Desipramine - Indications, Contraindications, and Dosage

Overview:

Desipramine is a secondary amine that belongs to the class of tricyclic antidepressant drugs. It is an FDA (Food and Drug Administration) approved drug for treating depression. The off-label uses of the drug include:

• Bulimia nervosa (life-threatening eating disorder).

• Irritable bowel syndrome (an intestinal disorder that causes pain in the stomach and diarrhea).

• Neuropathic pain (severe chronic pain of nerve).

• Overactive bladder (bladder problem with a frequent need to urinate).

• Post-herpetic neuralgia (chronic pain where shingles had appeared).

It also improves mood, sleep, and appetite, thus, increasing the body's energy levels and restoring interest. It works by restoring the balance of norepinephrine in the brain.

What Is Depression?

Depression is one of the common mental disorders. The symptoms range from mood fluctuations to emotional changes. It is a mental disorder with a loss of interest accompanied by sadness. It affects the person mentally and emotionally, making them feel weak and lose interest in living. Some of the common symptoms of depression are:

• Loss of interest.

• Frustration.

• Sadness.

• Feeling of guilt.

• Lack of concentration.

• Inability to think.

• Suicidal thoughts.

• Anxiety.

• Sleep disturbances or insomnia.

Indications of Desipramine:

Desipramine is indicated and approved for the treatment of depression. However, it has some off-label uses in treating bulimia nervosa, irritable bowel syndrome, neuropathic pain, overactive bladder, and post-herpetic neuralgia.

Contraindications of Desipramine:

• It is contraindicated in cases with an increased serotonin syndrome risk.

• It is also contraindicated in monoamine oxidase inhibitors (MAOI) patients.

• Contraindicated in the cases of myocardial infarction patients during recovery periods.

Dosage:

• Dose Form - Tablets.

• Dose Strength - 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.

• Dose Administration - Oral.

• Dose Recommendation - A single dose is taken orally once a day.

Mechanism of Action of Desipramine:

Desipramine blocks the reuptake of norepinephrine and serotonin in the presynaptic neuronal membrane. It has greater norepinephrine-blocking properties when compared to other tertiary amine tricyclic antidepressants, which have more significant blockade at serotonin receptors. Reuptake blockade increases the neurotransmitter at the synapse.

Desipramine has also shown antinociceptive effects by manipulation of norepinephrine. Apart from all these, it also downregulates beta-adrenergic receptors and serotonin receptors. In addition, it also expresses alpha-1 blocking, antihistamine, and anticholinergic effects.

Metabolism of Desipramine:

Desipramine is absorbed from the gastrointestinal tract. It has metabolites excreted by the gastric mucosa and reabsorbed from the gastrointestinal tract. Desipramine is metabolized in the liver and excreted in the urine.

Warnings:

• Suicide Risks - Patients who suffer from significant depression issues have a chance of worsening depression and suicidal ideas. They may also feel unusual changes in behavior.

• Bipolar Disorders - The patient can show major depressive episodes of bipolar disorder. So, doctors should screen for bipolar disorders to determine their depressive nature and diagnose bipolar symptoms.

• Serotonin Syndrome - Serotonin syndrome can occur if the monoamine oxidase inhibitors are used along with Desipramine. Serotonin syndrome symptoms include mental status changes with hallucinations, agitation, delirium, or blood pressure variation, temperature changes, seizures, nausea, and vomiting.

• Angled Glaucoma - The eye pupil gets dilated with the use of antidepressants. Desipramine is one of them that can worsen glaucoma.

Special Considerations:

• Pregnancy - The safe use of Desipramine during pregnancy has not been determined, so it is preferably not used.

• Lactating Mothers - The safety of Desipramine in lactating mothers has not been determined. Desipramine must be used very cautiously in such cases.

• Geriatric Use - Conclusive results on older populations have been established. Only lower dosages are preferred in these cases.

• Pediatric Use - Use of Desipramine in children, has not been established. Hence its usage in children is regarded unsafe.

For Patients -

What Is the Use of Desipramine Medicine?

Desipramine is a medicine used to treat depression. However, it is not used as a first-line medicine for depression because it has many side effects. Desipramine enhances the patient's mood, sleep, appetite, and energy.

Why Is Desipramine Prescribed for Treating Depression?

Desipramine is prescribed for treating depression because it works by increasing the amounts of natural substances like epinephrine in the brain that are needed for mental stability.

How Is It Taken?

Desipramine is provided in tablet forms to intake orally. It is usually taken once a day but can be taken more than once a day. It can be taken without meals and at the same time every day. Desipramine is started in low doses, and then gradually, the dose is increased as prescribed by the doctor. The patient should not stop the dose without consulting the doctor; otherwise, the patient may experience withdrawal symptoms like headache and nausea.

