Fluvoxamine

Fluvoxamine is an antidepressant drug belonging to the selective serotonin reuptake inhibitor (SSRI) class. This drug was one of the first SSRIs to be approved and marketed.

Fluvoxamine - Chemical Structure

Indications

For what it uses

The use of fluvoxamine is indicated for the treatment of:

Major depressive episode;
Obsessive-compulsive disorder.

In reality - besides having antidepressant action - fluvoxamine also has a certain anxiolytic activity, therefore it could be useful in the treatment of forms of anxious depression.

Warnings

Depression increases the risk of suicidal thoughts, self-harm and suicide. Since the improvement of these symptoms may not occur in the first periods of treatment, it is good to monitor the patients until the above improvement is achieved.

Patients with pre-existing renal and / or hepatic impairment should be carefully monitored.

Fluvoxamine intake may alter glycemic control in patients with diabetes, especially during the first treatment period. For this reason, a dose adjustment of oral administered hypoglycemic agents may be necessary.

Caution should be exercised when administering fluvoxamine in patients with a history of seizure disorders. The use of fluvoxamine in patients with uncontrolled epilepsy should be avoided. While the use of the drug in patients with controlled epilepsy requires careful monitoring.

The combination of fluvoxamine with other drugs able to increase the serotonin signal can favor the appearance of serotonin syndrome.

Care must be taken with the administration of fluvoxamine in patients with a history of coagulation disorders, especially when it is given in combination with drugs that can cause a reduction in the number of platelets in the bloodstream.

Caution should be exercised when administering fluvoxamine in patients with a history of mania or hypomania.

Special attention should be paid to the administration of fluvoxamine in patients who have suffered from myocardial infarction.

In children and adolescents under 18 with depression, treatment with fluvoxamine is not indicated.

Care must be taken with the administration of fluvoxamine performed simultaneously with electroconvulsive therapy.

Interactions

Concomitant administration of fluvoxamine with St. John's wort (or St. John's wort, a plant with antidepressant properties) may increase the side effects of fluvoxamine itself.

The combination of fluvoxamine with monoamine oxidase inhibitors ( MAOIs ) should be avoided.

Patients treated with fluvoxamine and oral anticoagulants are more susceptible to the risk of developing bleeding.

Concomitant administration of the following drugs in combination with fluvoxamine may increase the risk of developing serotonin syndrome:

Lithium (used for the treatment of bipolar disorders);
Tryptophan (the amino acid from which serotonin is synthesized);
Hypericum .

Fluvoxamine should not be administered concomitantly with terfenadine, an antihistamine drug used in the treatment of asthma.

A lot of attention must be paid to the concomitant administration of fluvoxamine to the following drugs, as interactions able to influence the mutual activity can be established:

Antipsychotics, such as phenothiazine, pimozide, clozapine and haloperidol ;
Tricyclic antidepressants (TCA), such as imipramine, desipramine and amitriptyline ;
Benzodiazepines;
Acetylsalicylic acid (an anti-inflammatory drug);
Ciclosporina (a drug used for the prevention of rejection in transplants);
Methadone (a synthetic opioid used for the treatment of pain and for the palliative treatment of drug withdrawal symptoms);
Mexiletine (an antiarrhythmic drug);
Phenytoin and carbamazepine (drugs used to treat epilepsy);
Propranolol (an antihypertensive);
Terfenadine (an antihistamine drug);
Ropinirole (a drug used to treat Parkinson's disease);
Triptans (medicines used for the treatment of migraine);
Sildenafil (a drug used for erectile dysfunction);
Tramadol (an opioid painkiller).

The combination of alcohol with drugs that inhibit serotonin reuptake (including fluvoxamine) should be avoided.

It would be good to reduce the consumption of caffeinated beverages (such as tea and coffee), as excessive caffeine intake in conjunction with fluvoxamine therapy can cause discomfort, hand tremor, tachycardia, restlessness and insomnia.

Side effects

Fluvoxamine can induce various types of side effects. Each individual has his own sensitivity to the drug, so the type of adverse effects and the intensity with which they occur vary between patients.

Nervous system disorders

Treatment with fluvoxamine can cause headache, dizziness, sleepiness, tremor, ataxia and extrapyramidal symptoms (ie Parkinson's-like symptoms).

Convulsions, psychomotor agitation and events similar to the neuroleptic malignant syndrome may also occur.

Serotonin syndrome

Fluvoxamine can cause serotonin syndrome, especially when it is given in combination with other drugs that can enhance the serotonin signal.

