Clomipramine is a drug belonging to the class of tricyclic antidepressants (TCA). It is a very powerful antidepressant, synthesized for the first time in the 1960s.
Clomipramine - Chemical Structure
Clomipramine is on the list of essential drugs compiled by the World Health Organization (WHO); a list listing all the drugs that must be present in a basic health system.
Indications
For what it uses
The use of clomipramine is indicated in the following cases:
- Endogenous depression;
- Reactive depression;
- Neurotic depression;
- Masked depression;
- Involutive forms of depression;
- Depression associated with schizophrenia;
- Depression associated with personality disorders;
- Depressive presenility and senility syndromes;
- Depression associated with chronic pain states;
- Depression associated with chronic somatic disorders;
- Obsessive-compulsive syndromes;
- Phobias;
- Panic attacks;
- Chronic painful states.
Warnings
Depression increases the risk of suicidal thoughts, self-injurious behavior and suicide. The improvement of the depressive state may not occur immediately after taking clomipramine, therefore, it is necessary to carefully monitor the patients until the aforementioned improvement occurs.
Clomipramine should not be given to children and adolescents under 18 years of age.
In patients suffering from panic attacks, an increase in anxiety may occur at the beginning of treatment with clomipramine; this paradoxical effect, however, disappears with the continuation of the therapy.
Clomipramine may cause psychotic states to increase in patients with schizophrenia.
Caution should be used in the administration of clomipramine in patients suffering from pre-existing cardiovascular diseases, especially in patients suffering from cardiovascular insufficiency.
Administration of clomipramine to patients with seizure disorders - or epileptic patients - should only be performed under the strict supervision of a doctor. Since this effect is dose-dependent, it is advisable not to exceed the maximum administrable daily dose.
Because of its anticholinergic effects, clomipramine should be administered with caution in patients with a history of ocular hypertension and / or glaucoma.
Particular caution should be used in the administration of clomipramine in patients suffering from hepatic, renal and / or tumors of the adrenal glands, as hypertensive crises may occur.
The administration of clomipramine in hyperthyroid patients - or those taking thyroid preparations - can cause an increase in cardiac side effects.
During treatment with clomipramine it is a good idea to periodically check the blood levels of white blood cells.
Sudden interruption of treatment should be avoided due to the side effects that may occur.
Interactions
Concomitant administration of clomipramine and MAOI (monoamine oxidase inhibitors) should be avoided due to the side effects that may occur.
Selective serotonin reuptake inhibitors ( SSRIs ) - such as, for example, fluoxetine, fluvoxamine and paroxetine - can increase plasma concentrations of clomipramine, thereby increasing its toxic effects.
The concomitant administration of clomipramine and other antidepressant drugs capable of increasing serotonin transmission may favor the appearance of serotonin syndrome.
Concomitant administration of clomipramine and diuretic drugs may induce hypokalaemia (ie a decrease in blood levels of potassium), with consequent onset of cardiac problems.
Clomipramine can increase the action of sedative, hypnotic, anxiolytic and anesthetic drugs.
Concomitant administration of clomipramine and neuroleptic drugs may increase the plasma concentration of antidepressant, lower the seizure threshold and promote the onset of seizures.
Concomitant use of clomipramine and thioridazine (an antipsychotic drug) may induce severe cardiac arrhythmias.
Clomipramine may increase the anticoagulant effect of warfarin .
The toxic effects of clomipramine on the eye, bladder, intestine and central nervous system may be increased by concomitant administration of phenothiazines (a group of drugs with antipsychotic and antihistamine activity), antihistamines and atropine .
During therapy with clomipramine the administration of sympathomimetic drugs should be avoided, due to a possible worsening of cardiovascular side effects.
Concomitant administration of clomipramine and antihypertensive drugs may cause orthostatic hypotension.
Concomitant administration of clomipramine and antiarrhythmic drugs should be avoided.
Some types of phenothiazines, haloperidol (an antipsychotic) and cimetidine (a drug used to treat gastric ulcer) can delay the elimination of clomipramine, thereby increasing blood concentration and increasing the risk of adverse effects.
Concomitant administration of clomipramine and estrogen may cause a decrease in the efficacy of the antidepressant and at the same time an increase in its side effects.
Side effects
Clomipramine can induce various types of side effects. The types of adverse effects and the intensity with which they occur vary from one individual to another, this happens because each person has his own sensitivity to the drug and - consequently - each patient responds to therapy differently.
The following are the main side effects that may occur following therapy with clomipramine.
Psychiatric disorders
Clomipramine can induce various psychiatric disorders, including:
- Mental confusion;
- Disorientation;
- Hallucinations;
- Anxiety;
- agitation;
- Sleep disorders;
- Nightmares;
- Delusions;
- Aggression;
- Mania;
- Hypomania;
- Memory lapses;
- depersonalization;
- Worsening of depression;
- Psychotic symptoms.
Nervous system disorders
Clomipramine can cause dizziness, tremor, headache, myoclonia (short and involuntary contraction of a muscle or a group of muscles), paraesthesia, speech disorders and difficulty maintaining concentration. Furthermore, clomipramine can cause convulsions.
Anticholinergic effects
Because of its anticholinergic action, clomipramine can cause:
- Dry mouth;
- Sweating;
- Constipation;
- Vision disorders and blurred vision;
- Urination disorders;
- Urinary retention;
- Mydriasis (dilation of the pupil);
- Hot flashes;
- Glaucoma;
- Alterations in the sense of taste.
