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Desipramine (Norpramin) - Uses, Dosage, Side effects, Brands

Desipramine (Norpramin) is a tricyclic antidepressant that is used in the treatment of depression and neuropathic pain. Compared to other TCAs, it has got less anticholinergic adverse effects.

Indications of Desipramine (Norpramin):

Depression:
- It is indicated for the treatment of depression.
Off Label Use of Desipramine in Adults:
- Bulimia nervosa
- Diabetic neuropathy
- Irritable bowel syndrome
- Postherpetic neuralgia

Desipramine (Norpramin) dose in adults:

Desipramine (Norpramin) dose in the treatment of bulimia nervosa (off-label):

Initial: For three days, take 25 mg per oral, then increase by 25 to 50 mg every three to five days, depending on response and tolerance, up to 300 mg per day.
Clinical trial dosages typically ranged from 100 to 200 mg per day.

Desipramine (Norpramin) dose in the treatment of depression:

Initial dose: Depending on tolerance and reaction, dosages can be increased from 25 to 50 mg orally once daily or in divided doses.
The typical maintenance dose is 100 to 200 mg once daily or in divided doses; patients with severe depression may need doses up to 300 mg daily.
The maximum dose is 300 mg/day.

Desipramine (Norpramin) dose in the treatment of Diabetic neuropathy (off-label):

Initial: Once daily at bedtime, 12.5 mg by mouth, followed by increments of 12.5 to 25 mg every two to three days, up to a daily maximum dose of 250 mg, depending on response and tolerability.
If tolerance testing is required, split dosages into two daily parts.
To more clearly identify the function of desipramine in this condition, more information could be required.

Desipramine (Norpramin) dose in the treatment of Irritable bowel syndrome (off-label):

Initial: 5 to 10 mg orally every day before bed.;
Depending on response and tolerance, progressively increase the dose
Doses above 30 mg daily are generally not necessary.
Clinical trials have investigated doses up to 150 mg per day, and the American Gastroenterological Association advises achieving this dosage.

Desipramine (Norpramin) dose in the treatment of Postherpetic neuralgia (off-label):

Initial: 12.5 to 25 mg per oral once or twice daily
Every two to seven days, up to 150 mg/day, increase the dose based on response and tolerability.
Discontinuation of therapy:
- Upon discontinuation of antidepressant therapy, in order to reduce the risk of withdrawal symptoms and allow for the detection of re-emerging symptoms, the dose should be slowly tapered.
- Evidence supporting ideal taper rates is limited.
- Tapering therapy should be done over at least several weeks with consideration to the half-life of the antidepressant;
- Antidepressants with a shorter half-life may need to be tapered more conservatively as per APA and NICE.
- For chronic users, the WFSBP recommendations advise weaning over the course of 4-6 months.
- Therapy should be resumed on the previous prescribed or decreased dose at a more gradual rate in case of bothering withdrawal symptoms.

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
- The interval between stopping an MAO inhibitor and starting desipramine for treating psychiatric disorders should be two weeks.
- The interval between discontinuing desipramine and starting an MAO inhibitor in treating psychiatric disease should be two weeks

Desipramine dose in children:

Desipramine (Norpramin) dose in the treatment of Attention-deficit Hyperactivity Disorder (ADHD):

Titrate dose based on tolerance and response;
Note:
- In conditions where other medications did not provide an adequate response or are not tolerated, desipramine should be considered, it may be beneficial for patients with comorbid conditions (eg, Tourette's syndrome) but it should not be given as the first-line drug.
- Weight-directed dosing:
  - Children ≥5 years and Adolescents:
  - Initial: 1.5 mg/kg/day per oral divided twice daily;
  - Titrate the dose weekly up to a target dose of 3.5 mg/kg/day in 2 divided doses by week 3.
- Fixed-dose Desipramine:
  - Children ≥7 years and Adolescents ≤13 years:
  - Initial: 25 mg per oral at bedtime;
  - Increase the dose at weekly intervals in 25 mg/day increments up to a maximum dose of 25 mg four times daily (100 mg/day) not to exceed 3 mg/kg/day.

