How clomipramine works
Clomipramine interacts with numerous docking sites (receptors) of nerve messengers (neurotransmitters). This explains its mood-lifting, anti-obsessive and analgesic effects.
Signal transmission in the brain occurs via neurotransmitters such as serotonin and norepinephrine. When an electrical impulse excites a nerve cell, it releases a messenger into the synaptic cleft – a tiny gap that acts as a contact point with the neighboring nerve cell.
The messenger migrates to the neighboring cell, binds there to special receptors and thereby transmits the signal. The neurotransmitter is then reabsorbed into the cell of origin, which ends its effect.
This is where clomipramine comes in. It prevents messenger substances such as serotonin and norepinephrine from being reabsorbed into the nerve cell of origin, which means that they exert their effects for longer.
Absorption, degradation and excretion
Clomipramine is completely and rapidly absorbed from the small intestine into the blood after oral intake. The first stop for the blood coming from the intestine is the liver as the central metabolic organ. There, up to 50 percent of the active ingredient is immediately metabolized.
Maximum clomipramine blood plasma levels are reached two to eight hours after ingestion. Excretion occurs predominantly via the kidneys in the urine. Clomipramine itself is excreted after approximately 21 hours, and half of its active metabolite (metabolite) desmethylclomipramine is excreted after 36 hours.
When is clomipramine used?
Approved indications for clomipramine – with slight differences between Germany, Austria and Switzerland – are:
- Depression
- Cataplexy (sudden loss of muscle tension) in narcolepsy
- Hypnagogenic hallucinations (hallucinations when falling asleep) in narcolepsy: indication approved in Germany only
- Sleep paralysis: only approved for use in Germany
- long-term pain treatment as part of an overall therapeutic concept: only approved for use in Germany and Switzerland
- Enuresis nocturna (bedwetting) in children after the age of 5 (Germany) or after the age of 6 (Switzerland) as part of an overall therapeutic concept after exclusion of organic causes (no approval for this indication in Austria)
The use outside of the approved indications can take place after careful information of the patient in the course of a so-called “off-label use”.
How clomipramine is used
Treatment is started cautiously, i.e. with a lower dose, which is then slowly increased until the desired treatment effect occurs. This amount of active substance is then maintained as a maintenance dose.
To end the treatment, the dose is gradually reduced again. This “tapering” of therapy is intended to prevent side effects that can result from abrupt discontinuation.
The treatment generally begins to take effect about seven to 28 days after the patient starts taking it. How long the drug must be taken is determined by the doctor.
What are the side effects of clomipramine?
Common side effects include speech disorders, muscle weakness, hallucinations, confusion, sleep disorders, anxiety, vomiting, diarrhea, taste disorders, ringing in the ears (tinnitus), and itching.
Occasionally, patients experience seizures. Rarely, there is a decrease in white blood cells (leukocytes) and platelets (thrombocytes) and urinary retention as a result of treatment.
If you suffer from severe side effects or symptoms that are not known, please consult a doctor.
What should be considered when taking clomipramine?
Contraindications
Do not take clomipramine in the following cases:
- hypersensitivity to the active substance or any other component of the drug
- acute delirium
- acute urinary retention
- untreated narrow-angle glaucoma (form of glaucoma)
- prostate enlargement with residual urine formation
- pyloric stenosis (narrowing of the stomach outlet)
- paralytic ileus (intestinal obstruction due to intestinal paralysis)
- congenital QT syndrome (prolongation of the QT interval – a section of the ECG)
Drug interactions
Clompiramine may interact with several other agents. For example, irreversible MAO inhibitors (drugs for depression and Parkinson’s disease) must be stopped at least 14 days before starting treatment with clomipramine.
Also, some other agents must not be used together with clomipramine, such as quinidine-type antiarrhythmic agents or certain other antidepressants (such as SSRIs).
Clomipramine may potentiate the effects of anticholinergic and central depressant drugs.
Clomipramine is degraded in the liver mainly with the help of the enzymes CYP2D6 and CYP2C19. Substances that inhibit these enzymes or increase their production may therefore impair or accelerate the breakdown of clomipramine.
The simultaneous consumption of alcohol can increase the drug’s depressant effect.
If tricyclic antidepressants such as clomipramine are taken together with a high-fiber diet or laxatives, this hinders their absorption into the body.
Driving and operating machinery
Because clomipramine impairs responsiveness, patients should not drive, operate machinery, or engage in other hazardous activities, at least during the first few days of treatment.
Age Limitation
Clomipramine is approved for the treatment of certain indications in children after the age of five (Germany and Austria) and in children after the age of six (Switzerland).
Pregnancy and lactation
When clomipramine is used during pregnancy, the growth of the unborn child should be closely monitored by ultrasound. When used until birth, the newborn may show adjustment disorders, so it should be closely monitored in the first few days.
The use of clomipramine during breastfeeding must be weighed very strictly, as the active substance passes into breast milk. Depending on the dosage, the child’s condition may be impaired. However, to date, no symptoms have been described in breastfed infants whose mothers took clomipramine.
How to obtain medication with clomipramine
Clomipramine is available on prescription in Germany, Austria, and Switzerland, i.e., only after presentation of a doctor’s prescription at the pharmacy.
