Citalopram is an antidepressant drug belonging to the selective serotonin reuptake inhibitor (SSRI) class. In reality, citalopram is a raceme, ie it is made up of a mixture of the S-citalopram and R-citalopram enantiomers.
(R, S) - Citalopram - Chemical Structure
It was discovered by pharmaceutical chemist Lundbeck in an attempt to invent a new antidepressant drug capable of inhibiting noradrenaline reuptake. Lundbeck succeeded in synthesizing two new molecules (the talopram and the tasulopram), however, he did not continue with the experiments due to the numerous suicide attempts that were recorded during the clinical studies. Lundbeck, however, did not give up and - by making changes to the chemical structure of talopram - he was able to synthesize citalopram.
Citalopram came on the market in the United States in 1996 and is considered the most selective SSRI there is and, therefore, endowed with fewer side effects than other antidepressants.
Indications
For what it uses
The use of citalopram is indicated in the treatment of:
- Major (or endogenous) depression and prevention of relapses or recurrences;
- Anxiety disorders with panic attacks, with or without agoraphobia.
Furthermore, citalopram can be used as an off-label drug for the treatment of anxiety, dysthymia, premenstrual dysphoric disorder and obsessive-compulsive disorder. The term "off-label" means the use of drugs known and used for a long time, for which scientific evidence suggests their use in clinical situations not expressly indicated on the illustrative leaflet of the drug itself.
Warnings
Depression is related to an increased risk of suicidal thoughts, self-injurious behavior and suicide. The improvement in the depressive state may not occur immediately after taking citalopram, therefore careful monitoring of the patients is necessary until a significant remission occurs.
Citalopram should not be given to children and adolescents under the age of 18, since - in this category of patients - the drug can promote the onset of suicidal behavior, aggression, hostility and anger.
Citalopram use should be discontinued if patients enter a manic phase.
The use of citalopram in patients with unstable epilepsy should be avoided. In patients with controlled epilepsy, on the other hand, the drug can be used, but only under strict medical supervision.
The use of citalopram in patients with diabetes may alter the blood sugar level. Therefore, an adjustment of the dose of insulin and / or oral hypoglycemic agents administered may be necessary.
Caution should be used in the concomitant administration of citalopram and electroconvulsive therapy (TEC).
Treatment with citalopram from psychotic patients may cause an increase in psychotic symptoms.
Citalopram therapy in patients with panic disorders can trigger an increase in anxiety symptoms, especially at the start of treatment. This paradoxical effect is generally attenuated with continued therapy.
Caution should be exercised when administering citalopram in bradycardic patients, in patients with uncompensated heart failure and in patients who have recently suffered from acute myocardial infarction.
Attention should be paid to the administration of citalopram in patients with narrow-angle glaucoma or with a history of glaucoma.
Abrupt discontinuation of treatment is not recommended due to side effects that may occur.
Since taking citalopram may alter your judgment and responsiveness, driving or using machines is not recommended.
Interactions
Concomitant administration of citalopram and MAOO (monoamine oxidase inhibitors) should be avoided due to the serious side effects that may occur, including serotonin syndrome.
Concomitant use of citalopram and selegiline (a selective MAO-B inhibitor) should be avoided.
The administration of citalopram with drugs that prolong the QT interval (the time it takes for the ventricular myocardium to depolarize and repolarize) should be avoided. These drugs include:
- Antiarrhythmics ;
- Tricyclic antidepressants ( TCA );
- Antipsychotics, such as phenothiazine derivatives, haloperidol and pimozide;
- Antimicrobial agents, such as sparfloxacin, moxifloxacin, erythromycin and halofantrine (an antimalarial);
- Antihistamines, such as astemizole and mizolastine.
Caution should be used in the administration of citalopram and drugs that increase the serotonin signal (such as lithium and tryptophan ) due to the increased serotonergic effect that is established.
The simultaneous use of citalopram and serotonin agonists, such as triptans (drugs used to treat migraine) and tramadol (an opioid painkiller) is not recommended.
Concomitant intake of citalopram and St. John's wort (or St. John's wort, a plant with antidepressant properties) should be avoided, as it may increase the risk of side effects.
A great deal of caution should be used in the concomitant administration of citalopram and anticoagulant drugs or drugs that can affect platelet activity, such as - for example - NSAIDs (non-steroidal anti-inflammatory drugs), acetylsalicylic acid, ticlopidine (an antiplatelet agent platelet) and dipyridamole (a drug used for the prevention of thromboembolism).