Desipramine (Norpramin) dose in the treatment of Depression:

Note:

It is not given as a first-line drug for depression, however, it may be effective in comorbid diseases.
Controlled clinical trials have not shown tricyclic antidepressants to be superior to placebo for the treatment of depression in children and adolescents.
Children 6 to 12 years: Limited data available:
- 1 to 3 mg/kg/day orally in divided doses;
- monitor carefully with doses >3 mg/kg/day.
- The maximum daily dose: 5 mg/kg/day.
Adolescents:
- Initial dose: Start at the lower range and increase based on tolerance and response;
- The usual maintenance dose is 25 to 100 mg/day
- Doses up to 150 mg/day may be necessary for severely depressed patients.
- Maximum daily dose: 150 mg/day.
Discontinuation of therapy:
- Upon discontinuation of antidepressant therapy, in order to reduce the risk of withdrawal symptoms and allow for the detection of re-emerging symptoms, the dose should be slowly tapered.
- Evidence supporting ideal taper rates is limited.
- Tapering therapy should be done over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively as per APA and NICE.
- For chronic users, the WFSBP recommendations advise weaning over the course of 4-6 months.
- Therapy should be resumed on the previous prescribed or decreased dose at a more gradual rate in case of bothering withdrawal symptoms.

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
- The interval between stopping an MAO inhibitor and starting desipramine for treating psychiatric disorders should be two weeks.
- The interval between discontinuing desipramine and starting an MAO inhibitor in treating psychiatric disease should be two weeks.
Use with other MAO inhibitors (linezolid or IV methylene blue):
- For treating psychiatric disorders in patients receiving linezolid or IV methylene blue, alternate drugs should be used.
- Desipramine should be stopped immediately if urgent treatment with linezolid or IV methylene blue is required. Monitoring for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first.
- Desipramine can be restarted 24 hours after the last dose of linezolid or IV methylene blue.

Desipramine (Norpramin) Pregnancy Risk Category: C

Studies on animal reproduction are not conclusive.
Tricyclic antidepressants can be used to treat convulsions, irritability and jitteriness in newborns.
According to ACOG, treatment for depression during pregnancy should be tailored to the patient and use the clinical knowledge of the mental healthcare professional, obstetrician, primary care physician, and paediatrician.
According to the American Psychiatric Association, medication treatment is not a good option.
Postpartum depression is a common condition in women at high risk. Women who have stopped taking antidepressants during pregnancy can resume the treatment after giving birth.
ACOG and APA have developed treatment protocols for women with depression before and during pregnancy.

Use of desipramine during breastfeeding

Desipramine is found in breast milk.
Based on information provided by one mother-infant couple, the estimated exposure to breast-feeding infants is close to 2% of the maternal weight-adjusted dose of 300mg/day desipramine.
Negative outcomes have never been observed.
Although serum concentration monitoring should not be done in infants, it is recommended.

Desipramine (Norpramin) Dose adjustment in kidney disease:

There are no dosage adjustments on labeling; use with caution.

Desipramine (Norpramin) Dose adjustment in liver disease:

There are no dosage adjustments on labeling.

Side effects of Desipramine (Norpramin):

Some reactions listed are based on reports for other agents in this same pharmacologic class, and may not be specifically reported for desipramine.

