine used in addiction treatment?

Depression during withdrawal is not just down to feelings of sadness about addiction; it is a common symptom of the neurochemical imbalances that substance dependence creates.

Physical dependence develops when prolonged drug or alcohol use alters the brain’s chemical and reward systems. Essentially, the brain begins to rely on the presence of the substance to maintain levels of certain transmitters which regulate mood.

When an individual ceases drug or alcohol use, the sudden lack of the substance can lead to a decrease in these neurotransmitters associated with mood regulation, notably norepinephrine and serotonin, which is what causes depressive withdrawal symptoms.

Desipramine’s role in addiction treatment is down to its effectiveness in alleviating these symptoms. By inhibiting the reuptake of norepinephrine and serotonin, desipramine helps to restore these neurotransmitters to more balanced levels, thereby mitigating the severity of depression during withdrawal.

It is essential to note that while desipramine can be a valuable component of treatment for withdrawal-related depression, it is most effective when used as part of a broader, holistic approach to addiction recovery. This approach includes psychological counselling, support groups and other therapeutic interventions designed to address the underlying causes of addiction and equip individuals with the skills needed for long-term sobriety.

Who can desipramine benefit?

Desipramine can benefit a wide range of individuals undergoing addiction recovery from the various substances that can trigger depression during withdrawal. These include alcohol, opioids, benzodiazepines and various prescription drugs. Desipramine can also be particularly beneficial for individuals who have not responded well to other antidepressants or those who experience specific types of depression where desipramine’s pharmacological profile offers unique advantages. Its potential for helping with ADHD symptoms may also provide knock-on benefits for patients with certain co-occurring conditions.

Desipramine side effects

Desipramine use can cause a number of side effects that require careful consideration by both the user and their healthcare provider. Desipramine side effects can range from mild to severe and vary widely among individuals depending on factors such as dosage, duration of treatment and their overall health and sensitivity to the medication.

Common desipramine side effects include:

    Dry mouth

    Dizziness
    Drowsiness
    Blurred vision
    Constipation
    Urinary retention

These desipramine side effects are often mild and may decrease in intensity as the body adjusts to the medication over time. However, they can be bothersome and may require medical attention if they persist or worsen.

More serious desipramine side effects, though less common, can also occur. These include but are not limited to:

    Sudden drops in blood pressure upon standing (orthostatic hypotension)

    Significant changes in heart rate or rhythm
    Severe constipation, confusion
    Hallucinations
    Exacerbation of certain pre-existing conditions, such as glaucoma, due to its anticholinergic effects
    Suicidal thoughts or behaviours
    Withdrawal symptoms – a sudden cessation of desipramine can cause withdrawal symptoms such as headache, weakness and nausea

It is crucial for individuals taking desipramine to communicate openly with their healthcare providers about any side effects they experience. Adjustments to the dosage or switching to an alternative medication may be necessary to manage side effects effectively.

Desipramine overdose

The risk of desipramine overdose is also a critical consideration, as the drug is notably more toxic than most other antidepressants. Desipramine overdose can be life-threatening, with symptoms including:

    Severe cardiac arrhythmias

    Seizures
    Central nervous system depression

Due to its narrow therapeutic index, even small overdoses can result in significant toxicity, underscoring the need for caution in dosing, particularly in those with a history of heart conditions.

Potential desipramine drug interactions

Understanding potential desipramine drug interactions is crucial for minimising adverse effects and ensuring treatment effectiveness. Both individuals and healthcare providers need to be aware of these interactions to manage them proactively. Some of the potential interactions include:

Monoamine oxidase inhibitors (MAOIs)
Combining desipramine with MAOIs can lead to severe and potentially life-threatening reactions, including hypertensive crisis and serotonin syndrome. This syndrome is characterised by symptoms such as confusion, rapid heart rate, high blood pressure, dilated pupils and, in severe cases, shock.
Central nervous system (CNS) depressants
Desipramine’s sedative effects can be amplified when taken in conjunction with other CNS depressants, such as benzodiazepines, opioids, antihistamines or alcohol. This can lead to increased drowsiness, dizziness and impaired cognitive and motor function, raising the risk of accidents and falls, particularly in elderly patients.
Anticholinergic medications
Since desipramine has anticholinergic properties (this means it blocks and inhibits the activity of the neurotransmitter acetylcholine), using it alongside other anticholinergic drugs can enhance these effects. This can lead to an increased risk of urinary retention, constipation and glaucoma.
Sympathomimetic drugs
The combination of desipramine with sympathomimetic agents (e.g., epinephrine, dopamine or amphetamines) can lead to hypertension and arrhythmias due to the enhanced effects on the cardiovascular system.
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs and other antidepressants can alter the metabolism of desipramine, potentially leading to increased plasma levels and enhanced risk of side effects.
Warfarin and other anticoagulants
Desipramine can affect the plasma levels of anticoagulants like warfarin, either increasing or decreasing their effects, which could lead to an elevated risk of bleeding or thrombosis.

It is imperative for patients to inform their healthcare providers about all medications they are taking, including over-the-counter drugs, supplements and herbal products. This information allows for a comprehensive assessment of potential drug interactions and the implementation of appropriate strategies to manage them.

What is the next step?

If you or someone you know is struggling with addiction, it is crucial to seek professional help. Reach out to your GP or a specialised addiction treatment centre to find out your options for medically assisted detox and comprehensive rehabilitation. These resources are equipped to provide the support, medical care and guidance necessary for a safe and effective recovery process.

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FAQ’s

What is desipramine used for?
Desipramine is primarily used for treating depression, including major depressive disorder and depression associated with drug and alcohol withdrawal. It modulates neurotransmitter levels in the brain, notably norepinephrine and serotonin, which affect mood regulation. Desipramine is also used off-label for a number of other conditions with varying levels of evidence of its effectiveness.