Caution should be used in the concomitant administration of citalopram and drugs that induce hypokalemia and / or hypomagnesaemia (a decrease in the potassium and magnesium circulation, respectively).
Since citalopram lowers the seizure threshold, great caution should be used in the concomitant administration of drugs that can also lower the seizure threshold, including neuroleptics, tramadol, mefloquine (an antimalarial) and bupropion (an antidepressant).
Cimetidine (a drug used to treat gastric ulcer) may increase the plasma concentration of citalopram; therefore, caution should be used in the event of simultaneous administration.
The combination of citalopram with moclobemide (another antidepressant drug) is not recommended due to the interactions that could occur.
The combination of citalopram and alcohol should be avoided.
Side effects
Citalopram - like any other drug - can induce various side effects. The type of adverse effects and the intensity with which they occur vary between patients depending on the individual's sensitivity to the drug.
The following are the main side effects that can occur during citalopram therapy.
Blood and lymphatic system disorders
Treatment with citalopram may affect the hemolymphopoietic system (the system responsible for the synthesis of blood cells). In particular, citalopram can induce thrombopenia, which can cause a reduction in the number of platelets in the bloodstream, with consequent increased susceptibility to abnormal bleeding and / or bleeding.
Endocrine disorders
Citalopram can trigger the syndrome of inappropriate production of antidiuretic hormone (SIADH). This syndrome could be attributed to the onset of hyponatremia, ie a decrease in sodium levels in the bloodstream.
Metabolism and nutrition disorders
Decreased appetite and body weight following treatment with citalopram is very common. However - although more rarely - citalopram can also promote an increase in appetite and body weight.
Furthermore, the drug can cause hypokalemia, which is a decrease in blood levels of potassium. This decrease could give rise to heart problems.
Psychiatric disorders
Treatment with citalopram may give rise to several adverse psychiatric effects, including:
- agitation;
- Anxiety;
- Nervousness;
- Decreased libido;
- Confusional state;
- Disorders of dream activity;
- Aggression;
- depersonalization;
- Hallucinations;
- Mania;
- Panic attacks;
- Restlessness;
- Suicidal ideation and behavior.
Nervous system disorders
Citalopram therapy can cause drowsiness, headache, insomnia, tremors, paraesthesia, dizziness and attention disorders. Furthermore, the drug can cause convulsions, extrapyramidal disorders (ie Parkinson-like symptoms), dyskinesia and movement disorders.
Eye disorders
Following the intake of citalopram mydriasis (dilation of the pupil) and visual disturbances may occur.
Ear disorders
The use of citalopram can cause tinnitus, a disorder characterized by the perception of noises such as rustling, buzzing, whistling, etc.
Cardiovascular disorders
Citalopram therapy can cause bradycardia, tachycardia, ventricular arrhythmias and prolongation of the QT interval.
On the vascular level, however, citalopram can cause orthostatic hypotension, ie the abrupt lowering of blood pressure following the passage from a sitting or lying position to an upright position.
Gastrointestinal disorders
Citalopram can cause nausea, vomiting, diarrhea or constipation, dry mouth and even gastrointestinal and rectal bleeding.
Hepatobiliary disorders
Treatment with citalopram may cause abnormal liver function tests and promote hepatitis.
Skin and subcutaneous tissue disorders
Citalopram can cause skin reactions, hives, itching, increased sweating, alopecia, bruising (bruising) and angioedema. Furthermore, the drug can cause photosensitivity reactions and purpura (appearance of spots on skin, organs and mucous membranes due to capillary rupture).
Breast and reproductive disorders
In men, treatment with citalopram can cause impotence, ejaculation disorders, ejaculation failure, priapism (long and painful erection not accompanied by sexual arousal) and galactorrhoea (secretion of milk from the nipples).
In women, however, citalopram therapy can cause menorrhagia (excessive blood loss during the menstrual cycle) and metrorrhagia (abnormal uterine bleeding - abundant and for a long period - which occurs between two consecutive menstrual cycles).
Serotonin syndrome
Treatment with citalopram can cause serotonin syndrome, especially when used in combination with other drugs that increase the serotonin signal.
This syndrome is characterized by an excess of serotonergic activity in the central nervous system. It can also be defined as a serotonin poisoning . The syndrome can occur in mild, moderate or severe form.