Cardiac disorders
Clomipramine therapy may cause arrhythmias, increased blood pressure, alterations in cardiac impulse conduction and clinically relevant changes in the ECG (electrocardiogram).
Furthermore, clomipramine can induce orthostatic hypotension, ie a sharp drop in blood pressure following the passage from a sitting or lying position to an upright position.
Gastrointestinal disorders
Treatment with clomipramine may induce nausea, vomiting, diarrhea, abdominal discomfort and anorexia.
Hepatobiliary disorders
Following the intake of clomipramine there may be an increase in transaminase levels in the bloodstream. In addition, hepatitis may occur with or without jaundice.
Skin and subcutaneous tissue disorders
Clomipramine therapy can cause allergic skin reactions that occur in the form of skin rashes, hives, itching and photosensitivity reactions. Furthermore, clomipramine can cause edema and alopecia.
Endocrine disorders
Treatment with clomipramine may promote the onset of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Changes in blood and bone marrow function
Clomipramine therapy can cause reduced bone marrow function resulting in decreased blood cell production.
In particular, leukopenia (ie a decrease in white blood cells in the bloodstream with consequent increased susceptibility to contraction of infections) and thrombocytopenia (ie a decrease in the number of blood platelets, with an increased risk of abnormal bleeding and / or bleeding) .
Clomipramine can also cause purpura . This term refers to a set of pathologies characterized by the appearance of small spots on skin, organs and mucous membranes due to the rupture of small blood vessels.
Interruption symptoms
If treatment with clomipramine is stopped abruptly, so-called withdrawal symptoms may occur. These symptoms are nausea, vomiting, abdominal pain, diarrhea, insomnia, anxiety, nervousness and headache.
Other side effects
Clomipramine therapy may also cause other side effects, including:
- Allergic reactions in sensitive subjects;
- Feeling of not being able to rest;
- Increased appetite;
- Increased body weight;
- Tinnitus (ie an auditory disorder characterized by noises such as buzzing, hissing, whistling, etc.);
- Muscle weakness;
- Fatigue;
- Libido disorders;
- Mammary hypertrophy;
- Galactorrhea, ie the abnormal secretion of milk in women who are not breastfeeding;
- Muscular hypertonia.
Overdose
Since there is no specific antidote, treatment is purely symptomatic in the event of an overdose of clomipramine.
The symptoms that may occur following a clomipramine overdose consist of an increase in the side effects of the drug itself, especially of those effects on the cardiovascular system and the central nervous system.
Induction of vomiting and gastric lavage may be useful. In any case, if you suspect you have taken an overdose of clomipramine, you must contact a doctor immediately and go to a hospital.
Action mechanism
Clomipramine is a tricyclic antidepressant and - as such - is able to inhibit the reuptake of serotonin (5-HT) and noradrenaline (NA) within the presynaptic nerve termination.
In particular, clomipramine binds to the transporters responsible for the reuptake of NA and 5-HT, thus preventing their re-uptake. In this way, noradrenaline and serotonin remain in the synaptic wall for a prolonged period of time and interact with their receptors at the postsynaptic termination level.
The prolonged receptor interaction results in an increase in the serotoninergic and noradrenergic signal which favors the improvement of the pathologies for which the use of the drug is indicated.
Mode of Use - Posology
Clomipramine is available as tablets for oral administration and as a solution for injection for intramuscular or intravenous administration.
The dosage of clomipramine must be established by the doctor on an individual basis according to the type of pathology that must be treated and according to the conditions and the clinical picture of each patient.
In elderly patients an adjustment of the administered clomipramine dose may be necessary.
The doses of drug usually given are given below.
Depression, obsessive-compulsive syndromes, phobias
For oral administration, the usual dose of clomipramine is 25 mg given 2-3 times a day. The maximum daily dose should not exceed 250 mg of drug.
For intramuscular administration, the usual dose of clomipramine is 25-50 mg a day. Subsequently, the dose can be increased.
For intravenous infusion, the usual clomipramine dose is 50-75 mg - to be diluted in 250-500 ml of isotonic saline solution - to be administered once a day.
Panic attacks
The usual starting dose is 10 mg of clomipramine a day. The amount of the drug can be increased - depending on the case and at the discretion of the doctor - up to a maximum of 150 mg per day.
Chronic painful states
In this case, the usual clomipramine dosage varies from 10 mg to 150 mg of drug per day. It is also necessary to bear in mind a possible concomitant therapy with analgesic drugs.
Pregnancy and breastfeeding
Pregnant women - confirmed or suspected - should not take clomipramine.
Breast-feeding mothers should not take the drug because clomipramine is excreted in breast milk.
Contraindications
The use of clomipramine is contraindicated in the following cases:
- Known hypersensitivity to clomipramine or to other tricyclic antidepressants belonging to the dibenzoazepine group;
- In case of simultaneous therapy with IMAO;
- In patients with glaucoma;
- In patients with prostatic hypertrophy or other disorders of the genitourinary tract;
- In patients suffering from liver and / or kidney diseases;
- In patients with heart failure and / or myocardial rhythm and conduction disorders;
- In patients suffering from mania;
- In pregnancy and during lactation;
- In children and adolescents under the age of 18 years.
