Clomipramine is a tricyclic antidepressant that acts by reducing the re-uptake of norepinephrine and serotonin in the central nervous system, thereby enhancing the effects of these neurotransmitters. This drug also binds to alpha-adrenergic, histaminergic, and cholinergic receptors which are responsible for the many side effects seen with this agent.
Clomipramine is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive-compulsive disorder, panic disorder, major depressive disorder, and chronic pain. Clomipramine, the 3-colors analog of imipramine, 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, clomipramine does not affect mood or arousal but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake It may decrease the risk of suicide in those over the age of 65.
Mechanism of Action of Clomipramine
Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α1-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.
Indications of Clomipramine
- Obsessive Compulsive Disorder
- Irritable Bowel Syndrome
- Panic Disorder
- Premature Ejaculation
- Depression
- Diabetic neuropathies
- Migraines
- Agitation
- Panic Disorder
- Sleep Paralysis
- Diabetic neuropathies
- Migraines
- Sleep disorders and disturbances
- Body dysmorphic disorder
- Premature ejaculation
- Depersonalization disorder
- For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance
- Chronic pain with or without organic disease, particularly headache of the tension type.
- Sleep paralysis, with or without narcolepsy
- Enuresis (involuntary urinating in sleep) in children. The effect may not be sustained following treatment, and alarm therapy may be more effective in both the short-term and the long-term. Combining a tricyclic (such as clomipramine) with anticholinergic medication may be more effective for treating enuresis than the tricyclic alone.
Contra Indications of Clomipramine
- Neuroblastoma
- Pheochromocytoma
- Overactive thyroid gland
- Manic-depression
- Having thoughts of suicide
- Alcoholism
- Serotonin syndrome – adverse drug interaction
- Closed angle glaucoma
- Heart attack within the last 30 days
- Disorder in heart’s electrical atrioventricular conduction
- prolonged QT interval on EKG
- Abnormal EKG with QT changes from Birth
- Liver problems
- Severe renal impairment
- Seizures
- Cannot Empty Bladder
- Malignant Hyperthermia
Dosage of Clomipramine
Strengths: 25 mg; 50 mg; 75 mg
Obsessive Compulsive Disorder
Initial dose: 25 mg orally once a day at bedtime
- Maintenance dose: 100 mg orally per day
- Maximum dose: 250 mg/day
Pediatric Obsessive Compulsive Disorder
10 to 17 years
- Initial dose: 25 mg orally once a day at bedtime
- Maintenance dose: May increase to 3 mg/kg or 100 mg orally per day, whichever is the smaller dose
- Maximum dose: 3 mg/kg/day or 200 mg/day, whichever is the smaller dose
Side Effects of Clomipramine
The most common
- Constipation
- dizziness
- drowsiness
- dry mouth
- chest pain
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- 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
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 Clomipramine
Clomipramine may interact with following drugs ,suppliments & may decrease the efficacy of drug
- alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- amphetamines (e.g., dextroamphetamine, lisdexamphetamine)
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- carvedilol
- celecoxib
- ciprofloxacin
- clobazam
- baclofen
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- carvedilol
- ciprofloxacin
- clobazam
- oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- doxycycline
- estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
- folic acid
- gabapentin
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- lansoprazole
- loperamide
- losartan
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- methylphenidate
- montelukast
- ondansetron
- phenytoin
- progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- ranitidine
- selective serotonin reuptake inhibitors (SSRIs;e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
- sildenafil
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, desipramine, )
- warfarin
Pregnancy & Lactation of Clomipramine
Pregnancy
The safety of this medication for use by pregnant women has not been established. It 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
This medication passes into breast milk. If you are a breast-feeding mother and are taking clomipramine, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding, or whether you should gradually withdraw the medication. Clomipramine has not been studied for use by people under 10 years of age, and specific recommendations for its use by this age group cannot be provided.
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