It is a syndrome characterized by an excess of serotonergic activity in the central nervous system; it is also referred to as serotonin poisoning .

Intoxication can be mild, moderate or severe.

The symptoms that can manifest are:

Tachycardia;
Chills;
Increased sweating;
Headache;
Mydriasis (dilation of the pupils);
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 their release into the bloodstream);
Convulsions;
Kidney failure.

In the case of severe intoxication, there is a marked increase in heart rate and blood pressure. The patient may also enter a state of shock.

Gastrointestinal disorders

Fluvoxamine therapy can cause nausea and vomiting, but these symptoms are transient and disappear within a few weeks. Abdominal pain, dry mouth, diarrhea, dyspepsia or constipation may also occur.

Cardiac disorders

Treatment with fluvoxamine can cause palpitations and tachycardia .

Endocrine disorders

Fluvoxamine can cause the syndrome of inappropriate antidiuretic hormone secretion.

Skin and subcutaneous tissue disorders

Fluvoxamine therapy may cause skin rash, pruritus, angioedema and photosensitivity . An increase in sweating may also occur.

Reproductive system and breast disorders

Treatment with fluvoxamine can cause delayed ejaculation in men and galactorrhea in women, ie the abnormal production of milk in women who are not breastfeeding.

Psychiatric disorders

Fluvoxamine can induce agitation, anxiety, insomnia, restlessness, confusion, hallucinations, mania and suicidal ideas and behavior.

Suspension symptoms

Abrupt discontinuation of fluvoxamine treatment can cause so-called withdrawal symptoms which are:

Dizziness;
Sensory disorders;
Sleep disorders;
agitation;
Anxiety;
Confusion;
Emotional irritability;
Nausea and / or vomiting;
Diarrhea;
Palpitations;
Sweating;
Tremor;
Headache.

Generally, these symptoms occur in mild or moderate form and are self-limiting. However, in some patients they may also occur in severe and / or prolonged form.

Other side effects

Other adverse effects that may arise following treatment with fluvoxamine are:

Allergic reactions in sensitive subjects;
Hyponatraemia (ie the decrease in the amount of sodium in the bloodstream);
paresthesia;
Taste alterations;
Arthralgia and myalgia;
Anorexia;
Orthostatic hypotension (ie a sudden drop in blood pressure when moving from a sitting or lying position to an upright position);
Asthenia and malaise;
Abnormal liver function;
Plateletopenia, ie a reduction in the number of platelets in the bloodstream with consequent increased risk of developing abnormal bleeding and / or bleeding.

Overdose

The symptoms of fluvoxamine overdose are:

Nausea, vomiting and diarrhea;
Drowsiness and dizziness;
Tachycardia or bradycardia;
Hypotension;
Changes in liver function;
Convulsions;
Coma.

There is no antidote for overdosage. Drug therapy is only symptomatic. If you suspect you have taken an overdose of medication, you must immediately contact a doctor who can arrange for gastric emptying and administration of medicinal charcoal, possibly in association with an osmotic laxative.

Action mechanism

Serotonin (or 5-HT) is a neurotransmitter synthesized in presynaptic nerve endings. It is then released into the synaptic wall (the space between the presynaptic and postsynaptic nerve endings) following certain stimuli. Once outside the nerve endings, 5-HT - to carry out its biological activity - interacts with its receptors.

Finally, after explaining its action, serotonin binds to the transporter that operates its reuptake (the SERT) and is brought back into the nerve termination.

Fluvoxamine is a drug capable of inhibiting the reuptake of serotonin.

More in detail, fluvoxamine binds to SERT instead of 5-HT; in this way, it causes the neurotransmitter to remain within the synaptic wall for a prolonged time. The greater permanence of serotonin in the synaptic space produces an increase in the serotonergic signal on postsynaptic receptors. This induces an improvement of the depressive pathology within a few weeks (usually 2-4 weeks).

Mode of Use - Posology

Fluvoxamine is available for oral administration in the form of tablets to be taken without chewing and, preferably, in the evening.

Major depression (adults)

The usual dosage is 50-100 mg of drug, to be taken once a day.

Obsessive-compulsive disorder

For adults, the usual dose of fluvoxamine is 50 mg a day.

For adolescents and children aged 8 and over, suffering from obsessive-compulsive disorder, the usual dose of fluvoxamine is 25 mg, to be taken once a day.

The maximum daily dose of medication should not exceed 300 mg for adults and 200 mg for children and adolescents.