Cardiovascular:
- Ventricular Fibrillation
- Cerebrovascular Accident
- Premature Ventricular Contractions
- Flushing
- Myocardial Infarction
- Hypertension
- Palpitations
- Heart Block
- Tachycardia
- Edema
- Ventricular Tachycardia
- Cardiac Arrhythmia
- Hypotension
Central Nervous System:
- Hallucination
- Anxiety
- Ataxia
- Tingling Of Extremities
- Delusions
- Psychosis (Exacerbation)
- Dizziness
- Numbness
- Drug Fever
- Neuroleptic Malignant Syndrome
- Extrapyramidal Reaction
- Hypomania
- Fatigue
- Headache
- Insomnia
- Nightmares
- Falling
- Peripheral Neuropathy
- EEG Pattern Changes
- Restlessness
- Disorientation
- Seizure
- Drowsiness
- Tingling Sensation
- Confusion
- Withdrawal Syndrome
- Agitation
Dermatologic:
- Skin Photosensitivity
- Diaphoresis (Excessive)
- Skin Rash
- Pruritus
- Urticaria
- Alopecia
Endocrine & Metabolic:
- Increased Libido
- Decreased Serum Glucose
- Weight Gain
- Galactorrhea
- Increased Serum Glucose
- Gynecomastia
- SIADH
- Weight Loss
- Decreased Libido
Gastrointestinal:
- Nausea
- Anorexia
- Vomiting
- Constipation
- Paralytic Ileus
- Epigastric Distress
- Sublingual Adenitis
- Increased Pancreatic Enzymes
- Parotid Gland Enlargement
- Melanoglossia
- Stomatitis
- Unpleasant Taste
- Diarrhea
- Xerostomia
- Abdominal Cramps
Genitourinary:
- Painful Ejaculation
- Impotence
- Testicular Swelling
- Urinary Retention
- Nocturia
- Urinary Hesitancy
- Urinary Tract Dilation
- Breast Hypertrophy
Hematologic & Oncologic:
- Purpura
- Eosinophilia
- Thrombocytopenia
- Petechia
- Agranulocytosis
Hepatic:
- Increased Liver Enzymes
- Cholestatic Jaundice
- Increased Serum Alkaline Phosphatase
- Hepatitis
- Abnormal Hepatic Function Tests
Neuromuscular & Skeletal:
- Weakness
- Tremor
Ophthalmic:
- Increased Intraocular Pressure
- Blurred Vision
- Mydriasis
- Accommodation Disturbance
Otic:
- Tinnitus
Renal:
- Polyuria
Miscellaneous:
- Fever

Contraindications to Desipramine (Norpramin):

hypersensitivity to desipramine plus any other formulation ingredient
treating psychiatric diseases with a combination of treatment and MAO inhibitors (or within fourteen days of stopping desipramine, or an MAO inhibitor)
Desipramine therapy for a patient who is receiving intravenous methyleneblue or linezolid
It is not recommended for use in patients during acute recovery phases of MI.
There are few documented cases of cross-reactivity between drugs of this class and allergenic ones.
Due to similarities in chemical structure and/or pharmacological pharmacologic activity, cross-sensitivity is a possibility. It can't be completely ruled out, though.

Warnings and precautions

Anticholinergic effects
- Desipramine may cause constipation, xerostomia and blurred vision.
- Patients with reduced gastrointestinal motility, paralytic and ileus, urinary retentions, BPH, xerostomia or visual problems are at greater risk. Therefore, caution should be exercised.
- This agent produces a low degree of anticholinergic blockingade relative to other antidepressants.
Depression in the CNS:
- CNS depression can lead to impairment of physical and mental abilities.
- It is important to warn patients about driving or operating machinery.
Fractures
- Antidepressant therapy may lead to bone fractures.
- A fragility fracture is recommended for patients who are taking antidepressants and have undiagnosed bone pain, tenderness, swelling, or bruising.
Hematologic effects
- Antidepressant therapy can cause bone marrow suppression.
- Therefore, it's crucial to keep an eye out for infection symptoms as well as CBC results in cases of fever or sore throat.
Ocular effects
- Mild pupillary dilatation brought on by antidepressant medication can result in narrow-angle glaucoma.
- It is suggested that patients who have never undergone an iridectomy have their risk factors for developing narrow-angle glaucoma assessed.
Orthostatic hypotension
- Orthostatic hypotension may occur (risk is moderate in comparison to other antidepressants).
- Patients at high risk for this effect, as well as patients who cannot tolerate hypotensive episodes (e.g., hypokalemia, cerebrovascular diseases, cardiovascular disease) or those taking drugs that may cause hypotension/bradycardia should be cautious.
Serotonin syndrome
- Fatal serotonin syndrome is a condition that causes mental changes such as agitation, hallucinations and delirium.
- These symptoms or signs should prompt you to stop taking any medication.
- Serotonergic drugs (eg SSRIs, SNRIs), concurrent treatment with serotonergic medications (eg triptans TCAs, fentanyl and buspirone, tryptophan, St John's wort) or drugs causing impaired serotonin metabolism (eg MAO inhibitors for psychiatric disorders or other MAO inhibitors [ie linezolid, intravenous methyleneblue]) increase the risk.
SIADH and Hyponatremia
- Hyponatremia or SIADH can be caused by antidepressant therapy.
- This risk is much higher in the elderly, females, patients who have a low body mass index, are suffering from severe physical illness or use diuretics concurrently.
- TCAs are less likely to cause hyponatremia than SSRIs.
Cardiovascular disease
- Conduction abnormalities can be caused by tricyclic antidepressants.
- Patients with a history or cardiovascular disease (including stroke or MI), are at greater risk.
Diabetes:
- Desipramine can alter glucose regulation so patients with diabetes mellitus should be cautious.
Hepatic impairment
- Patients with hepatic impairment should be cautious.
Hypomania and mania:
- FDA has not approved desipramine as a treatment for bipolar depression.
- In bipolar individuals, it may cause mania or hypomania.
- Desipramine should not be used by itself to treat bipolar disorder.
- Patients with depression symptoms should be screened for bipolar disorder.
- This includes details about their family history, suicide attempts, bipolar disorder, depression, and other mental disorders.
Renal impairment
- Patients with impaired renal function should be cautious.
Seizure disorder
- Desipramine shouldn't be taken in people who are at high risk for seizures since it may lower the seizure threshold.
- This includes those who have had seizures, brain damage or a history of head trauma.
- In some cases, seizures may be preceded by cardiac dysrhythmias or death.