What Are the Precautions Taken While Having Desipramine?

• The patient should not take medicine if allergic to Desipramine.

• They should also avoid Desipramine when taking monoamine oxidase inhibitors (MAOI). Inform the doctor if the patient has stopped taking the monoamine oxidase inhibitors; the doctor will recommend having a 14 days gap before starting Desipramine.

• The patient should inform the doctor about medical conditions like a history of heart disease.

• The patient should inform the doctor about the pregnancy or the lactating period, based on which the doctor may not recommend Desipramine.

• The drug can worsen closed or narrow-angled glaucoma, so the patient should eye checkups on regular bases.

• Cigarette smoking and alcohol intake must be avoided when taking Desipramine.

What Are the Side Effects of Desipramine?

Side effects of Desipramine are:

• Nausea.

• Drowsiness.

• Weakness.

• Night hallucinations.

• Dry mouth.

• Skin sensitivity to sunlight.

• Changes in weight and appetite.

• Constipation.

• Excessive urination.

• Excessive sweating.

• Changes in sex drive.

Adverse side effects are:

• Difficulty in speaking.

• Muscle spasms.

• Shaking hands.

• Difficulty in breathing.

• Irregular heartbeat.

• Seizures.

• Sore throat.

• Fever.

• Difficulty in eating.

How to Store and Dispose of the Medicine Desipramine?

The medicine is stored in closed, tight containers and at room temperature. It should be kept away from the approach of children and pets. When the medicine is not required, Desipramine should be disposed of in special ways to prevent it from reaching pets and children. The patient should avoid flushing it into the toilet. After learning about the take-back programs provided by the Food and Drug Administration (FDA), proper medicine disposal should be done.

What if It Causes an Overdose?

Overdosage of Desipramine can occur. If the patient experiences any symptoms regarding overdose, consulting the doctor at the earliest is important. Some symptoms regarding overdose include:

• Irregular heartbeat.

• Seizures.

• Coma.

• Confusion.

• Fever.

• Drowsiness.

• Stiffness in muscles.

• Vomiting and nausea.

• Hallucinations.

• Pupil widening.

• Agitation.

For Doctors -

Desipramine:

Desipramine is a secondary amine tricyclic antidepressant used in depression treatments. It has a chemical name- 5H-Dibenzazepine-5-propanamide,10,11-dihydro-N-methyl-monohydrochloride. It has an active ingredient Desipramine Hydrochloride. Other inactive ingredients are acacia, calcium carbonate, corn starch, iron oxide, mineral oil, mannitol, sodium benzoate, sucrose, talc, and titanium dioxide.

Indication of Desipramine:

• It is indicated for the treatment of depression.

Contraindications of Desipramine:

• Desipramine is avoided in patients taking monoamine oxidase inhibitors (MAOI).

• It is also contraindicated in cases of allergy to Desipramine.

• Contraindicated in the recovery period of myocardial infarction.

• Desipramine is not administered in children under age 18.

Mechanism of Action of Desipramine:

The complete mechanism of action of Desipramine is unknown. Still, it is said that Desipramine restores the normal levels of neurotransmitters by inhibiting the reuptake of neurotransmitter substances (norepinephrine) at the synapses. Desipramine is a secondary amine tricyclic antidepressant that blocks the reuptake of norepinephrine, whereas tertiary amine tricyclic antidepressants block the reuptake of serotonin. It does not work primarily on the central nervous system but has a more rapid onset of action than Imipramine. It takes nearly two to three weeks for the complete treatment and benefit.

Metabolism:

The liver metabolizes it, and nearly 70 % is excreted in the urine.

Dosage and Administrations:

Dosage Form - Tablets.

Dosage Strength - 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 200 mg, 300 mg.

Desipramine is administered orally.

• Adult Dosages - 100 to 200 mg per day are recommended. After observing the patient's condition, the doctor may increase the dosage gradually to 300 mg per day if required. The initial dosage can be given as a single dose daily or in divided doses. The drug is started with lower doses, and the dose is gradually increased based on the patient's tolerance.

• Adolescent and Geriatric Doses - 25 mg to 100 mg daily are recommended. The initial dose is 25 mg (lower) and increased to 100 mg daily. In cases of patient severity, the dosage can be increased to 150 mg daily. Although the initial dosage is lower, further doses are increased gradually after observing the patient's signs and symptoms.

