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Desipramine; Uses, Dosage, Side Effects, Drug Interactions

Desipramine is an active metabolite of imipramine, a tertiary amine and a synthetic tricyclic derivative of the antidepressant. Desipramine enhances monoamine neurotransmission in certain areas of the brain by inhibiting the re-uptake of noradrenaline and serotonin at the noradrenergic and serotoninergic nerve endings, respectively. It also induces sedation through histamine 1 receptor blockage and hypotension through the beta-adrenergic blockage.

Desipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, desipramine does not affect mood or arousal but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine.

Mechanism of Action of Desipramine

Desipramine is a tricyclic antidepressant (TCA) that selectively blocks the reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases the stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.

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Desipramine is an active metabolite of imipramine, a tertiary amine and a synthetic tricyclic derivative of the antidepressant. Desipramine enhances monoamine neurotransmission in certain areas of the brain by inhibiting the re-uptake of noradrenaline and serotonin at the noradrenergic and serotoninergic nerve endings, respectively. It also induces sedation through histamine 1 receptor blockage and hypotension through the beta-adrenergic blockage.

Indications of Desipramine

ADHD
Dysautonomia
Depression
Vulvodynia
Irritable bowel syndrome
Anorexia nervosa
Bulimia nervosa
Diabetic neuropathies
panic disorder
Pain, neuropathic
Panic disorders
Postherpetic neuralgia
Sleeplessness

Contra-Indications of Desipramine

Overactive thyroid gland
Schizophrenia
Manic-depression
Having thoughts of suicide
Alcoholism
Serotonin syndrome – adverse drug interaction
Lower seizure dhreshold
Closed angle glaucoma
Heart attack within the last 30 days
Very rapid heartbeat – torsades de Pointes
Prolonged QT interval on EKG
Abnormal heart rhythm
Abnormal EKG with QT changes from Birth
Stroke
Liver problems
Kidney disease with reduction in kidney function
Enlarged prostate
Seizures
Cannot empty bladder
CYP2D6 poor metabolizer
Risk of angle-closure glaucoma due to narrow angle of anterior chamber of eye

Dosage of Desipramine

Strengths: 25 mg; 50 mg; 75 mg; 10 mg; 100 mg; 150 mg

Depression

100 to 200 mg orally per day
Maximum dose: 300 mg/day

Geriatric Depression

25 to 100 mg orally per day
Maximum dose: 150 mg/day

Side Effects of Desipramine

The most common

decreased sexual desire or ability
Failure to discharge semen (in men)
chest pain
headache
joint painPain
dizziness
nausea and vomiting
Severe stomach ache
epigastric pain,
diarrhoea,
anorexia,
flatulence,
headache,
dizziness,
fainting, fast or pounding heartbeats.

More common

Fast or irregular heartbeat
fever
Back pain
dizziness
headache
increased cough
Acid or sour stomach
decreased appetite
Agitation
chest congestion
chest pain
cold sweats
confusion
decreased sexual ability or desire
diarrhea or loose stools
heartburn
sleepiness or unusual drowsiness
stomach or abdominal cramps, gas, or pain
trouble sleeping

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Less common

Abnormal dreams
change in sense of taste
congestion
discouragement, feeling sad, or empty
Suicide attempts
Acting on dangerous impulses
Aggressive or violent behavior
Thoughts about suicide or dying
New or worse depression
New or worse anxiety or panic attacks
Agitation, restlessness, anger, or irritability
Trouble sleeping
An increase in activity or talking more than normal

Drug Interactions of Desipramine

Desipramine may interact with following drugs ,suppliments & may decrease the efficacy of drug

anticholinergic medications (e.g., atropine, diphenhydramine, hydroxyzine)
barbiturates (e.g., phenobarbital)
benzodiazepines (e.g., diazepam, lorazepam)
butyrophenones (e.g., haloperidol)
carbamazepine
clarithromycin
cimetidine
domperidone
erythromycin
epinephrine or
guanethidine
MAO inhibitors (e.g., phenelzine, moclobemide)
methadone
methylphenidate
metoclopramide
phenothiazines (e.g., chlorpromazine, thioridazine)
phenylephrine
sibutramine
sotalol
SSRI antidepressants (e.g., fluoxetine, fluvoxamine, paroxetine)
terbinafine
tramadol
ziprasidone

Pregnancy & Lactation of Desipramine

FDA Pregnancy Category C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

Desipramine passes into breast milk. If you are a breast-feeding mother and are taking desipramine, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.