Desipramine: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Acetylcholinesterase inhibitors	Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors.
Ajmaline	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Alcohol (Ethyl).	CNS Depressants can increase the CNS depressant effects of Alcohol (Ethyl).
Alizapride	CNS Depressants may increase the CNS depressant effects.
Alpha1-Agonists	Tricyclic Antidepressants could decrease the therapeutic effects of Alpha1Agonists. Tricyclic Antidepressants could decrease the vasopressor effects of Alpha1Agonists. Tricyclic Antidepressants could enhance Alpha1-Agonists' therapeutic effects. Tricyclic Antidepressants could enhance Alpha1-Agonists' vasopressor effects.
Alpha2-Agonists (Ophthalmic).	Tricyclic Antidepressants could decrease the therapeutic effects of Alpha2-Agonists.
Altretamine	May increase the orthostatic hypotensive effects of Tricyclic Antidepressants.
Amantadine	Anticholinergic Agents may have an enhanced anticholinergic effect.
Amezinium	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Amifampridine	Agents with Seizure Threshold Lower Potential can enhance the neuroexcitatory or seizure-potentiating effects of Amifampridine.
Amphetamines	Tricyclic Antidepressants can enhance Amphetamines' stimulatory effects. Tricyclic Antidepressants can also increase the cardiovascular effects of Amphetamines.
Anticholinergic Agents	Other Anticholinergic Agents may have an adverse/toxic effect.
Antiemetics (5HT3 Antagonists).	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Antipsychotic Agents	Antipsychotic Agents may have a greater adverse/toxic effect if they are regulated with serotonin modulators. Serotonin modulators can increase dopamine blockade and, therefore, may increase the risk of developing neuroleptic malignant syndrome. Serotonin modulators may have a serotonergic effect that is enhanced by antipsychotic agents. This could lead to serotonin syndrome.
Beta2-Agonists	Tricyclic Antidepressants can increase the toxic/adverse effect of Beta2Agonists.
Botulinum Toxin-Containing Product	Anticholinergic Agents may have an enhanced anticholinergic effect.
Brexanolone	CNS Depressants can increase the CNS depressant effects of Brexanolone.
Brimonidine	CNS Depressants may increase the CNS depressant effects.
Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Cannabis	CNS Depressants may increase the CNS depressant effects.
CarBAMazepine	Might decrease serum Tricyclic Antidepressants.
Chloral Betaine	Anticholinergic Agents may have an adverse/toxic effect.
Chlorphenesin Carbamate	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Cimetidine	May reduce the metabolism of Tricyclic Antdepressants.
CloBAZam	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
CNS Depressants	Can increase the toxic/adverse effects of CNS Depressants.
Cobicistat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Moderate CYP2D6 inhibitors	Might decrease metabolism of CYP2D6 substrates (High Risk with Inhibitors).
Darunavir	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Desmopressin	Tricyclic Antidepressants can increase the toxic/adverse effects of Desmopressin.
Dexmethylphenidate	Might increase the toxic/adverse effects of Tricyclic Antidepressants. The serum concentrations of Tricyclic Antidepressants may be increased by Dexmethylphenidate.
Dimethindene (Topical).	CNS Depressants may intensify the effects of CNS Depressants.
Doxylamine	CNS Depressants may have a greater CNS depressant effect if taken with other CNS Depressants. Management: Diclegis (doxylamine/pyridoxine), which is intended for pregnancy, has specifically stated that it should not be used with any other CNS depressants.
Dronabinol	CNS Depressants may increase the CNS depressant effects.
DULoxetine	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. DULoxetine could decrease the metabolism Tricyclic Antidepressants.
Esketamine	CNS Depressants may increase the CNS depressant effects.
Gastrointestinal Agents (Prokinetic).	Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions.
Guanethidine	Guanethidine's therapeutic effects can be diminished by tricyclic antidepressants.
HydrOXYzine	CNS Depressants may intensify the effects of CNS Depressants.
Imatinib	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Itopride	Itopride's therapeutic effects may be diminished by anticholinergic agents.
Kava Kava	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Lumefantrine	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Magnesium Sulfate	CNS Depressants may intensify the effects of CNS Depressants.