Cautious Use of Desipramine:

• Patients with cardiovascular disease should use Desipramine cautiously because Desipramine can cause arrhythmias, tachycardia, and even strokes.

• Desipramine should be used cautiously in a patient with a family history of sudden death or cardiac dysrhythmias.

• The patient has a history of glaucoma or urinary retentions.

• The patient is on thyroid medications.

• If the patient has a history of seizure disorders, then also cautious use of Desipramine is recommended, as seizures can further proceed to cardiac dysrhythmias and sometimes death.

• As the safety of pregnant and lactating mothers is not determined, cautious use of Desipramine is advised in these cases.

Precautions After Using Desipramine:

• Desipramine can cause drowsiness, so the patient should avoid driving after taking the drug.

• The patient who is an alcohol abuser should not take alcohol along with Desipramine because it can cause more frequent suicidal attempts with ideation.

• The patient can get suicidal ideation, and even their symptoms of depression can worsen after the use of Desipramine initially. The doctor should inform the patient regarding such changes in behavior and thinking.

• The doctor should acknowledge the patient regarding closed-angled glaucoma that can occur after regular use of Desipramine. So, the patient should go for regular eye checkups.

Drug Interactions:

• If Desipramine is co-administered with drugs that are cytochrome P450 2D6 inhibitors, then a lower dosage of the Desipramine is used. If these drugs are co-administered, supervision and dosage adjustment should be made.

• If Desipramine is co-administered with psychotropic agents like hypnotics or sedatives, then close observation of the patient is required as the sedative drugs are additive.

• Concomitant use of both Desipramine and monoamine oxidase inhibitors can be threatening.

• The use of Desipramine with alcohol can also be dangerous.

Adverse Reactions of Desipramine:

• Cardiovascular Changes - Cardiac changes include hypotension, hypertension, heart attack, irregular rhythms, tachycardias, stroke, and myocardial infarction.

• Neurologic Changes - Neurological changes involve tingling, numbness, paresthesias, seizures, and tinnitus.

• Anticholinergic Effects - It include dry mouth, blurred vision, mydriasis, increased intraocular pressure, constipation, urinary retention, and urinary tract dilation.

• Psychiatric Effects - The patient can suffer from confusion, hallucinations, nightmares, insomnia, restlessness, and agitation.

• Allergic Reactions - Allergy includes skin rashes, edema, itchiness, urticaria, fever, and skin rashes.

• Hematologic Effects - The effects include bone marrow depressions with thrombocytopenia and purpura.

• Gastrointestinal Changes - Gastric changes involve nausea and vomiting, hepatitis, diarrhea, jaundice, anorexia, and increased liver and pancreatic effects.

• Endocrine Changes - In males, impotence, painful ejaculations, and libido can occur, whereas enlarged breasts and galactorrhea can occur in females.

• Other Changes - It include increased urination, weakness, fatigue, fever, weight increase or decrease, drowsiness, and dizziness.

Overdosage:

The overdosages of Desipramine can cause life-threatening symptoms and death. Medical attention is required to handle the patient when the toxicity is developed or recognized. Symptoms for overdosage of Desipramine involve:

• Cardiac dysrhythmias.

• Hypotension.

• Central nervous system depression.

• Coma.

• Confusion.

• Hyperthermia.

• Vomitings.

• Hallucinations.

• Drowsiness.

• Muscle stiffness.

• Hyperactive reflexes.

Managements of Overdosage:

• Management of overdosage is done by supportive care and serum alkalinizations.

• Close monitoring of cardiac results is done with ECG (electrocardiogram).

• The airway is maintained by intravenous line and gastric decontamination.

• Gastric decontamination is done under activated charcoal.

• Serum alkalinizations with sodium bicarbonate are administered to treat cases of QRS widening.

• Patients suffering from central nervous system depression should be given benzodiazepines.

• Psychiatric appointments for psychiatric recovery are performed.

Clinical Trials:

Short-term placebo-controlled trials of antidepressant drugs were performed to conclude that antidepressants increased the risk of suicidal thinking and behavior changes in children and adults with major depressive disorders.

• One of the analyses of placebo-controlled trials in children and adults with major depressive disorders, obsessive-compulsive disorder, or other psychiatric disorders had 24 short-term trials with nine antidepressant drugs in the 4400 population.

• Another pooled analysis of the placebo-controlled trials in adults dealing with major depressive or psychiatric disorders of 295 short-term trials with 11 different antidepressant drugs in 77000 populations.

• Results - The analyses reported suicides in adult trials, but conclusive counts do not appear, and no suicides were noted in children. In addition, the report stated that the usage of antidepressants in adults dealing with depression had delayed the recurrence of the depression.