The main symptoms that can arise are:
- Tachycardia;
- Chills;
- Increased sweating;
- Headache;
- mydriasis;
- Tremors;
- Myoclonia (short and involuntary contraction of a muscle or a group of muscles);
- spasms;
- Accurate reflexes;
- Accentuation of intestinal sounds (borborigmas);
- Diarrhea;
- Hypertension;
- Temperature;
- Rhabdomyolysis (rupture of skeletal muscle cells and subsequent release into the bloodstream of substances present in the musculature);
- Convulsions;
- Kidney failure.
If the syndrome occurs in severe form, there is a marked increase in heart rate and blood pressure and the patient can enter a state of shock.
Bone fractures
An increased risk of bone fractures during citalopram therapy has been shown, predominantly in patients over 50 years of age.
Suspension symptoms
Following the abrupt cessation of treatment with citalopram, so-called withdrawal symptoms may arise. These symptoms are dizziness, sensory disturbance, agitation, anxiety, nausea, vomiting, tremor, confusion, palpitations, headache, diarrhea, emotional instability and visual disturbances.
Other side effects
Other side effects that may occur during treatment with citalopram are:
- Allergic reactions in sensitive subjects;
- Fatigue;
- Myalgia;
- arthralgia;
- Urinary retention;
- Edema;
- Temperature.
Overdose
There is no antidote for citalopram overdose, therefore, the therapy is only symptomatic and supportive. The symptoms that can manifest are tiredness, weakness, sedation, nausea, tremor and tachycardia. In cases of more serious overdose, convulsions and rhabdomyolysis may also occur.
In case of overdosage, the use of activated charcoal, osmotic laxatives and gastric lavage may be useful. In any case, if you suspect you have taken an overdose of medication, you must immediately contact a doctor and / or contact the nearest hospital.
Action mechanism
Citalopram is a highly selective inhibitor of serotonin reuptake.
Serotonin (5-HT) is a neurotransmitter that is produced within the presynaptic nerve termination and is released following certain stimuli.
Once in the synaptic wall (the space between the presynaptic and postsynaptic termination), 5-HT interacts with its receptors placed on the postsynaptic nerve termination to perform its biological function. After that, serotonin binds to the receptor responsible for its reuptake (SERT) and is brought back into the presynaptic termination.
Citalopram is able to bind to SERT instead of serotonin which therefore remains in the synaptic wall for a prolonged period of time. Prolonged permanence in the synaptic space causes serotonin to continue to interact with its postsynaptic receptors. In this way there is an increase in the serotonergic signal with consequent improvement of the psychiatric pathologies treated.
Mode of Use - Posology
Citalopram is available for oral administration and is found in the form of oral tablets and drops.
The dosage must be established by the doctor on an individual basis according to the pathology to be treated and according to the patient's condition and clinical picture.
Generally, elderly patients and patients with reduced liver and / or kidney function need a reduced dose.
The following are the doses of citalopram usually used.
Endogenous depression
The dose of citalopram - usually used in adults - is 20 mg of drug per day, which can be increased up to 40 mg. The antidepressant effect occurs within 2-4 weeks of starting therapy.
Anxiety disorders with panic crisis, with or without agoraphobia
In this case, the recommended starting dose of citalopram is 10 mg per day, which can be increased up to 20 mg. Depending on the patient's response, the dose may be increased up to a maximum of 40 mg. For this type of pathology, maximum effectiveness is reached after about three months of treatment.
Pregnancy and breastfeeding
Citalopram can be used during pregnancy only in cases of real need. In any case, the newborn must be carefully monitored after giving birth, especially if the mother took the drug during the third trimester of gestation.
Following the use of citalopram during the later stages of pregnancy, the newborn may experience symptoms such as respiratory disorders, cyanosis, apnea, convulsions, unstable temperature, difficulty in nutrition, vomiting, hypoglycemia, hypertonia, hypotonia, tremor, nervousness, irritability, lethargy, chronic crying, drowsiness and difficulty sleeping.
Furthermore, citalopram can promote the appearance in newborns of a severe syndrome called persistent pulmonary hypertension that manifests itself with an increase in the respiratory rate and a bluish complexion of the skin. These symptoms usually occur within 24 hours after birth
Citalopram is excreted - albeit minimally - in breast milk, so great caution is advised during breastfeeding.
Contraindications
The use of citalopram is contraindicated in the following cases:
- Known hypersensitivity to citalopram;
- In children and adolescents under the age of 18;
- In patients with congenital long QT syndrome or who suffer from prolongation of the QT interval;
- In patients already being treated with MAOIs.