Metaxalone	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Methylphenidate	May increase the toxic/adverse effects of Tricyclic Antidepressants. The serum concentrations of Tricyclic Antidepressants may be increased by Methylphenidate.
Methylphenidate	Can increase the toxic/adverse effects of Serotonin Modulators. In particular, there may be an increase in the risk of serotonin syndrome and serotonin toxicities.
MetyroSINE	MetyroSINE may have a sedative effect that can be enhanced by CNS depressants.
MetyroSINE	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Mianserin	Anticholinergic Agents may have an enhanced anticholinergic effect.
Minocycline	CNS Depressants may intensify the effects of CNS Depressants.
Mirabegron	May increase serum Desipramine concentrations
Mirtazapine	CNS Depressants can increase the CNS depressant effects of Mirtazapine.
Nabilone	CNS Depressants may increase the CNS depressant effects.
Nicorandil	Tricyclic Antidepressants can increase the hypotensive effects of Nicorandil.
Nitroglycerin	The absorption of Nitroglycerin may be decreased by anticholinergic agents. Anticholinergic Agents may reduce the dissolution sublingual nitroglycerin tablet, which could impair or slow down nitroglycerin absorbtion.
Panobinostat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Peginterferon Al-2b	Inhibitors carry a high danger. may reduce the levels of CYP2D6 substrates in serum. Serum levels of CYP2D6 Substrates may rise after administration of peginterferon Alf-2b.
Perhexiline	CYP2D6 Substrates may lead to an increase in perhexiline. The serum concentrations of CYP2D6 substrates can rise in response to perhexiline (High Risk with Inhibitors)
Piribedil	Piribedil's CNS depressing effects could be amplified by other CNS depressants.
Pitolisant	Pitolisant's therapeutic effects can be lessened by tricyclic antidepressants.
Pramipexole	Pramipexole may have a greater sedative effect if it is combined with CNS depressants.
Protease inhibitors	May increase serum Tricyclic Antidepressants.
QuiNINE	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Ramosetron	Ramosetron's constipating effects may be enhanced by anticholinergic agents.
ROPINIRole	CNS Depressants can increase the sedative effects of ROPINIRole.
Rotigotine	CNS Depressants can increase the sedative effects of Rotigotine.
Rufinamide	CNS Depressants may have an adverse/toxic effect that can be exacerbated by this. Particularly, dizziness and sleepiness may be increased.
Selective Serotonin Reuptake inhibitors	CNS Depressants can increase the toxic/adverse effects of Selective Serotonin Resuptake Inhibitors. Particularly, psychomotor impairment could be increased.
Serotonin Modulators	This may increase the toxic/adverse effects of other Serotonin Activators. Serotonin syndrome can develop. Tedizolid; Nicergoline are exceptions.
Sodium Phosphates	Tricyclic antidepressants have the potential to make sodium phosphates more toxic or harmful.Patients who experience significant sodium phosphate-induced fluid/electrolyte imbalances may be more likely to experience convulsions and lose consciousness.
Sulfonylureas	Cyclic Antidepressants can increase the hypoglycemic effects of Sulfonylureas.
Tedizolid	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Tetrahydrocannabinol	CNS Depressants may increase the CNS depressant effects.
Tetrahydrocannabinol, and Cannabidiol	CNS Depressants may intensify the effects of CNS Depressants.
Thiazide and Thiazide -Like Diuretics	Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics.
Thyroid Products	May increase the arrhythmogenic effects of Tricyclic Antidepressants. Thyroid Products can increase the stimulatory effects of Tricyclic Antidepressants.
Topiramate	Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents.
Trimeprazine	CNS Depressants may increase the CNS depressant effects.
Valproate Products	May increase serum Tricyclic Antidepressants.
Vitamin K antagonists (eg warfarin)	Tricyclic Antidepressants can increase the anticoagulant effects of Vitamin K Antagonists.
Yohimbine	Tricyclic Antidepressants can increase Yohimbine's serum concentration.
Risk Factor D (Keep in mind therapy modification)
Abiraterone Acetate	High chance that inhibitors will raise serum levels of CYP2D6 substrates. Avoid using abiraterone and CYP2D6 Substrates with a restricted therapeutic index together whenever possible. If concurrent use is unavoidable, keep a close eye on the patient for any harmful effects.
Direct-Acting Alpha-/Beta Agonists	Tricyclic Antidepressants can increase the vasopressor effects of Alpha/Beta-Agonists (Direct Acting). Patients on tricyclic antidepressants should avoid direct-acting alpha/beta-agonists. Monitor for increased pressure effects when combined and reduce the initial doses of alpha/beta-agonists.
Alpha2-Agonists	Tricyclic Antidepressants can reduce the antihypertensive effects of Alpha2Agonists. Management: Avoid this combination. Monitor for any decreased alpha2-agonist effects if the combination is used. If you are discontinuing the use of an alpha2-agonist for a patient who is on a TCA, be careful. Lofexidine, Brimonidine (Ophthalmic), Apraclonidine are exceptions.
Asunaprevir	High likelihood that inhibitors will raise serum levels of CYP2D6 substrates
Barbiturates	Tricyclic antidepressants' metabolism might be increased.
Blonanserin	CNS Depressants can increase the CNS depressant effects of Blonanserin.
Buprenorphine	CNS Depressants can increase the CNS depressant effects of buprenorphine. Management: Reduced doses of CNS depressants should be considered and avoidance of such drugs for patients at high risk of buprenorphine self-injection/overuse. Buprenorphine patches (Butrans) should be initiated at 5 mg/hr for adults when taken with other CNS depression drugs.
Chlormethiazole	CNS Depressants may increase the CNS depressant effects. Monitoring: Look out for signs of CNS depression. If a combination of chlormethiazole and other drugs is required, a reduced dose should be used.
Cinacalcet	It may increase serum levels of Tricyclic Antidepressants. Management: Look for alternatives whenever possible. These combinations should be monitored closely to ensure that there are no increased effects/toxicity or elevated serum levels (if testing is possible) of the tricyclic-antidepressant.
Citalopram	Tricyclic antidepressants may intensify Citalopram's hazardous or severe effects.Citalopram's serum levels can rise in the presence of tricyclic antidepressants.Tricyclic Depressants' serum levels may rise as a result of citalopram.Management: If at all possible, take into account different combinations.Keep an eye out for any negative effects like serotonin syndrome or QT prolongation when citalopram is used with a TCA.
Strong CYP2D6 inhibitors	Might decrease metabolism of CYP2D6 substrates (High Risk with Inhibitors).
Dacomitinib	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. Management: Do not use dacomitinib concurrently with CYP2D6 Substrates that have a narrow therapeutic Index.
Droperidol	CNS Depressants may increase the CNS depressant effects. Management: Droperidol and other CNS agents, such as opioids, may be reduced or used in combination with droperidol. Separate drug interaction monographs provide more detail on exceptions to this monograph.
Escitalopram	Escitalopram's toxic and unpleasant effects can be increased by tricyclic antidepressants. Escitalopram may cause Tricyclic Antidepressant serum concentrations to rise. Management: If at all possible, take into account different combinations. If you combine escitalopram with a tricyclic antidepressant (TCA), keep an eye out for any side effects, such as serotonin syndrome or QT prolongation.
Flunitrazepam	Flunitrazepam's CNS depressing effects can be amplified by other CNS depressants.
FLUoxetine	Tricyclic antidepressants' toxic/unfavorable effects could rise.Tricyclic Antidepressants can accumulate in the serum when Fluoxetine is used.Management: If at all possible, take into account different combinations.Keep an eye out for any negative side effects like serotonin syndrome or QT prolongation when fluoxetine is used with a TCA.
FluvoxaMINE	Tricyclic antidepressants' toxic/unfavorable effects could rise. Tricyclic Antepressants' serum levels may rise as a result of fluvoxaMINE. Management: If at all possible, take into account different combinations. When fluvoxamine is used with a TCA, keep an eye out for any negative effects, such serotonin syndrome or QT prolongation..
HYDROcodone	CNS Depressants can increase the CNS depressant effects of HYDROcodone. When possible, avoid concomitant use with hydrocodone, benzodiazepines, or other CNS depressionants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Iohexol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iohexol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iohexol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Iomeprol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iomeprol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iomeprol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Iopamidol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iopamidol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iopamidol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Linezolid	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. Management: If possible, consider other combinations. Linezolid should be initiated only if it is clinically approved.
Linezolid	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome. Management: Serotonin syndrome/serotonin toxicemia can occur if serotonin modulators are stopped 2 weeks before linezolid is administered. Stop using serotonin modators immediately if you need to initiate linezolid immediately.
Lithium	May increase the neurotoxic effects of tricyclic antidepressants. You should exercise caution when using this combination. If combined treatment is clinically recommended, be sure to monitor for signs of serotonin toxicities/serotonin syndrome.
Lofexidine	Tricyclic Antidepressants can reduce the therapeutic effects of Lofexidine. This combination should be avoided. Monitor for decreased alpha2-agonist effects if the combination is used. If you are discontinuing the use of an alpha2-agonist for a patient who is receiving a TCA, be careful.
Methotrimeprazine	Methotrimeprazine may have a higher CNS depressant activity than CNS Depressants. Methotrimeprazine can increase the CNS depressant effects of CNS Depressants. Management: Lower the adult dose of CNS Depressants by 50% and start concomitant methotrimeprazine treatment. After clinically proven efficacy of methotrimeprazine, further CNS depressant dose adjustments should only be made.
Metoclopramide	This may increase the toxic/adverse effects of Tricyclic Antidepressants. Management: If possible, seek alternatives to this combination. Patients receiving metoclopramide and tricyclic antidepressants should be monitored for extrapyramidal symptoms, neuroleptic malignant Syndrome, or serotonin syndrome.
Opioid Agonists	CNS Depressants can increase the CNS depressant effects of Opioid Aggonists. Management: When possible, avoid concomitant use opioid agonists, benzodiazepines, or other CNS depressionants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
OxyCODONE	CNS Depressants can increase OxyCODONE's CNS depressant effects. When possible, avoid the simultaneous use of oxycodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
PARoxetine	Tricyclic antidepressants' toxic/unfavorable effects could rise. Tricyclic Antidepressants' serum levels can rise when PARoxetine is taken. Management: If at all possible, take into account different combinations. Keep an eye out for any negative effects like serotonin syndrome or QT prolongation when a TCA is used with paroxetine.
Perampanel	CNS Depressants may have a greater CNS depressant effect. Perampanel and any other CNS depressant drug should be used in combination. Patients who take perampanel together with other drugs that have CNS depressant activity should not engage in complex or high-risk activities until they are familiar with the combination.
Pramlintide	Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract.
QuiNIDine	Tricyclic Antidepressants could increase the QTc-prolonging effects of QuiNIDine. QuiNIDine could increase serum levels of Tricyclic Antepressants. Management: The drug interactions monographs for drugs listed as an exception to this monograph will discuss the management of these drugs in greater detail.
Secretin	Secretin's therapeutic effects may be diminished by anticholinergic agents. Concomitant use: Secretin and anticholinergic agents should be avoided. Stop using anticholinergic drugs for at least five half-lives before administering secretin.
Sertraline	Tricyclic antidepressants' toxic/unfavorable effects could rise.Tricyclic Antidepressants' serum levels can rise in response to sertraline.Management: If at all possible, take into account different combinations.Monitor for negative effects, such as serotonin syndrome or QT-interval prolongation, when sertraline is used with a tricyclic antidepressant (TCA).
Sodium Oxybate	CNS Depressants may have a greater depressant effect if taken in combination. Management: Look for alternatives to the combination use. If you must combine use, reduce the doses of any one or more drugs. It is not recommended to combine sodium oxybate and alcohol, or any sedative hypnotics.
St John's Wort	May increase metabolism of tricyclic antidepressants. The possibility of serotonin syndrome could theoretically increase.
Suvorexant	CNS Depressants can increase the CNS depressant effects of Suvorexant. Management: Suvorexant or any other CNS depressionant can be reduced in doses. Suvorexant should not be taken with alcohol. It is also not recommended to take suvorexant along with any other drugs for insomnia.
Tapentadol	CNS Depressants may increase the CNS depressant effects. Tapentadol, benzodiazepines and other CNS depressants should be avoided when possible. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Terbinafine Systemic	Desipramine may increase serum concentrations. Concomitant administration of terbinafine and desipramine should be monitored for any increased or decreased toxic effects. It may be necessary to reduce the dosage of desipramine.
Zolpidem	CNS Depressants can increase the CNS depressant effects of Zolpidem. Management: For men who also take CNS depressants, reduce the adult Intermezzo brand sublingual Zolpidem dose to 1.75mg. For women, no dose adjustment is advised. Avoid using CNS depressants at night; do not use alcohol.
Risk Factor X (Avoid Combination)
Aclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Azelastine - Nasal	CNS Depressants could increase the CNS depressant effects of Azelastine.
Bromopride	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Bromperidol	CNS Depressants may increase the CNS depressant effects.
Cimetropium	Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents.
Dronedarone	Tricyclic Antidepressants can increase Dronedarone's arrhythmogenic effects. Management: The drug interactions monographs for drugs listed as an exception to this monograph provide more information.
Eluxadoline	Eluxadoline may cause constipation by using anticholinergic agents.
Oral Inhalation	Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation).
Glycopyrronium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Iobenguane Radiopharmaceutical Products	Tricyclic Antidepressants can decrease the therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Stop using any drug that could inhibit or interfere catecholamine transport and uptake for at most 5 biological half-lives prior to iobenguane Administration. These drugs should not be administered until 7 days following each iobenguane dosage.
Oral Inhalation with Ipratropium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Levosulpiride	Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride.
Methylene Blue	Tricyclic Antidepressants could increase the serotonergic effects of Methylene Blue. This could lead to serotonin syndrome.
Methylene Blue	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Monoamine Oxidase inhibitors	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. Although methylene blue is expected to interact with linezolid via this mechanism, management guidelines differ from those for other monoamine-oxidase inhibitors. For more information, refer to monographs pertaining to these agents. Linezolid, Methylene Blue, Tedizolid are exceptions.
Orphenadrine	Orphenadrine may be more effective against CNS depression than other drugs.
Oxatomide	Anticholinergic Agents may have an enhanced anticholinergic effect.
Oxomemazine	CNS Depressants may increase the CNS depressant effects.
Paraldehyde	Paraldehyde may be enhanced by CNS depressants.
Potassium Chloride	Potassium Chloride may have an ulcerogenic effect that can be exacerbated by anticholinergic agents. Treatment: Patients taking drugs that have significant anticholinergic effects should not consume any oral dose form of potassium chloride.
Potassium Citrate	Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents.
Revefenacin	Revefenacin may be enhanced by anticholinergic agents.
Thalidomide	CNS Depressants can increase Thalidomide's CNS depressant effects.
Tiotropium	Anticholinergic agents may increase the anticholinergic effects of Tiotropium.
Umeclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.

Monitoring parameters:

BP, pulse, temperature, weight, and BMI before and during therapy
Serum sodium in at-risk populations (as clinically indicated)
CBC
Blood glucose
mental status
suicide ideation
ECG (older adults and those with cardiac disease)
Signs/symptoms of serotonin syndrome

Treatment of ADHD:

Cardiovascular risk should be assessed thoroughly.
Heart rate, blood pressure monitoring, and ECG should be done before starting therapy (ensure PR interval ≤200 ms, QRS duration ≤120 ms, and QT ≤460 ms).

How to administer Desipramine (Norpramin)?

It is administered orally with or without food in one or more divided doses.

Mechanism of action of Desipramine (Norpramin):

Desipramine acts by blocking norepinephrine's reuptake by the presynaptic neural membrane, leading to an increase in synaptic norepinephrine and to a lesser degree serotonin concentrations in the central nervous systems.
Additional effects include adenylcyclase desensitization and down-regulation of beta-adrenergic and serotonin receptors.

The onset of action:

Depression: